BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and tech...BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.展开更多
BACKGROUND Patients with gastric cancer may have a risk of depression after radical surgery,which affects recovery and requires intensive intervention.AIM To explore the role of Bifidobacterium triple viable bacteria-...BACKGROUND Patients with gastric cancer may have a risk of depression after radical surgery,which affects recovery and requires intensive intervention.AIM To explore the role of Bifidobacterium triple viable bacteria-assisted mirtazapine in patients with depression after radical surgery for gastric cancer.METHODS This study included 80 patients with gastric cancer who experienced depression after undergoing radical surgery from January 2022 to December 2023 at Jiangnan University Hospital in Wuxi city in Jiangsu province.The patients were categorized into the control group(n=40)treated with mirtazapine and observation group(n=40)treated with combined Bifidobacterium triple viable bacteria-assisted mirtazapine.Neuroendocrine index,intestinal flora level,nutrition status,and patient quality of life were analyzed.RESULTS Before drug index level,no statistically significant difference was observed between the two groups (P>0.05).After drug administration,both groups experienced a decline in depression scores,cortisol,Escherichia coli,Enterococcus faecalis levels,and quality of life scores,whereas dopamine,serotonin,Lactobacillus,Bifidobacteria,hemoglobin,serum albumin and prealbumin levels increased.The observation group demonstrated significantly greater improvements across these indicators,with significant differences within groups and between groups(P<0.05).CONCLUSION Bifidobacterium has a relieving effect on depression in patients after radical surgery for gastric cancer,improves neuroendocrine status,regulates intestinal flora,and improves nutritional status and quality of life.展开更多
BACKGROUND Total hip arthroplasty(THA)is an increasingly common treatment for older patients with hip osteoarthritis.Psychological stress is common before THA,although its clinical effects on selected parameters such ...BACKGROUND Total hip arthroplasty(THA)is an increasingly common treatment for older patients with hip osteoarthritis.Psychological stress is common before THA,although its clinical effects on selected parameters such as joint function,quality of life,and postoperative complications remain unclear.AIM To investigate the effects of preoperative psychological stress on selected parameters in older patients who underwent THA.METHODS Ninety older patients who underwent THA between January 2023 and August 2024 were divided into two groups by their preoperative self-rated anxiety scale and self-rated depression scale scores,including high-stress(n=42)and lowstress(n=48).The postoperative joint function,short form-36 health survey(SF36)score,incidence of postoperative complications,and other indicators were compared between the two groups.Pearson’s correlation coefficient analysis of the relationship among preoperative psychological stress,quality of life,and postoperative complications was performed.RESULTS Postoperative joint function and quality of life were lower in the high-stress group than they were in the low-stress group(P<0.05).The incidence of postoperative complications was higher in the high-stress group(29.27%)than it was in the low-stress group(9.30%)(P<0.05).Cor-relation analysis revealed that psychological stress was correlated with the Harris hip and SF-36 scores.Total scores on the scale,including physical function,physical pain,general health,mental health,social function,vitality,and emotional function,were negatively correlated(P<0.05).CONCLUSION Preoperative psychological stress results in adverse effects on quality of life and complications in older patients undergoing THA.Therefore,pre-operative psychological interventions should be strengthened to improve postoperative outcomes.展开更多
Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secret...Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.展开更多
BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increas...BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.展开更多
BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherap...BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.AIM To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil(5-FU),bleomycin and cisplatin.METHODS Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon,followed by an end-to-end anastomosis under general anesthesia.The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days.The control group(A)received normal saline.Group B received chemotherapy with 5-FU(20 mg/kg),bleomycin(4 mg/kg)and cisplatin(0.7 mg/kg).Group C received GH(2 mg/kg),and group D received the aforementioned combination chemotherapy and GH,as described.The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscop-ically examined.Body weight,bursting pressure,hydroxyproline levels and inflammation markers were measured.RESULTS All rats survived until the day of sacrifice,with no infections or other complications.A decrease in the body weight of group D rats was observed,not statistically significant compared to group A(P=1),but significantly different to groups C(P=0.001)and B(P<0.01).Anastomotic dehiscence rate was not statistically different between the groups.Bursting pressure was not significantly different between groups A and D(P=1.0),whereas group B had a significantly lower bursting pressure compared to group D(P<0.001).All groups had significantly more adhesions than group A.Hydroxyproline,as a measurement of collagen deposition,was significantly higher in group D compared to group B(P<0.05),and higher,but not statistically significant,compared to group A.Significant changes in group D were recorded,compared to group A regarding inflammation(3.450 vs 2.900,P=0.016)and fibroblast activity(2.75 vs 3.25,P=0.021).Neoangiogenesis and collagen deposition were not signifi-cantly different between groups A and D.Collagen deposition was significantly increased in group D compared to group B(P<0.001).CONCLUSION Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis.However,GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.展开更多
We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from...We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from the angle of the mandible to the upper mediastinum.Disruption of the thymic descent can result in ectopically/abnormally localised islets of accessory thymic tissue,which may undergo cystic changes,as described in a case report by Sun et al.This anatomical variation of the thymus may be clinically misinterpreted as a neoplasm or other congenital anomalies as a branchial cyst,lymphatic malformation or cystic hygroma.The present editorial focuses on the challenge of establishing a diagnosis of ectopically localised tissue of thymus often presented as a lateral cervical mass,especially in the case of cystic variation/degeneration of this thymic tissue.We summarise hypotheses on the origin of such congenital cervical thymic cysts from the point of view of evolutionary history and embryology.We also discuss lesser-known facts about the anatomy,histopathology and developmental biology of the thymus as one of the most enigmatic organs in the human body.展开更多
Laparoscopic cholecystectomy(LC)remains one of the most commonly performed procedures in adult and paediatric populations.Despite the advances made in intraoperative biliary anatomy recognition,iatrogenic bile duct in...Laparoscopic cholecystectomy(LC)remains one of the most commonly performed procedures in adult and paediatric populations.Despite the advances made in intraoperative biliary anatomy recognition,iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems.A series of methods have been proposed to prevent bile duct injury,among them the use of indocyanine green(ICG)fluorescence.The most commonly reported method of ICG injection is the intravenous administration,while literature is lacking studies investigating the direct intragallbladder ICG injection.This narrative mini-review aims to assess the potential applications,usefulness,and limitations of intragallbladder ICG fluorescence in LC.Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy,as well as special issues regarding its use.Literature search retrieved four prospective cohort studies,three case-control studies,and one case report.In the three case-control studies selected,intragallbladder near-infrared cholangiography(NIRC)was compared with standard LC under white light,with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography(IOC).In total,133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC.Literature includes several reports of intragallbladder ICG administration,but a standardized technique has not been established yet.Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping,overwhelming limitations of IOC including intervention and radiation exposure,as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence.Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.展开更多
Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension.The transition from compensated to decom-pensated cirrhosis involves hemodynamic changes leading t...Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension.The transition from compensated to decom-pensated cirrhosis involves hemodynamic changes leading to multiorgan dysfun-ction,managed predominantly in outpatient settings with regular monitoring.The mortality risk is elevated in decompensated patients.Therefore,diligent outpatient management should focus on regular medical follow-ups,medication adjustments,patient education,addressing emergent issues and evaluation for liver transplantation.The ultimate goal is to improve quality of life,prevent di-sease progression,reduce complications,and assess possible recompensation.This guide provides valuable recommendations for medical experts managing de-compensated cirrhotic patients post-hospitalization.展开更多
BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patien...BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.展开更多
BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and co...BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.展开更多
The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth,survival,migration and angiogenesis,and its abnormal activation is closely related to the occur...The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth,survival,migration and angiogenesis,and its abnormal activation is closely related to the occurrence and development of various tumors.This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors.In terms of diagnosis,the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient,providing a reliable basis for individualized treatment.In terms of treatment,MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials.In addition,the combination of immunotherapy and MET inhibitors also demonstrated potential synergies,further improving the therapeutic effect.However,the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research.In the future,it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients.The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization,and have broad application prospects.展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
BACKGROUND Electronic cigarettes(ECs)have been promoted as alternatives to traditional cigarettes.To investigate ECs’effects on respiratory system,especially in patients with respiratory diseases.METHODS We randomly ...BACKGROUND Electronic cigarettes(ECs)have been promoted as alternatives to traditional cigarettes.To investigate ECs’effects on respiratory system,especially in patients with respiratory diseases.METHODS We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers.All were subjucted to pulmonary function tests(PFTs),impulse oscillometry(IOS),fraction exhaled Nitric Oxide(FeNO),exhaled breathe condensate(EBC)and biomarker measurements before and after vaping one nicotinecontaining EC.RESULTS The increase in FeNO 30 minutes after EC,reflecting airway inflammation,significantly correlated with increase of residual volume(RV),total lung capacity,respiratory impedance at 5 Hz(Z5Hz)and respiratory resistance at 5 and 20 Hz(R5Hz and R20Hz).No significant correlations were found between EBC biomarkers'changes and respiratory mechanics.CONCLUSION This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.展开更多
AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral ...AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.展开更多
Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pa...Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pancreatic juice and bile are constantly mixed, producing a variety of harmful substances. Because of this, the biliary mucosa is repeatedly damaged and repaired, which causes an acceleration of cell proliferative activity and multiple gene mutations. Histological changes such as hyperplasia, metaplasia, and dysplasia ultimately result in a high incidence of carcinogenesis. In a nationwide survey by the Japanese Study Group on PBM, coexisting biliary tract cancer was detected in 278 of the 1627 registered cases of PBM (17.1%). Of these cases, in those with dilatation of the extrahepatic bile duct, cancer was often detected not only in the gallbladder but also in the bile ducts. More than 90% of cancer cases without dilatation of the extrahepatic bile duct develop in the gallbladder. Standard treatment for PBM is a cholecystectomy and resection of the extrahepatic bile duct. However, cholecystectomy alone is performed at nearly half of institutions in Japan. Conversely, reports of carcinogenesis in the remnant bile duct or pancreas after diversion surgery are steadily increasing. One of the causes for this is believed to be an accumulation of gene mutations which were present before surgery. Anticancer drugs are ineffective in preventing such carcinogenesis following surgery, thus the postoperative administration of chemopreventive agents may be necessary.展开更多
Hepatopulmonary syndrome(HPS) is a frequent pulmonary complication of end-stage liver disease, characterized by impaired arterial oxygenation induced by intrapulmonary vascular dilatation. Its prevalence ranges from 4...Hepatopulmonary syndrome(HPS) is a frequent pulmonary complication of end-stage liver disease, characterized by impaired arterial oxygenation induced by intrapulmonary vascular dilatation. Its prevalence ranges from 4% to 47% in patients with cirrhosis due to the different diagnostic criteria applied among different studies. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of HPS according to the severity of hypoxemia has been suggested. Contrast-enhanced echocardiography represents the gold standard method for the detection of intrapulmonary vascular dilatations which is required, in combination with an elevated alveolar arterial gradient to set the diagnosis. The only effective treatment which can modify the syndrome's natural history is liver transplantation. Although it is usually asymptomatic, HPS imparts a high risk of pretransplantation mortality, independently of the severity of liver disease, while there is variable data concerning survival rates after liver transplantation. The potential of myocardial involvement in the setting of HPS has also gained increasing interest in recent research. The aim of this review is to critically approach the existing literature of HPS and emphasizeunclear points that remain to be unraveled by future research.展开更多
Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that...Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gutliver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.展开更多
Osteoclast-like giant cell tumors （OGCT） are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with...Osteoclast-like giant cell tumors （OGCT） are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient＇s survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is as...Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.展开更多
文摘BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.
文摘BACKGROUND Patients with gastric cancer may have a risk of depression after radical surgery,which affects recovery and requires intensive intervention.AIM To explore the role of Bifidobacterium triple viable bacteria-assisted mirtazapine in patients with depression after radical surgery for gastric cancer.METHODS This study included 80 patients with gastric cancer who experienced depression after undergoing radical surgery from January 2022 to December 2023 at Jiangnan University Hospital in Wuxi city in Jiangsu province.The patients were categorized into the control group(n=40)treated with mirtazapine and observation group(n=40)treated with combined Bifidobacterium triple viable bacteria-assisted mirtazapine.Neuroendocrine index,intestinal flora level,nutrition status,and patient quality of life were analyzed.RESULTS Before drug index level,no statistically significant difference was observed between the two groups (P>0.05).After drug administration,both groups experienced a decline in depression scores,cortisol,Escherichia coli,Enterococcus faecalis levels,and quality of life scores,whereas dopamine,serotonin,Lactobacillus,Bifidobacteria,hemoglobin,serum albumin and prealbumin levels increased.The observation group demonstrated significantly greater improvements across these indicators,with significant differences within groups and between groups(P<0.05).CONCLUSION Bifidobacterium has a relieving effect on depression in patients after radical surgery for gastric cancer,improves neuroendocrine status,regulates intestinal flora,and improves nutritional status and quality of life.
文摘BACKGROUND Total hip arthroplasty(THA)is an increasingly common treatment for older patients with hip osteoarthritis.Psychological stress is common before THA,although its clinical effects on selected parameters such as joint function,quality of life,and postoperative complications remain unclear.AIM To investigate the effects of preoperative psychological stress on selected parameters in older patients who underwent THA.METHODS Ninety older patients who underwent THA between January 2023 and August 2024 were divided into two groups by their preoperative self-rated anxiety scale and self-rated depression scale scores,including high-stress(n=42)and lowstress(n=48).The postoperative joint function,short form-36 health survey(SF36)score,incidence of postoperative complications,and other indicators were compared between the two groups.Pearson’s correlation coefficient analysis of the relationship among preoperative psychological stress,quality of life,and postoperative complications was performed.RESULTS Postoperative joint function and quality of life were lower in the high-stress group than they were in the low-stress group(P<0.05).The incidence of postoperative complications was higher in the high-stress group(29.27%)than it was in the low-stress group(9.30%)(P<0.05).Cor-relation analysis revealed that psychological stress was correlated with the Harris hip and SF-36 scores.Total scores on the scale,including physical function,physical pain,general health,mental health,social function,vitality,and emotional function,were negatively correlated(P<0.05).CONCLUSION Preoperative psychological stress results in adverse effects on quality of life and complications in older patients undergoing THA.Therefore,pre-operative psychological interventions should be strengthened to improve postoperative outcomes.
基金the Biochemical Imaging Center at UmeåUniversity and the National Microscopy Infrastructure(VR-RFI 2019-00217),for providing assistance in microscopy.
文摘Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.
基金thank the staff of the accredited animal facility of the laboratory of anatomy,Histology and Embryology of Aristotle University of Thessaloniki’s veterinary school for their assistance in animal handling and care.
文摘BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.
文摘BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.AIM To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil(5-FU),bleomycin and cisplatin.METHODS Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon,followed by an end-to-end anastomosis under general anesthesia.The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days.The control group(A)received normal saline.Group B received chemotherapy with 5-FU(20 mg/kg),bleomycin(4 mg/kg)and cisplatin(0.7 mg/kg).Group C received GH(2 mg/kg),and group D received the aforementioned combination chemotherapy and GH,as described.The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscop-ically examined.Body weight,bursting pressure,hydroxyproline levels and inflammation markers were measured.RESULTS All rats survived until the day of sacrifice,with no infections or other complications.A decrease in the body weight of group D rats was observed,not statistically significant compared to group A(P=1),but significantly different to groups C(P=0.001)and B(P<0.01).Anastomotic dehiscence rate was not statistically different between the groups.Bursting pressure was not significantly different between groups A and D(P=1.0),whereas group B had a significantly lower bursting pressure compared to group D(P<0.001).All groups had significantly more adhesions than group A.Hydroxyproline,as a measurement of collagen deposition,was significantly higher in group D compared to group B(P<0.05),and higher,but not statistically significant,compared to group A.Significant changes in group D were recorded,compared to group A regarding inflammation(3.450 vs 2.900,P=0.016)and fibroblast activity(2.75 vs 3.25,P=0.021).Neoangiogenesis and collagen deposition were not signifi-cantly different between groups A and D.Collagen deposition was significantly increased in group D compared to group B(P<0.001).CONCLUSION Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis.However,GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.
文摘We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from the angle of the mandible to the upper mediastinum.Disruption of the thymic descent can result in ectopically/abnormally localised islets of accessory thymic tissue,which may undergo cystic changes,as described in a case report by Sun et al.This anatomical variation of the thymus may be clinically misinterpreted as a neoplasm or other congenital anomalies as a branchial cyst,lymphatic malformation or cystic hygroma.The present editorial focuses on the challenge of establishing a diagnosis of ectopically localised tissue of thymus often presented as a lateral cervical mass,especially in the case of cystic variation/degeneration of this thymic tissue.We summarise hypotheses on the origin of such congenital cervical thymic cysts from the point of view of evolutionary history and embryology.We also discuss lesser-known facts about the anatomy,histopathology and developmental biology of the thymus as one of the most enigmatic organs in the human body.
文摘Laparoscopic cholecystectomy(LC)remains one of the most commonly performed procedures in adult and paediatric populations.Despite the advances made in intraoperative biliary anatomy recognition,iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems.A series of methods have been proposed to prevent bile duct injury,among them the use of indocyanine green(ICG)fluorescence.The most commonly reported method of ICG injection is the intravenous administration,while literature is lacking studies investigating the direct intragallbladder ICG injection.This narrative mini-review aims to assess the potential applications,usefulness,and limitations of intragallbladder ICG fluorescence in LC.Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy,as well as special issues regarding its use.Literature search retrieved four prospective cohort studies,three case-control studies,and one case report.In the three case-control studies selected,intragallbladder near-infrared cholangiography(NIRC)was compared with standard LC under white light,with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography(IOC).In total,133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC.Literature includes several reports of intragallbladder ICG administration,but a standardized technique has not been established yet.Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping,overwhelming limitations of IOC including intervention and radiation exposure,as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence.Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.
文摘Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension.The transition from compensated to decom-pensated cirrhosis involves hemodynamic changes leading to multiorgan dysfun-ction,managed predominantly in outpatient settings with regular monitoring.The mortality risk is elevated in decompensated patients.Therefore,diligent outpatient management should focus on regular medical follow-ups,medication adjustments,patient education,addressing emergent issues and evaluation for liver transplantation.The ultimate goal is to improve quality of life,prevent di-sease progression,reduce complications,and assess possible recompensation.This guide provides valuable recommendations for medical experts managing de-compensated cirrhotic patients post-hospitalization.
文摘BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.
文摘BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition.
基金2023 Anhui Province Clinical Medical Research Transformation Project,No.202304295107020016.
文摘The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth,survival,migration and angiogenesis,and its abnormal activation is closely related to the occurrence and development of various tumors.This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors.In terms of diagnosis,the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient,providing a reliable basis for individualized treatment.In terms of treatment,MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials.In addition,the combination of immunotherapy and MET inhibitors also demonstrated potential synergies,further improving the therapeutic effect.However,the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research.In the future,it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients.The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization,and have broad application prospects.
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
文摘BACKGROUND Electronic cigarettes(ECs)have been promoted as alternatives to traditional cigarettes.To investigate ECs’effects on respiratory system,especially in patients with respiratory diseases.METHODS We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers.All were subjucted to pulmonary function tests(PFTs),impulse oscillometry(IOS),fraction exhaled Nitric Oxide(FeNO),exhaled breathe condensate(EBC)and biomarker measurements before and after vaping one nicotinecontaining EC.RESULTS The increase in FeNO 30 minutes after EC,reflecting airway inflammation,significantly correlated with increase of residual volume(RV),total lung capacity,respiratory impedance at 5 Hz(Z5Hz)and respiratory resistance at 5 and 20 Hz(R5Hz and R20Hz).No significant correlations were found between EBC biomarkers'changes and respiratory mechanics.CONCLUSION This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.
基金Supported by in part Grant-in-Aid for Scientific Research (C) (toK.K)
文摘AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.
文摘Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pancreatic juice and bile are constantly mixed, producing a variety of harmful substances. Because of this, the biliary mucosa is repeatedly damaged and repaired, which causes an acceleration of cell proliferative activity and multiple gene mutations. Histological changes such as hyperplasia, metaplasia, and dysplasia ultimately result in a high incidence of carcinogenesis. In a nationwide survey by the Japanese Study Group on PBM, coexisting biliary tract cancer was detected in 278 of the 1627 registered cases of PBM (17.1%). Of these cases, in those with dilatation of the extrahepatic bile duct, cancer was often detected not only in the gallbladder but also in the bile ducts. More than 90% of cancer cases without dilatation of the extrahepatic bile duct develop in the gallbladder. Standard treatment for PBM is a cholecystectomy and resection of the extrahepatic bile duct. However, cholecystectomy alone is performed at nearly half of institutions in Japan. Conversely, reports of carcinogenesis in the remnant bile duct or pancreas after diversion surgery are steadily increasing. One of the causes for this is believed to be an accumulation of gene mutations which were present before surgery. Anticancer drugs are ineffective in preventing such carcinogenesis following surgery, thus the postoperative administration of chemopreventive agents may be necessary.
文摘Hepatopulmonary syndrome(HPS) is a frequent pulmonary complication of end-stage liver disease, characterized by impaired arterial oxygenation induced by intrapulmonary vascular dilatation. Its prevalence ranges from 4% to 47% in patients with cirrhosis due to the different diagnostic criteria applied among different studies. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of HPS according to the severity of hypoxemia has been suggested. Contrast-enhanced echocardiography represents the gold standard method for the detection of intrapulmonary vascular dilatations which is required, in combination with an elevated alveolar arterial gradient to set the diagnosis. The only effective treatment which can modify the syndrome's natural history is liver transplantation. Although it is usually asymptomatic, HPS imparts a high risk of pretransplantation mortality, independently of the severity of liver disease, while there is variable data concerning survival rates after liver transplantation. The potential of myocardial involvement in the setting of HPS has also gained increasing interest in recent research. The aim of this review is to critically approach the existing literature of HPS and emphasizeunclear points that remain to be unraveled by future research.
文摘Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gutliver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.
文摘Osteoclast-like giant cell tumors （OGCT） are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient＇s survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.
