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 elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

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.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.