Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are ...Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are of growing interest for potential use in cosmetics and fragrance industries due to their bioactive properties.Methods:Leaves of C.olitorius cultivated in Egypt were extracted using microwave-assisted hydrodistillation(MAHD)and conventional hydrodistillation(HD).The oils were analyzed by gas chromatography-mass spectrometry(GC-MS)to characterize their chemical profiles.In vitro assays were conducted to evaluate their anti-elastase and anti-collagenase activities,and in silico studies were performed to predict the pharmacokinetic and pharmacodynamic properties of major constituents.Results:GC-MS analysis showed that aldehydes,alkanes,fatty alcohols,fatty acids,and their derivatives were the predominant compound classes in both oils.Notably,oxygenated diterpenes(11.22%)were present exclusively in the MAHD oil,while triterpenoids(16.37%)were found only in the HD oil.The MAHD oil demonstrated stronger In vitro anti-elastase(IC_(50)=42.5μg/mL)and anti-collagenase(IC_(50)=131.5μg/mL)activities compared to the HD oil(IC_(50)=66.7 and 206.8μg/mL,respectively),reflecting an approximate 36.3%improvement in elastase inhibition and 36.4%improvement in collagenase inhibition.In silico docking indicated that the triterpenoidβ-amyrin acetate showed the highest predicted binding affinity for porcine pancreatic elastase(PDB ID:6QEO,ΔG=−8.1 kcal/mol)and collagenase(PDB ID:456C,ΔG=−9.1 kcal/mol)among the major compounds analyzed.Conclusion:These findings demonstrate that MAHD is a greener and more efficient extraction method,yielding oil with enhanced enzyme inhibitory activity compared to conventional HD.The promising anti-elastase and anti-collagenase properties suggest that C.olitorius MAHD oil could serve as a potential candidate for anti-aging cosmetic formulations,following further validation.展开更多
Aim: The purpose of this study was to explore the impact of attributes of medical care organizations and patients on medical resource utilization by hemophilia (hemophilia A and hemophilia B;Hemophilia with musculoske...Aim: The purpose of this study was to explore the impact of attributes of medical care organizations and patients on medical resource utilization by hemophilia (hemophilia A and hemophilia B;Hemophilia with musculoskeletal system and without). Methods: Hospitalization due to hemophilia (ICD9: 286.0 and 286.1) and hemophilia with musculoskeletal system (ICD9: 710.xx-739.xx) between 2001 and 2010 were identified from a national health insurance database. Calculated by patients and hospital characteristics, length of hospital stay, medical cost of hospitalization was analyzed. Results: Of the total of 2150 patients, a systemic analysis of the results showed a mean patient age of 30.2 and average medical costs per patient of NT $672,335 (US $21,010). We found the mean cost of cases being significantly higher during the hemophilia A that in the hemophilia B (NT $708,620 vs. NT $422,322, P展开更多
Artificial intelligence(AI)is defined as the digital computer or computer-controlled robot's ability to mimic intelligent conduct and crucial thinking commonly associated with intelligent beings.The application of...Artificial intelligence(AI)is defined as the digital computer or computer-controlled robot's ability to mimic intelligent conduct and crucial thinking commonly associated with intelligent beings.The application of AI technology and machine learning in medicine have allowed medical practitioners to provide patients with better quality of services;and current advancements have led to a dramatic change in the healthcare system.However,many efficient applications are still in their initial stages,which need further evaluations to improve and develop these applications.Clinicians must recognize and acclimate themselves with the developments in AI technology to improve their delivery of healthcare services;but for this to be possible,a significant revision of medical education is needed to provide future leaders with the required competencies.This article reviews the potential and limitations of AI in healthcare,as well as the current medical application trends including healthcare administration,clinical decision assistance,patient health monitoring,healthcare resource allocation,medical research,and public health policy development.Also,future possibilities for further clinical and scientific practice were also summarized.展开更多
Background:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how i...Background:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how individuals may use different coping methods to deal with their mental health needs.Psychological distress(e.g.,depression and stress)could lead to overuse of social media and smartphones.When using social media or smartphones,individuals are likely to be exposed to negative comments regarding weight/shape/size posted on the social media.Consequently,individuals who experience problematic social media use(PSMU)or problematic smartphone use(PSPU)may develop WRSS.Therefore,the present study examined the roles of PSMU and PSPU as mediators in the relationship between psychological distress and WRSS.Methods:Using convenience sampling via an online survey,622 participants with a mean age of 23.70 years(SD=4.33)completed questions assessing sociodemographic variables,psychological distress,PSMU,PSPU,WRSS,and self-reported weight and height.Results:The hierarchical regression models showed that sex(β=0.08,p=0.01),BMI(β=0.39,p<0.001),depression(β=0.21,p=0.001),stress(β=0.18,p=0.01),PSMU(β=0.09,p=0.045),and PSPU(β=0.14,p=0.001)were significant factors for WRSS.Conclusion:The mediation models showed that both PSMU and PSPU were significant mediators in the relationships between depression and stress with WRSS.The present findings provide some evidence for understanding WRSS and has important implications for developing interventions to reduce its negative impact on individuals’health and well-being.展开更多
BACKGROUND Accurate identification of tumor invasion depth and lymph node(LN)involve-ment in patients with colon cancer(CC)is critical for guiding treatment strategies.However,the preoperative prediction of tumor inva...BACKGROUND Accurate identification of tumor invasion depth and lymph node(LN)involve-ment in patients with colon cancer(CC)is critical for guiding treatment strategies.However,the preoperative prediction of tumor invasion depth and LN metastasis in CC remains challenging.As the intestinal tumor develops,the fat density in the mesentery increases.METHODS Patients,who were diagnosed with CC and underwent surgery,were included and divided into the training and validation cohorts.CT-T values of the mesen-tery were extracted from the CT images.Cutoff points were determined using the receiver operating characteristic(ROC)curve,and the area under the ROC curve was employed to assess the performance of the CT-T value for tumor invasion depth and LN status prediction.RESULTS Cutoff values of 11.83 and 17.17 were identified to discriminate T1/2 vs T3/4 and N0 vs N1/2,respectively.With a cutoff CT-T value of 11.83,the total diagnostic accuracy for T stage was 83.1%(81.5%for the training cohort and 86.2%for the validation cohort).With a cutoff CT-T value of 17.17,the total diagnostic accuracy for N stage was 77.3%(75.8%for the training cohort and 80.1%for the validation cohort),which was higher than that of CT-reported LN metastasis.CONCLUSION In this study,we explored an efficient method for predicting preoperative T and N stages using the tumor-contributed CT value of the mesentery in CC,which displayed superior predictive accuracy.展开更多
TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity ...TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.展开更多
BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-Eu...BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.展开更多
By using a certain hybrid-type convolution operator,we first introduce a new subclass of normalized analytic functions in the open unit disk.For members of this analytic function class,we then derive several propertie...By using a certain hybrid-type convolution operator,we first introduce a new subclass of normalized analytic functions in the open unit disk.For members of this analytic function class,we then derive several properties and characteristics including(for example)the modified Hadamard products,Holder's inequalities and convolution properties as well as some closure properties under a general family of integral transforms.展开更多
BACKGROUND Rhabdomyolysis(RML)as an etiological factor causing acute kidney injury(AKI)is sparsely reported in the literature.AIM To study the incidence of RML after surgical repair of an ascending aortic dissection(A...BACKGROUND Rhabdomyolysis(RML)as an etiological factor causing acute kidney injury(AKI)is sparsely reported in the literature.AIM To study the incidence of RML after surgical repair of an ascending aortic dissection(AAD)and to correlate with the outcome,especially regarding renal function.To pinpoint the perioperative risk factors associated with the development of RML and adverse renal outcomes after aortic dissection repair.METHODS Retrospective single-center cohort study conducted in a tertiary cardiac center.We included all patients who underwent AAD repair from 2011-2017.Post-operative RML workup is part of the institutional protocol;studied patients were divided into two groups:Group 1 with RML(creatine kinase above cut-off levels 2500 U/L)and Group 2 without RML.The potential determinants of RML and impact on patient outcome,especially postoperative renal function,were studied.Other outcome parameters studied were markers of cardiac injury,length of ventilation,length of stay in the intensive care unit),and length of hospitalization.RESULTS Out of 33 patients studied,21 patients(64%)developed RML(Group RML),and 12 did not(Group non-RML).Demographic and intraoperative factors,notably body mass index,duration of surgery,and cardiopulmonary bypass,had no significant impact on the incidence of RML.Preoperative visceral/peripheral malperfusion,though not statistically significant,was higher in the RML group.A significantly higher incidence of renal complications,including de novo postoperative dialysis,was noticed in the RML group.Other morbidity parameters were also higher in the RML group.There was a significantly higher incidence of AKI in the RML group(90%)than in the non-RML group(25%).All four patients who required de novo dialysis belonged to the RML group.The peak troponin levels were significantly higher in the RML group.CONCLUSION In this study,we noticed a high incidence of RML after aortic dissection surgery,coupled with an adverse renal outcome and the need for post-operative dialysis.Prompt recognition and management of RML might improve the renal outcome.Further large-scale prospective trials are warranted to investigate the predisposing factors and influence of RML on major morbidity and mortality outcomes.展开更多
BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting in...BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting incident MetS in young adults.AIM To investigate the associations of various non-insulin-based IR(NI-IR)indices with new-onset MetS in young military personnel.METHODS A total of 2890 armed forces personnel in Taiwan who were aged 18-39 years and did not have MetS at baseline were followed to monitor the incidence of new-onset MetS from 2014 to the end of 2020.Six NI-IR indices,including the metabolic score for IR(METS-IR),triglyceride(TG)-to-high-density lipoprotein cholesterol(HDL-C)ratio,TG glucose(TyG)index,Zhejiang University(ZJU)index,total cholesterol(TC)-to-HDL-C ratio,and alanine transaminase(ALT)-to-aspartate transaminase(AST)ratio,were defined according to specific criteria.Incident MetS was identified on the basis of each annual health examination using the International Diabetes Federation criteria.Multiple Cox regression analyses were conducted,adjusting for age,sex,waist circumference,smoking status,alcohol consumption status,and physical activity,to assess the associations of the NI-IR indices with incident MetS.The area under the receiver operating characteristic curve(AUROC)was used to compare the capacities of these NI-IR indices for predicting new-onset MetS.RESULTS During a median follow-up of 5.8 years,there were 673 patients with new-onset MetS(23%).All six of the NI-IR indices were significantly and positively associated with incident MetS.In the entire cohort,the greatest AUROC was found for the METS-IR[0.782;95%confidence interval(CI):0.762-0.801;all P values compared to the other NIIR indices<0.05],followed by the TG/HDL-C ratio(0.752;95%CI:0.731-0.772),ZJU index(0.743;95%CI:0.722-0.764),TyG index(0.734;95%CI:0.713-0.756),TC/HDL-C ratio(0.731;95%CI:0.709-0.752),and then the ALT/AST ratio(0.734;95%CI:0.713-0.756).CONCLUSION This study suggests that almost all the NI-IR indices are associated with the development of MetS in military young adults.The METS-IR is the strongest predictor of new-onset MetS before midlife.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
Asthma is the most common allergic disorder and represents a significant global public health problem.Strong evidence suggests a link between ascariasis and asthma.This study aims primarily to determine the prevalence...Asthma is the most common allergic disorder and represents a significant global public health problem.Strong evidence suggests a link between ascariasis and asthma.This study aims primarily to determine the prevalence of Ascaris lumbricoides infection among various risk factors,to assess blood parameters,levels of immunoglobulin E(IgE)and interleukin-4(IL-4),and to explore the relationship between ascariasis and asthma in affected individuals.The secondary objective is to examine a fractal-fractional mathematical model that describes the four stages of the life cycle of Ascaris infection,specifically within the framework of the Caputo-Fabrizio derivative.A case-control study was conducted that involved 270 individuals with asthma and 130 healthy controls,all of whom attended general hospitals in Duhok City,Iraq.Pulmonary function tests were performed using a micromedical spirometer.The presence of Ascaris lumbricoides antibodies-Immunoglobulin M(IgM),Immunoglobulin G(IgG),and Immunoglobulin E(IgE)-was detected using ELISA.Blood parameters were analyzed using a Coulter counter.The overall infection rate was(42.5%),with the highest rates observed among asthmatic men(70.0%)and rural residents(51.4%).Higher infection rates were also recorded among low-income individuals(64.3%)and those with frequent contact with the soil(58.6%).In particular,infected individuals exhibited a significant decrease in red blood cell count and hemoglobin concentration,while a marked increase in white blood cell count was recorded.In addition,levels of Immunoglobulin E(IgE)and interleukin-4 were significantly higher in the infected group compared to the controls.Effective disease awareness strategies that incorporate health education and preventive measures are needed.Exposure to Ascaris has been associated with reduced lung function and an increased risk of asthma.More research is required to elucidate the precise mechanisms that link Ascaris infection with asthma.Furthermore,the existence and uniqueness of solutions for the proposed model are investigated using the Krasnosel’skii and Banach fixed-point theorems.The Ulam-Hyers and Ulam-Hyers-Rassias stability types are explained within the framework of nonlinear analysis inŁp-space.Finally,an application is presented,including tabulated results and figures generated using MATLAB to illustrate the validity of the theoretical findings.展开更多
BACKGROUND The impact of psychiatric disorder,especially depression,on the prognosis of sarcopenic patients is gaining prominence.Yet,there have been very few studies focusing on this issue,let alone the related targe...BACKGROUND The impact of psychiatric disorder,especially depression,on the prognosis of sarcopenic patients is gaining prominence.Yet,there have been very few studies focusing on this issue,let alone the related targeted mental health prevention.This cohort-based nested case-control study is geared to compare risk of depression and the depression-related ambulatory care utilization for sarcopenia persons with and without receiving add-on Chinese herbal medicines(CHMs)treatment.AIM To compare risk of depression and the depression-related ambulatory care utili-zation for sarcopenia persons with and without receiving add-on CHMs treat-ment.METHODS In the beginning,we recruited those aged 20-70 years with newly diagnosed sarcopenia and free of depression between 2002 and 2010 from a nationwide insurance database.From them,we identified cases with depression onset occurring after sarcopenia until December 31,2013.To cautiously isolate the effect of CHMs,we established the matched sets of treated and untreated subjects with CHMs use by randomly frequency matching.A conditional logistic regression was executed to explore the association of CHMs to depression risk,and the frequency and costs of depression-related ambulatory care were compared using Mann-Whitney U test.RESULTS Addition of CHMs to routine care of sarcopenia notably correlated with a lower risk of depression.A remarkable effect of CHMs in reducing depression was detected when sarcopenia subjects received CHMs for more than three years,lowering depression risk by as much as 65%.As compared to CHMs users,the non-CHMs users indeed incurred higher frequency and costs of depression-related ambulatory care after depression attack(P<0.05).Notably,the costs for per depression-related ambulatory care profoundly increased with the years after depression attack.CONCLUSION Sarcopenic patients can greatly benefit from add-on CHMs treatment,underscoring the urgent need for interdisciplinary collaboration and proactive treatment planning.展开更多
Background:Weight stigma is prevalent and has multiple sources,which have significant effects on individual,social,physical,and psychological health.This study evaluated the psychometric properties of the Thai version...Background:Weight stigma is prevalent and has multiple sources,which have significant effects on individual,social,physical,and psychological health.This study evaluated the psychometric properties of the Thai version of WeSEI to provide a valid tool to assess weight stigma in Thai young adults.Methods:A cross-sectional online survey recruited 517 Thai university students from October 2024 to May 2025.All participants completed demographic information and standardized self-reported instruments,including WeSEI,Depression,Anxiety,and Stress scale 21(DASS-21),Weight Self-Stigma Questionnaire(WSSQ),and Perceived Weight Stigma Scale(PWSS).The psychometric properties of the Thai version of WeSEI were examined via confirmatory factor analysis(CFA)with some validity indices.Results:The 7-factor structure of the Thai version of the WeSEI was supported across sex and weight status subgroups,indicating good construct validity.In addition,internal consistency(Cronbach’sα=0.972;McDonald’sω=0.972),convergent,and discriminant validity also indicated that the Thai version of the WeSEI had good psychometric properties and assessed weight stigma among young people in Thailand.Conclusions:Sound psychometric properties of the Thai adaptation of WeSEI allows the identification of various sources contributing to weight stigma and to identify those experiencing high levels of weight stigma.It also provides evidence to support targeted interventions to reduce weight stigma and its associated mental health impacts in further research.Further studies are necessary to explore the utilization of WeSEI for weight stigma in Thailand.展开更多
Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using d...Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using deep learning algorithms further enhances performance;nevertheless,it is challenging due to the nature of small-scale and imbalanced PD datasets.This paper proposed a convolutional neural network-based deep support vector machine(CNN-DSVM)to automate the feature extraction process using CNN and extend the conventional SVM to a DSVM for better classification performance in small-scale PD datasets.A customized kernel function reduces the impact of biased classification towards the majority class(healthy candidates in our consideration).An improved generative adversarial network(IGAN)was designed to generate additional training data to enhance the model’s performance.For performance evaluation,the proposed algorithm achieves a sensitivity of 97.6%and a specificity of 97.3%.The performance comparison is evaluated from five perspectives,including comparisons with different data generation algorithms,feature extraction techniques,kernel functions,and existing works.Results reveal the effectiveness of the IGAN algorithm,which improves the sensitivity and specificity by 4.05%–4.72%and 4.96%–5.86%,respectively;and the effectiveness of the CNN-DSVM algorithm,which improves the sensitivity by 1.24%–57.4%and specificity by 1.04%–163%and reduces biased detection towards the majority class.The ablation experiments confirm the effectiveness of individual components.Two future research directions have also been suggested.展开更多
Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and wheth...Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index(BMI).Methods:This retrospective cohort study used electronic health records from the TriNetX U.S.research network.Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis.Following 1:1 propensity score matching,both the GLP-1 RA user and non-user groups included 183,264 patients.The study outcome was defined as a diagnosis of malignant neoplasms.Hazard ratios(HRs)for overall and site-specific cancer risk were estimated using Cox proportional hazards models.Kaplan–Meier analysis and stratified analysis by BMI were performed.Results:Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk(HR 0.93;95%CI:0.90–0.96).Reduced risks were noted for cancers of the digestive(HR 0.81),respiratory(HR 0.66),and female genital(HR 0.87)systems.In stratified analysis,benefits were more pronounced in patients with BMI≥30,particularly for pancreatic and colorectal cancers.Conclusion:Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk,particularly among individuals with obesity.These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.展开更多
Recent molecular cytogenetic studies demonstrate that extensive centromere-telomere fusions are the main chromosomal rearrangements underlying the karyotypic evolution of extant muntjacs. Although the molecular mechan...Recent molecular cytogenetic studies demonstrate that extensive centromere-telomere fusions are the main chromosomal rearrangements underlying the karyotypic evolution of extant muntjacs. Although the molecular mechanism of tandem fusions remains unknown, satellite DNA is believed to have facilitated chromosome fusions by non-allelic homologous recombination. Previous studies detected non-random hybridization signals of cloned satellite DNA at the postulated fusion sites on the chromosomes in Indian and Chinese muntjacs. But the genomic distribution and organization of satellite DNAs in other muntjacs have not been investigated. In this study, we have isolated four satellite DNA clones （BMCS, BM700, BM 1.1 k and FM700） from the black muntjac （Muntiacus crinifrons） and Fea＇s muntjac （M. feae）, and hybridized these four clones onto chromosomes of four muntjac species （M. reevesi, M. crinifrons, M. gongshanenisis and M. feae）. Besides the predominant centromeric signals, non-random interstitial hybridization signals from satellite I and II DNA clones （BMC5, BM700 and FM700） were also observed on the arms of chromosomes of these four muntjacs. Our results provide additional support for the notion that the karyotypes of M. crinifrons, M. feae and M. gongshanensis have evolved from a 2n = 70 ancestral karyotype by a series of chromosome fusions.展开更多
The prevalence of type 2 diabetes mellitus （T2DM） is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhos...The prevalence of type 2 diabetes mellitus （T2DM） is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhosis. It is suggested that there is a pathogenic link between the presence of T2DM and the severity of liver injury. However, evidence related to the impact of hepatic inflammation on the development of T2DM has not yet emerged. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases, the impact of liver diseases on insulin resistance and 13 cell dysfunction, and the potential mechanisms whereby coexistent liver diseases exacerbate the development of T2DM.展开更多
Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search f...Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search for and identify novel and potent therapeutic targets to improve patient outcomes.Sorafenib is the first and only approved targeted therapy for the treatment of hepatocellular carcinoma.Besides functioning as a multiple tyrosine kinase,sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3(STAT3) signaling in hepatocellular carcinoma cells.STAT3 is a key regulator of inflammation,cell survival,and tumorigenesis of liver cells,and the high percentage of hepatocellular carcinoma cells with constitutively active STAT3 justifies targeting it for the development of novel therapeutics.Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a conformational change in and releasing the autoinhibition of Src homology region 2 domaincontaining phosphatase-1.This phosphatase negatively regulates STAT3 activity,which leads to the subsequent apoptosis of cancer cells.The novel anti-cancer property of sorafenib will be discussed in this review,not only adding information regarding its mechanism of action but also providing an innovative approach for the development of cancer therapeutics in the future.展开更多
AIM： To enhance the differentiation of insulin producing cell （IPC） ability from embryonic stem （ES） cells in vitro. METHODS： Four-day embryoid body （EB）-formatted ES cells were dissociated as single cells for...AIM： To enhance the differentiation of insulin producing cell （IPC） ability from embryonic stem （ES） cells in vitro. METHODS： Four-day embryoid body （EB）-formatted ES cells were dissociated as single cells for the followed plasmid DNA delivery. The use of NucleofectorTM electroporator （Amaxa biosystems, Germany） in combination with medium-contained G418 provided a high efficiency of gene delivery for advanced selection. Neucleofected cells were plated on the top of fibronectincoated Petri dishes. Addition of Ly294002 and raised the glucose in medium at 24 h before examination.The differentiation status of these cells was monitored by semi-quantitative PCR （SQ-PCR） detection of the expression of relative genes, such as oct-4, sox-17, foxa2, mixll, pdx-1, insulin 1, glucagons and somatostatin. The percentage of IPC population on d 18 of the experiment was investigated by immunohistochemistry （IHC）, and the content/secretion of insulin was estimated by ELISA assay. The mice with severe combined immunodeficiency disease （SCID） pretreated with streptozotocin （STZ） were used to eliminate plasma glucose restoration after pax4^＋ ES implantation. RESULTS： A high efficiency of gene delivery was demonstrated when neucleofection was used in the present study; approximately 70% cells showed DsRed expression 2 d after neucleofection. By selection of medium-contained G418, the percentage of DsRed expressing cells kept high till the end of study. The pancreatic differentiation seemed to be accelerated by pax4 nucleofection. When compared to the group of cells with mock control, foxa2, mixll, pdxl, higher insulin and somatostatin levels were detected by SQ-PCR 4 d after nucleofection in the group of pax4 expressing plasmid delivery. Approximately 55% of neucleofected cells showed insulin expression 18 d after neucleofection, and only 18% of cells showed insulin expression in mock control. The disturbance was shown by nucleofected pax4 RNAi vector; only 8% of cells expressed insulin 18 d after nucleofection. A higher IPC population was also detected in the insulin content by ELISA assay, and the glucose dependency was demonstrated in insulin secretion level. In the animal model, improvement of average plasma glucose concentration was observed in the group of pax-4 expressed ES of SCID mice pretreated with STZ, but no significant difference was observed in the group of STZ-pretreated SCID mice who were transplanted ES with mock plasmid. CONCLUSION： Enhancement of IPC differentiation from EB-dissociated ES cells can be revealed by simply using pax4 expressing plasrnid delivery. Not only more IPCs but also pancreatic differentiation-related genes can be detected by SQ-PCR. Expression of relative genes, such as foxa 2, mixl 1, pdx-1, insulin 1 and somatostatin after nucleofection, suggests that pax4 accelerates the whole differentiation progress. The higher insulin production with glucose dependent modulation suggests that pax4 expression can drive more mature IPCs. Although further determination of the entire mechanism is required, the potential of pax-4-nucleofected cells in medical treatment is promising.展开更多
基金Egyptian Science and Technology and Innovation Fund(STIFA)for the support of the study through grant No.46667 entitled“Sustainability of Lab Capacities of the Center of Drug Discovery Research and Development”.
文摘Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are of growing interest for potential use in cosmetics and fragrance industries due to their bioactive properties.Methods:Leaves of C.olitorius cultivated in Egypt were extracted using microwave-assisted hydrodistillation(MAHD)and conventional hydrodistillation(HD).The oils were analyzed by gas chromatography-mass spectrometry(GC-MS)to characterize their chemical profiles.In vitro assays were conducted to evaluate their anti-elastase and anti-collagenase activities,and in silico studies were performed to predict the pharmacokinetic and pharmacodynamic properties of major constituents.Results:GC-MS analysis showed that aldehydes,alkanes,fatty alcohols,fatty acids,and their derivatives were the predominant compound classes in both oils.Notably,oxygenated diterpenes(11.22%)were present exclusively in the MAHD oil,while triterpenoids(16.37%)were found only in the HD oil.The MAHD oil demonstrated stronger In vitro anti-elastase(IC_(50)=42.5μg/mL)and anti-collagenase(IC_(50)=131.5μg/mL)activities compared to the HD oil(IC_(50)=66.7 and 206.8μg/mL,respectively),reflecting an approximate 36.3%improvement in elastase inhibition and 36.4%improvement in collagenase inhibition.In silico docking indicated that the triterpenoidβ-amyrin acetate showed the highest predicted binding affinity for porcine pancreatic elastase(PDB ID:6QEO,ΔG=−8.1 kcal/mol)and collagenase(PDB ID:456C,ΔG=−9.1 kcal/mol)among the major compounds analyzed.Conclusion:These findings demonstrate that MAHD is a greener and more efficient extraction method,yielding oil with enhanced enzyme inhibitory activity compared to conventional HD.The promising anti-elastase and anti-collagenase properties suggest that C.olitorius MAHD oil could serve as a potential candidate for anti-aging cosmetic formulations,following further validation.
文摘Aim: The purpose of this study was to explore the impact of attributes of medical care organizations and patients on medical resource utilization by hemophilia (hemophilia A and hemophilia B;Hemophilia with musculoskeletal system and without). Methods: Hospitalization due to hemophilia (ICD9: 286.0 and 286.1) and hemophilia with musculoskeletal system (ICD9: 710.xx-739.xx) between 2001 and 2010 were identified from a national health insurance database. Calculated by patients and hospital characteristics, length of hospital stay, medical cost of hospitalization was analyzed. Results: Of the total of 2150 patients, a systemic analysis of the results showed a mean patient age of 30.2 and average medical costs per patient of NT $672,335 (US $21,010). We found the mean cost of cases being significantly higher during the hemophilia A that in the hemophilia B (NT $708,620 vs. NT $422,322, P
文摘Artificial intelligence(AI)is defined as the digital computer or computer-controlled robot's ability to mimic intelligent conduct and crucial thinking commonly associated with intelligent beings.The application of AI technology and machine learning in medicine have allowed medical practitioners to provide patients with better quality of services;and current advancements have led to a dramatic change in the healthcare system.However,many efficient applications are still in their initial stages,which need further evaluations to improve and develop these applications.Clinicians must recognize and acclimate themselves with the developments in AI technology to improve their delivery of healthcare services;but for this to be possible,a significant revision of medical education is needed to provide future leaders with the required competencies.This article reviews the potential and limitations of AI in healthcare,as well as the current medical application trends including healthcare administration,clinical decision assistance,patient health monitoring,healthcare resource allocation,medical research,and public health policy development.Also,future possibilities for further clinical and scientific practice were also summarized.
基金supported in part by(received funding from)the Ministry of Science and Technology,Taiwan(MOST 110-2410-H-006-115,MOST 111-2410-H-006-100)the National Science and Technology Council,Taiwan(NSTC 112-2410-H-006-089-SS2)+1 种基金the Higher Education Sprout Project,the Ministry of Education at the Headquarters of University Advancement at the National Cheng Kung University(NCKU)the 2021 Southeast and South Asia and Taiwan Universities Joint Research Scheme(NCKU 31).
文摘Background:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how individuals may use different coping methods to deal with their mental health needs.Psychological distress(e.g.,depression and stress)could lead to overuse of social media and smartphones.When using social media or smartphones,individuals are likely to be exposed to negative comments regarding weight/shape/size posted on the social media.Consequently,individuals who experience problematic social media use(PSMU)or problematic smartphone use(PSPU)may develop WRSS.Therefore,the present study examined the roles of PSMU and PSPU as mediators in the relationship between psychological distress and WRSS.Methods:Using convenience sampling via an online survey,622 participants with a mean age of 23.70 years(SD=4.33)completed questions assessing sociodemographic variables,psychological distress,PSMU,PSPU,WRSS,and self-reported weight and height.Results:The hierarchical regression models showed that sex(β=0.08,p=0.01),BMI(β=0.39,p<0.001),depression(β=0.21,p=0.001),stress(β=0.18,p=0.01),PSMU(β=0.09,p=0.045),and PSPU(β=0.14,p=0.001)were significant factors for WRSS.Conclusion:The mediation models showed that both PSMU and PSPU were significant mediators in the relationships between depression and stress with WRSS.The present findings provide some evidence for understanding WRSS and has important implications for developing interventions to reduce its negative impact on individuals’health and well-being.
基金Supported by National Natural Science Foundation of China,No.82303785and Medical Scientific Research Foundation of Guangdong Province,No.A2024096.
文摘BACKGROUND Accurate identification of tumor invasion depth and lymph node(LN)involve-ment in patients with colon cancer(CC)is critical for guiding treatment strategies.However,the preoperative prediction of tumor invasion depth and LN metastasis in CC remains challenging.As the intestinal tumor develops,the fat density in the mesentery increases.METHODS Patients,who were diagnosed with CC and underwent surgery,were included and divided into the training and validation cohorts.CT-T values of the mesen-tery were extracted from the CT images.Cutoff points were determined using the receiver operating characteristic(ROC)curve,and the area under the ROC curve was employed to assess the performance of the CT-T value for tumor invasion depth and LN status prediction.RESULTS Cutoff values of 11.83 and 17.17 were identified to discriminate T1/2 vs T3/4 and N0 vs N1/2,respectively.With a cutoff CT-T value of 11.83,the total diagnostic accuracy for T stage was 83.1%(81.5%for the training cohort and 86.2%for the validation cohort).With a cutoff CT-T value of 17.17,the total diagnostic accuracy for N stage was 77.3%(75.8%for the training cohort and 80.1%for the validation cohort),which was higher than that of CT-reported LN metastasis.CONCLUSION In this study,we explored an efficient method for predicting preoperative T and N stages using the tumor-contributed CT value of the mesentery in CC,which displayed superior predictive accuracy.
基金supported by Research institute/Center Supporting Program(RICSP-25-3),King Saud University,Riyadh,Saudi Arabia.
文摘TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.
基金Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
文摘BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.
文摘By using a certain hybrid-type convolution operator,we first introduce a new subclass of normalized analytic functions in the open unit disk.For members of this analytic function class,we then derive several properties and characteristics including(for example)the modified Hadamard products,Holder's inequalities and convolution properties as well as some closure properties under a general family of integral transforms.
基金Supported by Hamad Medical Corporation,No.MRC-01-18-073.
文摘BACKGROUND Rhabdomyolysis(RML)as an etiological factor causing acute kidney injury(AKI)is sparsely reported in the literature.AIM To study the incidence of RML after surgical repair of an ascending aortic dissection(AAD)and to correlate with the outcome,especially regarding renal function.To pinpoint the perioperative risk factors associated with the development of RML and adverse renal outcomes after aortic dissection repair.METHODS Retrospective single-center cohort study conducted in a tertiary cardiac center.We included all patients who underwent AAD repair from 2011-2017.Post-operative RML workup is part of the institutional protocol;studied patients were divided into two groups:Group 1 with RML(creatine kinase above cut-off levels 2500 U/L)and Group 2 without RML.The potential determinants of RML and impact on patient outcome,especially postoperative renal function,were studied.Other outcome parameters studied were markers of cardiac injury,length of ventilation,length of stay in the intensive care unit),and length of hospitalization.RESULTS Out of 33 patients studied,21 patients(64%)developed RML(Group RML),and 12 did not(Group non-RML).Demographic and intraoperative factors,notably body mass index,duration of surgery,and cardiopulmonary bypass,had no significant impact on the incidence of RML.Preoperative visceral/peripheral malperfusion,though not statistically significant,was higher in the RML group.A significantly higher incidence of renal complications,including de novo postoperative dialysis,was noticed in the RML group.Other morbidity parameters were also higher in the RML group.There was a significantly higher incidence of AKI in the RML group(90%)than in the non-RML group(25%).All four patients who required de novo dialysis belonged to the RML group.The peak troponin levels were significantly higher in the RML group.CONCLUSION In this study,we noticed a high incidence of RML after aortic dissection surgery,coupled with an adverse renal outcome and the need for post-operative dialysis.Prompt recognition and management of RML might improve the renal outcome.Further large-scale prospective trials are warranted to investigate the predisposing factors and influence of RML on major morbidity and mortality outcomes.
基金Supported by Medical Affairs Bureau Ministry of National Defense,No.MND-MAB-D-114222Hualien Armed Forces General Hospital,No.HAFGH-D-114008.
文摘BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting incident MetS in young adults.AIM To investigate the associations of various non-insulin-based IR(NI-IR)indices with new-onset MetS in young military personnel.METHODS A total of 2890 armed forces personnel in Taiwan who were aged 18-39 years and did not have MetS at baseline were followed to monitor the incidence of new-onset MetS from 2014 to the end of 2020.Six NI-IR indices,including the metabolic score for IR(METS-IR),triglyceride(TG)-to-high-density lipoprotein cholesterol(HDL-C)ratio,TG glucose(TyG)index,Zhejiang University(ZJU)index,total cholesterol(TC)-to-HDL-C ratio,and alanine transaminase(ALT)-to-aspartate transaminase(AST)ratio,were defined according to specific criteria.Incident MetS was identified on the basis of each annual health examination using the International Diabetes Federation criteria.Multiple Cox regression analyses were conducted,adjusting for age,sex,waist circumference,smoking status,alcohol consumption status,and physical activity,to assess the associations of the NI-IR indices with incident MetS.The area under the receiver operating characteristic curve(AUROC)was used to compare the capacities of these NI-IR indices for predicting new-onset MetS.RESULTS During a median follow-up of 5.8 years,there were 673 patients with new-onset MetS(23%).All six of the NI-IR indices were significantly and positively associated with incident MetS.In the entire cohort,the greatest AUROC was found for the METS-IR[0.782;95%confidence interval(CI):0.762-0.801;all P values compared to the other NIIR indices<0.05],followed by the TG/HDL-C ratio(0.752;95%CI:0.731-0.772),ZJU index(0.743;95%CI:0.722-0.764),TyG index(0.734;95%CI:0.713-0.756),TC/HDL-C ratio(0.731;95%CI:0.709-0.752),and then the ALT/AST ratio(0.734;95%CI:0.713-0.756).CONCLUSION This study suggests that almost all the NI-IR indices are associated with the development of MetS in military young adults.The METS-IR is the strongest predictor of new-onset MetS before midlife.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
文摘Asthma is the most common allergic disorder and represents a significant global public health problem.Strong evidence suggests a link between ascariasis and asthma.This study aims primarily to determine the prevalence of Ascaris lumbricoides infection among various risk factors,to assess blood parameters,levels of immunoglobulin E(IgE)and interleukin-4(IL-4),and to explore the relationship between ascariasis and asthma in affected individuals.The secondary objective is to examine a fractal-fractional mathematical model that describes the four stages of the life cycle of Ascaris infection,specifically within the framework of the Caputo-Fabrizio derivative.A case-control study was conducted that involved 270 individuals with asthma and 130 healthy controls,all of whom attended general hospitals in Duhok City,Iraq.Pulmonary function tests were performed using a micromedical spirometer.The presence of Ascaris lumbricoides antibodies-Immunoglobulin M(IgM),Immunoglobulin G(IgG),and Immunoglobulin E(IgE)-was detected using ELISA.Blood parameters were analyzed using a Coulter counter.The overall infection rate was(42.5%),with the highest rates observed among asthmatic men(70.0%)and rural residents(51.4%).Higher infection rates were also recorded among low-income individuals(64.3%)and those with frequent contact with the soil(58.6%).In particular,infected individuals exhibited a significant decrease in red blood cell count and hemoglobin concentration,while a marked increase in white blood cell count was recorded.In addition,levels of Immunoglobulin E(IgE)and interleukin-4 were significantly higher in the infected group compared to the controls.Effective disease awareness strategies that incorporate health education and preventive measures are needed.Exposure to Ascaris has been associated with reduced lung function and an increased risk of asthma.More research is required to elucidate the precise mechanisms that link Ascaris infection with asthma.Furthermore,the existence and uniqueness of solutions for the proposed model are investigated using the Krasnosel’skii and Banach fixed-point theorems.The Ulam-Hyers and Ulam-Hyers-Rassias stability types are explained within the framework of nonlinear analysis inŁp-space.Finally,an application is presented,including tabulated results and figures generated using MATLAB to illustrate the validity of the theoretical findings.
文摘BACKGROUND The impact of psychiatric disorder,especially depression,on the prognosis of sarcopenic patients is gaining prominence.Yet,there have been very few studies focusing on this issue,let alone the related targeted mental health prevention.This cohort-based nested case-control study is geared to compare risk of depression and the depression-related ambulatory care utilization for sarcopenia persons with and without receiving add-on Chinese herbal medicines(CHMs)treatment.AIM To compare risk of depression and the depression-related ambulatory care utili-zation for sarcopenia persons with and without receiving add-on CHMs treat-ment.METHODS In the beginning,we recruited those aged 20-70 years with newly diagnosed sarcopenia and free of depression between 2002 and 2010 from a nationwide insurance database.From them,we identified cases with depression onset occurring after sarcopenia until December 31,2013.To cautiously isolate the effect of CHMs,we established the matched sets of treated and untreated subjects with CHMs use by randomly frequency matching.A conditional logistic regression was executed to explore the association of CHMs to depression risk,and the frequency and costs of depression-related ambulatory care were compared using Mann-Whitney U test.RESULTS Addition of CHMs to routine care of sarcopenia notably correlated with a lower risk of depression.A remarkable effect of CHMs in reducing depression was detected when sarcopenia subjects received CHMs for more than three years,lowering depression risk by as much as 65%.As compared to CHMs users,the non-CHMs users indeed incurred higher frequency and costs of depression-related ambulatory care after depression attack(P<0.05).Notably,the costs for per depression-related ambulatory care profoundly increased with the years after depression attack.CONCLUSION Sarcopenic patients can greatly benefit from add-on CHMs treatment,underscoring the urgent need for interdisciplinary collaboration and proactive treatment planning.
基金Hualien Tzu-Chi Hospital of the Buddhist Tzu Chi Medical Foundation.
文摘Background:Weight stigma is prevalent and has multiple sources,which have significant effects on individual,social,physical,and psychological health.This study evaluated the psychometric properties of the Thai version of WeSEI to provide a valid tool to assess weight stigma in Thai young adults.Methods:A cross-sectional online survey recruited 517 Thai university students from October 2024 to May 2025.All participants completed demographic information and standardized self-reported instruments,including WeSEI,Depression,Anxiety,and Stress scale 21(DASS-21),Weight Self-Stigma Questionnaire(WSSQ),and Perceived Weight Stigma Scale(PWSS).The psychometric properties of the Thai version of WeSEI were examined via confirmatory factor analysis(CFA)with some validity indices.Results:The 7-factor structure of the Thai version of the WeSEI was supported across sex and weight status subgroups,indicating good construct validity.In addition,internal consistency(Cronbach’sα=0.972;McDonald’sω=0.972),convergent,and discriminant validity also indicated that the Thai version of the WeSEI had good psychometric properties and assessed weight stigma among young people in Thailand.Conclusions:Sound psychometric properties of the Thai adaptation of WeSEI allows the identification of various sources contributing to weight stigma and to identify those experiencing high levels of weight stigma.It also provides evidence to support targeted interventions to reduce weight stigma and its associated mental health impacts in further research.Further studies are necessary to explore the utilization of WeSEI for weight stigma in Thailand.
基金The work described in this paper was fully supported by a grant from Hong Kong Metropolitan University(RIF/2021/05).
文摘Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using deep learning algorithms further enhances performance;nevertheless,it is challenging due to the nature of small-scale and imbalanced PD datasets.This paper proposed a convolutional neural network-based deep support vector machine(CNN-DSVM)to automate the feature extraction process using CNN and extend the conventional SVM to a DSVM for better classification performance in small-scale PD datasets.A customized kernel function reduces the impact of biased classification towards the majority class(healthy candidates in our consideration).An improved generative adversarial network(IGAN)was designed to generate additional training data to enhance the model’s performance.For performance evaluation,the proposed algorithm achieves a sensitivity of 97.6%and a specificity of 97.3%.The performance comparison is evaluated from five perspectives,including comparisons with different data generation algorithms,feature extraction techniques,kernel functions,and existing works.Results reveal the effectiveness of the IGAN algorithm,which improves the sensitivity and specificity by 4.05%–4.72%and 4.96%–5.86%,respectively;and the effectiveness of the CNN-DSVM algorithm,which improves the sensitivity by 1.24%–57.4%and specificity by 1.04%–163%and reduces biased detection towards the majority class.The ablation experiments confirm the effectiveness of individual components.Two future research directions have also been suggested.
基金financial support fromthe Chung Shan Medical University Hospital,Taiwan(CSH-2022-A-009).
文摘Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index(BMI).Methods:This retrospective cohort study used electronic health records from the TriNetX U.S.research network.Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis.Following 1:1 propensity score matching,both the GLP-1 RA user and non-user groups included 183,264 patients.The study outcome was defined as a diagnosis of malignant neoplasms.Hazard ratios(HRs)for overall and site-specific cancer risk were estimated using Cox proportional hazards models.Kaplan–Meier analysis and stratified analysis by BMI were performed.Results:Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk(HR 0.93;95%CI:0.90–0.96).Reduced risks were noted for cancers of the digestive(HR 0.81),respiratory(HR 0.66),and female genital(HR 0.87)systems.In stratified analysis,benefits were more pronounced in patients with BMI≥30,particularly for pancreatic and colorectal cancers.Conclusion:Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk,particularly among individuals with obesity.These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.
基金the grant from the National Natural Science Foundation of China (30270719)
文摘Recent molecular cytogenetic studies demonstrate that extensive centromere-telomere fusions are the main chromosomal rearrangements underlying the karyotypic evolution of extant muntjacs. Although the molecular mechanism of tandem fusions remains unknown, satellite DNA is believed to have facilitated chromosome fusions by non-allelic homologous recombination. Previous studies detected non-random hybridization signals of cloned satellite DNA at the postulated fusion sites on the chromosomes in Indian and Chinese muntjacs. But the genomic distribution and organization of satellite DNAs in other muntjacs have not been investigated. In this study, we have isolated four satellite DNA clones （BMCS, BM700, BM 1.1 k and FM700） from the black muntjac （Muntiacus crinifrons） and Fea＇s muntjac （M. feae）, and hybridized these four clones onto chromosomes of four muntjac species （M. reevesi, M. crinifrons, M. gongshanenisis and M. feae）. Besides the predominant centromeric signals, non-random interstitial hybridization signals from satellite I and II DNA clones （BMC5, BM700 and FM700） were also observed on the arms of chromosomes of these four muntjacs. Our results provide additional support for the notion that the karyotypes of M. crinifrons, M. feae and M. gongshanensis have evolved from a 2n = 70 ancestral karyotype by a series of chromosome fusions.
基金Supported by The National Science Council, No. NSC98-2320-B-016-011 MY3TTri-Service General Hospital, No. TSGH-C100-011-015-S03
文摘The prevalence of type 2 diabetes mellitus （T2DM） is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhosis. It is suggested that there is a pathogenic link between the presence of T2DM and the severity of liver injury. However, evidence related to the impact of hepatic inflammation on the development of T2DM has not yet emerged. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases, the impact of liver diseases on insulin resistance and 13 cell dysfunction, and the potential mechanisms whereby coexistent liver diseases exacerbate the development of T2DM.
文摘Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search for and identify novel and potent therapeutic targets to improve patient outcomes.Sorafenib is the first and only approved targeted therapy for the treatment of hepatocellular carcinoma.Besides functioning as a multiple tyrosine kinase,sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3(STAT3) signaling in hepatocellular carcinoma cells.STAT3 is a key regulator of inflammation,cell survival,and tumorigenesis of liver cells,and the high percentage of hepatocellular carcinoma cells with constitutively active STAT3 justifies targeting it for the development of novel therapeutics.Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a conformational change in and releasing the autoinhibition of Src homology region 2 domaincontaining phosphatase-1.This phosphatase negatively regulates STAT3 activity,which leads to the subsequent apoptosis of cancer cells.The novel anti-cancer property of sorafenib will be discussed in this review,not only adding information regarding its mechanism of action but also providing an innovative approach for the development of cancer therapeutics in the future.
基金grants of Stem Cell Project of TVGHthe Joint Projects of UTVGH, No. 94-P1-04/06/10+1 种基金Yen Tjing-Ling Medical FoundationNational Yang-Ming University, Taiwan, China
文摘AIM： To enhance the differentiation of insulin producing cell （IPC） ability from embryonic stem （ES） cells in vitro. METHODS： Four-day embryoid body （EB）-formatted ES cells were dissociated as single cells for the followed plasmid DNA delivery. The use of NucleofectorTM electroporator （Amaxa biosystems, Germany） in combination with medium-contained G418 provided a high efficiency of gene delivery for advanced selection. Neucleofected cells were plated on the top of fibronectincoated Petri dishes. Addition of Ly294002 and raised the glucose in medium at 24 h before examination.The differentiation status of these cells was monitored by semi-quantitative PCR （SQ-PCR） detection of the expression of relative genes, such as oct-4, sox-17, foxa2, mixll, pdx-1, insulin 1, glucagons and somatostatin. The percentage of IPC population on d 18 of the experiment was investigated by immunohistochemistry （IHC）, and the content/secretion of insulin was estimated by ELISA assay. The mice with severe combined immunodeficiency disease （SCID） pretreated with streptozotocin （STZ） were used to eliminate plasma glucose restoration after pax4^＋ ES implantation. RESULTS： A high efficiency of gene delivery was demonstrated when neucleofection was used in the present study; approximately 70% cells showed DsRed expression 2 d after neucleofection. By selection of medium-contained G418, the percentage of DsRed expressing cells kept high till the end of study. The pancreatic differentiation seemed to be accelerated by pax4 nucleofection. When compared to the group of cells with mock control, foxa2, mixll, pdxl, higher insulin and somatostatin levels were detected by SQ-PCR 4 d after nucleofection in the group of pax4 expressing plasmid delivery. Approximately 55% of neucleofected cells showed insulin expression 18 d after neucleofection, and only 18% of cells showed insulin expression in mock control. The disturbance was shown by nucleofected pax4 RNAi vector; only 8% of cells expressed insulin 18 d after nucleofection. A higher IPC population was also detected in the insulin content by ELISA assay, and the glucose dependency was demonstrated in insulin secretion level. In the animal model, improvement of average plasma glucose concentration was observed in the group of pax-4 expressed ES of SCID mice pretreated with STZ, but no significant difference was observed in the group of STZ-pretreated SCID mice who were transplanted ES with mock plasmid. CONCLUSION： Enhancement of IPC differentiation from EB-dissociated ES cells can be revealed by simply using pax4 expressing plasrnid delivery. Not only more IPCs but also pancreatic differentiation-related genes can be detected by SQ-PCR. Expression of relative genes, such as foxa 2, mixl 1, pdx-1, insulin 1 and somatostatin after nucleofection, suggests that pax4 accelerates the whole differentiation progress. The higher insulin production with glucose dependent modulation suggests that pax4 expression can drive more mature IPCs. Although further determination of the entire mechanism is required, the potential of pax-4-nucleofected cells in medical treatment is promising.
