Objective To explore the applicable conditions of the Cox-TEL(Cox PH-Taylor expansion adjustment for long-term survival data)method for analysis of survival data that contain cured patients.Methods The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates,censored rates,and cure rate differences.The Cox-TEL method was used for analysis of the generated simulation data,and its performance was evaluated by calculating its type I error and power.Results Almost all the type I error of the hazard ratios(HRs)obtained by the Cox-TEL method under different conditions were slightly greater than 0.05,and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions(DPs).For the data of cured patients,the type I error of the DPs obtained by the Cox-TEL method was well around 0.05,and its test power was robust in most of the scenarios.Conclusion The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size,a low censored rates,and a large difference in cure rates.The method is capable of accurately estimating the DPs regardless of the sample size,censored rates,or the cure rates.

Objective To explore the applicable conditions of the Cox-TEL(Cox PH-Taylor expansion adjustment for long-term survival data)method for analysis of survival data that contain cured patients.Methods The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates,censored rates,and cure rate differences.The Cox-TEL method was used for analysis of the generated simulation data,and its performance was evaluated by calculating its type I error and power.Results Almost all the type I error of the hazard ratios(HRs)obtained by the Cox-TEL method under different conditions were slightly greater than 0.05,and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions(DPs).For the data of cured patients,the type I error of the DPs obtained by the Cox-TEL method was well around 0.05,and its test power was robust in most of the scenarios.Conclusion The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size,a low censored rates,and a large difference in cure rates.The method is capable of accurately estimating the DPs regardless of the sample size,censored rates,or the cure rates.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the role and relationship between oxidative stress and immune infiltration in idiopathic pul-monary fibrosis(IPF),and to predict the relevant therapeutic herbal medicines and active ingredients.Methods:GSE10667 gene expression profiles were downloaded from GEO database to obtain differential expression genes,differential expression of oxidative stress genes(DEOSGs)were identified in combination with oxidative stress genes.GSEA was used to evaluate the pathways and biologi-cal processes in IPF,and GO,KEGG and PPI network analysis were performed on DEOSGs.Candidate central genes were derived from PPI results and CytoHubba,and GSE110147 was validated as an independent group to identify central genes;in addition,the immune microenvironment of samples was evaluated using CIBERSORTF,and correlation between central gene levels and relative proportion of immune cells was explored;finally,therapeutic herbal medicines and components were predicted by central genes,and mole-cular docking verification was carried out.Results:A total of 51 DEOSGs,four central genes(ICAM-1,APOE,MMP-1,TGF-β2)were obtained;DEOSGs were mainly related to oxidative stress,immune response,etc;four central gene levels were closely correlated with 8 relative proportions of immune cells;therapeutic herbal medicines included 4 flavors such as Huangqi and Chuanxiong,and the active ingredients included 8 kinds of β-carotene,etc,the molecular docking results were stable.Conclusion:Oxidative stress and immune firing are exist in IPF,and oxidative stress may be recognized by immune cells or directly activate immune cells.

ObjectiveTo monitor the microbes in urban drinking water in Jiangxi from 2016 to 2020， to analyze the change in microbial qualification rate， and to provide a scientific basis for government decision-making. MethodsAccording to the Standard Examination Method for Drinking Water （GB/T 5750‒2006） and the Standards for Drinking Water Quality （GB 5749‒2006）， the water samples were collected， tested and evaluated for hygienic safety. The chi-square test was used to compare the qualification rates among different water periods， water source types， water supply modes， water samples， treatment processes， and disinfection methods. ResultsA total of 10 584 water samples were collected and examined from 2016 to 2020，with a qualification rate of 97.72%. The qualified rate of the microbiological index increased gradually over the years. There was no statistically significant difference in the microbiological qualification rate of water samples monitored in different water periods （χ²=0.718，P=0.398）， and the qualification rates were 97.85% and 97.60% in dry and abundant water periods respectively. There was a statistically significant difference in the qualification rates of water samples monitored in different water source types （χ²=79.560，P=0.398）， with groundwater having a higher qualification rate of 98.83% than surface water （97.70%）. The microbiological pass rate of water samples differed among different water supply methods （χ²=201.836，P<0.001）. The microbiological pass rates of municipal centralized water supply， self-built centralized water supply and secondary water supply were 97.51%， 88.94% and 96.56% respectively. The microbiological pass rates of water samples differed among different treatment processes. There were differences in the qualification rates of the water samples between different treatment processes（χ²=855.034，P<0.001）， with 98.22%， 67.19%， 95.60% and 53.13% of the conventionally treated， precipitated filtered， disinfected only and untreated water samples， respectively. The differences in the microbiological qualification rates of the monitored water samples between different disinfection methods were statistically significant （χ²=904.993，P<0.001）. Chlorination disinfection， chlorine dioxide disinfection， other disinfection methods and non-disinfected water samples had the pass rates of 98.35%， 98.19%， 84.38% and 60.16%， respectively. ConclusionThe qualified rate of the microbiological index of drinking water in Jiangxi increases year by year， but there are still some drinking water without appropriate disinfectants and water quality treatment processes. There is still a need to strengthen the purification， disinfection and monitoring of drinking water.

Objective To evaluate the causal relationship between gastroesophageal reflux disease(GERD)and obstructive sleep apnea(OSA)using two-sample Mendelian randomization(2SMR)and to identify potentially beneficial drugs and pathways for OSA from GERD treatment options.Methods The 2SMR was used as the primary analysis method,and multivariable Mendelian randomization(MVMR)was used to adjust for the potential impact of obesity on both diseases.Secondly,the DrugBank database was used to search for target genes of anti-reflux drugs used to treat GERD,and the dbSNP database was used to determine the target gene loci to identify the genetic tools of anti-reflux drugs.Significant target genes related to OSA risk were obtained through 2SMR analysis.Finally,the target genes were subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and Gene Ontology(GO)analysis using the DAVID database.Results The genetically predicted risk of GERD was significantly associated with an increased risk of OSA[OR=1.43,95%CI=(1.33,1.54),P=5.29×10-22],and MVMR analysis showed that this result remained robust after adjusting for obesity.Four significant genes,including BCHE,DRD2,GRM5,and PTGER3,were identified,which are related to drugs such as nizatidine,bromperidol,ADX10059,and misoprostol.KEGG analysis identified three pathways.Conclusion GERD increases the risk of developing OSA,and anti-reflux drug targets can provide useful genetic clues for drug development in OSA treatment.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION TPCN2 might be a potential protective factor against SLE.
Apoptosis/genetics* ; Cell Division ; Humans ; Jurkat Cells ; Lupus Erythematosus, Systemic/genetics* ; RNA, Small Interfering/genetics*

Abstract: To explore the inflammatory changes and the changes of β-amyloid in the brain of rats with experimental periodontitis induced by ligation. Methods: Eighteen Sprague Dawley rats were randomly divided into 3 groups(n=6): the negative control group, chronic periodontitis group and chronic periodontitis treated with intraperitoneal injection of TAK-242 group. The experimental periodontitis model was established by ligation of the necks of bilateral maxillary first molar and inoculation ofPorphyromonas gingivalis(P.gingivalis). At the end of the second month after the successful modeling, the samples were collected from the rats. The damage of the alveolar bone was analyzed by Micro-CT. The mRNA expression levels of interleukin(IL)-6, IL-1β and tumor necrosis factor-α(TNF-α) in gingival tissue and hippocampal tissue, the mRNA expression level of Toll like receptors-4(TLR4), leukocyte differentiation antigen 14(CD14) and NF-κB in hippocampal tissue of rats were detected by qPCR. The protein expression levels of IL-6, IL-1β, TNF-α, myloid-beta protein-40(Aβ40) and Aβ42in hippocampal tissue of rats were evaluated by ELISA. Results: Experimental periodontitis model of rats could be successfully established by ligation of the neck of the rat's bilateral maxillary first molars and inoculation with porphyromonas gingivalis. The results of qPCR and ELISA showed that experimental periodontitis up-regulated the expression levels of inflammatory factors(IL-6, IL-1β and TNF-α) in hippocampus of rats and the result of ELISA showed that the level of Aβ42in hippocampus of experimental periodontitis rats increased. But the pretreatment with TAK-242 intraperitoneal injection could reduce the up-regulated the expression of inflammatory factors and Aβ42by down-regulating the TLR4/NF-κB signaling pathway. Conclusion Experimental periodontitis in rats induced by ligation combined with inoculation of porphyromonas gingivalis can result in inflammation in the brain and promote the accumulation of Aβ42in the brain, and it is reasonable to speculate that inflammation may play an important role in the correlation between periodontitis and systemic diseases such as Alzheimer's disease.

Objective:To establish a risk prediction model of acute myocardial infarction(AMI)in elderly patients with hyperuricemia(HUA).Methods:A total of 148 elderly patients with HUA in Shanghai Fourth People's Hospital Affiliated to Tongji University for prospective study from March 2020 to March 2021 were divided into AMI group and non-AMI group according to whether they were complicated with AMI.The baseline data of patients were recorded at admission and compared between the two groups.Multivariate Logistic regression analysis was used to examine the risk factors for AMI in elderly patients with HUA.And AMI risk prediction model was established.The ROC curves were plotted.Using the ROC curve, the prediction efficiency of AMI risk prediction model was evaluated.Results:Among 148 elderly patients with HUA, 22 cases(14.86%)had AMI.The proportion of smoking history in AMI group was higher than non-group( χ2=6.192, P=0.013). The diastolic blood pressure, systolic blood pressure, fasting blood glucose(FPG), low density lipoprotein cholesterol(LDL-C), serum uric acid(SUA)and homocysteine(Hcy)were statistically significantly higher in AMI group than in non-AMI group( U=1.973, 2.652, 2.016, 1.364, 2.151, 2.973, 5.972, P=0.049, 0.008, 0.044, 0.032, 0.003, <0.001). The multiple Logistic regression analysis showed that smoking history, high DBP, high SBP, high FPG, high LDL-C, high SUA and high Hcy were risk factors for AMI in elderly HUA patients( OR=3.120, 1.072, 1.887, 2.358, 3.365, 1.031, 3.773, P=0.016, 0.001, <0.001, 0.008, 0.028, 0.001, <0.001). By substituting the risk factor index and the regression coefficient into the Logistic regression equation formula, the obtained final fitting equation was: AMI=1.138×smoking history(no=0, yes=1)+ 0.070×DBP+ 0.635×SBP+ 0.858×FPG+ 1.213×low density lipoprotein+ 0.030×SUA+ 1.328×Hcy.The ROC curve was drawn and showed that the AUC of forecast value of AMI risk prediction model in predicting the risk of AMI in elderly HUA patients was 0.847, >0.80, which had certain predictive value.Hosmer-Leme show goodness of fit test χ2=5.743, P=0.676, P>0.05, the model had good correction ability and satisfactory fitting. Conclusions:AMI in elderly hyperuricemia patients are affected by multiple risk factors.The AMI risk prediction model is established via combining with multiple risk factors.The model has certain efficiency in predicting the occurrence of AMI in elderly patients with hyperuricemia.

Objective:To investigate the clinical effect of lateral rectus abdominis approach combined with presacral decompression for surgical treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.Methods:A retrospective case series study was performed on the clinical data of 9 patients with old Denis type II sacral fractures complicated with upper sacral plexus injury (L 4-S 1) admitted to Zhongnan Hospital of Wuhan University from June 2010 to December 2016. There were 6 males and 3 females, aged (33.1±7.5)years (range, 15-58 years). Embolization of internal iliac artery and preimplantation of abdominal aortic balloon were performed 2 hours before operation under the guidance of digital subtraction angiography (DSA). Surgery was performed using a single lateral rectus abdominis approach combined with presacral decompression. The operation time, intraoperative blood loss and full weight-bearing time were recorded. The visual analogue scale (VAS) and European QOL Five Dimensional health scale (EQ-5D) were compared before and after operation. The Gibbons' impairment scale was used to assess neurological function. X-ray and CT scan were used to observe internal fixation and fracture healing. The complications during and after operation were recorded. Results:The patients were followed up for 24-52 months [(35.2±5.2)months]. The operation time was (2.9±0.6)hours. The intraoperative bleeding was (573±138)ml, and the full weight-bearing time was (11.6±1.2)weeks. X-ray and CT scan showed bone healing in all patients at the latest follow-up. The VAS and EQ-5D scale improved from preoperative (7.8±0.6)points and (0.34±0.07)points to the final follow-up of (0.8±0.3)points and (0.81±0.05)points ( P<0.05). According to Gibbons classification, 8 patients were grade I and 1 patient was grade II one year after operation ( P<0.01). Namely, the radiation pain of lower extremities was significantly improved in all patients, among which 8 patients showed pain disappeared and completely returned to normal and 1 patient showed residual numbness and hypoesthesia of the affected limbs. No major complications (eg, iatrogenic lumbosacral plexus injury, vital blood vessels or pelvic organs injury) occurred during the operation. During the follow-up period, only one patient developed traumatic hip arthritis and underwent total hip arthroplasty 6 months after operation. Fractures of the remaining patients were healed well without complications like infection, pressure ulcer or implant failure. Conclusions:For old Denis type II sacral fractures complicated with upper sacral plexus injury, lateral rectus abdominis approach combined with presacral decompression can fully decompress the upper sacral plexus nerve, relieve pain, and promote functional rehabilitation, with low incidence of complications. It is an alternative surgical method for the treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.