BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To establish the diagnostic criteria for psoriasis vulgaris of spleen deficiency with dampness accumulation syndrome by using the methods of literature research,subjective experts'experience evaluation and mathematical statistical analysis together.Methods An alternative item pool of symptoms and signs related to psoriasis vulgaris of spleen deficiency with dampness accumulation syndrome was constructed on the basis of the results of literature research.A four-round questionnaire survey was carried out among 32 experts nationwide using the Delphi method,and then the concentration and coordination of the experts'opinions on each of the alternative items were analyzed.In the third round of the survey,all of diagnostic indicators were classified into primary or secondary symptoms according to the weighting coefficients of each item,and then the judgment condition options for the diagnostic criteria of the symptoms were formed.Through the fourth-round of expert survey,the diagnostic mode and diagnostic conditions of spleen deficiency with dampness accumulation syndrome were clarified.Results The alternative diagnostic indicators were screened according to the concentration degree and the variation coefficient of experts'opinions,and 24 diagnostic indicators were obtained after merging the similar indicators,of which there were three primary symptoms(poor appetite and anorexia,loose stool,and pale and swollen tongue with tooth marks)and 21 secondary symptoms(abdominal distension,tastelessness in the mouth without thirst,obesity,drowsiness,fatigue and lack of strength,thready and smooth pulse,soft pulse,undigested food in the stool,and light-red skin lesions,etc.).The fourth-round expert survey confirmed that the necessary conditions for the diagnosis of psoriasis vulgaris of spleen deficiency with dampness accumulation syndrome were"the disease-location of the spleen","the disease-nature of qi deficiency"and"the disease-nature of dampness";the diagnostic criteria for psoriasis of spleen deficiency with dampness accumulation syndrome were as follows:(1)with three primary symptoms;(2)with two primary symptoms and any two of the secondary symptoms.Conclusion The diagnostic criteria for psoriasis vulgaris of spleen deficiency with dampness accumulation syndrome constructed in this study include both primary and secondary symptoms,with clarified conditions and being easy to be practiced clinically,and have good clinical credibility.

Objective:To explore the influence of learning input and professional commitment on the core competence of rural order-oriented medical students,and to provide theoretical reference for improving the quality of the grassroots health workforce.Methods:520 rural order-oriented medical students from two medical colleges in S province were selected as research subjects.Stratified regression method was used to analyze the effect of learning input on the core competence of rural order-oriented medical students,and simple slope test was used to analyze the moderating effect of professional commitment on the aforementioned relationship.Results:The overall mean score of core competence of rural order-oriented medical students in S province was(3.39±0.549),learning input had a significant positive effect on the core competence of rural order-oriented medical students(β=0.358),and there was a moderating effect of professional commitment on the relationship between the two,which made the effect of learning input on core competence stronger(β=0.206).Conclusion:Improve the policy of training rural order-oriented medical students,strictly control the quality of admission,increase the construction and investment in grass-roots bases,emphasize students'vocational quality education,and enhance their core competencies.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

OBJECTIVE To study the possible effects and mechanism of Jinxin oral liquid and its main ingredient baicalin on Re-spiratory syncytial virus(RSV)-induced abnormal cardiolipin metabolism.METHODS BALB/c mice were randomly divided into control group,RSV group and Jinxin oral liquid treatment group.Mice were nasally administrated of RSV suspension to establish RSV infection model at the first 3 days.Then Jinxin oral liquid 27.6 g·kg-1·d-1 was administrated intragastrically for the next 3 days from the afternoon of the third day.Raw264.7 cells were infected by RSV to establish an in vitro infection model and baicalin(100 mg·kg-1·d-1)was given for intervention.The changes of cardiolipin metabolism profiles in mice lung tissue and Raw264.7 cells were detected by chromatography-mass spectrometry.Transcriptional mRNA levels of RSV surface proteins RSV-F and RSV-G,inflammatory cytokines IL-6,IL-1β and Tnf-α,cardiolipin metabolic enzymes Tafazzin(TAZ),Cardiolipin Synthase 1(Crls1),Phospholipid Scramblase 3(PLSCR3)and autophagy-related protein p62 were detected by qPCR.The protein level of p62 was detec-ted by Western blot.Molecular docking was used to detect the binding ability of p62 to CL14 ∶ 0-16 ∶ 1-16 ∶ 1-18 ∶ 2.RESULTS The expression of IL-6,IL-1β,and Tnf-α mRNA increased in RSV-infected mice and cell models(P<0.05,P<0.01,P<0.001).Jinxin oral liquid and baicalin plays a certain restoration effect.The cardiolipin metabolism profile changes after RSV infec-tion,and Jinxin oral liquid and baicalin can play a certain regulatory role.The expression of Crls1 and TAZ mRNA in the lung tissue of mice in the model group was significantly up-regulated(P<0.01),after administration of Jinxin oral liquid,the expression of Crls1 and TAZ mRNA was significantly reduced(P<0.01);the expression of Crls1 mRNA in the cell model group was significantly in-creased(P<0.001),and after baicalin intervention,the expression of Crls1 mRNA was significantly reduced(P<0.000 1).The ex-pression of p62 protein in the lung tissue of RSV-infected mice was significantly reduced(P<0.001),and the expression of p62 pro-tein was significantly increased after administration of Jinxin oral liquid(P<0.01).The p62 protein expression in the Raw264.7 cell model group increased significantly(P<0.05),and the p62 protein level further increased significantly after administration of baicalin(P<0.000 1).Molecular docking results showed that cardiolipin CL14 ∶ 0-16 ∶ 1-16 ∶ 1-18 ∶ 2 can threshold-bind with the UBA structure of p62.CONCLUSION Jinxin oral liquid and baicalin can improve RSV-induced cardiolipin metabolism disorder,regulate mitochondrial function,and thus exert anti-RSV infection effects.

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
Male ; Humans ; Epididymis ; Disorder of Sex Development, 46,XY/genetics* ; Disorders of Sex Development ; Mutation ; Mutation, Missense ; Steroidogenic Factor 1/genetics*

Humans ; Gemcitabine ; Neoplasms

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia