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
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
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
[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 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
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
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
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
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
White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fung...White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin(including the muzzle)of hibernating bats.Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS.However,the role of G.destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking.The debate is fuelled,in part,by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction.Additionally,the recent discovery that G.destructans commonly colonizes the skin of bats of Europe,where no unusual bat mortality events have been reported,has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS.展开更多
BACKGROUND:Individualized positive end-expiratory pressure(PEEP)titration is a crucial technique in mechanical ventilation therapy for acute respiratory distress syndrome(ARDS)patients with intra-abdominal hypertensio...BACKGROUND:Individualized positive end-expiratory pressure(PEEP)titration is a crucial technique in mechanical ventilation therapy for acute respiratory distress syndrome(ARDS)patients with intra-abdominal hypertension(IAH).This study aimed to evaluate the eff ectiveness of electrical impedance tomography(EIT)-guided PEEP titration in this population.METHODS:This prospective study enrolled 36 ARDS patients,including 22 patients with IAH and 14 without IAH.All the patients underwent EIT-guided PEEP titration at the intersection point between alveolar overdistension and collapse during a decremental PEEP trial.The changes in pulmonary ventilation distribution,respiratory mechanics and hemodynamics during the titration process were observed.RESULTS:After EIT-guided PEEP titration was performed,the PEEP,peak inspiratory pressure and plateau pressure increased significantly(P<0.05).Furthermore,no significant differences were observed in respiratory system compliance,tidal volume,driving pressure,or the 4*DP+RR index between the two groups(P>0.05).The mechanical power increased in the non-IAH(NIAH)group after PEEP titration(P<0.05).Ventilation in gravity-dependent lung regions significantly increased(P<0.05),and the oxygenation index(PaO2/FiO2)improved signifi cantly(P<0.05)in both groups.However,blood pressure,heart rate,respiratory rate,central venous pressure,and lactate levels did not signifi cantly change.In the IAH group,the PaO2/FiO2 ratio improved less than that in the NIAH group did(P<0.05).CONCLUSION:In our study,individualized PEEP titration guided by EIT improved oxygenation in ARDS patients with concomitant IAH without signifi cantly aff ecting hemodynamics.The presence of IAH may limit the improvement of oxygenation during EIT-guided PEEP titration.展开更多
It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and er...It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and erythropoietic protoporphyria(EPP),which has not been previously documented.CASE SUMMARY We present a rare case of coexisting GS and EPP in a 23-year-old Chinese male with a long history of jaundice and recently found splenomegaly.Serial nonspecific hemolysis screening tests yielded inconsistent results,and investigations for common hemolytic etiologies were negative.However,Levitt’s carbon monoxide breath test,which measures erythrocyte lifespan(the gold-standard marker of hemolysis),demonstrated significant hemolysis,revealing a markedly shortened erythrocyte lifespan of 11 days(normal average 120 days).Genetic testing subsequently confirmed EPP with a homozygous ferrochelatase gene mutation and GS with a heterozygous uridine diphosphate glucuronosyl trans-ferase 1A1 gene mutation.CONCLUSION The rapid,non-invasive Levitt’s carbon monoxide breath test resolved the diagnostic challenge posed by a rare and complex cause of hyperbilirubinemia.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
BACKGROUND Phelan-McDermid syndrome(PMS)is a rare genetic disorder characterized by intellectual disability,delayed language development,autism spectrum disorders,motor tone abnormalities,and a high risk of psychiatri...BACKGROUND Phelan-McDermid syndrome(PMS)is a rare genetic disorder characterized by intellectual disability,delayed language development,autism spectrum disorders,motor tone abnormalities,and a high risk of psychiatric symptoms,including bipolar disorder.CASE SUMMARY This report presented an 18-year clinical history of a 36-year-old woman with PMS,marked by intellectual disabilities,social withdrawal,and stereotyped behaviors.Diagnosed with bipolar disorder at the age of 18 years old,she encountered significant treatment challenges,including severe adverse reactions to antipsychotic medications in 2022,which led to speech and functional regression.Through rehabilitation and comprehensive therapy,her condition gradually improved.In 2024,after further treatment,her symptoms stabilized,highlighting the complexities and successes of long-term management.CONCLUSION Effective management of PMS requires a thorough clinical history,genetic testing,and long-term supportive care.展开更多
OBJECTIVE:To reach consensus on the diagnostic criteria of syndrome of dampness obstruction in idiopathic membranous nephropathy(IMN)patients by literature research and expert investigation(interviews and a Delphi met...OBJECTIVE:To reach consensus on the diagnostic criteria of syndrome of dampness obstruction in idiopathic membranous nephropathy(IMN)patients by literature research and expert investigation(interviews and a Delphi method).METHODS:Our study was consistent with T/CACM 1336-2020.We searched the monographs and references published in the past 40 years(1983-2022),and established the diagnostic criteria pool of waterdampness syndrome and dampness-turbidity syndrome in Traditional Chinese Medicine(TCM)based on literature by using frequency statistics and correlation analysis.Expert investigation(interview method and two rounds of Delphi method)was used to form the diagnostic criteria of water-dampness syndrome and dampnessturbidity syndrome of idiopathic membranous nephropathy.Clinical diagnostic test research was carried out,and compared with“Diagnostic Criteria for dampness syndrome”(T/CACM 1454-2023)to evaluate the authenticity,reliability and clinical application value of the standard.RESULTS:A total of 122 relevant guides,standards,monographs and documents were included through searching books and Chinese databases.Four experts were interviewed and two rounds of delphi method(75 experts nationwide)were carried out.The experts'opinions are relatively concentrated and the differences are small.Based on the weight of each index,the diagnostic criteria indexes of water-dampness syndrome and dampness-turbidity syndrome were selected.After discussion by the core group members,the diagnostic model of"necessary symptoms and optional symptoms"was established,and the final diagnostic criteria of waterdampness syndrome and dampness-turbidity syndrome were established.One hundred and ninety-one inpatients and outpatients of Guangdong Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were included in Diagnostic test study.There was no statistical difference in gender,age and course of disease(P>0.05).The sensitivity and specificity of the trial standard were 90.34%and 73.33%respectively,while the sensitivity and specificity of T/CACM 1454-2023 were 99.43%and 6.67%,respectively.CONCLUSIONS:The consensus-based diagnostic criteria for IMN can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our IMN criteria.展开更多
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.
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.
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 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 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.
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.
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White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin(including the muzzle)of hibernating bats.Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS.However,the role of G.destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking.The debate is fuelled,in part,by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction.Additionally,the recent discovery that G.destructans commonly colonizes the skin of bats of Europe,where no unusual bat mortality events have been reported,has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS.
基金PEEP titration in ARDS patients using EIT combined with lung ultrasound,Key Laboratory of Emergency Trauma Research,Ministry of Education (KLET-202201)airway clearance protocol in ICU mechanically ventilated patients based on electrical impedance imaging technology,Natural Science Foundation of Hunan Province (2024JJ9148)effects of end expiratory positive pressure on lung re-expansion in patients with ARDS and intra-abdominal hypertension monitored using lung ultrasound,Natural Science Foundation of Hunan Province (2023JJ60308)
文摘BACKGROUND:Individualized positive end-expiratory pressure(PEEP)titration is a crucial technique in mechanical ventilation therapy for acute respiratory distress syndrome(ARDS)patients with intra-abdominal hypertension(IAH).This study aimed to evaluate the eff ectiveness of electrical impedance tomography(EIT)-guided PEEP titration in this population.METHODS:This prospective study enrolled 36 ARDS patients,including 22 patients with IAH and 14 without IAH.All the patients underwent EIT-guided PEEP titration at the intersection point between alveolar overdistension and collapse during a decremental PEEP trial.The changes in pulmonary ventilation distribution,respiratory mechanics and hemodynamics during the titration process were observed.RESULTS:After EIT-guided PEEP titration was performed,the PEEP,peak inspiratory pressure and plateau pressure increased significantly(P<0.05).Furthermore,no significant differences were observed in respiratory system compliance,tidal volume,driving pressure,or the 4*DP+RR index between the two groups(P>0.05).The mechanical power increased in the non-IAH(NIAH)group after PEEP titration(P<0.05).Ventilation in gravity-dependent lung regions significantly increased(P<0.05),and the oxygenation index(PaO2/FiO2)improved signifi cantly(P<0.05)in both groups.However,blood pressure,heart rate,respiratory rate,central venous pressure,and lactate levels did not signifi cantly change.In the IAH group,the PaO2/FiO2 ratio improved less than that in the NIAH group did(P<0.05).CONCLUSION:In our study,individualized PEEP titration guided by EIT improved oxygenation in ARDS patients with concomitant IAH without signifi cantly aff ecting hemodynamics.The presence of IAH may limit the improvement of oxygenation during EIT-guided PEEP titration.
文摘It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and erythropoietic protoporphyria(EPP),which has not been previously documented.CASE SUMMARY We present a rare case of coexisting GS and EPP in a 23-year-old Chinese male with a long history of jaundice and recently found splenomegaly.Serial nonspecific hemolysis screening tests yielded inconsistent results,and investigations for common hemolytic etiologies were negative.However,Levitt’s carbon monoxide breath test,which measures erythrocyte lifespan(the gold-standard marker of hemolysis),demonstrated significant hemolysis,revealing a markedly shortened erythrocyte lifespan of 11 days(normal average 120 days).Genetic testing subsequently confirmed EPP with a homozygous ferrochelatase gene mutation and GS with a heterozygous uridine diphosphate glucuronosyl trans-ferase 1A1 gene mutation.CONCLUSION The rapid,non-invasive Levitt’s carbon monoxide breath test resolved the diagnostic challenge posed by a rare and complex cause of hyperbilirubinemia.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金Supported by the Zhejiang Province Medicine and Health Science and Technology Program,No.2023KY980Hangzhou Municipal Health and Family Planning Commission,No.A20220133.
文摘BACKGROUND Phelan-McDermid syndrome(PMS)is a rare genetic disorder characterized by intellectual disability,delayed language development,autism spectrum disorders,motor tone abnormalities,and a high risk of psychiatric symptoms,including bipolar disorder.CASE SUMMARY This report presented an 18-year clinical history of a 36-year-old woman with PMS,marked by intellectual disabilities,social withdrawal,and stereotyped behaviors.Diagnosed with bipolar disorder at the age of 18 years old,she encountered significant treatment challenges,including severe adverse reactions to antipsychotic medications in 2022,which led to speech and functional regression.Through rehabilitation and comprehensive therapy,her condition gradually improved.In 2024,after further treatment,her symptoms stabilized,highlighting the complexities and successes of long-term management.CONCLUSION Effective management of PMS requires a thorough clinical history,genetic testing,and long-term supportive care.
基金the Special Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine:Study on Criteria for Diagnosis of Dampness Syndrome of Idiopathic Membranous Nephropathy,Cohort Study on Pathogenesis and Material Basis of Dampness Syndrome of Idiopathic Membranous Nephropathy,Randomized Controlled Clinical Study of Sanqi Qushi Granule in Treatment of Membranous Nephropathy(No.SZ2021ZZ02,SZ2021ZZ09 and SZ2021ZZ36)the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund:Guangdong-Hong Kong-Macao Joint Lab(No.2020B1212030006)+2 种基金the Natural Science Foundation of Guangdong Province:Study on the Mechanism of Sanqi Qushi Prescription Delaying Podocellular Senescence in Membranous Nephropathy based on Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes-Nuclear Factor Kappa-B Signaling Pathway(No.2022A1515011628)the Guangzhou Science and Technology Plan Project:to Explore the Mechanism of Treating Membranous Nephropathy from the Perspective of Regulating Amino Acid Metabolism Disorder(No.2023A03J0746)Special Funding for Scientific and Technological Research on Traditional Chinese Medicine,Guangdong Provincial Hospital of Chinese Medicine:a Multimodular Machine Learning Prediction Model based on Pathological Image-transcriptomics and Traditional Chinese Medicine Syndromes was Used to Investigate the Prognostic Correlation of Long non-coding RNA Molecules in Nephropathy and the Intervention Mechanism of Sanqi Qushi Formula,to Investigate the Pathogenesis and Microbiological Mechanism of Dampness Syndrome of Membranous Nephropathy based on the Microecological Changes of Tongue Coating(No.YN2023MB02,YN2023MB10)。
文摘OBJECTIVE:To reach consensus on the diagnostic criteria of syndrome of dampness obstruction in idiopathic membranous nephropathy(IMN)patients by literature research and expert investigation(interviews and a Delphi method).METHODS:Our study was consistent with T/CACM 1336-2020.We searched the monographs and references published in the past 40 years(1983-2022),and established the diagnostic criteria pool of waterdampness syndrome and dampness-turbidity syndrome in Traditional Chinese Medicine(TCM)based on literature by using frequency statistics and correlation analysis.Expert investigation(interview method and two rounds of Delphi method)was used to form the diagnostic criteria of water-dampness syndrome and dampnessturbidity syndrome of idiopathic membranous nephropathy.Clinical diagnostic test research was carried out,and compared with“Diagnostic Criteria for dampness syndrome”(T/CACM 1454-2023)to evaluate the authenticity,reliability and clinical application value of the standard.RESULTS:A total of 122 relevant guides,standards,monographs and documents were included through searching books and Chinese databases.Four experts were interviewed and two rounds of delphi method(75 experts nationwide)were carried out.The experts'opinions are relatively concentrated and the differences are small.Based on the weight of each index,the diagnostic criteria indexes of water-dampness syndrome and dampness-turbidity syndrome were selected.After discussion by the core group members,the diagnostic model of"necessary symptoms and optional symptoms"was established,and the final diagnostic criteria of waterdampness syndrome and dampness-turbidity syndrome were established.One hundred and ninety-one inpatients and outpatients of Guangdong Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were included in Diagnostic test study.There was no statistical difference in gender,age and course of disease(P>0.05).The sensitivity and specificity of the trial standard were 90.34%and 73.33%respectively,while the sensitivity and specificity of T/CACM 1454-2023 were 99.43%and 6.67%,respectively.CONCLUSIONS:The consensus-based diagnostic criteria for IMN can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our IMN criteria.
