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:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Objective:To evaluate the accuracy and output stability of online general natural language processing(NLP)models for staging diagnosis and identifying medium-and high-risk factors in cervical cancer patients based on pathology reports.Methods:Surgical pathological reports of 65 patients with cervical cancer who received postoperative adjuvant radiotherapy at Shanghai General Hospital from January 2022 to December 2023 were retrospectively selected.These reports were input into two online NLP models,Kimi and ChatGPT-4o,and their output staging diagnosis results were recorded.Then,the results were classified into 3 categories and scored as follows:correct(2 points),basically correct(1 point)and incorrect(0 point).Each pathologic report was tested 5 times to assess the stability of the outputs form Kimi and ChatGPT-4o,and the consistency between the NLP models and clinical physicians in cervical cancer staging was compared.Prompt-based questioning was used to evaluate Kimi's ability to extract medium-and high-risk factors from the pathology reports of cervical cancer patients.Results:There was no statistical significant difference in the staging diagnosis results between the two NLP models and the clinical physicians(x2=5.740,P=0.057).Kimi and ChatGPT-4o respectively produced 56 and 47 correct results,6 and 15 basically correct results,and 3 and 3 incorrect results.Their mean scores were 7.08±2.70 and 7.97±2.97,and the difference between them was statistically significant(P=0.040).In the extraction of risk factors from 65 cervical cancer patients,involving a total of 390 factors,Kimi made only three false-positive errors,with all other factors correctly identified.Conclusion:Online general NLP models can stably output the stage of cervical cancer patients with diagnostic accuracy comparable to clinical physicians.With the assistance of prompt-based questioning,these NLP models can accurately extract medium-and high-risk factors from pathology reports of cervical cancer patients,demonstrating promising clinical application potential.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To delineate clinical characteristics of infantile myofibroma/myofibromatosis (IM) .Methods:A retrospective analysis was conducted on histologically confirmed IM cases from Beijing Children's Hospital, Henan Children's Hospital, and Maternity and Child Health Care of Guangxi Zhuang Autonomous Region between August 2014 and July 2021. The clinical, pathological, imaging features, and outcomes were analyzed and summarized.Results:A total of 44 IM patients were included, comprising 28 males (63.6%) and 16 females (36.4%). Their ages at onset ( M[ Q1, Q3]) were 14.8 (4.7, 42.4) months, and 26 patients (59.1%) developed IM before the age of 1 year. Seven patients (15.9%) were initially diagnosed with IM. Skin involvement occurred in 42 patients (95.5%), of whom 30 (71.4%) presented with a solitary lesion and 12 (28.6%) with multiple lesions. Skin lesions mainly manifested as painless, firm nodules or masses. The most commonly involved extracutaneous site was the skeletal system (21/44, 47.7%). Histopathological examination of all 44 IM cases revealed a biphasic architecture pattern, characterized by the coexistence of two distinct morphologies or cell types within the tumor tissues (including spindle cell areas composed of fascicularly and densely arranged myofibroblasts, and primitive mesenchymal cell areas composed of small, round undifferentiated cells. Immunohistochemical study was performed in 42 cases; 40 (95.2%) were positive for smooth muscle actin, and 20 (47.6%) were positive for CD34. Genetic testing was conducted in 3 cases, and NOTCH mutations were identified in 2. Among the 44 patients, 30 patients (68.2%) underwent surgical excision, 5 patients (11.4%) received intralesional injections of triamcinolone acetonide, 1 patient (2.3%) received chemotherapy for intestinal involvement, and 8 patients were managed expectantly. During the follow-up of 49 (36, 60) months, lesions completely resolved in 42 cases (95.5%), while 2 cases died of pulmonary infection following chemotherapy or postoperative airway compression. Conclusions:IM predominantly affected infants and young children, with the skin and skeletal system being the most commonly involved sites. Skin lesions often manifested as firm nodules or masses, and histopathological examination was crucial for definitive diagnoses. Most IM cases exhibited favorable outcomes.

BACKGROUND:Metformin is currently considered the first-line medication for the treatment of type 2 diabetes.Metformin may delay the progression of osteoarthritis,but its specific mechanism of action remains unclear.OBJECTIVE:To evaluate the therapeutic effects and the related action mechanisms of metformin on osteoarthritis in rats.METHODS:(1)Network pharmacology:Potential common targets for metformin,osteoarthritis,and ferroptosis were screened using the CTD,SwissTargetPrediction,GeneCards,and OMIM databases.After importing the targets into the STRING database,protein-protein interaction analysis was conducted to identify the key targets for metformin,osteoarthritis,and ferroptosis.(2)Molecular docking:P53 and its downstream factor SLC7A11 protein structures in PDB format were downloaded from the PDB database.The 2D structure of metformin was converted to a 3D structure,and molecular docking of metformin with the proteins was performed using Discovery Studio 2019 Client.(3)In vivo experiments:Thirty male SD rats were randomly divided into three groups(n=10).The blank group did not receive surgery.The osteoarthritis model was established using the modified Hulth method for the model and metformin groups.One day after the surgery,rats in the metformin group were gavaged with metformin 200 mg/kg per day,while the blank and model groups were gavaged with physiological saline.Treatment continued for 4 weeks.Hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the pathological morphology and structure of the knee cartilage,and Mankin scoring was performed.ELISA was used to measure the levels of tumor necrosis factor-α and interleukin-6 in the serum.The microplate method was used to measure serum ferroptosis-related indicators,including glutathione,malondialdehyde,and Fe2+.Immunofluorescence staining,western blot assay,and real-time qPCR were used to detect the protein and mRNA expression of P53,SLC7A11,glutathione peroxidase 4,proteoglycans,and matrix metalloproteinase 13 in the cartilage tissue of the rats.RESULTS AND CONCLUSION:(1)A total of 96 intersecting targets among metformin,osteoarthritis,and ferroptosis were identified.After protein-protein interaction analysis,77 potential targets were found.Further screening identified the core targets as TP53,AKT1,JUN,interleukin-6,MYC,interleukin-1β,and tumor necrosis factor-α,among others.(2)Docking analysis results showed that metformin bound strongly and stably with P53 and its downstream factor SLC7A11.(3)In the model group,the knee cartilage surface was irregular,with cartilage tissue defects and reduced chondrocyte numbers.Compared to the model group,the knee cartilage structure damage in the metformin group was significantly improved,with a smoother cartilage surface and increased chondrocyte numbers.The Mankin score in the model group was significantly higher than that in the blank group,while the Mankin score in the intervention group was significantly lower than that in the model group.(4)Compared with the model group,the metformin group had significantly lower levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and Fe2+,and significantly higher glutathione levels.(5)Compared to the model group,the metformin group had significantly increased protein and mRNA expression of SLC7A11,glutathione peroxidase 4,and proteoglycans,and significantly decreased protein and mRNA expression of P53 and matrix metalloproteinase 13 in their cartilage tissue.(6)The results indicate that metformin can effectively improve cartilage damage in osteoarthritis rats and alleviate chondrocyte ferroptosis by inhibiting the aberrantly activated P53/SLC7A11/glutathione peroxidase 4 signaling pathway.This improvement in chondrocyte iron metabolism and lipid peroxidation response further reduces cartilage matrix degradation and prevents further cartilage damage and inflammatory response.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Background Personal protection is crucial for reducing the risk of zoonotic pathogen infection among livestock workers. Investigating the current status of its implementation and associated influencing factors can provide empirical evidence for developing more effective intervention measures. Objective To investigate the current status of personal protection implementation among livestock workers in Xinjiang, China and its influencing factors, providing a reference for formulating targeted intervention measures. Methods This study was conducted in Bayingolin Mongol Autonomous Prefecture, Kashgar region, and the First and Eighth Divisions of Xinjiang Production and Construction Corps. We selected large-scale cattle and sheep farms, cooperatives, individual livestock households, livestock trading markets, slaughterhouses, and retail markets. Using cluster sampling, we recruited all livestock workers (1074 participants) at sampled sites. During the period from April to July 2024, we conducted face-to-face surveys with a self-designed questionnaire among livestock workers, collecting general demographic information, occupational exposure history, and information related to the use of personal protective equipment, resulting in 939 valid questionnaires. EpiData 3.1 was used for data entry and SPSS 26.0 for statistical analysis. We employed logistic regression to compare the implementation of personal protection among workers by selected categories. Results Among the study subjects, there were 300 workers from large-scale farms (31.95%) and 583 self-employed livestock farmers (62.09%). The sample included 600 males (63.90%) and 339 females (36.10%). The majority of the study subjects was farmers, breeders, or aged 18-60 years (87.75%), auxiliary workers (87.97%) and had an education level of junior high school or below (81.36%). The proportion of workers who consistently and correctly implemented all five personal protective measures (washing hands after work, wearing gloves, wearing masks, wearing dedicated work clothes, and using rubber boots) was 35.14% (330/939). The implementation rates for these five protective measures were 93.61% (879/939), 58.68% (551/939), 57.93% (544/939), 46.01% (432/939), and 42.81% (402/939), respectively. There were statistically significant differences in the implementation rates of differen personal protective measures among the workers by occupation and education level (P<0.05). Among them, workers with lower education levels had lower implementation rates for various protective measures. The results of logistic regression indicated that, compared to male workers, female workers (OR=2.26, 95%CI: 1.68, 3.04) showed a higher rate of non-standard implementation of personal protection. Using the age group of 18 to less than 36 years as a reference, those aged 36 to less than 60 years (OR=1.82, 95%CI: 1.33, 2.50) and 60 years or older (OR=4.45, 95%CI: 2.56, 7.73) reported higher rates of non-standard implementation of personal protection. Compared to those with an education level of primary school or below, those with a junior high school education (OR=0.64, 95%CI: 0.47, 0.88) and a high school education or above (OR=0.13, 95%CI: 0.19, 0.29) showed lower rates of non-standard implementation of personal protection. Compared to farmers, veterinarians (OR=0.03, 95%CI: 0.02, 0.07) reported the lowest rate of non-standard implementation of personal protection, followed by auxiliary workers (OR=0.08, 95%CI: 0.05, 0.12), breeders (OR=0.10, 95%CI: 0.07, 0.15), and other occupational groups (OR=0.28, 95%CI: 0.15, 0.52). Using large-scale farms as a reference, self-employed farmers (OR=13.5, 95%CI: 9.65, 18.88) reported a higher rate of non-standard implementation of personal protection, followed by workers from other workplaces (OR=3.63, 95%CI: 2.01, 6.54). Conclusion The implementation of personal protective measures among livestock workers in Xinjiang is generally satisfactory. However, significant disparities in the execution of these measures exist among different types of workers, indicating the need to enhance occupational health promotion to reduce the risk of zoonotic pathogen infection among the workers.