In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective:To propose a novel refined subtyping of Neer type Ⅵ proximal humerus fracture-dislocation and explore its clinical application.Methods:A retrospective study was conducted to analyze the data of 36 patients who had been admitted to Department of Orthopaedics, Beijing Friendship Hospital between January 2018 and December 2022 for surgical treatment with proximal humeral internal locking system (PHILOS) for Neer type Ⅵ proximal humerus fracture-dislocation. There were 25 males and 11 females with an age of (46.1±4.7) years. According to the fracture-dislocation and the separation between the humeral head and the stem, the patients with Neer type Ⅵ proximal humerus fracture-dislocation were further subdivided into 3 subtype groups (known as STAB subtypes): subtype-T group (dislocation of the shoulder joint with macro-capitellar fracture, n=14), subtype-A group (proximal humerus fracture-dislocation without separation of the humeral head from the humeral stem, n=12), and subtype-B group (dislocation of the proximal humerus fracture with separation of the humeral head from the humeral stem, n=10). STAB subtyping was performed on the same imaging data from all the patients at admission and 2 weeks later by 4 surgeons with different qualifications. Interobserver and intraobserver agreements of the STAB typing were verified. The operation time, fracture healing time, visual analogue scale (VAS) pain score, Constant-Murley score, and complications were recorded for patients in the 3 subtype groups. Results:The differences in the preoperative general data were not statistically significant between the 3 subtype groups, indicating comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The inter-observer and intra-observer Kappa values for STAB subtyping were 0.94 and 0.95, respectively. For subtype-T group, subtype-A group, and subtype-B group, respectively, the operation time was (68.9±5.6) min, (90.0±5.2) min, and (113.0±9.2) min; the fracture healing time was (9.0±0.8) weeks, (10.3±1.2) weeks, and (11.8±0.9) weeks; the VAS scores at the last follow-up were 1.0(1.0, 2.0) points, 2.0(1.0, 2.0) points, 2.0(2.0, 3.0) points; the Constant-Murley scores at the last follow-up were (83.6±2.8) points, (74.5±3.0) points, and (62.7±5.5) points. The differences between the 3 subtype groups in the above items were statistically significant ( P<0.05). The overall success rate of closed reduction was 61.1% (22/36). In subtype-T, subtype-A, and subtype-B groups, respectively, the number of patients with successful closed reduction was 13, 7, and 2, while complications occurred in 2, 3, and 6 patients. The differences in closed reduction and complications among the 3 groups were statistically significant ( P<0.05). Conclusions:The STAB subtyping proposed in this study demonstrates strong intra- and inter-group consistency. Because the refined STAB subtyping can reveal differences among all the Neer type Ⅵ proximal humeral fractures and dislocations, it may provide more precise guidance for personalized clinical decision-making.

OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective:To investigate the allele distribution of aldehyde dehydrogenase 2 (ALDH2) gene polymorphism in elderly patients with type 2 diabetes mellitus (T2DM) and to analyze its correlation with the presence and severity of coronary stenosis.Methods:A total of 94 elderly patients with T2DM who were admitted to the Affiliated Hospital of Jining Medical University from March 2020 to March 2022 were selected as the observation group, and 50 age- gender-matched healthy subjects were selected as the control group. The observation group was further divided into stenosis group and non-stenosis group based on the presence of coronary stenosis. Clinical data were collected from all participants, and blood samples were taken for analysis. The ALDH2 gene polymorphism (rs671 locus) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The distribution of ALDH2 genotypes was observed in elderly patients with T2DM, and multivariate logistic regression analysis was used to identify independent factors associated with the development of coronary stenosis in elderly patients with T2DM. The degree of coronary stenosis was compared between patients with different genotypes.Results:The allele A frequency of ALDH2 gene (rs671 locus) was significantly higher in the observation group than in the control group ( P<0.05). The proportion of patients with diabetes duration≥5 years and smoking history in the stenosis group was significantly higher than that in the non-stenosis group (all P<0.05). Serum levels of glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the stenosis group than in the non-stenosis group, while high-density lipoprotein cholesterol (HDL-C) level was significantly lower in the stenosis group than in the non-stenosis group (all P<0.05). The proportion of ALDH2 genotypes AA and allele A frequency were significantly higher in the stenosis group than in the non-stenosis group (all P<0.05). Long duration of diabetes, low HDL-C level, and ALDH2 genotypes AA were independent risk factors for the development of coronary stenosis in elderly patients with T2DM (all P<0.05). The proportion of patients with three or more coronary artery lesions in the stenosis group with genotype AA was significantly higher than that in the stenosis group with genotypes GG and GA (all P<0.05). Conclusions:ALDH2 gene polymorphism is associated with the development of T2DM in elderly patients, and allele A carriers may have a higher risk of developing coronary stenosis and more severe disease severity.

Objective:To compare the effects of anterograde elastic stable intramedullary nailing (ESIN-A), retrograde K-wires fixation (KW-R) and retrograde precision shaping of elastic stable intramedullary nailing (ESIN-RPS) in the treatment of fractures of distal radial metaphyseal diaphyseal junction (DRMDJ) in children.Methods:A retrospective study was conducted to analyze the data of 112 eligible children with DRMDJ fracture who had been treated at Department of Orthopedics, Children's Hospital, Anhui Medical University and Department of Orthopedics, The People's Hospital of Fuyang City,Anhui Medical University, from January 2016 to May 2022. There were 64 males and 48 females, with an age of (8.4±2.3) years. The children were divided into 3 groups according to different surgical fixation methods: group ESIN-A of 36 cases, group KW-R of 52 cases, and group ESIN-RPS of 24 cases. The operation time, intraoperative bleeding, fluoroscopy times, alignment rates and residual angulations by the anteroposterior and lateral X-ray films immediately after reduction were compared among the 3 groups. The Gartland-Werley evaluation of wrist function and complications were compared at the last follow-up.Results:There was no statistically significant difference in the preoperative general data among the 3 groups, indicating comparability ( P>0.05). In the operation time, group KW-R [(71.2±9.2) min] > group ESIN-A [(65.1±13.1) min] > group ESIN-RPS [(51.7±17.1) min]; in the fluoroscopy times, group KW-R [(13.9±6.3) times] > group ESIN-A [(9.0±2.8) times] > group ESIN-RPS [(6.4±2.0) times]; in the alignment rates by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (93.1%±4.6% and 95.2%±3.3%) > group KW-R (82.1%±11.0% and 88.1%±7.4%) > group ESIN-A (80.4%±9.9% and 86.7%±6.9%); in the residual angulations by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (3.3°±1.8° and 2.9°±2.1°) < group ESIN-A (5.2°±1.0° and 5.0°±3.2°) < group KW-R (6.6°±1.6°and 7.5°±2.7°). Pairwise comparisons in the above items were statistically significant ( P<0.05). In group ESIN-A, the incision length [(1.8±0.3) cm] was significantlylonger than that in group ESIN-RPS [(1.4±0.2) cm], and the intraoperative blood loss [(8.3±2.2) mL] significantly larger than that in group ESIN-RPS [(5.5±1.6) mL] ( P<0.05). One year after operation, the excellent and good rate by the Gartland-Werley evaluation of wrist function in groups ESIN-RPS, ESIN-A and KW-R, respectively, were 95.8% (23/24), 86.5% (31/36) and 86.1% (46/52), showing no statistically significant difference between the 3 group ( P>0.05), and the major incidence of complications in group KW-R (25.0%, 13/52) and in group ESIN-A (25.0%, 9/36) were significantly higher than that in group ESIN-RPS (4.2%, 1/24) ( P<0.05). Conclusion:In the treatment of DRMDJ fractures in children, compared with ESIN-A and KW-R, ESIN-RPS is an effective choice due to its advantages of shorter operation time, less intraoperative blood loss, less radiation, better alignment, and fewer complications.

Objective:To investigate the epidemic situation of drinking water-borne endemic fluorosis in Henan Province, evaluate the effectiveness of prevention and control measures, and provide a basis for formulating further prevention and control policies.Methods:From April to November 2021, a census of all diseased villages registered in 112 drinking water-borne endemic fluorosis counties (cities, districts, hereinafter referred to as counties) of 17 provincial-level cities and 9 provincial-level counties (cities) in Henan Province was conducted to collect the basic information of diseased counties and villages. The content of fluoride in drinking water and the prevalence of dental fluorosis in children aged 8 - 12 years old were measured on a village by village basis.Results:By the end of 2021, drinking water-borne endemic fluorosis was prevalent in 112 diseased counties in Henan Province, involving 17 450 diseased villages. Among them, 17 433 villages had implemented measures to reduce fluoride and improve water quality, with a water improvement rate of 99.90% (17 433/17 450). There were 14 920 villages with qualified water, and the qualified rate of water fluoride was 85.50% (14 920/17 450). There were a total of 4 232 water improvement projects in all diseased villages, with a normal operation rate of 97.09% (4 109/4 232) and a qualified rate of 93.03% (3 937/4 232) for water fluoride in the projects. The total detection rate of dental fluorosis in children in the province was 9.64% (39 391/408 584), with moderate to severe dental fluorosis accounted for 8.08% (3 182/39 391), the dental fluorosis index was 0.18. The prevalence of fluorosis was negative.Conclusions:In 2021, the prevalence of drinking water-borne endemic fluorosis is widespread in Henan Province, and measures to reduce fluoride and improve water quality in diseased villages have been basically implemented. However, the fluoride content of water in some villages still does not meet the standard, and some water improvement projects cannot operate normally throughout the year. In the future, it is necessary to address the above issues one by one and consolidate the achievements in prevention and control of drinking water-borne endemic fluorosis.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Diacylglycerol (DAG) is an intermediate product in lipid metabolism and plays an important physiological role in human body. It is mainly prepared by hydrolyzing lipid with lipase. However, research on the detection method of 1, 2-diacylglycerol (1, 2-DAG) and 1, 3-diacylglycerol (1, 3-DAG) and catalytic specificity of lipase was not enough, which limits its wide application. To address these challenges, an efficient quantitative detection method was first established for 1, 2-DAG (0.025-0.200 g/L) and 1, 3-DAG (0.025-0.150 g/L) by combining supercritical fluid chromatography with evaporative light scattering detector and optimizing the detection and analysis parameters. Based on the molecular docking between Thermomyces lanuginosus lipase (TLL) and triolein, five potential substrate binding sites were selected for site-specific saturation mutation to construct a mutation library for enzyme activity and position specificity screening. The specificity of sn-1, 3 of the I202V mutant was the highest in the library, which was 11.7% higher than the specificity of the wild type TLL. In summary, the position specificity of TLL was modified based on a semi-rational design, and an efficient separation and detection method of DAG isomers was also established, which provided a reference for the study of the catalytic specificity of lipase.
Humans ; Diglycerides ; Molecular Docking Simulation ; Binding Sites ; Catalysis ; Lipase/genetics*