Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

OBJECTIVE To observe the effect of early warning mechanisms based on nosocomial infection surveil-lance system on precise prevention and control of spread of multidrug-resistant organisms(MDROs)infections in intensive care unit of neurosurgery department.METHODS The dynamic monitoring was performed in the ICU of neurosurgery department of a three-A general hospital by using real-time surveillance system of nosocomial infec-tion from Jan.2023 to Dec.2023.The warning information was sent to the doctor' station immediately once the MDROs infections were detected,the detection of drug-resistant bacteria was carried out for the relevant personnel and their surroundings,and the precise prevention and control measures were implemented.The impact on the iso-lation rate of MDROs,isolation rate of MDROs from the relevant personnel and surroundings,incidence of noso-comial MDROs infections and incidence of surgical site infection was observed after the measures were taken.RESULTS The carrying rate of MDROs was decreased from 21.80％to 5.74％among the relevant personnel after the precise prevention and control measures were taken(P＜0.05),which was improved remarkably among the doctors(decreasing from 21.43％to 6.07％),nurses(decreasing from 23.68％to 3.98％),nursing workers(decreasing from 25.15％to 8.65％),and cleaning staff(decreasing from 25.49％to 5.05％)(P＜0.001).The isolation rate of MDROs was decreased from 20.77％to 7.12％among the surroundings(P＜0.05),which was decreased most remarkably among head cushions(decreasing from 32.28％to 12.13％),bed rails(decreasing from 16.70％to 3.27％),ventilator panels(decreasing from 23.00％to 6.95％)and bedside floors(decreasing from 31.99％to 9.96％)(P＜0.001).The incidence of nosocomial MDROs infections declined from 3.84％to 1.71％(P＜0.05),with incidence of incision infections decreasing from 4.00％to 1.45％(P＜0.05),the inci-dence of intracranial infections decreasing from 2.38％to 0.56％(P＜0.05).CONCLUSION The detection of drug-resistant bacteria is carried out immediately and precisely for the patients with MDROs infection,relevant personnel and their surroundings by using the real-time surveillance system of nosocomial infection,which achieve remarkable effect on prevention of transmission of MDROs and reduction of incidence of hospital-associated infec-tions and surgical site infections.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Cell death is classified into programmed cell death(PCD)and non-programmed cell death(NCD).Necroptosis is a form of PCD that does not rely on caspases and is regulated by four signaling pathways:receptor-interacting protein kinase 1/3(RIPK1-RIPK3),TIR-domain-containing adapter-in-ducing interferon-β(TRIF)-RIPK3,Z-DNA binding protein 1(ZBP1)-RIPK3,and type Ⅰ/Ⅱ interferon receptors(IFNRs).These pathways interact to regulate the activity of core molecules such as RIPK1,RIPK3,and mixed lineage kinase domain-like protein(MLKL),thereby determining the occurrence of necroptosis.The dysregulation of these pathways can lead to the development of various diseases,inclu-ding cancer.Necroptosis not only inhibits tumor occurrence and progression by promoting tumor cell death,but also creates a tumor microenvironment(TME)conducive to tumor cell growth through its pro-inflammatory properties,thereby promoting tumor growth and metastasis.Therefore,the dual role of nec-roptosis in cancer makes it an important research direction in tumor treatment.This article reviews the key signaling pathways of necroptosis,explores its interactions with other cell death pathways such as cell survival,apoptosis,and pyroptosis.Meanwhile,it analyzes the dual regulatory mechanisms of necropto-sis in cancer progression and discusses the issue of overcoming tumor treatment resistance by modulating necroptosis.It further explores its potential therapeutic targets and application prospects,aiming to pro-vide new intervention strategies and theoretical basis for cancer treatment.

The Diagnosis-Intervention Packet(DIP)payment exerts notable effects on hospitals' economic operations.As centralized hubs of high-quality medical resources,tertiary hospitals face a functional mismatch with the provision of services for primary care diseases.By analyzing the admission and payment practices for primary care diseases in sample hospitals in Henan Province,it identifies key challenges,including inadequate alignment between healthcare payment reform policies and management systems,weak foundational capabilities in hospital health insurance informatization,and insufficient awareness of health insurance policies among medical staff.It is recommended that hospitals should strengthen communication and coordination with health insurance administration agencies to foster positive interactions between healthcare providers and insurers;continuously advance in-house health insurance informatization and enhance data governance capabilities;improve strategic awareness and innovate value-based health insurance management models.

Objective This study aims to investigate the association between remnant cholesterol(RC)and the risk of metabolic-associated fatty liver disease(MAFLD)under the optimal triglyceride(TG)levels recom-mended by different guidelines.Methods The data were derived from the annual physical examinations of elderly people aged 65 and above in a community in 2023.Regression analysis was used to evaluate the association between RC and MAFLD risk.According to the TG normal level(<1.7 mmol/L)recommended by the Chinese Lipid Management Consensus and the TG ideal target(<1.2 mmol/L)proposed by the European Atherosclerosis Society,the individuals were divided into subgroups with different TG levels to explore the association between RC and MAFLD risk in each subgroup.Results A total of 2,800 elderly individuals aged 65 and above were included in this study.The proportion of the individuals meeting the diagnostic criteria for MAFLD was 20.85%,and RC was identified as an independent risk factor for MAFLD(P<0.001).In the elderly individuals with TG<1.7 mmol/L,RC level was not significantly associated with MAFLD risk(P=0.888).In contrast,in the elderly individuals with TG≥1.7 mmol/L,RC level was significantly and positively correlated with MAFLD risk(P<0.001).Interaction tests revealed no significant interaction between the stratification factor and the effect size of RC(P=0.115).In the elderly individuals with TG<1.2 mmol/L,RC level was not associated with MAFLD risk(P=0.505),while in the elderly individuals with TG≥1.2 mmol/L,RC level was significantly associated with MAFLD risk(P<0.001).Interaction tests showed a significant interaction between the stratification factor and the effect size of RC(P=0.011).Conclusion RC is an independent risk factor for MAFLD in older individuals.To reduce the risk of MAFLD related to RC in the elderly,a triglyceride level of<1.2 mmol/L can serve as a reference for identifying early-stage risk.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.