Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) is a rare disease characterized by total or partial vagina agenesis, karyotype 46, XX with normal secondary sexual characters. Still, it is the second leading cause of pr...Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) is a rare disease characterized by total or partial vagina agenesis, karyotype 46, XX with normal secondary sexual characters. Still, it is the second leading cause of primary amenorrhea. The absence of obvious signs and symptoms often causes the syndrome to be diagnosed only after puberty. The case presented here highlights exactly this difficulty of early diagnosis, which meets the objective of the study, and is precisely to provide reliable material that facilitates the diagnosis and management of patients with MRKH syndrome.展开更多
Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
The feasibility and clinical therapeutic effects of laparoscopic sigmoid vaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser syndrome(MRKHs)were explored.The records of 11 MRKHs patients who underwent laparoscop...The feasibility and clinical therapeutic effects of laparoscopic sigmoid vaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser syndrome(MRKHs)were explored.The records of 11 MRKHs patients who underwent laparoscopic sigmoid vaginoplasty from 2003 to 2005 were reviewed,and long-term results were evaluated by follow-up.The mean operating time was 234 min(range,130–300 min),the mean hospital stay was 9.4 days(range,7–15 days),and the mean hemoglobin drop was 1.91 g/dL(range,1.6–3.2 g/dL).A functional neovagina was created measuring 11 to 14 cm in length and twofingers in breadth in all patients.No introitus stenosis was observed.No intra-operative or postoperative bowel complication occurred.At the 3rd postoperative month,thefirst intercourse began.One patient was lost to follow-up.One had no intercourse and was required to wear vaginal mold occasionally.None of the other nine women(100%)complained of local irritation or dyspar-eunia.They were satisfied with their sexual life.The cosmetic results were excellent.The laparoscopic sigmoid vaginoplasty realizes to make a functional neovagina.The main advantage is its minimal invasiveness.It is an ideal procedure for MRKHs patients.展开更多
The liver is increasingly recognized as a major regulator of systemic cardio-renal-metabolic health.Evidence is mounting that sex-chromosome dosage per se itself,independent of gonadal sex hormones,modulates hepatic p...The liver is increasingly recognized as a major regulator of systemic cardio-renal-metabolic health.Evidence is mounting that sex-chromosome dosage per se itself,independent of gonadal sex hormones,modulates hepatic physiology and liver disease risk.Turner syndrome(TS;monosomy X)and Klinefelter syndrome(KS;47,XXY and variants)are the two most common sex-chromosome aneuploidies and carry a clinically relevant,yet often under-appreciated,burden of liver disease.Population studies show that individuals with TS have 2-to sixfold higher odds of raised liver enzymes,steatotic liver disease,advanced fibrosis,and even hepatocellular malignancy compared with to sex-and age-matched controls.In KS,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)reaches approximately 45%,with testosterone deficiency,visceral adiposity,and systemic inflammation acting as key drivers.Pathogenetic mechanisms converge on vascular dysgenesis and estrogen deficiency in TS,and on hypogonadism-related metabolic derangements in KS,together accelerating steatosis,inflammation,and fibrogenesis.This concise review/Comprehensive perspective reviews discusses historical background,epidemiology,hepatic phenotypes,pathophysiology,and current diagnostic and management recommendations.It also highlights critical knowledge gaps,including the need for prospective cohorts,optimized hormone-replacement protocols,and trials of emerging pharmacological approaches anti-MASH agents.Raising awareness among all stakeholders,endocrinologists,hepatologists,and primary-care physicians is essential for early detection,multidisciplinary management,and improved hepatic and extra-hepatic outcomes in these vulnerable patient populations.展开更多
Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is sig...Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.展开更多
Takotsubo syndrome(TTS),also known as stressinduced cardiomyopathy,presents clinical manifestations similar to acute coronary syndrome(ACS).[1] Accurate and timely differentiation is crucial in emergency settings.Para...Takotsubo syndrome(TTS),also known as stressinduced cardiomyopathy,presents clinical manifestations similar to acute coronary syndrome(ACS).[1] Accurate and timely differentiation is crucial in emergency settings.Paraganglioma is a rare neuroendocrine tumor originating from extra-adrenal chromaffin tissue.It is characterized by excessive catecholamine secretion,which can lead to severe hemodynamic and metabolic disturbances.We herein report a case of TTS complicated by cardiac shock caused by paraganglioma.Following mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation(V-A ECMO) and appropriate preoperative management,the patient underwent successful tumor resection and achieved full recovery.展开更多
AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A...AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.展开更多
Objective:To investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urolo...Objective:To investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urology,First Affiliated Hospital of Jinan University,were selected and treated with electrophysiological therapy.They were randomly divided into three groups:the fixed-parameter AA7 treatment group,the P2+P4 treatment group,and the precision treatment group(individualized parameter treatment).Pain scores of patients in each group were compared before and after treatment,with a pain score of 0 indicating cure.The cure rate of each group was observed.Results:The average ages of the AA7 group,P2+P4 group,and precision treatment group were 34±14.17 years,35.58±12.57 years,and 35.5±11.27 years,respectively.There was no significant difference in age among the three groups(p>0.05).Before treatment,the pain scores of the AA7 group,P2+P4 group,and precision treatment group were 4.14±1.74,4.64±1.72,and 3.50±1.89,respectively,with no significant differences among the groups(p>0.05).After treatment,the pain scores were 0.71±0.99 for the AA7 group(cure rate:57%),0.49±0.79 for the P2+P4 group(cure rate:67%),and 0.50±0.77 for the precision treatment group(cure rate:64%),with no significant differences among the groups(p>0.05).The cure rates for different pain locations were as follows:83%for lower abdominal pain,74%for perineal pain,62%for dysuria,49%for testicular pain,and 75%for inguinal pain.Conclusion:The pathogenesis of CPPS is complex and diverse,with numerous treatment options and uncertain efficacy,posing significant challenges to clinical practice.This study showed that electrophysiological therapy under different parameter modes significantly reduced pain scores before and after treatment,indicating significant therapeutic effects on CPPS.All three modes demonstrated good cure rates.Individualized precision treatment and fixed-mode P2+P4 or AA7 treatment were safe and effective in CPPS treatment and are worth promoting.Fixed-mode P2+P4 and AA7,due to their easier standardization of parameters and patch modes,reduced the learning curve and had better potential for widespread application.展开更多
[Objectives]To analyze the clinical characteristics,distribution of traditional Chinese medicine(TCM)syndrome types,spectrum of comorbidities,and complications among inpatients with gout.[Methods]Data from 592 gout pa...[Objectives]To analyze the clinical characteristics,distribution of traditional Chinese medicine(TCM)syndrome types,spectrum of comorbidities,and complications among inpatients with gout.[Methods]Data from 592 gout patients admitted in the Department of Rheumatology at Wuxi Traditional Chinese Medicine Hospital between January 2018 and December 2024 were retrospectively collected.The data collected encompassed patient gender,age,TCM syndrome types,underlying comorbidities,infection status,and major complications,including renal insufficiency,interstitial lung disease,and osteoporosis.Descriptive statistical analyses were subsequently performed.[Results]Among the 592 inpatients,80.75%were male and 19.25%were female.A total of 94.76%patients had at least one underlying condition,with hypertension(80.74%),cerebral infarction(29.59%),heart disease(24.24%),and diabetes(21.56%)being the most prevalent.The primary TCM syndrome types identified were damp-heat obstruction syndrome(63.51%)and phlegm-stasis obstruction syndrome(21.11%).During hospitalization,20.94%of patients experienced concurrent infections,predominantly pulmonary infections(38.10%).The principal complications observed included renal insufficiency(32.09%),interstitial lung disease(18.75%),and osteoporosis(9.29%).[Conclusions]Inpatients diagnosed with gout often present with complex conditions and a high burden of comorbidities,predominantly cardiovascular and cerebrovascular diseases,as well as metabolic disorders.Additionally,there is a high incidence of infections and renal insufficiency within this population.TCM syndrome types in these patients are primarily characterized by damp-heat obstruction.In clinical practice,a comprehensive management approach that incorporates multidisciplinary collaboration is recommended.Alongside the control of uric acid levels and joint inflammation,proactive screening and management of comorbidities and related complications are essential.展开更多
Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network...Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network pharmacology,molecular docking,and experimental validation.Methods Bioactive constituents in LV tablets were identified using liquid chromatographymass spectrometry(LC-MS).Network pharmacology analysis was performed to predict LVrelated targets and PCOS-associated genes using BindingDB,Super-PRED,GeneCards,and DisGeNET databases.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to clarify biological processes and signaling pathways.Molecular docking simulations evaluated binding affinities between LV phytoconstituents and key predicted targets.For in vivo validation,PCOS was induced in 36 female Wistar rats by daily subcutaneous administration of DHEA(60 mg/kg)for 21 d,and after successful model establishment,rats were randomly divided into DHEA,metformin(MET),clomiphene citrate(CC),and LV low-dose(LV-L,51.5 mg/kg),medium-dose(LV-M,103 mg/kg),and high-dose(LV-H,206 mg/kg)groups(n=6 each),which were orally administered for 21 d,respectively.Additional 6 rats were kept as normal control(NC)group,which did not receive any DHEA treatment.Estrous cyclicity,body weight,ovarian weight and diameter,fasting blood glucose(FBG),serum hormones[testosterone,progesterone,estrogen,follicle-stimulating hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH)],insulin resistance[homeostatic model assessment for insulin resistance(HOMAIR)],lipid profile[total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)],inflammatory cytokines[tumor necrosis factor(TNF)-αand interleukin(IL)-6],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GPx),malondialdehyde(MDA),and nitric oxide(NO)],myeloperoxidase(MPO),and ovarian histopathology were evaluated.Results LC-MS analysis identified eight major phytoconstituents in LV:sitosterol,citrulline,bonducellin,oleic acid,δ-caesalpin,heptocosane,palmitic acid,and stearic acid.Network pharmacology revealed 36 overlapping targets between LV and PCOS,with key targets including estrogen receptor 1(ESR1),nuclear receptor subfamily 3 group C member 1(NR3C1),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR).GO and KEGG enrichment analyses indicated involvement in lipid metabolism regulation,steroid hormone receptor activity,prolactin signaling pathway,hypoxia-inducible factor(HIF)-1 signaling pathway,and insulin resistance pathways.Molecular docking demonstrated strong binding affinities between LV phytoconstituents and predicted targets,with sitosterol showing the strongest binding to EGFR(−9.9 kcal/mol)and ESR1(−8.3 kcal/mol).In vivo experiments confirmed that LV treatment restored normal estrous cyclicity and significantly reduced body weight,ovarian weight,and ovarian diameter compared with DHEA group(P<0.05,P<0.01,or P<0.001).LV dose-dependently restored FBG,insulin,and HOMA-IR levels(P<0.01 or P<0.001),and improved lipid profile,including reduced TC,TG,and LDL,and increased HDL(P<0.05,P<0.01,or P<0.001).Hormonal abnormalities were corrected with testosterone,LH,and AMH decreased and progesterone,estrogen,and FSH increased(P<0.05,P<0.01,or P<0.001).Furthermore,LV enhanced activities of antioxidant enzymes(SOD,CAT,and GPx),and reduced oxidative stress markers(MDA and NO)(P<0.05,P<0.01,or P<0.001).Pro-inflammatory cytokines TNF-αand IL-6 were significantly suppressed,and MPO activity decreased compared with DHEA group(P<0.05,P<0.01,or P<0.001).Histopathological examination showed that after LV treatment,ovarian morphology recovered with cystic follicles decreased and corpus luteum increased.Among the three LV-treated groups,LV-H group exhibited the most pronounced improvements across all parameters,indicating a clear dose-dependent therapeutic effects.Conclusion LV showed protective effects against DHEA-induced pcos by restoring endocrine balance and mitigating metabolic,oxidative,and inflammatory disturbances.The involvement of key regulatory targets,including ESR1,NR3C1,STAT3,and EGFR,supports its multi-target therapeutic potential.These findings highlight LV as a promising herbal candidate for polycystic ovarian syndrome management.展开更多
Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.Ho...Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.展开更多
AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyse...AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.展开更多
BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suita...BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.展开更多
Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neu...Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).展开更多
Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend ...Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.展开更多
Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chron...Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
OBJECTIVE:To compare the efficacy of Tongxie Yaofang(痛泻要方,TXYF)versus pinaverium bromide for the treatment of diarrheal irritable bowel syndrome(IBSD)with liver depression and spleen deficiency.METHODS:A search of...OBJECTIVE:To compare the efficacy of Tongxie Yaofang(痛泻要方,TXYF)versus pinaverium bromide for the treatment of diarrheal irritable bowel syndrome(IBSD)with liver depression and spleen deficiency.METHODS:A search of the China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,Pub Med,EMBASE,Cochrane Library and Web of Science databases was conducted from database creation to the 28th of September 2022.Meta-analysis was performed using Revman 5.4 software.RESULTS:Twelve randomized controlled trials comprising 1058 patients were included in the analysis.TXYF was more efficacious in improving the clinical symptoms of patients.Comparison of the efficacy rate,Traditional Chinese Medicine Evidence Score(TCMPES),self-rating anxiety scale anxiety score,self-rating depression scale depression score,adverse reaction rate and calcitonin gene-related peptide(CGRP)levels showed that TXYF was significantly superior to pinaverium bromide treatment(P<0.05);there was no statistically significant difference in the plasma vasoactive peptide level between the two groups(P>0.05).Funnel plots of the total efficacy rate and TCM-PES were asymmetrically distributed,suggesting publication bias.The GRADEpro Guideline Development Tool was also used to evaluate the studies,and the evidence rating of the included studies was not high.CONCLUSIONS:Although the results of this study suggest that TXYF may be superior for the treatment of IBS-D with liver depression and spleen deficiency,as compared to pinaverium bromide,definitive conclusions are unable to be drawn at this time due to flaws in the overall design of the included trials.Therefore,more rigorous trials are needed to determine the benefit and safety of TXYF.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the ...This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the phenotypes of bile acid dysregulation in IBS-D patients,and the related pathogenic molecular mechanisms.A primary focus is placed on dissecting the interaction mechanisms between the gut microbiota and bile acids,specifically the regulatory role of the gut microbiota in bile acid transformation and the influence of bile acids on the structure of the gut microbiota.Based on current research evidence,this article proposes the gut microbiota-bile acid axis as a potential therapeutic target for IBS-D.It aims to provide theoretical insights and novel perspectives for exploring innovative treatment strategies for IBS-D and elucidating its pathogenesis.展开更多
文摘Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) is a rare disease characterized by total or partial vagina agenesis, karyotype 46, XX with normal secondary sexual characters. Still, it is the second leading cause of primary amenorrhea. The absence of obvious signs and symptoms often causes the syndrome to be diagnosed only after puberty. The case presented here highlights exactly this difficulty of early diagnosis, which meets the objective of the study, and is precisely to provide reliable material that facilitates the diagnosis and management of patients with MRKH syndrome.
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
文摘The feasibility and clinical therapeutic effects of laparoscopic sigmoid vaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser syndrome(MRKHs)were explored.The records of 11 MRKHs patients who underwent laparoscopic sigmoid vaginoplasty from 2003 to 2005 were reviewed,and long-term results were evaluated by follow-up.The mean operating time was 234 min(range,130–300 min),the mean hospital stay was 9.4 days(range,7–15 days),and the mean hemoglobin drop was 1.91 g/dL(range,1.6–3.2 g/dL).A functional neovagina was created measuring 11 to 14 cm in length and twofingers in breadth in all patients.No introitus stenosis was observed.No intra-operative or postoperative bowel complication occurred.At the 3rd postoperative month,thefirst intercourse began.One patient was lost to follow-up.One had no intercourse and was required to wear vaginal mold occasionally.None of the other nine women(100%)complained of local irritation or dyspar-eunia.They were satisfied with their sexual life.The cosmetic results were excellent.The laparoscopic sigmoid vaginoplasty realizes to make a functional neovagina.The main advantage is its minimal invasiveness.It is an ideal procedure for MRKHs patients.
文摘The liver is increasingly recognized as a major regulator of systemic cardio-renal-metabolic health.Evidence is mounting that sex-chromosome dosage per se itself,independent of gonadal sex hormones,modulates hepatic physiology and liver disease risk.Turner syndrome(TS;monosomy X)and Klinefelter syndrome(KS;47,XXY and variants)are the two most common sex-chromosome aneuploidies and carry a clinically relevant,yet often under-appreciated,burden of liver disease.Population studies show that individuals with TS have 2-to sixfold higher odds of raised liver enzymes,steatotic liver disease,advanced fibrosis,and even hepatocellular malignancy compared with to sex-and age-matched controls.In KS,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)reaches approximately 45%,with testosterone deficiency,visceral adiposity,and systemic inflammation acting as key drivers.Pathogenetic mechanisms converge on vascular dysgenesis and estrogen deficiency in TS,and on hypogonadism-related metabolic derangements in KS,together accelerating steatosis,inflammation,and fibrogenesis.This concise review/Comprehensive perspective reviews discusses historical background,epidemiology,hepatic phenotypes,pathophysiology,and current diagnostic and management recommendations.It also highlights critical knowledge gaps,including the need for prospective cohorts,optimized hormone-replacement protocols,and trials of emerging pharmacological approaches anti-MASH agents.Raising awareness among all stakeholders,endocrinologists,hepatologists,and primary-care physicians is essential for early detection,multidisciplinary management,and improved hepatic and extra-hepatic outcomes in these vulnerable patient populations.
文摘Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.
文摘Takotsubo syndrome(TTS),also known as stressinduced cardiomyopathy,presents clinical manifestations similar to acute coronary syndrome(ACS).[1] Accurate and timely differentiation is crucial in emergency settings.Paraganglioma is a rare neuroendocrine tumor originating from extra-adrenal chromaffin tissue.It is characterized by excessive catecholamine secretion,which can lead to severe hemodynamic and metabolic disturbances.We herein report a case of TTS complicated by cardiac shock caused by paraganglioma.Following mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation(V-A ECMO) and appropriate preoperative management,the patient underwent successful tumor resection and achieved full recovery.
基金Supported by Ongoing Research Funding Program(ORFFT-2025-054-1),King Saud University,Riyadh,Saudi Arabia.
文摘AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.
文摘Objective:To investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urology,First Affiliated Hospital of Jinan University,were selected and treated with electrophysiological therapy.They were randomly divided into three groups:the fixed-parameter AA7 treatment group,the P2+P4 treatment group,and the precision treatment group(individualized parameter treatment).Pain scores of patients in each group were compared before and after treatment,with a pain score of 0 indicating cure.The cure rate of each group was observed.Results:The average ages of the AA7 group,P2+P4 group,and precision treatment group were 34±14.17 years,35.58±12.57 years,and 35.5±11.27 years,respectively.There was no significant difference in age among the three groups(p>0.05).Before treatment,the pain scores of the AA7 group,P2+P4 group,and precision treatment group were 4.14±1.74,4.64±1.72,and 3.50±1.89,respectively,with no significant differences among the groups(p>0.05).After treatment,the pain scores were 0.71±0.99 for the AA7 group(cure rate:57%),0.49±0.79 for the P2+P4 group(cure rate:67%),and 0.50±0.77 for the precision treatment group(cure rate:64%),with no significant differences among the groups(p>0.05).The cure rates for different pain locations were as follows:83%for lower abdominal pain,74%for perineal pain,62%for dysuria,49%for testicular pain,and 75%for inguinal pain.Conclusion:The pathogenesis of CPPS is complex and diverse,with numerous treatment options and uncertain efficacy,posing significant challenges to clinical practice.This study showed that electrophysiological therapy under different parameter modes significantly reduced pain scores before and after treatment,indicating significant therapeutic effects on CPPS.All three modes demonstrated good cure rates.Individualized precision treatment and fixed-mode P2+P4 or AA7 treatment were safe and effective in CPPS treatment and are worth promoting.Fixed-mode P2+P4 and AA7,due to their easier standardization of parameters and patch modes,reduced the learning curve and had better potential for widespread application.
基金Supported by Wuxi Taihu Talent Program(202101)Project of Wu Jieping Medical Foundation(320.6750.2023-03-33).
文摘[Objectives]To analyze the clinical characteristics,distribution of traditional Chinese medicine(TCM)syndrome types,spectrum of comorbidities,and complications among inpatients with gout.[Methods]Data from 592 gout patients admitted in the Department of Rheumatology at Wuxi Traditional Chinese Medicine Hospital between January 2018 and December 2024 were retrospectively collected.The data collected encompassed patient gender,age,TCM syndrome types,underlying comorbidities,infection status,and major complications,including renal insufficiency,interstitial lung disease,and osteoporosis.Descriptive statistical analyses were subsequently performed.[Results]Among the 592 inpatients,80.75%were male and 19.25%were female.A total of 94.76%patients had at least one underlying condition,with hypertension(80.74%),cerebral infarction(29.59%),heart disease(24.24%),and diabetes(21.56%)being the most prevalent.The primary TCM syndrome types identified were damp-heat obstruction syndrome(63.51%)and phlegm-stasis obstruction syndrome(21.11%).During hospitalization,20.94%of patients experienced concurrent infections,predominantly pulmonary infections(38.10%).The principal complications observed included renal insufficiency(32.09%),interstitial lung disease(18.75%),and osteoporosis(9.29%).[Conclusions]Inpatients diagnosed with gout often present with complex conditions and a high burden of comorbidities,predominantly cardiovascular and cerebrovascular diseases,as well as metabolic disorders.Additionally,there is a high incidence of infections and renal insufficiency within this population.TCM syndrome types in these patients are primarily characterized by damp-heat obstruction.In clinical practice,a comprehensive management approach that incorporates multidisciplinary collaboration is recommended.Alongside the control of uric acid levels and joint inflammation,proactive screening and management of comorbidities and related complications are essential.
文摘Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network pharmacology,molecular docking,and experimental validation.Methods Bioactive constituents in LV tablets were identified using liquid chromatographymass spectrometry(LC-MS).Network pharmacology analysis was performed to predict LVrelated targets and PCOS-associated genes using BindingDB,Super-PRED,GeneCards,and DisGeNET databases.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to clarify biological processes and signaling pathways.Molecular docking simulations evaluated binding affinities between LV phytoconstituents and key predicted targets.For in vivo validation,PCOS was induced in 36 female Wistar rats by daily subcutaneous administration of DHEA(60 mg/kg)for 21 d,and after successful model establishment,rats were randomly divided into DHEA,metformin(MET),clomiphene citrate(CC),and LV low-dose(LV-L,51.5 mg/kg),medium-dose(LV-M,103 mg/kg),and high-dose(LV-H,206 mg/kg)groups(n=6 each),which were orally administered for 21 d,respectively.Additional 6 rats were kept as normal control(NC)group,which did not receive any DHEA treatment.Estrous cyclicity,body weight,ovarian weight and diameter,fasting blood glucose(FBG),serum hormones[testosterone,progesterone,estrogen,follicle-stimulating hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH)],insulin resistance[homeostatic model assessment for insulin resistance(HOMAIR)],lipid profile[total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)],inflammatory cytokines[tumor necrosis factor(TNF)-αand interleukin(IL)-6],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GPx),malondialdehyde(MDA),and nitric oxide(NO)],myeloperoxidase(MPO),and ovarian histopathology were evaluated.Results LC-MS analysis identified eight major phytoconstituents in LV:sitosterol,citrulline,bonducellin,oleic acid,δ-caesalpin,heptocosane,palmitic acid,and stearic acid.Network pharmacology revealed 36 overlapping targets between LV and PCOS,with key targets including estrogen receptor 1(ESR1),nuclear receptor subfamily 3 group C member 1(NR3C1),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR).GO and KEGG enrichment analyses indicated involvement in lipid metabolism regulation,steroid hormone receptor activity,prolactin signaling pathway,hypoxia-inducible factor(HIF)-1 signaling pathway,and insulin resistance pathways.Molecular docking demonstrated strong binding affinities between LV phytoconstituents and predicted targets,with sitosterol showing the strongest binding to EGFR(−9.9 kcal/mol)and ESR1(−8.3 kcal/mol).In vivo experiments confirmed that LV treatment restored normal estrous cyclicity and significantly reduced body weight,ovarian weight,and ovarian diameter compared with DHEA group(P<0.05,P<0.01,or P<0.001).LV dose-dependently restored FBG,insulin,and HOMA-IR levels(P<0.01 or P<0.001),and improved lipid profile,including reduced TC,TG,and LDL,and increased HDL(P<0.05,P<0.01,or P<0.001).Hormonal abnormalities were corrected with testosterone,LH,and AMH decreased and progesterone,estrogen,and FSH increased(P<0.05,P<0.01,or P<0.001).Furthermore,LV enhanced activities of antioxidant enzymes(SOD,CAT,and GPx),and reduced oxidative stress markers(MDA and NO)(P<0.05,P<0.01,or P<0.001).Pro-inflammatory cytokines TNF-αand IL-6 were significantly suppressed,and MPO activity decreased compared with DHEA group(P<0.05,P<0.01,or P<0.001).Histopathological examination showed that after LV treatment,ovarian morphology recovered with cystic follicles decreased and corpus luteum increased.Among the three LV-treated groups,LV-H group exhibited the most pronounced improvements across all parameters,indicating a clear dose-dependent therapeutic effects.Conclusion LV showed protective effects against DHEA-induced pcos by restoring endocrine balance and mitigating metabolic,oxidative,and inflammatory disturbances.The involvement of key regulatory targets,including ESR1,NR3C1,STAT3,and EGFR,supports its multi-target therapeutic potential.These findings highlight LV as a promising herbal candidate for polycystic ovarian syndrome management.
基金supported by the Fundamental Research Funds for the Central Universities(226-2022-00035)the National Natural Science Foundation of China(81600986).
文摘Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.
文摘AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.
基金supported by the special fund of the National Clinical Key Specialty Construction Program[(2022)301-2305].
文摘BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.
基金Research into Wolfram syndrome in the De Groef team has been supported by the Eye Hope Foundation(Belgium),Wolfram UK(UK)and The Snow Foundation(USA).
文摘Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).
基金supported by the Sanming Project of Medicine in Shenzhen[SZZYSM202206001]National Natural Science Foundation of China[82004320 and 82374383]+3 种基金Natural Science Foundation of Guangdong Province of China[2022A1515011710 and 2022A1515010679]Shenzhen Science and Technology Innovation Committee[JCYJ20220530141407017 and JCYJ20240813153619026]2024 High-quality Development Research Project of Shenzhen Bao’an Public Hospital[YNXM2024078]and Shenzhen Bao’an Chinese Medicine Hospital Research Program[BAZYY20220702].
文摘Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.
基金supported by the Judith Jane Mason and Harold Stannett Williams Memorial Foundation National Medical Program(#Mason2210)to JX。
文摘Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
基金Supported by the National Key Basic Research and Development Plan(973 Plan):Research on Traditional Chinese Medicine Original Thinking and Health State Identification Method System(2011CB505406)。
文摘OBJECTIVE:To compare the efficacy of Tongxie Yaofang(痛泻要方,TXYF)versus pinaverium bromide for the treatment of diarrheal irritable bowel syndrome(IBSD)with liver depression and spleen deficiency.METHODS:A search of the China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,Pub Med,EMBASE,Cochrane Library and Web of Science databases was conducted from database creation to the 28th of September 2022.Meta-analysis was performed using Revman 5.4 software.RESULTS:Twelve randomized controlled trials comprising 1058 patients were included in the analysis.TXYF was more efficacious in improving the clinical symptoms of patients.Comparison of the efficacy rate,Traditional Chinese Medicine Evidence Score(TCMPES),self-rating anxiety scale anxiety score,self-rating depression scale depression score,adverse reaction rate and calcitonin gene-related peptide(CGRP)levels showed that TXYF was significantly superior to pinaverium bromide treatment(P<0.05);there was no statistically significant difference in the plasma vasoactive peptide level between the two groups(P>0.05).Funnel plots of the total efficacy rate and TCM-PES were asymmetrically distributed,suggesting publication bias.The GRADEpro Guideline Development Tool was also used to evaluate the studies,and the evidence rating of the included studies was not high.CONCLUSIONS:Although the results of this study suggest that TXYF may be superior for the treatment of IBS-D with liver depression and spleen deficiency,as compared to pinaverium bromide,definitive conclusions are unable to be drawn at this time due to flaws in the overall design of the included trials.Therefore,more rigorous trials are needed to determine the benefit and safety of TXYF.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
文摘This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the phenotypes of bile acid dysregulation in IBS-D patients,and the related pathogenic molecular mechanisms.A primary focus is placed on dissecting the interaction mechanisms between the gut microbiota and bile acids,specifically the regulatory role of the gut microbiota in bile acid transformation and the influence of bile acids on the structure of the gut microbiota.Based on current research evidence,this article proposes the gut microbiota-bile acid axis as a potential therapeutic target for IBS-D.It aims to provide theoretical insights and novel perspectives for exploring innovative treatment strategies for IBS-D and elucidating its pathogenesis.
