ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

Caspase-2, a highly conserved member of the caspase family, is considered an initiator caspase that triggers apoptosis in response to some cellular stresses. Previous studies suggest that an intracellular multi-protein complex PIDDosome, induced by genotoxic stress, serves as a platform for caspase-2 activation. Due to caspase-2's inability to process effector caspases, however, the mechanism underlying caspase-2-mediated cell death upon PIDDosome activation remains unclear. Here, we conducted an unbiased genome-wide genetic screen and identified that the Bcl2 family protein BID is required for PIDDosome-induced, caspase-2-mediated apoptosis. PIDDosome-activated caspase-2 directly and functionally processes BID to signal the mitochondrial pathway for apoptosis induction. In addition, a designed chemical screen identified a compound, HUHS015, which specifically activates caspase-2-mediated apoptosis. HUHS015-stimulated apoptosis also requires BID but is independent of the PIDDosome. Through extensive structure-activity relationship efforts, we identified a derivative with a potency of ~60 nmol/L in activating caspase-2-mediated apoptosis. The HUHS015-series of compounds act as efficient agonists that directly target the interdomain linker in caspase-2, representing a new mode of initiator caspase activation. Human and mouse caspase-2 differ in two crucial residues in the linker, rendering a selectivity of the agonists for human caspase-2. The caspase-2 agonists are valuable tools to explore the physiological roles of caspase-2-mediated cell death and a base for developing small-molecule drugs for relevant diseases.
Caspase 2/genetics* ; Humans ; BH3 Interacting Domain Death Agonist Protein/metabolism* ; Apoptosis/drug effects* ; Death Domain Receptor Signaling Adaptor Proteins/metabolism* ; Animals ; Mice ; Cysteine Endopeptidases

Objective:To explore the correlation between lean nonalcoholic fatty liver disease (NAFLD) and metabolic indicators in a young and middle-aged population undergoing physical examination.Methods:It was a cross-sectional study. A total of 8 250 individuals who underwent routine physical examinations at the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University from January to December 2021 and met the inclusion and exclusion criteria were selected as the research subbjects. The general examination, fasting blood glucose, blood lipids, liver function, renal function, and fasting color ultrasound examination results were analyzed retrospectively to assess the correlation between lean NAFLD and major metabolic indicators using independent sample t-test, chi-square test, and multivariable logistic regression. Results:The prevalence of lean NAFLD was higher in men than in women (50.7% vs. 49.3%, χ2=97.261, P<0.001). After stratifying the age of onset of lean NAFLD, the peak age of onset was found to be between 45 and 59 years, with the prevalence gradually increasing with age. When stratified by body mass index (BMI), the peak incidence of lean NAFLD was observed in individuals with a BMI of ≥20 and <23 kg/m 2, with the prevalence showing a significant upward trend as BMI increased. The systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and serum uric acid in lean NAFLD groupwere all significantly higher than those in lean non-NAFLD group (all P<0.01), and the level of high density lipoprotein was significantly lower than that of lean non-NAFLD group ( t=23.755, P<0.001). The logistic analysis showed that systolic blood pressure ( OR=1.258, 95% CI: 1.081-1.465), diastolic blood pressure ( OR=1.282, 95% CI: 1.056-1.557), total cholesterol ( OR=1.712, 95% CI: 1.525-1.923), triglyceride ( OR=4.115, 95% CI: 3.621-4.676), alanine aminotransferase ( OR=1.467, 95% CI: 1.104-1.950), γ-glutamyltransferase ( OR=1.482, 95% CI: 1.242-1.769), fasting blood glucose ( OR=2.479, 95% CI: 2.092-2.939) and serum uric acid ( OR=1.390, 95% CI: 1.236-1.563) were independent metabolic risk factors for lean NAFLD (all P<0.05). Conclusions:The levels of various metabolic markers in young and middle-aged patients with lean NAFLD increase, and the risk of lean NAFLD increases. Metabolic markers are helpful to screen people at risk of lean NAFLD.

Objective To explore the status of job burnout of medical staffs in minority border areas. Methods A total of 906 medical personnel from Pu'er hospitals in Yunnan Province were as-sessed with Maslach Burnout Inventory General Survey (MBI-GS) by t test, descriptive statistics, chi-square test, ANOVA and LSD-t pairwise comparison. Results ①The emotional exhaustion, cynicism and reduced personal accomplishment of medical staffs in minority border areas (1.55±1.40, 0.99± 1.29, 2.47±1.98) are significantly lower than general areas (P=0.000, 0.010, 0.000); ②emotional ex-haustion, cynicism and Maslach Burnout Inventory (MBI) total points of different levels of hospital medi-cal staff, the score of which in descending order are:municipal, county and township (town) levels (P=0.000, 0.000, 0.000); ③Female medical personnel's emotional exhaustion and cynicism are scored significantly higher than males medical staff (P=0.000, 0.025); ④The scores of emotional exhaustion, cynicism, reduced personal accomplishment and MBI total points of Bachelor medical staff are signifi-cantly higher than those of colleges as well as secondary schools and below (P=0.000, 0.000, 0.000, 0.012); ⑤The scores of reduced personal achievement of Lahu medical staff are higher than those of other ethnic groups (P=0.009). Conclusion In medical staffs in minority border areas there exists a certain extent of job burnout, which presents differences among genders, educational background, hos-pitals and ethnic groups.