Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

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.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

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 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.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)applied to the supplementary motor area(SMA)or primary motor cortex(M1)on upper limb function in stroke patients in terms of motor sequence learning.Methods From April,2024 to February,2025,60 inpatients were recruited from the First Affiliated Hospital with Nan-jing Medical University.They were randomly assigned into the control group,SMA group and M1 group,with 20 patients in each group.All the groups received medication and conventional rehabilitation.On this basis,SMA group underwent HF-rTMS on the affected side's SMA,while M1 group received HF-rTMS on the affected side's M1 for two weeks.All the groups were measured with motor evoked potentials(MEP),the serial reaction time(RT)task,Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after intervention.Results The SMA and M1 groups dropped one case respectively.MEP elicitation rate of the affected side's increased in SMA and M1 groups(P<0.05),and it was better than that in the control group(χ2>4.792,P<0.05).The intra-group effects of RTsequential sequence,FMA-UE and MBI scores were significant(|F|>81.546,P<0.05).The inter-group effects of RTrandom sequence,RTsequential sequence,?RT,and MBI scores were significant(F>3.228,P<0.05).The in-teractive effects of RTrandom sequence,RTsequential sequence,?RT,FMA-UE and MBI scores were significant(|F|>3.520,P>0.05).After intervention,RTsequential sequence,?RT,FMA-UE and MBI scores improved(P<0.05).RTrandom sequence was lower in SMA group than in the control group(P<0.017),RTsequential sequence,?RT,FMA-UE and MBI scores im-proved more in SMA and M1 groups than in the control group(P<0.05),but no significant difference was found between the SMA group and the M1 group(P>0.05).Conclusion HF-rTMS applied to the affected SMA or M1 can activate motor sequence learning and promote the recov-ery of upper limb function in stroke patients.