Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for both human bloodstream infections and mastitis in cows. However, little attention has been paid to the cross-host transmission of MRSA from cows to high-risk groups in China. Objective To determine the MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang, identify the antibiotic resistance profiles and molecular characteristics of the isolates, and provide scientific evidence for the formulation of targeted infection control strategies. Method A cross-sectional survey combined with laboratory pathogen analysis was conducted. From June to August 2024, large-scale dairy farms in Xinjiang region were selected as study sites. Nasal swabs (n=96) and skin swabs (n=39) were collected from workers, and bovine nasal swab samples (n=109) were collected simultaneously. All samples were subjected to MRSA isolation, cultivation, and identification, followed by antibiotic susceptibility testing to characterize resistance phenotypes. Staphylococcus aureus protein A (Spa) typing was performed to determine strain genotypes and elucidate MRSA colonization rates and molecular epidemiological patterns. Results A total of 35 MRSA strains was successfully isolated from 244 samples. The MRSA colonization rates among dairy farm workers and dairy cows were 20.83% (20/96) and 12.84% (14/109), respectively, with an overall isolation rate of 14.34% (35/244). Among the workers, the nasal colonization rate was 16.67% (16/96), and the skin colonization rate was 12.82% (5/39). One worker exhibited MRSA colonization at multiple body sites. All MRSA strains were resistant to cefoxitin (100%, 35/35). The resistance rates to erythromycin and clindamycin were 42.86% (15/35) and 34.29% (12/35), respectively. Thirteen strains showed a multidrug-resistant phenotype, whereas all strains were susceptible to vancomycin. The MRSA isolates exhibited high genetic diversity, with 13 Spa types identified, among which t441 was the most prevalent (8 strains). Both t441 and t034 types were detected in samples from both the dairy cows and their handlers. These two Spa types also carried and stably inherited specific resistance combinations, including erythromycin–clindamycin–cefoxitin and ciprofloxacin–erythromycin–clindamycin–gentamicin–cefoxitin–tetracycline, and a statistically significant association was also observed between the two resistance profiles and the bacterial types (P < 0.001). In addition, one novel Spa type strain was identified. Conclusion MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang are relatively high, with evidence of multi-site colonization. The isolates exhibit high levels of multidrug resistance and genetic diversity, indicating a potential risk of cross-host transmission.

Background Under intensive dairy farming conditions, Enterococcus spp. can be transmitted between animals, farm workers, and the environment via multiple vectors such as feces, soil, water, air, and farming equipment, posing a potential threat to public health. Objective To elucidate the prevalence, distribution, and antimicrobial resistance profiles of Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) among farm workers, dairy cattle, and the farm environment in Xinjiang, and to assess the risk of their cross-host transmission. Methods From May 2024 to January 2025, a total of 317 samples were collected from 11 large-scale dairy farms in Xinjiang, China, including feces from farm workers (n=130) and dairy cattle (n=154), and environmental samples (n=33). E. faecalis and E. faecium were isolated and identified, followed by antimicrobial susceptibility testing and multilocus sequence typing (MLST) to analyze their molecular characteristics. Results A total of 183 Enterococcus isolates were obtained (66 E. faecalis and 117 E. faecium isolated). The isolation rates of both species showed statistically significant differences among the three sources (χ²=29.21, P=0.003). Antimicrobial resistance analysis revealed that E. faecalis generally exhibited higher resistance rates across multiple antibiotic classes than E. faecium. High resistance to rifampicin was observed across all sources (50.00%–81.25%), with statistical variation among origins (χ²=8.03, P=0.024). Multidrug-resistant strains accounted for 69.10% of the isolates. Multidrug resistance patterns in E. faecium varied significantly by source (χ²=27.19, P=0.014), and one isolate displayed resistance to eight antibiotic classes. MLST indicated high genetic diversity; E. faecalis was dominated by ST472 and ST227 of which the distrubution was significantly different among sources, while E. faecium primarily clustered into clonal complexes CC94 (centered on ST94) and CC17 (centered on ST22). Conclusion Resistant Enterococcus strains exhibit cross-transmission among farm workers, animals, and the environment. Under the "One Health" framework, standardized farming protocols and prudent antimicrobial use are essential to disrupt the transmission chain of resistant clones and mitigate the spread of antimicrobial resistance at its source.

Background Under intensive dairy farming conditions, Enterococcus spp. can be transmitted between animals, farm workers, and the environment via multiple vectors such as feces, soil, water, air, and farming equipment, posing a potential threat to public health. Objective To elucidate the prevalence, distribution, and antimicrobial resistance profiles of Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) among farm workers, dairy cattle, and the farm environment in Xinjiang, and to assess the risk of their cross-host transmission. Methods From May 2024 to January 2025, a total of 317 samples were collected from 11 large-scale dairy farms in Xinjiang, China, including feces from farm workers (n=130) and dairy cattle (n=154), and environmental samples (n=33). E. faecalis and E. faecium were isolated and identified, followed by antimicrobial susceptibility testing and multilocus sequence typing (MLST) to analyze their molecular characteristics. Results A total of 183 Enterococcus isolates were obtained (66 E. faecalis and 117 E. faecium isolated). The isolation rates of both species showed statistically significant differences among the three sources (χ²=29.21, P=0.003). Antimicrobial resistance analysis revealed that E. faecalis generally exhibited higher resistance rates across multiple antibiotic classes than E. faecium. High resistance to rifampicin was observed across all sources (50.00%–81.25%), with statistical variation among origins (χ²=8.03, P=0.024). Multidrug-resistant strains accounted for 69.10% of the isolates. Multidrug resistance patterns in E. faecium varied significantly by source (χ²=27.19, P=0.014), and one isolate displayed resistance to eight antibiotic classes. MLST indicated high genetic diversity; E. faecalis was dominated by ST472 and ST227 of which the distrubution was significantly different among sources, while E. faecium primarily clustered into clonal complexes CC94 (centered on ST94) and CC17 (centered on ST22). Conclusion Resistant Enterococcus strains exhibit cross-transmission among farm workers, animals, and the environment. Under the "One Health" framework, standardized farming protocols and prudent antimicrobial use are essential to disrupt the transmission chain of resistant clones and mitigate the spread of antimicrobial resistance at its source.

Background Animal farming may affect the structure and diversity of gut microbiota of farm workers, but it needs more studies to provide solid evidence. Objective To analyze the diversity characteristics of gut microbiota in dairy farm workers, dairy cows, and the control population (non-animal contact occupational group), and to assess the impact of dairy farming on the gut microbiota of workers. Methods The 16S rRNA full-length amplicon sequencing technology was used to sequence 60 fecal samples from dairy farm workers, 89 from dairy cows, and 50 from the general population. The gut microbiota structure characteristics, including operational taxonomic units (OTUs), alpha diversity, beta diversity, and the composition of species at the phylum, family, and genus levels were analyzed. The differences in gut microbiota among the three groups of samples were compared to explore the impact of occupational exposure on the gut microbiota structure of dairy farm workers. Results A total of 50478 OTUs were identified in the gut microbiota of farm workers, dairy cows, and the general population, with 23613, 42723, and 16592 OTUs, respectively. The number of shared OTUs between the dairy cows and the general population was 12674 (27.17%), between the general population and the farm workers was 10099 (33.54%), and between the dairy cows and the farm workers was 17690 (36.36%). Compared with the general population, the farm workers and dairy cows showed more shared gut microbiota (P<0.01). The abundance of Firmicutes in the gut of the farm workers was higher than that of the general population (P<0.01), while Actinobacteriota and Proteobacteria were the opposite (P<0.01). The alpha diversity of gut microbiota in the farm workers was different from that of the general population. The ACE index of the farm workers was slightly lower than that of the general population and much lower than that of dairy cows (P<0.05), while their Shannon index was higher than that of the general population but lower than that of dairy cows (P<0.01). The linear discriminant analysis effect size (LefSe) showed that the abundances of Lachnospiraceae and Ruminococcaceae in the gut microbiota of the farm workers were significantly higher than those of the general population, while Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae were lower than those of the general population. Conclusion The dairy farm workers shares a certain proportion of common bacterial communities with dairy cows. Dairy farming operations can affect the structure and diversity of the gut microbiota of workers by increasing the abundances of Lachnospiraceae and Ruminococcaceae, while decreasing the abundances of Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae. The study results provide reference data for further exploring the cross-host transmission of pathogens related to occupational exposure in dairy farming.

OBJECTIVE To evaluate the cost-effectiveness of dapagliflozin and empagliflozin in the treatment of type 2 diabetic kidney disease from the perspective of healthcare system in China. METHODS Based on the data from the two multicenter clinical trials， DECLARE-TIMI 58 and EMPA-REG OUTCOME， a Markov model was constructed according to the urinary albumin-to-creatinine ratio （UACR） of the patients with type 2 diabetic kidney disease with a cycle of 1 year， simulating until 99% of patients died. The model outputs were total costs and quality-adjusted life year （QALY）. The cost-effectiveness of the two treatment regimens was assessed by comparing their incremental cost-effectiveness ratio （ICER） and the willingness-to-pay threshold （WTP，set at three times China’s 2023 per capita gross domestic product， i.e.， 268 074 yuan/QALY）. Additionally， oneway sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the base analysis results. RESULTS Compared with dapagliflozin， the ICER for empagliflozin regimen was 44 334.82 yuan/QALY， which was below the WTP ， indicating its cost-effectiveness. The results of the oneway sensitivity analysis indicated that the incidence of non-fatal myocardial infarction in both groups and the utility values associated with the microalbuminuria state had the most significant impact on the outcomes， but did not change the base-case conclusion. The probabilistic sensitivity analysis indicated that the results of the base-case analysis were robust. CONCLUSIONS With a WTP of three times China’s per capita gross domestic product in 2023， empagliflozin is more cost-effective than dapagliflozin in treating type 2 diabetic kidney disease.

To investigate the effect of capsaicin(CAP)on the replication of bovine viral diarrhea vi-rus(BVDV).Bovine nasal turbinate osteoblasts(BT)infected with BVDV served as the research model,and viral gene and protein levels were evaluated using RT-qPCR and Western blot.Moreo-ver,molecular docking,molecular dynamics simulation,and oil red O staining were applied to ana-lyze the mechanism by which CAP inhibits BVDV replication.The results revealed no significant effect of CAP at 6.25,12.5,25,and 50 mg/L on the viability of BT cells.CAP was found to signifi-cantly inhibit BVDV 5′UTR RNA and E2 protein levels,according to the antiviral effect study.Molecular docking and molecular dynamics simulations indicated that CAP could bind with high affinity to the active site of PI3K.Additional mechanistic studies indicated that CAP significantly reduced the activation of the PI3K/AKT signaling pathway triggered by BVDV.Furthermore,CAP notably decreased the mRNA levels of FASN,SREBP-1,and ACC-1,which are crucial fatty acid synthesis enzymes in the downstream PI3K/AKT signaling pathway,as well as the levels of lipid droplets.Interestingly,the addition of exogenous oleic acid greatly diminished the antiviral effec-tiveness of CAP and significantly lowered the mRNA levels of IFN-α and IFN-β.The results reveal for the first time that CAP can inhibit BVDV replication,establishing a foundation for its preven-tion and the development of feed additives.

Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.

AIM:A strain was isolated and identified as the H3N8 subtype of the avian influenza virus from a sick chicken at a farm in Yangjiang,Guangdong Province,named A/chicken/Yangjiang/552/2023(abbreviated as YJ/552).The aim of this research is to determine its genetic evolution,biological properties and pathogenicity in hamsters.This study may provide a theoretical strategy for preventing and treating the H3N8 subtype avian influenza virus-induced epidemic.METHODS:A strain of H3N8 avian influenza virus from chickens was characterised by phylogenetic analy-sis,antigenic diversity,receptor-binding specificity,neuraminidase activity,replication,and transmission in hamsters and a systematic pathological analysis was conducted.RESULTS:This novel avian influenza virus was generated through complex recombination of Eurasian avian H3 genes,North American avian N8 genes and six internal genes of H9N2 sub-type AIV.The cleavage site of the outer protein,HA,was PEKQTR↓GLF,which is characteristic of the low pathogenic avian influenza virus.The HA gene of YJ/552 exhibited the highest nucleotide homology with A/China/ZMD-22-2/2022(H3N8)at 99.09%,while the NA gene showed the highest homology with A/chicken/Dongguan/879/2022(H3N8)at 99.01%.This strain preferentially binds to avian-type receptors and could bind to human-type receptors.This virus could effectively replicate in the trachea and lungs of inoculated and contact hamsters.CONCLUSION:YJ/552 is a recombi-nant H3N8 avian influenza virus replicated in the upper respiratory system and transmitted in hamsters.This study pro-vides data support for the early warning and prevention of H3 subtype avian influenza viruses.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

OBJECTIVE To explore the indexes affecting the prognosis of the ICU patients with sepsis,establish the nomogram model for prediction of 28-day mortality rate,and validate it.METHODS On the basis of criteria for diagnosis of sepsis(3.0 version),the related data of the sepsis patients were extracted from Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database for retrospective study and were randomly divided into the train-ing set and the validation set in a 7∶3 ratio.Univariate analysis and multivariate Cox proportional risk regression analysis were performed for the screening of influencing factors for prediction of 28-day mortality of the sepsis pa-tients.The nomogram prediction model was established based on the screened factors and was validated by the val-idation set,and the effect was evaluated.RESULTS A total of 7 955 sepsis patients were included.Seven variables were selected to establish the nomogram model for prediction of the 28-day mortality rate.The nomogram showed favorable performance in identification between the two cohorts,the area under receiver operating characteristic curves(AUROCs)were 0.748 and 0.721,respectively.Calibration curves and Hosmer-Lemeshow test(x2=8.689,10.614;P=0.369,0.225)indicated that the model had remarkable effect on correction.With the per-formance of decision curve analysis(DCA)and clinical impact curve(CIC),the model was considered to have high clinical application value.CONCLUSIONS The nomogram model shows favorable performance in prediction of the 28-day mortality rate and calibration capability.It is worthy to be further promoted and applied.