Objective:To investigate the expression of RAD18 in colon cancer and its correlation with proliferating cell nuclear antigen (PCNA).Methods:The glass slice of colon cancer tissues and adjacent normal tissues from patients (73 cases) who underwent surgical treatment at the Second Hospital of Tianjin Medical University from November 2013 to November 2023 were collected.The expression of RAD18 in colon cancer tissues and adjacent normal tissues was analyzed in the gene expression profiling interactive analysis (GEPIA) database and verified by immunohistochemical staining. The relationship between RAD18 expression and clinicopathological features of colon cancer patients was analyzed. HCT116 and HT29 cells were cultured in vitro, and the control group and transfection group ( transfected with RAD18 shRNA to knock down RAD18 ) were set up. The expression of RAD18 was evaluated by quantitative real-time PCR (qRT-PCR) and Western Blot. The effect of RAD18 on colon cancer cell proliferation was explored using clonogenic assays and cell counting Kit-8 (CCK-8) assays. The correlation between RAD18 and PCNA was investigated by GEPIA and immunohistochemical staining. Results:The GEPIA database analysis showed that the expression of RAD18 in colon cancer tissue ( n = 275) was significantly higher than that in adjacent normal tissues ( n = 349, P < 0.05). RAD18 was expressed at higher levels in colon cancer tissue than that in adjacent normal tissues and was not expressed at high levels in the latter. The expression of RAD18 was closely related to tumor size in the low-expression group and high-expression group of patients ( P = 0.015) but was not related to age ( P = 0.115), gender ( P = 0.665), or tumor differentiation ( P = 0.733). Compared with the control group, the expressions of RAD18 in the transfection group of HCT116 and HT29 cells were both reduced (both P < 0.05). Compared with the control group, the clone cell number and absorbance ( A) value of HCT116 and HT29 cells in the transfection group were decreased (all P < 0.05). GEPIA database analysis showed that RAD18 was correlated with PCNA ( R = 0.27, P < 0.05), and the expression level of PCNA was higher in colon cancer tissues than in adjacent normal tissues. Conclusions:RAD18 is expressed at a higher level in colon cancer tissues and may promote colorectal cancer proliferation by affecting PCNA.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

Objective To compare the efficacies of retrograde tibial nailing(RTN)versus minimally invasive percutaneous plate osteosynthesis(MIPPO)in the treatment of distal tibial fractures.Methods A retrospective analysis was conducted on the clinical data of 55 patients with distal tibial fractures who underwent surgery in our hospital.Patients were divided into two groups based on the different surgical methods,patients in the RTN group(n=25)were treated with RTN,and patients in the MIPPO group(n=30)were treated with MIPPO.The surgical parameters(operation time,intraoperative blood loss,intraoperative fluoroscopy times,and success rate of closed reduction),fracture healing time,ankle dorsiflexion range of motion and American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scores 6 months after operation and at the last follow-up,and the incidence of complications during perioperative period and follow-up were compared between the two groups.Results The operation time,intraoperative blood loss,and intraoperative fluoroscopy times in the RTN group were significantly shorter/less than those in the MIPPO group(P＜0.05).The ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score 6 months after operation in the RTN group were significantly greater/higher than those in the MIPPO group(P＜0.05).There was no statistically significant difference in the fracture healing time,or ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score at the last follow-up between the two groups(P＞0.05).The success rate of closed reduction in the RTN group was 72.00％,which was lower than that of 96.67％in the MIPPO group(P＜0.05).The incidence of soft tissue-related complications in the RTN group was signifi-cantly lower than that in the MIPPO group(P＜0.05),while there was no statistically significant difference in the overall incidence of complica-tions between the two groups(P＞0.05).Conclusion RTN is an effective minimally invasive surgical technique for the treatment of distal tibial fractures,characterized by minimal trauma,low incidence of soft tissue complications,and fast recovery of joint function compared with MIPPO.

This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P＞0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P＜0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P＜0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P＜0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P＜0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P＜0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P＜0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

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 investigate the effects of sperm DNA fragmentation index(DFI)on embryonic development and live birth outcomes of in vitro fertilization-fresh embryo transfer(IVF-ET).Methods:We selected 947 cases of IVF-ET due to female factors from June 2015 to December 2020 and,according to the DFI,divided them into a low-(DFI＜15％),a medium-(15≤DFI≤30％)and a high-DFI(30％＜DFI)group.We obtained the female factors(including age,body mass index[BMI],and base-line levels of sexual hormones and anti-Müllerian hormone[AMH]),male factors(including age,BMI,and semen parameters),pa-rameters of superovulation induction,semen parameters before and after IVF treatment,outcome of ovulation induction,embryo quality and pregnancy outcome,and compared them among the three groups.Results:The patients in the medium-and high-DFI groups had a significantly older age than those in the low-DFI group.There were statistically significant differences among the three groups in the baseline percentages of progressively motile sperm,non-progressively motile sperm and immotile sperm,and total sperm motility and progressive sperm motility before IVF(P＜0.01).The baseline percentage of morphologically normal sperm,sperm concentration and total sperm count before IVF treatment,and sperm concentration after IVF treatment were significantly lower in the medium-and high-DFI groups than in the low-DFI group,and so was the total sperm count in the high-DFI than in the low-and medium-DFI groups either before or after semen treatment(P＜0.01).The fertilization rate was also markedly lower in the medium-and high-DFI than in the low-DFI group,but no statistically significant differences were observed in ovulation induction parameters,embryo quality and pregnan-cy outcome among the three groups.Conclusion:High DFI significantly affects sperm motility.The DFI level after semen treatment is negatively correlated with sperm concentration,total sperm count and fertilization rate,but does not affect embryo quality and preg-nancy outcome.

Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.

Objective:To investigate the resistance of Culex pipiens pallens to pyrethroid insecticides in Hangzhou City, and explore the mutation of knock down resistance (kdr) gene of Culex pipiens pallens, providing scientific basis for control of Culex pipiens pallens in the region. Methods:In September 2022, larvae and pupae of Culex pipiens pallens were collected from various locations at national monitoring sites in Shangcheng District and Gongshu District of Hangzhou City. They were bred in the laboratory and their resistance to three commonly used pyrethroid insecticides (permethrin, deltamethrin and beta-cypermethrin) was determined using the adult mosquito contact tube method and larval immersion method recommended by the World Health Organization. The genomic DNA was extracted from individual adult mosquito, and kdr gene mutation was detected via PCR amplification and Sanger sequencing. Results:The 24-hour mortality rates of adult mosquitoes of Culex pipiens pallens exposed to 0.25% permethrin, 0.025% deltamethrin, and 0.025% beta-cypermethrin were 20.00% (15/75), 17.33% (13/75), and 18.67% (14/75), respectively, indicating resistance. The resistance ratios of Culex pipiens pallens larvae to permethrin, deltamethrin, and beta-cypermethrin were 27.08, 341.00, and 15.88, respectively. Among 183 adult mosquitoes that survived under the diagnostic doses of pyrethroid insecticides, 180 mosquitoes (98.36%) had mutation at the L1014 site of the kdr gene. Among 42 adult mosquitoes that died under the diagnostic doses of pyrethroid insecticides, 5 mosquitoes (11.90%) had L1014 mutation in the kdr gene. Conclusions:Culex pipiens pallens in Hangzhou City has developed varying degrees of resistance to permethrin, deltamethrin and beta-cypermethrin, with a high frequency of kdr gene mutation in resistant mosquitoes. We should strengthen the monitoring of the resistance of Culex pipiens pallens in Hangzhou City and use chemical insecticides reasonably.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.