Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Astragalus, which was first documented in Shennong Bencao Jing, is the dried root of Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. The active ingredients astragalus membranaceus saponins (AMS), astragalus polysaccharides (APS) and astragalus flavonoids (AFS) have pharmacological effects such as anti-tumor properties, lowering blood sugar, regulating lipid metabolism, cardiovascular protection, anti-oxidation, bone protection, anti-fibrosis, etc. Fibrosis affects almost all organs, particularly vital organs such as the lungs, liver, heart and kidneys. The primary pathological changes of fibrosis involve abnormal increase of myofibroblasts and excessive deposition of extracellular matrix (ECM) components, which lead to the formation of scar tissue, ultimately resulting in fibrosis and even functional loss or failure of organs, which seriously threatens human health and life. Recent, studies have shown that Astragalus membranaceus has a good therapetuic effect on organ fibrosis. This article reviews the current advances of Astragalus in the prevention and treatment of fibrosis of lungs, liver, heart, kidneys and other important organs.

Objective: To analyze the association between exposure patterns of adverse childhood experiences (ACEs) and anxiety symptom trajectories in medical college students. Methods: A survey was conducted on first-year students from Anhui Medical College and Anqing Medical College, using the Childhood Abuse Questionnaire, Family Disability Questionnaire, Childhood Adverse Social Experience Item, and Anxiety Self Rating Scale. The baseline survey was conducted from November to December 2019, and two follow-up visits were conducted once every six months until November to December 2020. The latent class analysis (LCA) was used to analyze the exposure patterns of ACEs. The latent class growth analysis (LCGA) was used to analyze the development trajectory of anxiety symptoms. The multiple logistic regression model was used to analyze the correlation between different exposure patterns of ACEs and the trajectory of anxiety symptom trajectories. Results: A total of 3 662 college students aged (19.2±1.0) were surveyed. The LCA showed that the exposure patterns of ACEs could be divided into the "high ACEs" group (13.4%), "high neglect/emotional abuse" group (25.7%), "high family dysfunction" group (6.9%), "high neglect" group (27.1%), and "low ACEs" group (26.3%). The LCGA divided anxiety trajectories into four groups: "high anxiety decline" (7.1%),"anxiety increase "(4.1%), "moderate anxiety"(52.9%), and "low anxiety"(35.9%). Using the low ACEs group as a reference group, compared with the low anxiety trajectory, the high ACEs group, high neglect/emotional abuse group, high family dysfunction group, high neglect group, and medium to high-level anxiety trajectory were all associated with an increased risk (P<0.05). Conclusion: There is heterogeneity in ACEs exposure patterns among medical college students, and ACEs exposure patterns are important influencing factors for anxiety symptom trajectories.
Humans ; Adverse Childhood Experiences ; Anxiety/epidemiology* ; Child Abuse/psychology* ; Students/psychology* ; Surveys and Questionnaires ; Adolescent ; Young Adult

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.
Male ; Female ; Humans ; Risk Factors ; Diabetes Mellitus/epidemiology* ; Mortality, Premature ; Smoking ; Cost of Illness ; China/epidemiology* ; Global Burden of Disease

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L^-1.

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in diabetic nephropathy(DN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with DN was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from database inception to October 2022. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 software and RevMan 5.4.1 were used to analyze the data of the literature that met the quality standards. Finally, 53 RCTs were included, involving 6 Chinese patent medicines. The total sample size was 4 891 cases, including 2 449 cases in the test group and 2 442 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Jinshuibao Capsules + conventional western medicine, and Niaoduqing Granules + conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Shenshuaining Capsules/Granules/Tablets + conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(4) In terms of reducing UAER, the top 3 optimal interventions according to SUCRA were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Huangkui Capsules + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granules + conventional wes-tern medicine, and Tripterygium Glycosides Tablets + conventional western medicine.(6) In terms of reducing BUN, the first 3 optimal interventions according to SUCRA were Niaoduqing Granules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Huangkui Capsules + conventional western medicine.(7) In terms of improving the clinical total effective rate, the first 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granu-les + conventional western medicine, and Huangkui Capsules + conventional western medicine. The results showed that the combination of western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of western medicine and Chinese patent medicine was superior to western medicine alone in reducing Scr, BUN, and UAER, and improving the total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.
Humans ; Tumor Necrosis Factor-alpha ; Network Meta-Analysis ; Nonprescription Drugs ; Diabetic Nephropathies/drug therapy* ; C-Reactive Protein ; Capsules ; Interleukin-6 ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides ; Tablets ; Diabetes Mellitus/drug therapy*

Objective: This study sought to investigate the impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease. Methods: We retrospectively analyzed clinical data of male patients diagnosed with suspected coronary microvascular dysfunction (CMD) in the First Hospital of Shanxi Medical University between December 2015 and August 2021. All patients underwent the one-day rest and stress ¹³N-ammonia positron emission tomography myocardial perfusion imaging. Overall obesity was defined by body mass index (BMI) ≥28 kg/m² and abdominal obesity was defined by waist circumference ≥90 cm. Hyperemic myocardial blood flow (MBF)<2.3 ml·min^-1·g^-1 or coronary flow reserve (CFR)<2.5 were referred as CMD. All patients were grouped based on their BMI and waist circumference. MBF, CFR, the incidence of CMD, hemodynamic parameters, and cardiac function were compared among the groups. Results: A total of 136 patients were included. According to BMI and waist circumference, patients were categorized into 3 groups: control group (n=45), simple abdominal obesity group (n=53) and compound obesity group (n=38). Resting MBF did not differ between groups (F=0.02,P=0.994). Compared with the control group, hyperemic MBF was significantly lower in the simple abdominal obesity and compound obesity groups ((2.82±0.64) ml·min^-1·g^-1, (2.44±0.85) ml·min^-1·g^-1 and (2.49±0.71) ml·min^-1·g^-1, both P<0.05, respectively). Hyperemic MBF was comparable among the groups of patients with obesity (P=0.772). CFR was significantly lower in the simle abdominal obesity group compared with the control group (2.87±0.99 vs. 3.32±0.62,P=0.012). Compared with the control group, CFR tended to be lower in the compound obesity group (3.02±0.91 vs. 3.32±0.62,P=0.117). The incidence of CMD was significantly higher in both the simple abdominal obesity and compound obesity groups than in the control group (62.3%, 52.6% vs. 22.2%, both P<0.01, respectively). Waist circumference was an independent risk factor for male CMD (OR=1.057, 95%CI: 1.013-1.103, P=0.011). Conclusions: In male patients with non-obstructive coronary artery disease, abdominal obesity is associated with decreased coronary microvascular function. Male patients with simple abdominal obesity face the highest risk of CMD.
Humans ; Male ; Coronary Artery Disease ; Coronary Circulation/physiology* ; Obesity, Abdominal ; Retrospective Studies ; Obesity/epidemiology* ; Hyperemia

Background Since the outbreak of the COVID-19 epidemic, staff of the centers for disease control and prevention (CDC) have been burdened with heavy epidemic prevention control, and excessive occupational stress can cause depression and other psychological problems. Objective To explore the status of occupational stress, resilience, and depression of CDC staff and potential relationships between them. Methods From December 2020 to April 2021, a survey was conducted at provincial and municipal levels, and the stratified cluster sampling method was used at county (district) level to select a total of 3514 samples. Their occupational stress, resilience, and depression status were evaluated using the Chinese Effort-Reward Imbalance Scale (ERI), the Chinese Connor-Davidson Resilience Scale (CD-RISC), and the Patient Health Questionnaire (PHQ-9). Independent sample t test, analysis of variance, χ² test, Pearson correlation analysis, and mediation test (structural equation model) were conducted. Results The positive rate of occupational stress was 34.29% in the CDC staff, the resilience score was 66.28±15.32, and the positive rate of depression was 48.58%. Significant differences were found in the positive rates of occupational stress among different groups of gender, age, education background, marital status, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05); in the resilience scores among different groups of gender, age, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05); in the positive rates of depression among different groups of gender, age, educational background, personal monthly income, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05). Occupational stress was negatively correlated with resilience (r=−0.165, P<0.01). Resilience was negatively correlated with depression (r=−0.383, P<0.01). Occupational stress was positively correlated with depression (r=0.343, P<0.01). The structural equation embracing a partial mediating effect of resilience on the relationship occupational stress and depression was established, and the partial mediating effect was 0.039, accounting for 10.46% of the total effect. Conclusion High positive rates of occupational stress, reduced resilience, and depression are shown among CDC staff in the context of the COVID-19 epidemic, and resilience partially mediates the effect of occupational stress on depression. The study findings suggest that improving resilience may reduce occupational stress and depression in CDC staff.

Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) was applied to rapidly identify the phospholipids in human plasma and explore the mass spectrometric fragmentation pattern. An acquity UHPLC^TM BEH C18 column (50 mm × 2.1 mm, 1.7 μm) was utilized and eluted with a gradient system; the mobile phase consisted of 10 mmol·L^-1 ammonium formate aqueous solution-0.1% formic acid aqueous solution (A) and acetonitrile-isopropanol (1∶1) organic solution (B) containing 10 mmol·L^-1 ammonium formate-0.1% formic acid. The flow rate was 0.3 mL·min^-1 and the column temperature was set at 50 ℃. An electrospray ionization (ESI) source was used to collect mass spectra in positive and negative ion mode. Based on the precise relative molecular weight and elemental composition calculated by Masslynx 4.1 software, comparison with references, and secondary mass spectrometry fragment ions and lipid databases, a total of 82 plasma lipids were identified, including 14 lysophosphatidylcholines (LysoPCs), 39 phosphatidylcholines (PCs), 17 sphingomyelins (SMs), 7 ceramides (Cers), 4 phosphatidylethanolamines (PEs), and 1 phosphatidylinositol (PI). A simple, efficient, fast and stable analytical method was established in this study for the qualitative analysis of phospholipids in human plasma, and the fragmentation regularity of the main phospholipids was determined. This work provides a good foundation for further metabolomics studies of plasma phospholipids. This study was approved by the Second Affiliated Hospital of Guangzhou Medical University Clinical Research and Application Institutional Review Board Approval (No. 2020-hs-07).