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 investigate the efficacy of Tanzhuo Decoction in the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus and its effect on cystatin C (Cys-C), C-reactive protein (CRP), urinary albumin excretion rate (UAER), and creatinine clearance rate (CCr). Methods:Eighty patients with type 2 diabetes mellitus complicated by early diabetic nephropathy who received treatment at Maanshan Hospital of Traditional Chinese Medicine from 2019 to 2021 were included in this randomized controlled study. They were divided into a control group ( n = 40) and a treatment group ( n = 40) using the random number table method. Patients in the control group received conventional therapy including blood glucose and blood pressure control, while those in the treatment group received Tangzhuo Decoction in addition to the same treatment as that given to the control group. Both groups of patients were treated for 30 days. The clinical efficacy as well as pre- and post-treatment Cys-C, CRP, UAER, and CCr were compared between the two groups. Results:The total response rate in the treatment group was 92.5% (37/40), which was significantly higher than 75.0% (30/40) in the control group ( χ2 = 4.50, P < 0.05). After treatment, Cys-C, CRP, and UAER in the treatment group were (2.04 ± 0.08) mg/L, (3.97 ± 1.71) mg/L, and (91.18 ± 18.68) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 12.14, 5.59, 4.73, all P < 0.05). After treatment, CCr in the treatment group was (56.3 ± 5.01) mL/min, which was significantly increased compared with that before treatment ( t = -8.56, P < 0.05). After treatment, Cys-C, CRP, and UAER in the control group were (2.17 ± 0.04) mg/L, (4.66 ± 1.47) mg/L, and (103.93 ± 22.62) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 4.05, 5.00, 2.24, all P < 0.05). After treatment, CCr in the control group was (45.9 ± 4.9) mL/min, which was significantly increased compared with that before treatment ( t = -3.98, P < 0.05). There were significant differences in Cys-C, UAER, and CCr between the treatment and control groups ( t = -7.42, -2.29, 7.82, all P < 0.05). Conclusion:Tanzhuo Decoction for the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus has a definite effect. It can effectively reduce levels of Cys-C and UAER, reduce inflammatory reactions, improve kidney function, and delay the progression of kidney injury.

Objective To analyze the causes of changes in the prevalence of respiratory diseases and the reason for changes in medical visit behavior of children in Zhejiang Province during the winter and spring seasons of 2019-2021, and to provide important reference for the allocation of hospital resources, implementation of hierarchical diagnosis and treatment, and epidemic prevention and control. Methods A retrospective study was conducted on 256 937 outpatient medical records from January 23rd to April 23rd of each year from 2019 to 2021 at the Children's Hospital Affiliated to Zhejiang University School of Medicine. Statistical methods were used for data analysis. Results A total of 256 937 cases were selected in the present study, including 157 000 cases in 2019, 22 192 cases in 2020, and 77 745 cases in 2021. The number of patients to the Children's Hospital of Zhejiang University School of Medicine from outside Hangzhou accounted for 41.74%, 14.36% , and 18.53% in 2019-2021, respectively. For 0~2 years old , 3~6 years old , and 7~14 years old groups , the percentages of patients with upper respiratory tract infections were 49.54%, 45.95%, and 46.74%, respectively ; with lower respiratory tract infections were 42.90% , 31.76% , and 22.95% ; with influenza were 2.23% , 3.15% and 4.09%; and with asthma were 1.37%, 5.08%, and 8.15%, respectively. Conclusion From 2019 to 2021, there have been significant changes in the total number of respiratory diseases in children, the proportion of disease types, and the proportion of children's geographical composition. It is necessary to continue to monitor children's respiratory diseases, grasp the dynamic changes in their medical visits in real time, adjust the hospital admission model , implement the graded treatment policy, and promote the prevention and control of respiratory diseases in children.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

A LAMP-Taqman rapid detection system for porcine pseudorabies virus(PRV)was de-veloped based on LAMP and quantitative PCR.LAMP primers were designed for PRV conserved sequences,and the loop primer modified by the fluorescent quenching group was used as the Taq-man probe.The composition optimization,specificity,sensitivity and repeatability of the LAMP-Taqman system were tested using positive samples and recombinant plasmid as templates.Thirty-eight samples of pork swabs were tested with the commercial LAMP detection kit in parallel to verify the actual detection effect of the LAMP-Taqman detection system.The results showed that the optimal final concentration of each component was as follows:PRV-FIP/BIP 0.8 μmol/L,Bst DNA polymerase 0.7 U/μL,Taq DNA polymerase 0.24 U/μL,dNTPs 1.6 mmol/L,MgSO47.2 mmol/L.This system had good specificity and did not cross-react with other virus samples.The linear correlation coefficient of gradient samples was 0.995,the coefficient of variation of repeatable tests was less than 3.000％,and the minimum detection limit could reach 2.81 ×102 copies/μL.The test results of the actual swab samples were consistent with the commercial isothermal fluores-cence detection reagents.In conclusion,the PRV detection system established by LAMP-Taqman method in this study is specific,sensitive,stable and accurate,and is a reliable technical method suitable for the accurate detection of porcine PRV.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Liver cancer is the second leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the most common form of primary liver cancer. Glypican-3 (GPC3) is a cell membrane proteoglycan which is rarely expressed in normal adult tissues but is specifically upregulated in HCC, which makes GPC3 a reliable target for the diagnosis and treatment of HCC. The role of GPC3 in the regulation of cancer development through Wnt, YAP, hedgehog and other signaling pathways were reviewed in this article. GPC3-targeted therapies, such as monoclonal antibodies, bispecific antibodies, tumor vaccines, immunotoxins, CAR-T cells, and photosensitizer therapy were also summarized. These treatment methods offered promising approaches for HCC treatment and future treatment strategies for HCC based on GPC3 were prospected in this paper.

Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.

ObjectiveTo understand the changes of health related behaviors among residents with chronic diseases，and to provide a reference for targeted health intervention. MethodsBased on the surveillance data of chronic diseases and relevant risk factors of the residents in Huangpu District from 2014 to 2019. The study focused on health related behaviors and sociodemographic characteristics which was analyzed by chi-square test. The Cochran-Armitage trend chi-squared test was used to analyze the standardization rate. ResultsSeveral behaviors had been ameliorated such as the health examinations （Z=-3.667， P<0.001）， the measurement of blood glucose （Z=-5.793， P<0.001）， daily vegetables consumption （Z=-5.741， P<0.001）， daily animal food consumption （Z=-23.214， P<0.001）， daily physical activity （Z=-18.361， P<0.001）， sedentary behavior （Z=4.190， P<0.001）， and current smoking （Z=4.615， P<0.001）. ConclusionAn improving trend of health behaviors is found among Huangpu District residents．Targeted health education and health promotion should be carried out according to the characteristics of the population in the future.

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.