BACKGROUND Even though percutaneous coronary intervention(PCI)improved the survival of patients with acute myocardial infarction,still multivessel coronary artery disease remains an important factor burdening prognosi...BACKGROUND Even though percutaneous coronary intervention(PCI)improved the survival of patients with acute myocardial infarction,still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease(SVD).AIM To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease(MVD).METHODS The retrospective cohort of patients were divided into two groups:SVD and MVD group.The study population consisted of both male and female young(≤45 years)patients presented with ST-elevation myocardial infarction(STEMI)at the National Institute of Cardiovascular Disease,Karachi,Pakistan and undergone primary PCI from 1 st July 2017 to 31 st March 2018.Pre and postprocedure management of the patients was as per the guidelines and institutional protocols.RESULTS A total of 571 patients with STEMI,≤45 years were stratified into two groups by the number of vessels involved,342(59.9%)with SVD and 229(40.1%)with MVD.The average age of these patients was 39.04±4.86 years.A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group(25.1%vs 38%,P<0.01;11.7%vs 27.5%,P<0.001)respectively.While,smoking was more prevalent among the SVD group as compare to MVD group(36.3%vs 28.4%,P=0.05).The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group(48.8%vs 39.2%,P=0.021).Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98%vs 96.5%of the patients is SVD vs MVD group.CONCLUSION The MVD comprised of around 40%of the young patients presented with STEMI.Also,this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases,therefore,preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.展开更多
BACKGROUND:This study was undertaken to validate the use of the modified early warning score(MEWS) as a predictor of patient mortality and intensive care unit(ICU)/ high dependency(HD)admission in an Asian population....BACKGROUND:This study was undertaken to validate the use of the modified early warning score(MEWS) as a predictor of patient mortality and intensive care unit(ICU)/ high dependency(HD)admission in an Asian population.METHODS:The MEWS was applied to a retrospective cohort of 1 024 critically ill patients presenting to a large Asian tertiary emergency department(ED) between November 2006 and December2007.Individual MEWS was calculated based on vital signs parameters on arrival at ED.Outcomes of mortality and ICU/HD admission were obtained from hospital records.The ability of the composite MEWS and its individual components to predict mortality within 30 days from ED visit was assessed.Sensitivity,specificity,positive and negative predictive values were derived and compared with values from other cohorts.A MEWS of ≥4 was chosen as the cut-off value for poor prognosis based on previous studies.RESULTS:A total of 311(30.4%) critically ill patients were presented with a MEWS ≥4.Their mean age was 61.4 years(SD 18.1) with a male to female ratio of 1.10.Of the 311 patients,53(17%)died within 30 days,64(20.6%) were admitted to ICU and 86(27.7%) were admitted to HD.The area under the receiver operating characteristic curve was 0.71 with a sensitivity of 53.0%and a specificity of 72.1%in addition to a positive predictive value(PPV) of 17.0%and a negative predictive value(NPV)of 93.4%(MEWS cut-off of ≥4) for predicting mortality.CONCLUSION:The composite MEWS did not perform well in predicting poor patient outcomes for critically ill patients presenting to an ED.展开更多
Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology.Immunosuppression regulates antitumour immune responses.An immunosuppressive enzyme,indolea...Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology.Immunosuppression regulates antitumour immune responses.An immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO)mediates tumour immune escape in various malignancies including breast cancer.IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T(T-regs)cells into the tumour microenvironment,thus inhibiting local immune responses and promoting metastasis.Immunosuppression induced by myeloid derived suppressor cells activated in an IDOdependent manner may enhance the possibility of immune evasion in breast cancer.IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest,basal-like breast carcinoma.IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer.This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.展开更多
Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Method...Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.展开更多
BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin...BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immu...Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.展开更多
Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediat...Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.展开更多
Objective:To contribute to the development of clinical research on novel coronavirus by analyzing the clinical research data of COVID-19.Methods:Searches were performed on the database of“National Health Insurance In...Objective:To contribute to the development of clinical research on novel coronavirus by analyzing the clinical research data of COVID-19.Methods:Searches were performed on the database of“National Health Insurance Information Platform Medical Research Registration Information System”using the keywords“COVID-19”and“Novel coronavirus.”The search was performed till 31 December 2022.This paper presents a statistical analysis of the status quo of the registered projects in terms of the number of registered projects,the types of projects,the levels of the institutions,the types of research,the intervention measures,the research design,the main objectives of the research,and so on.Results:A total of 823 investigator-initiated clinical studies of COVID-19 were documented,and the number of studies registered peaked on December 31,2020,and December 31,2022.Among them,there were 819 items from general medical research(99.5%),812 items from medical institutions(98.7%),and 713 items from Medical Grade III,and Class A hospitals(86.6%).Among these items,534(64.9%)were observational studies.The most common intervention method used was administering existing drugs,with 140 studies utilizing them.This data analysis also included 128 case-control studies and 247 treatment-oriented studies.Conclusion:Researchers in local medical institutions have been actively carrying out clinical research related to COVID-19.However,they should refer to registered research to avoid duplicate research.展开更多
Simultaneous oncological and reconstructive plastic surgery on the mammary gland in the treatment of cancer is currently one of the important stages in the psychological rehabilitation of patients.In order to achieve ...Simultaneous oncological and reconstructive plastic surgery on the mammary gland in the treatment of cancer is currently one of the important stages in the psychological rehabilitation of patients.In order to achieve a good cosmetic result,reconstruction must be performed simultaneously with radical surgical treatment.Currently,there are a large number of methods for performing breast reconstruction.One of the most commonly used is radical subcutaneous/skin-sparing mastectomy with simultaneous reconstruction with a silicone endoprosthesis.Grand W Carlson type technique is used,with skin incisions in the form of an inverted T is usually performed in patients with large mammary gland with severe grade III ptosis,as the patients usually require reduction of excess skin.However,the most vulnerable aspects of this type of reconstruction is the impossibility of preserving the nipple-areolar complex(NAC),which is associated with a high risk of developing such complications as partial/complete necrosis of the NAC.The current study provides an overview of an original method to decrease the risk of necrosis of NAC with evaluation of blood supply of the nipple and inferior deepithelialized flap using real-time intraoperative Doppler ultrasonography and indocyanine green fluorescence system.展开更多
BACKGROUND For locally advanced gallbladder cancer,previous clinical studies have demon-strated that chemotherapy results in significant survival benefits when compared to surgery alone.However,data demonstrating a si...BACKGROUND For locally advanced gallbladder cancer,previous clinical studies have demon-strated that chemotherapy results in significant survival benefits when compared to surgery alone.However,data demonstrating a similar survival benefit with early-stage gallbladder cancer is limited.This study seeks to evaluate the impact chemotherapy has on survival in patients with early-stage gallbladder cancer using a large,multi-institution database.AIM To investigate the survival benefit of chemotherapy in patients with stage II gallbladder cancer.METHODS We performed a retrospective multivariable analysis of the National Cancer Database from 2010 to 2017 to evaluate the effect that chemotherapy has on the survival of patients with stage II gallbladder cancer.Our objective was to de-termine if there were any statistically significant survival differences between those who received surgery and chemotherapy vs those who only underwent surgery.RESULTS Of the 899 patients with stage II gallbladder cancer,328 patients had undergone chemotherapy and surgery.The average overall survival for those who had surgery and chemotherapy vs only surgery was 52.6 months and 51.1 months,respectively.This difference was not statistically significant(P=0.2).In the secondary analysis,the surgical group who had a liver resection had better overall survival(P<0.0001).CONCLUSION Practitioners should carefully consider chemotherapy for early-stage gallbladder cancer,as risks may outweigh survival benefits,and surgeons should also consider liver resections as part of their surgical management.展开更多
Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The ...Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The present study aimed to identify clinical and biological factors at admission associated with 30-day mortality in acute cholangitis,to build an efficient prognostic score based on these parameters and to study the performances of this new score.Methods:We enrolled all adult patients consecutively hospitalized for acute cholangitis between January 2017 and December 2021.We developed a score system named ProChol using variables significantly asso-ciated with 30-day mortality in multivariate logistic analysis and simplified this system(named sProChol)based on a simple points-based approach.Results:In total,528 patients were included,with an average age of 77±13 years,a male predominance(54.2%)and a majority of lithiasis etiology(66.5%).Mortality in 30 days was 11.9%.In multivariate logis-tic analysis,tumor etiology[adjusted odds ratio(aOR)=15.43,95%confidence interval(CI):5.90-40.40],stent obstruction(aOR=5.12,95%CI:2.02-12.99),hypoalbuminemia(aOR=3.50,95%CI:1.25-9.81),renal failure(aOR=6.51,95%CI:2.62-16.18),oxygen therapy(aOR=4.63,95%CI:1.02-20.92)and cu-rative anticoagulation(aOR=2.60,95%CI:1.23-5.52)were independently associated with the 30-day mortality while fever was a protective factor(aOR=0.37,95%CI:0.16-0.84).ProChol score using these 7 parameters and sProChol using the 3 robust factors(etiology,renal failure and anticoagulation)presented respectively an area under receiver operating characteristic(ROC)curves(AUC)of 0.81 and 0.77,higher than Tokyo(AUC=0.72)and Gravito-Soares et al.score(AUC=0.71).Patients with sProChol≥4 had a significantly higher risk of transfer to intensive care unit(13.3%vs.5.1%;P<0.001)and longer length of stay(P=0.0006).Conclusions:ProChol and sProChol constructed from simple clinico-biological parameters at admission,present interesting performances in predicting the 30-day mortality in acute cholangitis.展开更多
BACKGROUND Endoscopic bilateral biliary drainage is a first line palliative treatment for unresectable malignant hilar biliary obstruction(MHBO)but remains technically challenging.The emergence of self-expandable meta...BACKGROUND Endoscopic bilateral biliary drainage is a first line palliative treatment for unresectable malignant hilar biliary obstruction(MHBO)but remains technically challenging.The emergence of self-expandable metallic stents carried by an ultrathin(6 Fr or smaller)delivery system now permits simultaneous bilateral stent placement.To date,only a few studies have compared this new method with conventional sequential bilateral stenting.AIM To evaluate a possible superiority of simultaneous“side by side”(SBS)biliary drainage in unresectable MHBO.METHODS We identified 135 patients who benefited from bilateral drainage using uncovered self-expandable metallic stents between 2010 and 2023.Among them,62 benefited from simultaneous SBS bilateral drainage between 2017 and 2023,and 73 benefited from sequential bilateral drainage[38 using“stent in stent”(SIS)technique and 35 using SBS technique between 2010 and 2017].RESULTS Technical success was significantly increased in simultaneous drainage compared with sequential drainage(94%vs 75%,P=0.008).However,simultaneous SBS drainage and sequential SIS drainage had a similar technical success(94%vs 95%).We observed no differences regarding clinical success,procedure duration and recurrent biliary obstruction rate.Stent patency was shorter in the SIS group compared with the simultaneous group(103 days vs 144 days).Early adverse events were more frequent in the sequential group(31%vs 21%,P=0.205),with no differences regarding SIS or SBS technique.Technical failure was associated with a higher rate of infectious fatal adverse events(9.5%vs 1.7%,P=0.02).Reintervention after recurrent biliary obstruction seems to be more successful after using SBS rather than SIS techniques(83%vs 75%,P=0.53).CONCLUSION Simultaneous SBS metallic stent placement using an ultra-thin delivery system was technically easier and as efficient as sequential bilateral stenting in unresectable MHBO to achieve bilateral drainage.The SIS procedure remains a good option in unresectable MHBO.展开更多
BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects...BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects on pancreatic acinar cells.AIM To evaluate the synergistic effects of pirfenidone and simvastatin in an L-arginineinduced chronic pancreatitis model in mice.METHODS A preclinical,7-week study was performed using a mouse model of L-arginineinduced chronic pancreatitis.The mice were divided into five groups:Normal control;model control;pirfenidone-treated;simvastatin-treated;and combinationtreated(pirfenidone+simvastatin).Treatment started in week 3 after disease induction.Mice were euthanized at weeks 4 and 7 for blood collection and tissue sampling for histological and biomarker analysis,including cytokines,oxidative stress markers,and indicators of fibrosis.RESULTS Combination therapy significantly reduced levels of tumor necrosis factor-alpha(11.10±1.57 pg/mL vs 24.30±2.00 pg/mL),interleukin-10(11.70±1.12 pg/mL vs 19.60±1.27 pg/mL),and transforming growth factor-beta 1(236.13±6.95 pg/mL vs 550.52±42.18 pg/mL)at week 7(P<0.05 vs model control).The glutathione peroxidase 1 level increased across all treatment groups,significantly in the pirfenidonetreated group(5.47±0.34 IU/mL vs 5.04±0.43 IU/mL;P<0.05).Lipid peroxidation levels decreased significantly in the combination-treated group(111.87±7.36 mmol/mL vs 192.85±0.98 mmol/mL;P<0.05).Histology revealed extensive collagen accumulation and damage to the exocrine pancreas in the model control group(vs treatment groups).Combination therapy elicited the least damage.CONCLUSION Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation,fibrosis,and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model,suggesting promise for chronic pancreatitis management.展开更多
BACKGROUND End-stage renal disease is the final stage of chronic kidney disease,with hemodialysis as the primary treatment in India.Despite its prevalence,limited studies have focused on patient-reported outcomes,such...BACKGROUND End-stage renal disease is the final stage of chronic kidney disease,with hemodialysis as the primary treatment in India.Despite its prevalence,limited studies have focused on patient-reported outcomes,such as symptom burden and healthrelated quality of life.AIM To evaluate the symptom burden among adult hemodialysis patients and identify factors influencing their outcomes.METHODS A multi-center,cross-sectional study was conducted among 157 adult hemodialysis patients in Chennai from March 2024 to June 2024.The Dialysis Symptom Index tool was used to assess 30 physical and emotional symptoms.Correlations between symptom severity and clinical parameters,such as hemoglobin levels and urea reduction ratio(URR),were analyzed.RESULTS Moderate symptoms were reported by 48%of participants,with worry,insomnia,and feeling unwell identified as the most severe.Psychological symptoms significantly correlated with lower hemoglobin levels,while shortness of breath was linked to suboptimal URR values.Approximately 38%of patients had URR<65%,which was associated with increased symptom burden.CONCLUSION Hemodialysis patients experience a substantial psychological and sleep-related symptom burden,emphasizing the need for dialysis adequacy and better hemoglobin management.Enhanced strategies addressing these factors could significantly improve patient outcomes.展开更多
A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues&...A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues'differentiation,growth,and energy metabolism.Consequently,excess THs are expected to lead to profound organ function,regulation,and hemodynamic changes.In addition to their roles in metabolism and thermoregulation,THs play critical role in maintaining cardiovascular homeostasis through both genomic and non-genomic mechanisms.Receptors for THs are expressed in myocardial and vascular endothelial tissues,allowing fluctuations in circulating hormone levels to directly influence cardiovascular function.Excess TS induces a hyper-dynamic cardiovascular state,characterized by increased ventricular contractility and improved systolic and diastolic performance.The chronotropic and inotropic properties of THs result in dysregulation of blood pressure,heart rate,contractility,cardiac output,and systemic vascular resistance.This could lead to serious consequences such as cardiomyopathy,heart failure,and life-threatening arrhythmia,ultimately contributing to cardiocirculatory collapse and cardiac death.The management of TS necessitates a systematic approach that emphasizes the significance of resuscitation and identification of the underlying causes.It is crucial to prioritize assessing cardiac function in patients with TS.This review explores the clinical impact of TS on the heart and its clinical repercussions,emphasizing the intricate molecular and pathophysiological mechanisms and the interplay between TS and key cardiovascular parameters.This review summarizes the current knowledge of pathophysiology,pharmacological and mechanical interventions,ranging from beta-blocker use to the surgical approach.展开更多
Objective The aim of this study was to examine the relationship between the sonographic hepatorenal index and stroke risk in patients with nonalcoholic fatty liver disease(NAFLD).Methods From December 2023 to July 202...Objective The aim of this study was to examine the relationship between the sonographic hepatorenal index and stroke risk in patients with nonalcoholic fatty liver disease(NAFLD).Methods From December 2023 to July 2024,72 NAFLD patients with stroke,53 stroke-free NAFLD patients,and 54 healthy controls were enrolled in our study.The hepatorenal index was calculated as the ratio of the echo intensity of the liver to that of the renal cortex.The mean brightness values for one region of interest within the right hepatic lobe and the other size-matched region at the same depth of field within the right kidney were obtained with two-dimensional ultrasound and a 1-to 6-MHz convex array probe.Laboratory tests were performed with a Cobas 8000 automatic biochemical analyzer.Univariate and multivariate analyses were adopted to analyze the risk factors for stroke in NAFLD patients.Results NAFLD patients had a greater hepatorenal index than healthy controls did(P<0.05).Additionally,NAFLD patients with stroke had an even greater hepatorenal index than did those with stroke-free NAFLD(P<0.001).Multivariate regression analysis further revealed that the hepatorenal index was independently associated with stroke risk in NAFLD patients(β=8.897,P<0.001)after controlling for age,body mass index,systolic blood pressure,and serum glucose,total cholesterol,alanine transaminase,and creatinine concentrations.Receiver operating characteristic curve analysis revealed a sensitivity of 62.5%and specificity of 95.3%for the hepatorenal index,with a cutoff value of 1.255 and an area under the curve of 0.80.Conclusion The increased sonographic hepatorenal index could be an independent predictor of stroke development in patients with NAFLD.展开更多
Gastric Cancer(GC)is a highly prevalent and poorly prognostic gastrointestinal malignancy with low overall treatment efficacy worldwide.Early diagnostic markers and potential therapeutic targets for GC treatment are u...Gastric Cancer(GC)is a highly prevalent and poorly prognostic gastrointestinal malignancy with low overall treatment efficacy worldwide.Early diagnostic markers and potential therapeutic targets for GC treatment are urgently needed.UFMylation,a novel ubiquitin-like modification is indispensable for numerous fundamental cellular processes.Deficiency in this modification is reported to be associated with several human diseases including cancer.Accumulating evidence suggests that the expression of the key UFMylation components is closely associated with GC cell proliferation,invasion,metastasis,and chemotherapy resistance.Recent clinical studies have further highlighted the prognostic value and therapeutic potential of UFMylation in the clinical management of GC.However,the precise molecular mechanisms through which UFMylation contributes to GC remain largely unclear.This review aims to summarize recent findings on the functional roles of UFMylation in diverse cellular processes,such as endoplasmic reticulum(ER)homeostasis,DNA damage response(DDR),protein translation,and quality control pathways,discuss potential underlying mechanisms in GC development and progression,and to explore potential therapeutic implications targeting the UFMylation pathway in GC.展开更多
Purpose:This study aimed to describe the effects of a 1-year lifestyle intervention on hemoglobin A1c(HbA1c)and cardiovascular risk factors5 years after cessation of the lifestyle intervention in persons with type 2 d...Purpose:This study aimed to describe the effects of a 1-year lifestyle intervention on hemoglobin A1c(HbA1c)and cardiovascular risk factors5 years after cessation of the lifestyle intervention in persons with type 2 diabetes(T2D).Methods:From April 2015 to August 2016,98 persons with T2D(duration<10 years)were randomly allocated(2:1,stratified by sex)to a 1-year lifestyle intervention group(INT)(n=64)or a standard care group(StC)(n=34).All participants received standard care with blinded,targetdriven medical therapy.INT included up to 5-6 weekly supervised aerobic and strength training sessions and dietary plans targeting a body mass index≤25 kg/m^(2).No intervention was given during the follow-up period.Forty-nine(77%)and 19(56%)participants in INT and StC attended the 6-year follow-up.Based on the original intention-to-treat population,the primary outcome was the change in HbA1c from baseline to 6-year follow-up.Secondary outcomes included weight,Low density lipoprotein(LDL)cholesterol,blood pressure(BP),and cardiorespiratory fitness.Results:Ninety-eight participants(mean age=54.6 years;46%women;mean baseline Hemoglobin A1c(HbA1c)=49.8 mmol/mol)were analyzed.HbA1c changed 6%and 13%in the INT and StC from baseline to 6-year follow-up(between group difference=-6%(95%confidence interval(95%CI):-14%to 3%);p=0.18).While no differences were observed for most secondary outcomes,the diastolic BP decreased6.0(95%CI:2.1 to 9.8)mmHg more in the StC compared to INT.Conclusion:The sustained effect of the lifestyle intervention on glycemic control and cardiovascular risk factors was marginal,and it was surprisingly associated with inferior diastolic BP regulation.展开更多
In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2....In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2.237,P=0.03),advancedage(OR=1.05/year,P=0.002),fever(OR=2.999,P=0.015),severe hydronephrosis(OR=6.129,P=0.011),and elevated urinary markers-particularly urineleukocytes(U-LEU+++:OR=66.0,P<0.001)and glucose(U-GLU+++:OR=7.248,P=0.005)as independent risk factors.These readily accessible clinicalparameters offer significant potential for early risk stratification in high-riskpopulations.While this STROBE-adherent study provides actionable insights,limitations include its single-center design and unaddressed antibiotic protocols.Future multicenter validation should assess residual stone impacts and optimizeintervention thresholds.This work establishes a foundation for targeted surveillanceprotocols in diabetic urolithiasis management.展开更多
Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical I...Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.展开更多
基金support of the staff members of the Clinical Research Department of the National Institute of Cardiovascular Diseases(NICVD)Karachi,Pakistan.
文摘BACKGROUND Even though percutaneous coronary intervention(PCI)improved the survival of patients with acute myocardial infarction,still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease(SVD).AIM To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease(MVD).METHODS The retrospective cohort of patients were divided into two groups:SVD and MVD group.The study population consisted of both male and female young(≤45 years)patients presented with ST-elevation myocardial infarction(STEMI)at the National Institute of Cardiovascular Disease,Karachi,Pakistan and undergone primary PCI from 1 st July 2017 to 31 st March 2018.Pre and postprocedure management of the patients was as per the guidelines and institutional protocols.RESULTS A total of 571 patients with STEMI,≤45 years were stratified into two groups by the number of vessels involved,342(59.9%)with SVD and 229(40.1%)with MVD.The average age of these patients was 39.04±4.86 years.A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group(25.1%vs 38%,P<0.01;11.7%vs 27.5%,P<0.001)respectively.While,smoking was more prevalent among the SVD group as compare to MVD group(36.3%vs 28.4%,P=0.05).The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group(48.8%vs 39.2%,P=0.021).Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98%vs 96.5%of the patients is SVD vs MVD group.CONCLUSION The MVD comprised of around 40%of the young patients presented with STEMI.Also,this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases,therefore,preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.
基金supported by grants from SingHealth Talent Development Fund,Singapore(TDF/CS001/2006)InfoComm Research Cluster,Nanyang Technological University,Singapore(2006ICT09)
文摘BACKGROUND:This study was undertaken to validate the use of the modified early warning score(MEWS) as a predictor of patient mortality and intensive care unit(ICU)/ high dependency(HD)admission in an Asian population.METHODS:The MEWS was applied to a retrospective cohort of 1 024 critically ill patients presenting to a large Asian tertiary emergency department(ED) between November 2006 and December2007.Individual MEWS was calculated based on vital signs parameters on arrival at ED.Outcomes of mortality and ICU/HD admission were obtained from hospital records.The ability of the composite MEWS and its individual components to predict mortality within 30 days from ED visit was assessed.Sensitivity,specificity,positive and negative predictive values were derived and compared with values from other cohorts.A MEWS of ≥4 was chosen as the cut-off value for poor prognosis based on previous studies.RESULTS:A total of 311(30.4%) critically ill patients were presented with a MEWS ≥4.Their mean age was 61.4 years(SD 18.1) with a male to female ratio of 1.10.Of the 311 patients,53(17%)died within 30 days,64(20.6%) were admitted to ICU and 86(27.7%) were admitted to HD.The area under the receiver operating characteristic curve was 0.71 with a sensitivity of 53.0%and a specificity of 72.1%in addition to a positive predictive value(PPV) of 17.0%and a negative predictive value(NPV)of 93.4%(MEWS cut-off of ≥4) for predicting mortality.CONCLUSION:The composite MEWS did not perform well in predicting poor patient outcomes for critically ill patients presenting to an ED.
文摘Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology.Immunosuppression regulates antitumour immune responses.An immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO)mediates tumour immune escape in various malignancies including breast cancer.IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T(T-regs)cells into the tumour microenvironment,thus inhibiting local immune responses and promoting metastasis.Immunosuppression induced by myeloid derived suppressor cells activated in an IDOdependent manner may enhance the possibility of immune evasion in breast cancer.IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest,basal-like breast carcinoma.IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer.This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.
文摘Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.
基金Supported by the French patient’s association against cancer(ligue contre le cancer),No.00001005238the French government IDEXISITE initiative,No.16-IDEX-0001-CAP 20-25+2 种基金CPER(Nex-N-Mob)the Auvergne-Rhône-Alpes region(“Thématiquesémergentes”),No.AV0004111the Ministère de l'Enseignement supérieur,de la Recherche et de l'Innovation,INSERM,University of Clermont Auvergne[UMR1071,UMR1107],INRAE[USC-1382].
文摘BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
基金funded by the Swiss National Science Foundation(#184912,in 2019)funding from the German Research Foundation(SFB 1483,in 2021).
文摘Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.
基金This study was supported by the Project of Xi’an Science and Technology Plan(23YXYJ0163)the Education and Teaching Reform Research Project of Xi’an Medical University in 2023(S202311840061)funds from the First Affiliated Hospital of Xi’an Medical University of China(XYYFY-2023-01).
文摘Objective:To contribute to the development of clinical research on novel coronavirus by analyzing the clinical research data of COVID-19.Methods:Searches were performed on the database of“National Health Insurance Information Platform Medical Research Registration Information System”using the keywords“COVID-19”and“Novel coronavirus.”The search was performed till 31 December 2022.This paper presents a statistical analysis of the status quo of the registered projects in terms of the number of registered projects,the types of projects,the levels of the institutions,the types of research,the intervention measures,the research design,the main objectives of the research,and so on.Results:A total of 823 investigator-initiated clinical studies of COVID-19 were documented,and the number of studies registered peaked on December 31,2020,and December 31,2022.Among them,there were 819 items from general medical research(99.5%),812 items from medical institutions(98.7%),and 713 items from Medical Grade III,and Class A hospitals(86.6%).Among these items,534(64.9%)were observational studies.The most common intervention method used was administering existing drugs,with 140 studies utilizing them.This data analysis also included 128 case-control studies and 247 treatment-oriented studies.Conclusion:Researchers in local medical institutions have been actively carrying out clinical research related to COVID-19.However,they should refer to registered research to avoid duplicate research.
文摘Simultaneous oncological and reconstructive plastic surgery on the mammary gland in the treatment of cancer is currently one of the important stages in the psychological rehabilitation of patients.In order to achieve a good cosmetic result,reconstruction must be performed simultaneously with radical surgical treatment.Currently,there are a large number of methods for performing breast reconstruction.One of the most commonly used is radical subcutaneous/skin-sparing mastectomy with simultaneous reconstruction with a silicone endoprosthesis.Grand W Carlson type technique is used,with skin incisions in the form of an inverted T is usually performed in patients with large mammary gland with severe grade III ptosis,as the patients usually require reduction of excess skin.However,the most vulnerable aspects of this type of reconstruction is the impossibility of preserving the nipple-areolar complex(NAC),which is associated with a high risk of developing such complications as partial/complete necrosis of the NAC.The current study provides an overview of an original method to decrease the risk of necrosis of NAC with evaluation of blood supply of the nipple and inferior deepithelialized flap using real-time intraoperative Doppler ultrasonography and indocyanine green fluorescence system.
文摘BACKGROUND For locally advanced gallbladder cancer,previous clinical studies have demon-strated that chemotherapy results in significant survival benefits when compared to surgery alone.However,data demonstrating a similar survival benefit with early-stage gallbladder cancer is limited.This study seeks to evaluate the impact chemotherapy has on survival in patients with early-stage gallbladder cancer using a large,multi-institution database.AIM To investigate the survival benefit of chemotherapy in patients with stage II gallbladder cancer.METHODS We performed a retrospective multivariable analysis of the National Cancer Database from 2010 to 2017 to evaluate the effect that chemotherapy has on the survival of patients with stage II gallbladder cancer.Our objective was to de-termine if there were any statistically significant survival differences between those who received surgery and chemotherapy vs those who only underwent surgery.RESULTS Of the 899 patients with stage II gallbladder cancer,328 patients had undergone chemotherapy and surgery.The average overall survival for those who had surgery and chemotherapy vs only surgery was 52.6 months and 51.1 months,respectively.This difference was not statistically significant(P=0.2).In the secondary analysis,the surgical group who had a liver resection had better overall survival(P<0.0001).CONCLUSION Practitioners should carefully consider chemotherapy for early-stage gallbladder cancer,as risks may outweigh survival benefits,and surgeons should also consider liver resections as part of their surgical management.
文摘Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The present study aimed to identify clinical and biological factors at admission associated with 30-day mortality in acute cholangitis,to build an efficient prognostic score based on these parameters and to study the performances of this new score.Methods:We enrolled all adult patients consecutively hospitalized for acute cholangitis between January 2017 and December 2021.We developed a score system named ProChol using variables significantly asso-ciated with 30-day mortality in multivariate logistic analysis and simplified this system(named sProChol)based on a simple points-based approach.Results:In total,528 patients were included,with an average age of 77±13 years,a male predominance(54.2%)and a majority of lithiasis etiology(66.5%).Mortality in 30 days was 11.9%.In multivariate logis-tic analysis,tumor etiology[adjusted odds ratio(aOR)=15.43,95%confidence interval(CI):5.90-40.40],stent obstruction(aOR=5.12,95%CI:2.02-12.99),hypoalbuminemia(aOR=3.50,95%CI:1.25-9.81),renal failure(aOR=6.51,95%CI:2.62-16.18),oxygen therapy(aOR=4.63,95%CI:1.02-20.92)and cu-rative anticoagulation(aOR=2.60,95%CI:1.23-5.52)were independently associated with the 30-day mortality while fever was a protective factor(aOR=0.37,95%CI:0.16-0.84).ProChol score using these 7 parameters and sProChol using the 3 robust factors(etiology,renal failure and anticoagulation)presented respectively an area under receiver operating characteristic(ROC)curves(AUC)of 0.81 and 0.77,higher than Tokyo(AUC=0.72)and Gravito-Soares et al.score(AUC=0.71).Patients with sProChol≥4 had a significantly higher risk of transfer to intensive care unit(13.3%vs.5.1%;P<0.001)and longer length of stay(P=0.0006).Conclusions:ProChol and sProChol constructed from simple clinico-biological parameters at admission,present interesting performances in predicting the 30-day mortality in acute cholangitis.
文摘BACKGROUND Endoscopic bilateral biliary drainage is a first line palliative treatment for unresectable malignant hilar biliary obstruction(MHBO)but remains technically challenging.The emergence of self-expandable metallic stents carried by an ultrathin(6 Fr or smaller)delivery system now permits simultaneous bilateral stent placement.To date,only a few studies have compared this new method with conventional sequential bilateral stenting.AIM To evaluate a possible superiority of simultaneous“side by side”(SBS)biliary drainage in unresectable MHBO.METHODS We identified 135 patients who benefited from bilateral drainage using uncovered self-expandable metallic stents between 2010 and 2023.Among them,62 benefited from simultaneous SBS bilateral drainage between 2017 and 2023,and 73 benefited from sequential bilateral drainage[38 using“stent in stent”(SIS)technique and 35 using SBS technique between 2010 and 2017].RESULTS Technical success was significantly increased in simultaneous drainage compared with sequential drainage(94%vs 75%,P=0.008).However,simultaneous SBS drainage and sequential SIS drainage had a similar technical success(94%vs 95%).We observed no differences regarding clinical success,procedure duration and recurrent biliary obstruction rate.Stent patency was shorter in the SIS group compared with the simultaneous group(103 days vs 144 days).Early adverse events were more frequent in the sequential group(31%vs 21%,P=0.205),with no differences regarding SIS or SBS technique.Technical failure was associated with a higher rate of infectious fatal adverse events(9.5%vs 1.7%,P=0.02).Reintervention after recurrent biliary obstruction seems to be more successful after using SBS rather than SIS techniques(83%vs 75%,P=0.53).CONCLUSION Simultaneous SBS metallic stent placement using an ultra-thin delivery system was technically easier and as efficient as sequential bilateral stenting in unresectable MHBO to achieve bilateral drainage.The SIS procedure remains a good option in unresectable MHBO.
文摘BACKGROUND Chronic pancreatitis is a progressive,debilitating condition with no standardized treatment.Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects on pancreatic acinar cells.AIM To evaluate the synergistic effects of pirfenidone and simvastatin in an L-arginineinduced chronic pancreatitis model in mice.METHODS A preclinical,7-week study was performed using a mouse model of L-arginineinduced chronic pancreatitis.The mice were divided into five groups:Normal control;model control;pirfenidone-treated;simvastatin-treated;and combinationtreated(pirfenidone+simvastatin).Treatment started in week 3 after disease induction.Mice were euthanized at weeks 4 and 7 for blood collection and tissue sampling for histological and biomarker analysis,including cytokines,oxidative stress markers,and indicators of fibrosis.RESULTS Combination therapy significantly reduced levels of tumor necrosis factor-alpha(11.10±1.57 pg/mL vs 24.30±2.00 pg/mL),interleukin-10(11.70±1.12 pg/mL vs 19.60±1.27 pg/mL),and transforming growth factor-beta 1(236.13±6.95 pg/mL vs 550.52±42.18 pg/mL)at week 7(P<0.05 vs model control).The glutathione peroxidase 1 level increased across all treatment groups,significantly in the pirfenidonetreated group(5.47±0.34 IU/mL vs 5.04±0.43 IU/mL;P<0.05).Lipid peroxidation levels decreased significantly in the combination-treated group(111.87±7.36 mmol/mL vs 192.85±0.98 mmol/mL;P<0.05).Histology revealed extensive collagen accumulation and damage to the exocrine pancreas in the model control group(vs treatment groups).Combination therapy elicited the least damage.CONCLUSION Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation,fibrosis,and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model,suggesting promise for chronic pancreatitis management.
文摘BACKGROUND End-stage renal disease is the final stage of chronic kidney disease,with hemodialysis as the primary treatment in India.Despite its prevalence,limited studies have focused on patient-reported outcomes,such as symptom burden and healthrelated quality of life.AIM To evaluate the symptom burden among adult hemodialysis patients and identify factors influencing their outcomes.METHODS A multi-center,cross-sectional study was conducted among 157 adult hemodialysis patients in Chennai from March 2024 to June 2024.The Dialysis Symptom Index tool was used to assess 30 physical and emotional symptoms.Correlations between symptom severity and clinical parameters,such as hemoglobin levels and urea reduction ratio(URR),were analyzed.RESULTS Moderate symptoms were reported by 48%of participants,with worry,insomnia,and feeling unwell identified as the most severe.Psychological symptoms significantly correlated with lower hemoglobin levels,while shortness of breath was linked to suboptimal URR values.Approximately 38%of patients had URR<65%,which was associated with increased symptom burden.CONCLUSION Hemodialysis patients experience a substantial psychological and sleep-related symptom burden,emphasizing the need for dialysis adequacy and better hemoglobin management.Enhanced strategies addressing these factors could significantly improve patient outcomes.
文摘A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues'differentiation,growth,and energy metabolism.Consequently,excess THs are expected to lead to profound organ function,regulation,and hemodynamic changes.In addition to their roles in metabolism and thermoregulation,THs play critical role in maintaining cardiovascular homeostasis through both genomic and non-genomic mechanisms.Receptors for THs are expressed in myocardial and vascular endothelial tissues,allowing fluctuations in circulating hormone levels to directly influence cardiovascular function.Excess TS induces a hyper-dynamic cardiovascular state,characterized by increased ventricular contractility and improved systolic and diastolic performance.The chronotropic and inotropic properties of THs result in dysregulation of blood pressure,heart rate,contractility,cardiac output,and systemic vascular resistance.This could lead to serious consequences such as cardiomyopathy,heart failure,and life-threatening arrhythmia,ultimately contributing to cardiocirculatory collapse and cardiac death.The management of TS necessitates a systematic approach that emphasizes the significance of resuscitation and identification of the underlying causes.It is crucial to prioritize assessing cardiac function in patients with TS.This review explores the clinical impact of TS on the heart and its clinical repercussions,emphasizing the intricate molecular and pathophysiological mechanisms and the interplay between TS and key cardiovascular parameters.This review summarizes the current knowledge of pathophysiology,pharmacological and mechanical interventions,ranging from beta-blocker use to the surgical approach.
基金funded in part by grants from the University Natural Science Research Project of Anhui Province(No.KJ2020A0582)Health Research Program of Anhui Province(No.AHWJ2023A20372)Science and Technology Innovation Project of Bengbu City(No.20230129).
文摘Objective The aim of this study was to examine the relationship between the sonographic hepatorenal index and stroke risk in patients with nonalcoholic fatty liver disease(NAFLD).Methods From December 2023 to July 2024,72 NAFLD patients with stroke,53 stroke-free NAFLD patients,and 54 healthy controls were enrolled in our study.The hepatorenal index was calculated as the ratio of the echo intensity of the liver to that of the renal cortex.The mean brightness values for one region of interest within the right hepatic lobe and the other size-matched region at the same depth of field within the right kidney were obtained with two-dimensional ultrasound and a 1-to 6-MHz convex array probe.Laboratory tests were performed with a Cobas 8000 automatic biochemical analyzer.Univariate and multivariate analyses were adopted to analyze the risk factors for stroke in NAFLD patients.Results NAFLD patients had a greater hepatorenal index than healthy controls did(P<0.05).Additionally,NAFLD patients with stroke had an even greater hepatorenal index than did those with stroke-free NAFLD(P<0.001).Multivariate regression analysis further revealed that the hepatorenal index was independently associated with stroke risk in NAFLD patients(β=8.897,P<0.001)after controlling for age,body mass index,systolic blood pressure,and serum glucose,total cholesterol,alanine transaminase,and creatinine concentrations.Receiver operating characteristic curve analysis revealed a sensitivity of 62.5%and specificity of 95.3%for the hepatorenal index,with a cutoff value of 1.255 and an area under the curve of 0.80.Conclusion The increased sonographic hepatorenal index could be an independent predictor of stroke development in patients with NAFLD.
基金funded by Department of Science and Technology of Hunan province,grant number 2021SK4029 and 2023TP1014(Guoqing Li)Hunan Provincial Department of Education,grant number CX20240087(Ying Fang)and 24B0404(Anqi Wu)Hunan Provincial Natural Science Foundation,grant number 2023JJ40577(AnqiWu).
文摘Gastric Cancer(GC)is a highly prevalent and poorly prognostic gastrointestinal malignancy with low overall treatment efficacy worldwide.Early diagnostic markers and potential therapeutic targets for GC treatment are urgently needed.UFMylation,a novel ubiquitin-like modification is indispensable for numerous fundamental cellular processes.Deficiency in this modification is reported to be associated with several human diseases including cancer.Accumulating evidence suggests that the expression of the key UFMylation components is closely associated with GC cell proliferation,invasion,metastasis,and chemotherapy resistance.Recent clinical studies have further highlighted the prognostic value and therapeutic potential of UFMylation in the clinical management of GC.However,the precise molecular mechanisms through which UFMylation contributes to GC remain largely unclear.This review aims to summarize recent findings on the functional roles of UFMylation in diverse cellular processes,such as endoplasmic reticulum(ER)homeostasis,DNA damage response(DDR),protein translation,and quality control pathways,discuss potential underlying mechanisms in GC development and progression,and to explore potential therapeutic implications targeting the UFMylation pathway in GC.
基金funding from TrygFondenThe Centre for Physical Activity Research(CFAS)is supported by a grant from TrygFonden+4 种基金support for this work was provided by a grant from the Danish Diabetes Academyfunded by the Novo Nordisk Foundation(MR-L)and a grant from Rigshospitalet(MYJ)supported by the Canadian Institutes of Health Research(MFE-176582)the Section for Biostatistics and Evidence-Based Research,the Parker Institute,Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation(OCAY-18-774-OFIL)the strategic research alliance Excellence of Diabetes Research in Sweden(EXODIAB)funded by the Swedish Research Council(EXODIAB,2009-1039,2018-02837)。
文摘Purpose:This study aimed to describe the effects of a 1-year lifestyle intervention on hemoglobin A1c(HbA1c)and cardiovascular risk factors5 years after cessation of the lifestyle intervention in persons with type 2 diabetes(T2D).Methods:From April 2015 to August 2016,98 persons with T2D(duration<10 years)were randomly allocated(2:1,stratified by sex)to a 1-year lifestyle intervention group(INT)(n=64)or a standard care group(StC)(n=34).All participants received standard care with blinded,targetdriven medical therapy.INT included up to 5-6 weekly supervised aerobic and strength training sessions and dietary plans targeting a body mass index≤25 kg/m^(2).No intervention was given during the follow-up period.Forty-nine(77%)and 19(56%)participants in INT and StC attended the 6-year follow-up.Based on the original intention-to-treat population,the primary outcome was the change in HbA1c from baseline to 6-year follow-up.Secondary outcomes included weight,Low density lipoprotein(LDL)cholesterol,blood pressure(BP),and cardiorespiratory fitness.Results:Ninety-eight participants(mean age=54.6 years;46%women;mean baseline Hemoglobin A1c(HbA1c)=49.8 mmol/mol)were analyzed.HbA1c changed 6%and 13%in the INT and StC from baseline to 6-year follow-up(between group difference=-6%(95%confidence interval(95%CI):-14%to 3%);p=0.18).While no differences were observed for most secondary outcomes,the diastolic BP decreased6.0(95%CI:2.1 to 9.8)mmHg more in the StC compared to INT.Conclusion:The sustained effect of the lifestyle intervention on glycemic control and cardiovascular risk factors was marginal,and it was surprisingly associated with inferior diastolic BP regulation.
基金Supported by National Natural Science Foundation of China,No.82300780Natural Science Foundation of Jiangsu Province,No.BK20220306Yancheng Key Research and Development Plan(Social Development)Project,No.YCBE202214.
文摘In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2.237,P=0.03),advancedage(OR=1.05/year,P=0.002),fever(OR=2.999,P=0.015),severe hydronephrosis(OR=6.129,P=0.011),and elevated urinary markers-particularly urineleukocytes(U-LEU+++:OR=66.0,P<0.001)and glucose(U-GLU+++:OR=7.248,P=0.005)as independent risk factors.These readily accessible clinicalparameters offer significant potential for early risk stratification in high-riskpopulations.While this STROBE-adherent study provides actionable insights,limitations include its single-center design and unaddressed antibiotic protocols.Future multicenter validation should assess residual stone impacts and optimizeintervention thresholds.This work establishes a foundation for targeted surveillanceprotocols in diabetic urolithiasis management.
基金the National Social Science Foundation of China(No.16BGL183).
文摘Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.
