ObjectiveTo investigate microbial contamination status and distribution characteristics in laboratory animal barrier facilities, so as to provide a scientific basis for environmental quality control in barrier facilities. MethodsIn accordance with the national standard "Laboratory Animals—Environment and Housing Facilities" and the "Standard Operating Procedures" of the barrier facility, bacterial monitoring was performed on samples of air-settling bacteria, materials, and personnel gloves in the single-corridor barrier facility of the Animal Core Facility, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CEMCS). The monitoring data from January 2020 to December 2024 were collected, organized and statistically analyzed, and partial samples were subjected to species identification using PCR and sequencing methods. ResultsA total of 7 898 samples were collected from 2020 to 2024, including 3 175 air-settling bacteria samples, 3 353 material samples, and 1 370 glove samples. The overall compliance rate was 95.7% (7 559/7 898), among which the compliance rate of air-settling bacteria was 97.1% (3 084/3 175), that of materials was 93.2% (3 125/3 353), and that of personnel gloves was 98.5% (1 350/1 370). Over the five years, the compliance rates of all three types of monitored samples were above 90%. There were statistically significant differences in the compliance rates of air-settling bacteria and material samples among different quarters (P<0.05). Further investigation was conducted on samples collected from January to March 2024, and 190 bacterial strains were obtained through isolation and culture, including 126 strains from air-settling bacteria, 52 strains from materials, and 12 strains from personnel gloves. The strains were identified by PCR amplification and sequencing, and the 190 bacterial strains belonged to 9 genera and 20 species. Gram-positive bacteria accounted for the majority, with Staphylococcus as the dominant genus, accounting for 77.9% (148/190). ConclusionMicroorganisms carried by air, materials, and personnel gloves in barrier facilities are mainly Gram-positive bacteria. Regular monitoring of air-settling bacteria, materials, and personnel gloves in barrier facilities enables timely detection and control of potential risks during husbandry management and facility operation, which is of great significance for maintaining the sound operation of the barrier facility system and ensuring the quality of animal experiments.

ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

BACKGROUND:Rheumatoid arthritis is influenced by complex genetic and environmental factors.Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis,the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.OBJECTIVE:To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.METHODS:A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database(developed by Decode Genetics in Iceland,which contains genomic data from the Icelandic population),the MR-Base platform(developed by a team of researchers at the University of Oxford in the United Kingdom,specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses),and the GWAS Catalog platform(developed by the European Institute of Bioinformatics,which provides data for genome wide association studies worldwide).The causal effects were estimated using the Wald ratio and inverse variance weighting methods,with Bonferroni correction applied to control for false positives caused by multiple testing.To ensure the robustness of the results,sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis,and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy.Additionally,external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries.Finally,small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database(DsigDB),and molecular docking was performed to predict the binding patterns and energies between proteins and compounds,identifying the most stable and likely binding molecules and mechanisms.RESULTS AND CONCLUSION:(1)Sensitivity analyses,including Bayesian colocalization and phenome scanning,identified four plasma proteins with reliable causal relationships with rheumatoid arthritis:FCRL3,IL6R,ICOSLG,and TNFAIP3.Their genetic effects were estimated as follows:FCRL3[odds ratio(OR)=1.12,95％confidence interval(CI):1.07-1.17],IL6R(OR=0.94,95％CI:0.91-0.96),ICOSLG(OR=2.42,95％CI:1.67-3.52),and TNFAIP3(OR=2.19,95％CI:1.88-2.56).Furthermore,molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins,suggesting its potential as a therapeutic agent for rheumatoid arthritis.(2)This study provides a comprehensive analysis of the genetic causal relationships of FCRL3,IL6R,ICOSLG,and TNFAIP3 in rheumatoid arthritis.These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention,but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies.Although the study is based on European populations,its findings offer important insights for biomedical research in China.By incorporating Mendelian randomization methods to analyze genetic causality,future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences,offering theoretical support for localized risk assessment and treatment strategies.

Metabolic associated fatty liver disease （MAFLD） is the main type of chronic liver disease in the world， with an increasingly higher incidence rate and a younger age of onset. At present， the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management， and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family， aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism， relieving insulin resistance， reducing liver inflammation and oxidative stress response， exerting an anti-liver fibrosis effect， and inhibiting hepatocellular carcinoma， and therefore， it has the value of preventing disease onset， delaying disease progression， and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD， in order to provide more drug treatment options for MAFLD patients.

BACKGROUND:Rheumatoid arthritis is influenced by complex genetic and environmental factors.Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis,the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.OBJECTIVE:To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.METHODS:A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database(developed by Decode Genetics in Iceland,which contains genomic data from the Icelandic population),the MR-Base platform(developed by a team of researchers at the University of Oxford in the United Kingdom,specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses),and the GWAS Catalog platform(developed by the European Institute of Bioinformatics,which provides data for genome wide association studies worldwide).The causal effects were estimated using the Wald ratio and inverse variance weighting methods,with Bonferroni correction applied to control for false positives caused by multiple testing.To ensure the robustness of the results,sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis,and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy.Additionally,external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries.Finally,small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database(DsigDB),and molecular docking was performed to predict the binding patterns and energies between proteins and compounds,identifying the most stable and likely binding molecules and mechanisms.RESULTS AND CONCLUSION:(1)Sensitivity analyses,including Bayesian colocalization and phenome scanning,identified four plasma proteins with reliable causal relationships with rheumatoid arthritis:FCRL3,IL6R,ICOSLG,and TNFAIP3.Their genetic effects were estimated as follows:FCRL3[odds ratio(OR)=1.12,95％confidence interval(CI):1.07-1.17],IL6R(OR=0.94,95％CI:0.91-0.96),ICOSLG(OR=2.42,95％CI:1.67-3.52),and TNFAIP3(OR=2.19,95％CI:1.88-2.56).Furthermore,molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins,suggesting its potential as a therapeutic agent for rheumatoid arthritis.(2)This study provides a comprehensive analysis of the genetic causal relationships of FCRL3,IL6R,ICOSLG,and TNFAIP3 in rheumatoid arthritis.These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention,but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies.Although the study is based on European populations,its findings offer important insights for biomedical research in China.By incorporating Mendelian randomization methods to analyze genetic causality,future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences,offering theoretical support for localized risk assessment and treatment strategies.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Immunization represents the most effective strategy for the prevention and control of diseases. Nevertheless, some people may still get infected and contract the disease even after being fully vaccinated, which is known as a "breakthrough case." The presence of breakthrough cases shows that although vaccines significantly lower the rates of disease and death, they do not entirely eliminate the risk of illness.Addressing breakthrough cases, comprehending their epidemiological characteristics, and identifying the associated factors carry substantial public health implications for vaccine development, the optimization of vaccination strategies, and the implementation of intervention efforts. This review aims to provide a scientific reference for enhancing the prevention and control of vaccine-preventable diseases by summarizing the definitions, epidemiological characteristics, and relevant factors related to breakthrough infection cases across various diseases.

Objective:To determine the optimal cut-off value of serum cotinine for distinguishing smoking status among Chinese adults based on a large-scale national sample.Methods:A cross-sectional study was conducted among 8 987 Chinese adults aged 20-79 years from 152 administrative counties across 31 provinces during 2017-2018. Sociodemographic characteristics, lifestyle, smoking status, and health status were collected via questionnaires and physical examinations. Blood samples were analyzed for serum cotinine levels using liquid chromatography-mass spectrometry and for blood creatinine levels using the picric acid method. Receiver operating characteristic (ROC) curve analysis was performed with serum cotinine concentration as the test variable and self-reported smoking status as the state variable. The optimal cut-off value was determined based on the maximum Youden′s index, and the bootstrap method was used for repeated sampling (2 000 times) to evaluate the confidence interval of the cut-off value. The net reclassification index (NRI) was used to evaluate the discrimination ability of the cut-off value of this study, the cut-off value of the American population 1 (total population: 3.3 μg/L, men: 4.1 μg/L, women: 3.0 μg/L) and the cut-off value of the American population 2 (the recommended value of the United States Centers for Disease Control and Prevention for the total population: 10.0 μg/L) against the smoking status of the Chinese population. Statistical analyses were conducted using IBM SPSS 27 and Python 3.11, with a significance level of α=0.05.Results:The age of the research subjects was (49.2±15.2) years. Among them, males accounted for 49.8% (4 477); smokers accounted for 28.8% (2 586); the detection rate of serum cotinine was 94.6% (8 501), and the M ( Q1, Q3) concentration of serum cotinine was 0.9 (0.3, 85.4) μg/L. The ROC curve analysis results showed that the cut-off value (95% CI) of serum cotinine in the total population was 8.8 (6.7-11.7) μg/L, with the specificity (95% CI) about 93.6%(92.7%-94.3%), the sensitivity (95% CI) about 91.0%(89.7%-92.3%) and the area under the curve (AUC) (95% CI) about 0.93 (0.92-0.94). The cut-off value (95% CI) of cotinine for males was 17.1 (8.8-21.8) μg/L, with the specificity (95% CI) about 90.7%(87.9%-92.0%), the sensitivity (95% CI) about 89.4%(88.4%-92.2%) and the AUC (95% CI) about 0.92 (0.91-0.93). The cut-off value (95% CI) of cotinine for females was 7.4 (3.3-15.0) μg/L, with the specificity (95% CI) about 95.6%(92.7%-96.8%), the sensitivity (95% CI) about 87.6%(81.6%-92.8%) and the AUC (95% CI) about 0.92 (0.87-0.95). The NRI analysis results showed that compared with the cut-off value of the American population 2, the NRI of this study′s cut-off values in the total population, males and females were 0.020 ( P=0.015), 0.033 ( P=0.015) and 0.011 ( P=0.380), respectively, indicating that this study′s cutoff value could have better classification performance in the total population and males. Compared with the cut-off value of the American population 2, the NRI of the total population in this study was 0.001 ( P=0.285). Conclusion:The serum cotinine cut-off value based on the analysis of large sample data in China is more suitable for distinguishing the smoking status of Chinese adults.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective:To understand the incidence rate of herpes zoster (HZ) and postherpetic neuralgia (PHN) in Beijing, and analyze the incidence trend of HZ and PHN from 2015 to 2022.Methods:Cases of HZ and PHN from 2015 to 2022 were retrieved from the Hospital Information Systems (HIS) of all primary and above hospitals/clinics in three districts representing the urban, inner suburban, and outer suburban areas of Beijing. After duplication screening, the first visit cases were screened, and the incidence characteristics were described. The incidence rate of HZ and PHN in each year by sex and age group and the age-standardized incidence rate were calculated. The annual percentage increase (APC) of incidence rate was calculated using the Joint regression model, and the change trend was analyzed.Results:The age-standardized incidence rate of HZ in Beijing from 2015 to 2022 ranged from 7.44‰ to 10.05‰, with an average annual incidence rate of 8.95 ‰, significantly increasing with age ( P<0.001). The Joinpoint regression model showed that the overall age-standardized incidence of HZ remained relatively stable, with no significant difference (APC=2.28%, t=1.56, P=0.170). However, the incidence rate among the 0-19-year-old group exhibited a trend of decrease (APC=-10.70%, t=-6.29, P<0.001). For PHN, the age-standardized incidence in Beijing ranged from 0.77‰ to 2.67‰, with an average annual incidence rate of 1.59‰ and a proportion of 9.48% to 26.86% among HZ cases. Both the incidence of PHN and its proportion among HZ cases increased with age ( P<0.001). The age-standardized incidence of PHN increased annually (APC=18.56%, t=9.02, P<0.001). Conclusion:The incidence rate of HZ and PHN in Beijing continues to be at a high level, and PHN shows an increasing trend over time.