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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

This study was aimed at analyzing the effectiveness of vector control efforts at the 19th Asian Games in Hang-zhou,to provide a reference for future vector control at similar large-scale events.We collected and analyzed vector organism monitoring data for various venues at Asian Games(branch)villages and designated reception hotels(hotels and guesthouses)associated with the Asian Games in Hangzhou from April to October of 2023.Excel 2019 software and SPSS 20.0 software were used to organize the data.Paired t tests(for normally distributed data)or Wilcoxon signed rank tests(for data not nor-mally distributed)were performed,and count data were analyzed statistically with x2 tests.The larva mosquito path index at Asian Games venues peaked in June and then declined month by month.The first circle area of the adult mosquito human trapping index peaked in June,and the second circle area peaked in July.The mosquito indicators reached the corre-sponding control standards before the Asian Games.Moreo-ver,the differences in mosquito density before and after the Asian Games were statistically significant(all P＜0.05).Both the positivity rate and density of flies in rooms reached level A in the first and second circle areas from April to October.The proportion of indoor fly-proof facilities meeting the standards was lowest in May,then gradually increased.The corresponding control standards were reached in the first round in the fourth week of September,and in the second round in the first week of October.The difference in the density of positivity for room flies before and after the Asian Games was statistically significant(all P＜0.05).Rodent density reached the corre-sponding control standards in the second week of September.The proportion of anti-rodent facilities meeting the standards was lowest in June,and then gradually increased.The first round began to meet the corresponding control standards in the fourth week of September,and the second round began to meet the corresponding control standards in the first week of October.Ex-cept for the outdoor rat density path index,which was statistically significant before and after the Asian Games,the other indi-cators showed no statistical significance(P＞0.05).The cockroach density in the first circle area reached level A in all months,and that in the second circle area reached level B in mid-August.Vector control in the Hangzhou Asian Games achieved the ex-pected results,with no vector infringement or local vector-borne infectious diseases occurring.In future vector control for large-scale events,vector density monitoring should be performed as early as possible,and comprehensive prevention and control measures should be taken to maintain low vector density and prevent vector infringement incidents.

The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

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.

Cholinesterases/genetics* ; Dimethoate/analogs & derivatives* ; Humans ; Occupational Exposure/adverse effects* ; Polymorphism, Genetic ; Telomere

Aim To investigate the effectiveness and safety of alfentanil in general anesthesia.Methods In this study, a multicenter randomized double-blind con¬trolled study was conducted.A total of 352 subjects were selected and randomly assigned to fentanyl group (group A, n =176) and alfentanil group (group 15, n = 176).Anesthesia induction: intravenous midazolam 0.03 mg • kg-1 + fentanyl 25 p.g • kg"'(group A) or alfentanil 4 p,g • kg-1 ( group 15) + propofol 2 mg • kg"1 + rocuronium 0.8 mg • kg"1.Sevoflurane + fent¬anyl ( group A ) or alfentanil ( group B ) + rocuronium were used for anesthesia.The vital signs of patients re¬covery time and extuhation time, anesthesia-related complications and the use of related remedial drugs during anesthesia induction and maintenance were compared between the two groups.Results During the induction and maintenance period of anesthesia, alfentanil and fentanyl could equally effectively inhibit the stress response induced by endotracheal intubation and surgical stimulation.Alfentanil also showed more effective inhibition on stress response induced by endo¬tracheal intubation and surgical stimulation than that of fentanyl ( P < 0.05 ) .However, there was no signifi¬cant difference in the incidence of intraoperative hypo¬tension and hypertension and the time of anesthesia re¬covery and extubation between the two groups.Conclu¬sions Both alfentanil and fentanyl can effectively in¬hibit the stress response induced by surgical stimulation and could be safely used in general anesthesia in sur¬gery.Alfentanil has more advantages in maintaining the stability of blood pressure and heart rate during an¬esthesia induction and maintenance.

The structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia was investigated. Animal experiments strictly follow the regulations of Medical Laboratory Animal Ethics Committee of Qinghai University, School of Medicine. SD rats were randomly divided into a control group, a moderate altitude hypoxia group, and a high altitude hypoxia group. The pH value of the feces was measured and histopathological changes in the small intestine were determined by HE staining, and the intestinal flora were characterized by 16S rDNA high throughput sequencing technology on the 3rd, 7th, 15th, and 30th day of hypoxia exposure. Compared with the control group, the fecal pH value of rats in the moderate altitude hypoxia group and the high altitude hypoxia group was decreased significantly. The lamina propria and submucosa capillaries were slightly dilated and congested on the 3rd day in the moderate altitude hypoxia group. In the high altitude hypoxia group the submembrane capillaries were dilated and congested, the lamina propria of the mucosa showed mild edema, and the lymphatic vessels were dilated on the 7th day. The composition and diversity of intestinal flora in these rats changed significantly with prolonged exposure to the high altitude hypoxic environment. A total of 35 phyla, 87 classes, 205 orders, 337 families, 638 genera, and 256 species were annotated in the three groups of rats, including Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Akkermansia, and Lactobacillus_murinus. Compared with the control group, the intestinal flora of the hypoxic groups showed the most significant changes by the 15th day. There were 9 microbiota of gut microorganisms with relative abundance in the moderate altitude hypoxia group, of which Rikenellaceae_RC9_gut_group bacteria was the most common, there were 19 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group, of which Ruminococcaceae bacteria was the most common. The results of this study indicate significant changes in the intestinal flora with high altitude hypoxia, and establish a foundation for further research on the initiation and development of diseases and drug metabolism in high altitude hypoxia.

The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA (miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.

【Objective】 To investigate the effect of transfusion-transmitted Zika virus (ZIKV) on the expression of non-coding circular RNA (hsa_circ_0001613) and the role of hsa_circ_0001613 in Zika virus replication. 【Methods】 Human adenocarcinomic alveolar basal epithelial cells (A549) were seeded on a 12-well plate at 1.8×10⁵/ well and infected with ZIKV at 0.05 MOI. The Total RNAs were isolated every day for 5 days after infection, and the relative expression level of hsa_circ_0001613 was detected by qRT-PCR. In addition, 10nM siRNA-hsa_circ_0001613 was transfected into 2×10⁵/ well A549 cells to specifically knock down the expression level of hsa_circ_0001613. 24h later, the cells were infected with ZIKV (MOI=0.05). Total RNAs were isolated at day 1-5 post-infection, proteins were extracted 96h post-infection. ZIKV replication, relative host antiviral gene expression, and interferon stimulated response element (ISRE) activity were tested using qRT-PCR, western blot and dual luciferase assay, respectively. 【Results】 The relative expression of hsa_circ_0001613 decreased significantly after 1-5 days of ZIKV infection. Knockdown of hsa_circ_0001613 inhibited ZIKV replication. Meanwhile, hsa_circ_0001613 knockdown significantly upregulated IFN-α/β and its downstream interferon-stimulated genes (ISGs) expression, also increased ISRE activity. 【Conclusion】 ZIKV infection significantly suppressed hsa_circ_0001613 expression in A4549 cells. Preliminary study indicated that hsa_circ_0001613 knockdown inhibited ZIKV replication possibly through activating type-Ⅰ IFN signaling pathway as showed by increased ISGs expression and ISRE activity.