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.

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

AIM To investigate the flavor technology for Jiannaoning Mixture based on electronic tongue combined with preference index.METHODS Artificial sensory evaluation method was employed to screen the type of flavor agents,electronic tongue was applied to screening the consumption of flavor agents,and double-bottle preference test was adopted in the analysis of effects of rat gender and body weight on taste sensitivity,after which acceleration test was conducted.RESULTS Sucrose,stevioside and xylitol were taken as flavor agents,whose optimal consumptions were 15%,0.08%and 15%,respectively.Male rats demonstrated stable taste perception with the body weights of 220-280 g,and 0.08%stevioside displayed the best flavoring effect.After placed under accelerated condition for 3 months,the preparation exhibited stable appearance,pH value and contents of lobetyolin,salvianolic acid B,schizandrin,ruscogenin.CONCLUSION This stable and reliable method can provide reference for improving the terrible tastes of Jiannaoning Mixture and other oral liquid preparations of traditional Chinese medicines.

Objective To study the antifungal activity of N2 derivatives. Methods The anti-fungal activity of N2 compounds was investigated by micro-liquid dilution. Then the activity of N2 compounds on hyphal and biofilm formation was investigated. Results N2 compounds had significant antifungal activity against Candida albicans. It also expressed actively inhibitory effect on hyphal and biofilm formation. The mechanism of its fungicidal function was to damage the structure of candida albicans’ cell membrane and cell wall. Conclusion The results showed that N2 had obvious antifungal activity against Candida albicans., which provided a new idea for the development of antifungal drugs and the solution of antifungal drugs resistance.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.

The aim of this study was to investigate the incidence of erectile dysfunction (ED) in nonmuscle-invasive bladder cancer (NMIBC) patients before and after transurethral resection (TUR) in China. Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People's Hospital (Neijiang, China) between January 2010 and June 2019 were retrospectively reviewed. The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5 (IIEF-5). An age-specific subanalysis was performed among the patients: <45 years old (Group 1, n = 19) and ≥45 years old (Group 2, n = 146). Before and 1.5 years after TUR, the incidence rates of ED in Group 1 were 15.8% and 52.6%, and those in Group 2 were 54.1% and 61.0%, respectively. The difference between groups was statistically significant at the preoperative stage (15.8% vs 54.1%, P = 0.002) but not at the postoperative stage (52.6% vs 61.0%, P = 0.562). Compared with the preoperative stage, the incidence of ED at the postoperative stage was increased significantly in Group 1 (15.8% vs 52.6%, P = 0.017) but not in Group 2 (54.1% vs 61.0%, P = 0.345). In conclusion, the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China. These patients should be offered professional counseling during the follow-up period.
Administration, Intravesical ; Erectile Dysfunction ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Urinary Bladder Neoplasms

Objective:To analyze the early volume characteristics of patients with severe cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and the relationship between their early volume and the prognosis.Methods:This study reviewed patients of Emergency Medical University , treated with VA-ECMO and screened the patients with severe cardiogenic shock and VA-ECMO running more than 72 h for further study. The basic condition of the patients was recorded, and the fluid balance in the first 72 h was analyzed. The patients were grouped according to their fluid balance in the first 72 h. The gender, age, survival rate, continuous renal replacement therapy (CRRT) rate, intra-aortic balloon pump (IABP) rate, and invasive mechanical ventilation rate were compared between the two groups, and the relative risk to the prognosis was calculated. The prognosis was compared between the two groups. Results:Totally 77 patients with severe cardiogenic shock were enrolled. Forty-one cases survived, with an overall survival rate of 53.2%. The volume balance at 48-72 h and the total volume balance at the first 72 h were different between the survival and dead groups. Compared with the positive balance group, patients in the negative balance group were less likely to receive CRRT or invasive mechanical ventilation during the first 72 h. Patients in the negative balance group during the first 72 h had a better survival rate, and their relative risk of survival was 1.81 (95% confidence interval: 1.101, 2.985). However, there was no significant difference in survival rate according to every 24 h fluid balance.Conclusions:Patients with severe cardiogenic shock treated with VA-ECMO who had negative total volume balance during the first 72 h are more likely to survive and less likely to require CRRT or invasive mechanical ventilation.