BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on th...BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is dec...BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is decided according to the size,and the site of the tumor,according to practice guidelines.Alpha fetoprotein(AFP),the most used biomarker in the guidelines,although specific,lacks sensitivity.New biomarkers are needed to understand the underlying pathophysiology,and to be used in clinical practice.AIM To study the effect of loco-regional treatment on telomere length,as a diagnostic and short-term(3 months)prognostic marker.METHODS This is a prospective cohort study,and includes 60 patients visiting Ain Shams University Hospitals.The patients were divided into 2 groups:30 patients with liver cirrhosis(group 1)and 30 HCC patients undergoing RF or TACE(group 2).Laboratory investigations for all patients included:Telomere length in peripheral leukocytes by polymerase chain reaction,AFP,and liver function.In the HCC group,the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline,and after 3 months.RESULTS With regard to age,Child-Pugh and Model for End-Stage Liver Disease scores,there was no statistically significant correlation with telomere length.However,there was a correlation between telomere length and age,and both scores before and after 3 months of treatment among HCC patients.On dividing the HCC group according to tumor size with a cutoff of 5 cm,and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size≥5 cm than in those with tumor size<5 cm(30 patients;P=0.03).In addition,we found a positive Spearman's rank correlation between telomere length and tumor size in the≥5 cm only group(28 samples from the before and after intervention data;P=0.025).CONCLUSION Telomere length in leukocytes is a potential marker in HCC tumor prognosis.Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.展开更多
BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle fact...BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.展开更多
Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within...Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.展开更多
Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression....Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.展开更多
BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly lead...BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.展开更多
Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabol...Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.展开更多
BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidel...BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidelines recommend early transitioning from triple antithrombotic therapy to dual antithrombotic therapy,but there are limited data on elderly patients.METHODS We performed a post-hoc age-specific analysis of the PERSEO Registry population aimed to compare clinical features,therapeutic strategies,and outcomes of individuals aged≥80 years and<80 years who were on OAT and underwent PCI with stent.The primary endpoint was net adverse clinical events at 1-year follow-up.Secondary endpoints included major adverse cardiac and cerebral events(MACCE),major bleeding[Bleeding Academic Research Consortium(BARC)type 3–5],and clinically relevant bleeding(BARC type 2-5).RESULTS Among the 1234 patients enrolled,31%of patients were aged≥80 years(84±3 years,76% males).Compared to younger patients,elderly patients had higher rates of comorbidities such as hypertension,anaemia or chronic kidney disease,and atrial fibrillation was the leading indication for OAT.Elderly patients were more often discharged on dual antithrombotic therapy(23%)compared to younger patients(13%)(P<0.0001).They experienced higher net adverse clinical events(38%vs.21%,P<0.001),MACCE(24%vs.12%,P<0.001),as well as higher bleeding rates.Specifically,rates of major bleeding(9%vs.6%,P=0.026),and clinically relevant bleeding(21%vs.12%,P<0.001)were significantly higher in elderly patients.CONCLUSIONS Elderly patients on OAT undergoing PCI are a particular frail population with higher risk of MACCE and bleeding compared to younger patients despite a less aggressive antithrombotic therapy.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Objectives:This study aimed to evaluate the clinical effectiveness,durability,and acceptability of a Korean medicine-based online mental health self-care program for mothers.Methods:This non-randomized comparative stu...Objectives:This study aimed to evaluate the clinical effectiveness,durability,and acceptability of a Korean medicine-based online mental health self-care program for mothers.Methods:This non-randomized comparative study evaluated the clinical effectiveness,durability,and acceptability of a Korean medicine-based online mental health self-care program for mothers.Group 1(regular version)included 120 participants who attended one live session per week for 5 weeks,while Group 2(shortened version)included 30 participants who completed five recorded sessions within 1 week.A total of 112 participants(93.3%)in Group 1 and all 30 participants(100%)in Group 2 completed the program and surveys.Results:Within-group analyses demonstrated significant improvements for depression(ΔCESD-10[Center for Epidemiological Studies Depression Scale-10]=−2.38±2.10,p<0.001;Cohen’s d=1.10),anxiety(ΔGAD-7[Generalized Anxiety Disorder Scale-7]=−3.82±3.20,p<0.001;d=0.93),and stress(ΔPSS[Perceived Stress Scale]=−6.44±4.50,p<0.001;d=1.12)in Group 1.Between-group analysis of covariance(ANCOVA)of postintervention scores showed significant differences favoring Group 1 in CESD-10(p<0.001)and GAD-7(p=0.025).These improvements were largely maintained through the 12-week follow-up(all p<0.001),indicating both statistical and clinical significance.The average willingness-to-pay per session was 8562.5±3609 KRW,and overall satisfaction was high.Conclusion:These findings demonstrate that the regular 5-week Korean medicine-based online program is effective,cost-effective,and capable of sustaining improvements in maternal mental health,supporting its potential use in community-based care strategies.展开更多
Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This...Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This analysis aimed to assess the dose-response effects of exercise in combination with a caloric restriction on fat mass(FM)and FM percentage(FM%)in persons with diagnosed type 2 diabetes.Methods:In this secondary analysis of a 4-armed randomized trial,82 persons living with type 2 diabetes were randomly allocated to the control group(CON)(n=21),diet control(DCON)(25%caloric restriction;n=20),diet control and exercise 3 times per week(MED)(n=20),or diet control and exercise 6 times per week(HED)(n=21)for 16 weeks.The primary analysis was the change in FM%points.Secondary analyses included fat-free mass and visceral adipose tissue(VAT)volume(cm^(3)).Results:FM%decreased compared to CON by a mean difference of-3.5%(95%confidence interval(95%CI):-5.6%to-1.4%),-6.3%(95%CI:-8.4%to-4.1%),and-8.0%(95%CI:-10.2%to-5.8%)for DCON,MED,and HED,respectively.Compared to DCON,MED,and HED decreased FM%by-2.8%(95%CI:-4.9%to-0.7%)and-4.5%(95%CI:-6.6%to-2.4%),respectively.The difference in FM%between HED and MED was-1.8%(95%CI:-3.9%to 0.4%).DCON and MED decreased fat-free mass compared to CON,whereas HED preserved fat-free mass(-0.2%;95%CI:-2.0%to 1.7%).Compared to CON,VAT volume decreased by-666.0 cm^(3)(95%CI:-912.8 cm^(3) to-385.1 cm^(3)),-1264.0 cm^(3)(95%CI:-1679.6 cm^(3) to-655.9 cm^(3)),and-1786.4 cm^(3)(95%CI:-2264.6 cm^(3) to-1321.2 cm^(3))more for DCON,MED,and HED,respectively.HED decreased VAT volume more than DCON(-1120.4 cm^(3);95%CI:-1746.6 cm^(3) to-639.4 cm^(3))while the remaining comparisons did not reveal any differences.Conclusion:All interventions were superior in reducing FM%compared to standard care.Adding exercise to a caloric restriction was superior in reducing FM%compared to a caloric restriction alone.展开更多
The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however...The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.展开更多
Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop met...Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.展开更多
Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets...Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.展开更多
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.展开更多
基金Supported by National Natural Science Foundation of China,No.82160762Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230267+2 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598060XChina Undergraduate Innovation and Entrepreneurship Training Program,No.X202410598360Future Academic Star of Guangxi Medical University,No.WLXSZX24074.
文摘BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is decided according to the size,and the site of the tumor,according to practice guidelines.Alpha fetoprotein(AFP),the most used biomarker in the guidelines,although specific,lacks sensitivity.New biomarkers are needed to understand the underlying pathophysiology,and to be used in clinical practice.AIM To study the effect of loco-regional treatment on telomere length,as a diagnostic and short-term(3 months)prognostic marker.METHODS This is a prospective cohort study,and includes 60 patients visiting Ain Shams University Hospitals.The patients were divided into 2 groups:30 patients with liver cirrhosis(group 1)and 30 HCC patients undergoing RF or TACE(group 2).Laboratory investigations for all patients included:Telomere length in peripheral leukocytes by polymerase chain reaction,AFP,and liver function.In the HCC group,the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline,and after 3 months.RESULTS With regard to age,Child-Pugh and Model for End-Stage Liver Disease scores,there was no statistically significant correlation with telomere length.However,there was a correlation between telomere length and age,and both scores before and after 3 months of treatment among HCC patients.On dividing the HCC group according to tumor size with a cutoff of 5 cm,and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size≥5 cm than in those with tumor size<5 cm(30 patients;P=0.03).In addition,we found a positive Spearman's rank correlation between telomere length and tumor size in the≥5 cm only group(28 samples from the before and after intervention data;P=0.025).CONCLUSION Telomere length in leukocytes is a potential marker in HCC tumor prognosis.Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.
基金Supported by Shandong Province Biliary Pancreatic Cancer Clinical Quality Specialty Construction Fund,No.SLCZDZK-2401.
文摘BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
文摘Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.
基金partially supported by the Construction Fund of Key Medical Disciplines of Hangzhou(No.OO2020491)the National Key Research and Development Program of China(No.2023YFC2506200)+4 种基金the Zhejiang Provincial Key Research and Development Program(No.2021C03107)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2023001B)the Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(No.2021R52016)the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(No.2020R01001)the Chinese Medical Education Association(No.2022KTZ004).
文摘Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.
基金approved by the Institutional Review Board of the University Hospital Centre Zagreb(Approval No:02/013 AG).
文摘BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.
文摘Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
基金was given by a 2017 Research Grant of the Italian Society of Interventional Cardiology (SICI-GISE)
文摘BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidelines recommend early transitioning from triple antithrombotic therapy to dual antithrombotic therapy,but there are limited data on elderly patients.METHODS We performed a post-hoc age-specific analysis of the PERSEO Registry population aimed to compare clinical features,therapeutic strategies,and outcomes of individuals aged≥80 years and<80 years who were on OAT and underwent PCI with stent.The primary endpoint was net adverse clinical events at 1-year follow-up.Secondary endpoints included major adverse cardiac and cerebral events(MACCE),major bleeding[Bleeding Academic Research Consortium(BARC)type 3–5],and clinically relevant bleeding(BARC type 2-5).RESULTS Among the 1234 patients enrolled,31%of patients were aged≥80 years(84±3 years,76% males).Compared to younger patients,elderly patients had higher rates of comorbidities such as hypertension,anaemia or chronic kidney disease,and atrial fibrillation was the leading indication for OAT.Elderly patients were more often discharged on dual antithrombotic therapy(23%)compared to younger patients(13%)(P<0.0001).They experienced higher net adverse clinical events(38%vs.21%,P<0.001),MACCE(24%vs.12%,P<0.001),as well as higher bleeding rates.Specifically,rates of major bleeding(9%vs.6%,P=0.026),and clinically relevant bleeding(21%vs.12%,P<0.001)were significantly higher in elderly patients.CONCLUSIONS Elderly patients on OAT undergoing PCI are a particular frail population with higher risk of MACCE and bleeding compared to younger patients despite a less aggressive antithrombotic therapy.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2020R1A5A2019413).
文摘Objectives:This study aimed to evaluate the clinical effectiveness,durability,and acceptability of a Korean medicine-based online mental health self-care program for mothers.Methods:This non-randomized comparative study evaluated the clinical effectiveness,durability,and acceptability of a Korean medicine-based online mental health self-care program for mothers.Group 1(regular version)included 120 participants who attended one live session per week for 5 weeks,while Group 2(shortened version)included 30 participants who completed five recorded sessions within 1 week.A total of 112 participants(93.3%)in Group 1 and all 30 participants(100%)in Group 2 completed the program and surveys.Results:Within-group analyses demonstrated significant improvements for depression(ΔCESD-10[Center for Epidemiological Studies Depression Scale-10]=−2.38±2.10,p<0.001;Cohen’s d=1.10),anxiety(ΔGAD-7[Generalized Anxiety Disorder Scale-7]=−3.82±3.20,p<0.001;d=0.93),and stress(ΔPSS[Perceived Stress Scale]=−6.44±4.50,p<0.001;d=1.12)in Group 1.Between-group analysis of covariance(ANCOVA)of postintervention scores showed significant differences favoring Group 1 in CESD-10(p<0.001)and GAD-7(p=0.025).These improvements were largely maintained through the 12-week follow-up(all p<0.001),indicating both statistical and clinical significance.The average willingness-to-pay per session was 8562.5±3609 KRW,and overall satisfaction was high.Conclusion:These findings demonstrate that the regular 5-week Korean medicine-based online program is effective,cost-effective,and capable of sustaining improvements in maternal mental health,supporting its potential use in community-based care strategies.
基金supported by grants from Tryg Fonden(Grant No.123497 and Grant No.124708)Svend Andersen Fonden(this foundation does not use grant numbers,but the filename for the grant was 81-A.15)+2 种基金supported by TrygFonden(Grant No.101390,Grant No.20045,and Grant No.125132)supported by a research grant from the Danish Diabetes Academy(now called Danish Diabetes and Endocrine Academy),which is funded by the Novo Nordisk Foundation(Grant No.NNF17SA0031406)supported by the Canadian Institutes of Health Research(MFE-176582)。
文摘Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This analysis aimed to assess the dose-response effects of exercise in combination with a caloric restriction on fat mass(FM)and FM percentage(FM%)in persons with diagnosed type 2 diabetes.Methods:In this secondary analysis of a 4-armed randomized trial,82 persons living with type 2 diabetes were randomly allocated to the control group(CON)(n=21),diet control(DCON)(25%caloric restriction;n=20),diet control and exercise 3 times per week(MED)(n=20),or diet control and exercise 6 times per week(HED)(n=21)for 16 weeks.The primary analysis was the change in FM%points.Secondary analyses included fat-free mass and visceral adipose tissue(VAT)volume(cm^(3)).Results:FM%decreased compared to CON by a mean difference of-3.5%(95%confidence interval(95%CI):-5.6%to-1.4%),-6.3%(95%CI:-8.4%to-4.1%),and-8.0%(95%CI:-10.2%to-5.8%)for DCON,MED,and HED,respectively.Compared to DCON,MED,and HED decreased FM%by-2.8%(95%CI:-4.9%to-0.7%)and-4.5%(95%CI:-6.6%to-2.4%),respectively.The difference in FM%between HED and MED was-1.8%(95%CI:-3.9%to 0.4%).DCON and MED decreased fat-free mass compared to CON,whereas HED preserved fat-free mass(-0.2%;95%CI:-2.0%to 1.7%).Compared to CON,VAT volume decreased by-666.0 cm^(3)(95%CI:-912.8 cm^(3) to-385.1 cm^(3)),-1264.0 cm^(3)(95%CI:-1679.6 cm^(3) to-655.9 cm^(3)),and-1786.4 cm^(3)(95%CI:-2264.6 cm^(3) to-1321.2 cm^(3))more for DCON,MED,and HED,respectively.HED decreased VAT volume more than DCON(-1120.4 cm^(3);95%CI:-1746.6 cm^(3) to-639.4 cm^(3))while the remaining comparisons did not reveal any differences.Conclusion:All interventions were superior in reducing FM%compared to standard care.Adding exercise to a caloric restriction was superior in reducing FM%compared to a caloric restriction alone.
文摘The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
文摘Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.
基金funded by the Medical University of Lublin,Poland,grant number DS 458.
文摘Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.
基金supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
文摘Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
