OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

We report a case of a female farmer from the Yichang suburb, aged 68 years, who had been suffering from the infection for 3 years and had a history of seeking medical treatment at a community hospital and receiving blood transfusions. Her hemoglobin was as low as 28 g/L during this visit, and she had been ill for a long time with severe anemia. Routine stool examination revealed hookworm eggs. After active treatment, the patient recovered and was discharged from the hospital.

Objective: To analyze the status of outdoor activities on weekends among children and adolescents of different educational stages in Shanghai and their impact on myopia, so as to provide a basis for formulating more specific prevention and control protocol of myopia. Methods: From September to October 2022, a stratified cluster random sampling method was employed to select 84 schools (27 kindergartens, 21 primary schools, 15 junior high schools and 21 high schools) across Shanghai, enrolling a total of 28 654 children and adolescents aged 4 to 18 for the study. Ophthalmic examinations were conducted to ascertain the prevalence of myopia among children and adolescents. Additionally, a questionnaire survey was administered to collect data on outdoor activity duration and associated factors. Multivariate Logistic regression analysis was utilized to investigate the associated factors of outdoor activity levels on weekends. Results: The overall myopia detection rate among children and adolescents was 58.4%, with a higher rate observed in girls (59.2%) compared to boys (57.6%). The myopia detection rates for children and adolescents with an average daily outdoor activity duration of ≥2 h and <2 h on weekends were 54.6% and 68.8%, and the differences were statistically significant ( χ 2=8.12,460.89, P <0.01). Multivariable Logistic regression analysis revealed that girls ( OR =0.80), those with a myopic parent ( OR =0.68), schools from urban districts ( OR =0.72), higher education stages (primary school: OR =0.65, junior high school: OR =0.24, high school: OR =0.14) and spending≥2 h/d on homework during weekends ( OR =0.57) among children and adolescents were less likely to engage in outdoor activities for ≥2 h on weekends ( P <0.01). After incorporating gender, parental myopia status, educational stage, school location, average daily duration on weekends for spending on homework, electronic product usage and outdoor activities as dependent variables in a multivariate Logistic regression analysis, the results showed that children and adolescents with an average outdoor activity duration for ≥2 h on weekends had a lower risk of myopia ( OR =0.86, P < 0.01). Conclusions The level of outdoor activity among children and adolescents on weekends needs to be improved. Outdoor activities on weekends is an associated factor for myopia among children and adolescents. Particularly, girls, those with myopic parents, schools from urban districts, and spending long hours on homework during weekends among children and adolescents require increased attention.

Objective To explore the effects of hypoxia on spermatid differentiation and stability of sperm flagellar microtubule,and investigate the underlying molecular mechanisms in order to clarify the potential adverse effects of hypoxia on male reproductive function.Methods Forty-eight 8-week-old healthy male SD rats(weighing 300～399 g)were subjected in this study.The experiments included ① an oxygen concentration gradient experiment(n=6):21％oxygen was regarded as normoxia(control),and 13.5％,11.8％,and 10.4％ oxygen were used to simulate hypoxic environments at altitudes of 3 500,4 500 and 5 500 m,respectively,for a continuous exposure of 2 months;② a time gradient experiment(n=6):the rats were exposed to 10.4％ oxygen for 0,0.5,1,and 2 months,respectively.Flow cytometry was employed to isolate round spermatids,and the following methods were employed to measure relevant indicators:① RNA sequencing to analyze gene expression profile changes related to impaired spermatogenesis and abnormal flagellar structure under hypoxic stress;②Western blotting to detect the expression levels of key proteins CEP290,RING 1A,and H2AK119ub;③ fluorescence recovery after photobleaching(FRAP)to monitor microtubule assembly dynamics and assess the immediate impact of hypoxia on microtubule stability.Results In the oxygen concentration gradient experiment,after 2 months of exposure to 10.4％ oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids in rat seminiferous tubules were significantly increased(P＜0.05),reaching 1.33±0.04,1.06±0.01 and 1.60±0.02 times higher,respectively than that of the 21％ normoxia group.Conversely,the proportions of primary spermatocytes and elongated spermatids were obviously decreased(P＜0.05),taking 0.89±0.01 and 0.88±0.000 2 times respectively when compared with that of the 21％ normoxia group,in a oxygen concentration-depended manner.In the time gradient experiment,after 0.5 months of exposure to 10.4％oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids began to increase(P＜0.05),reaching 1.11±0.03,1.04±0.01 and 1.29±0.003 times higher,respectively than that of the 0-month control group.The proportions of primary spermatocytes and elongated spermatids started to significantly decrease(P＜0.05)after 1 month of exposure,only 0.94±0.03 and 0.95±0.008 times,respectively than that of the 0-month control group.After 2 months of exposure to 10.4％ oxygen,the rate of sperm tail abnormalities in the epididymis of rats was significantly increased(P＜0.05),rising from(12.1±1.7)％ in the 21％ normoxia group to(30.8±3.7)％.In G2 spermatocytes exposed to 1％ hypoxia for 24 h,FRAP revealed a decrease in microtubule assembly rate and enhanced microtubule dynamic instability,with the maximum fluorescence recovery value decreasing from 0.37±0.02 in the normoxia group to 0.29±0.01.The results of RNA sequencing showed that under hypoxic condition,the transcription level of the key cilium basal body molecule CEP290 was increased,with an upregulation of 1.81±0.11 times than that of the 21％ normoxia group.In contrast,the expression levels of PRC1 complex members RING 1A,RING 1B,CBX2,PHC1,and PCGF1 were decreased,to 0.74±0.02,0.73±0.01,0.78±0.02,0.71±0.01 and 0.86±0.03 times of that of the 21％ normoxia group,respectively.Western blotting indicated that the protein level of CEP290 was up-regulated in the hypoxia group,while that of RING 1A was down-regulated.ChIP-qPCR experiments showed that the binding of RING 1A and its product H2AK119ub to the CEP290 promoter were significantly decreased(P＜0.000 1),with binding strengths of 0.38±0.02 and 0.52±0.06 times of that of the 21％ normoxia group,respectively.In siRING 1A-treated G2 cells,the binding of H2AK119ub to the CEP290 promoter was significantly decreased(P＜0.000 1),with a binding strength of 0.74±0.06 times of that of the control group,while CEP290 mRNA level was significantly increased(P＜0.000 1),with an up-regulation of 3.35±0.37 times.Conclusion Hypoxic environment impair sperm flagellar microtubule stability via the RING 1A-H2AK119ub-CEP290 signaling axis,which affects spermatid differentiation and leads to spermatogenic dysfunction.

Objective To construct a competency evaluation model for forensic practitioners,providing a reference for their training and assessment.Methods Based on the iceberg and onion models of com-petency,and with reference to Spencer's Competency Dictionary,literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners.The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system.The analytic hierarchy process(AHP)was used to calculate the weights of the indices.Results A competency evaluation model for forensic practitioners was constructed,consisting of 7 core indices,encompassing forensic skills,identification service capabilities,and the ability to apply relevant legal knowledge and 49 mea-surement items.The weights of the core indices and measurement items were determined.Conclusion The constructed competency evaluation model for forensic practitioners is scientifically sound and inno-vative,and has unique characteristics of forensic medicine compared with other medical models.

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Perivascular spaces (PVS) are fluid-filled spaces surrounding the cerebral vessels,which are one of the important imaging markers of cerebral small vessel disease (CSVD). The severity of magnetic resonance imaging-visible PVS is associated with the disease burden of multiple neurological diseases. Visual Rating Scale is widely used to evaluate PVS severity. With the development of imaging and computer technology, computational methods based on threshold segmentation, morphological filtering and machine learning have been developed allowing automatically quantifying the number, morphology, and spatial distribution of PVS. The quantitative methods of PVS and the clinical applications were reviewed in this article.

Objective To investigate the clinical features of patients with China Liver Cancer Staging(CNLC)stage Ⅲhepatocellular carcinoma(HCC)achieving five-year sustained complete remission(CR)after local treatment combined with systemic therapy,as well as potential contributing factors,and to provide a reference for optimizing the treatment of advanced HCC.Methods A retrospective analysis was performed for the clinical data of six patients with CNLC stage Ⅲ HCC who were treated in Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2016 to December 2019 and achieved five-year sustained CR.Baseline characteristics,treatment modalities,and follow-up data were summarized,and a literature review was performed.Results The six patients had a mean age of 58.3±10.1 years,among whom five had stage Ⅲa HCC and one had stage Ⅲb HCC,and all patients had a history of hepatitis.The mean preoperative MELD score was 8.2±0.8 for the six patients,and there were five patients with Child-Pugh class A liver function and one with Child-Pugh class B liver function.All patients underwent transcatheter arterial chemoembolization,followed by sequential targeted drug therapy after surgery,with sorafenib for four patients and lenvatinib for two patients.Four patients with main portal vein tumor thrombus also received 125I seed implantation,one patient with the single-nodule type underwent radiofrequency ablation,and three patients received immunotherapy with camrelizumab.The median time to AFP normalization was 6 months,the median time from treatment to CR was 5.5 months,and the median follow-up time was 63 months.Conclusion Good liver function at baseline,an early and rapid reduction in AFP,and the combination of local treatment and systemic therapy are key factors for achieving long-term CR in patients with advanced HCC.Multi-center large-scale studies are needed in the future to further explore prognostic factors and optimize treatment regimens.

Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.