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.

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 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.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.