ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation

Objective:To evaluate the clinical efficacy of the modified medial gastrocnemius myocutaneous flap (MGMF) with extended anterior, posterior and (or) inferior boundaries.Methods:From January 2002 to September 2022, modified MGMFs were applied onto 33 patients who received reconstructive surgery for soft-tissue defects around knee or in calf, in the Department of Orthopaedics, the Second Xiangya Hospital of Central South University. The size of defects ranged from 10 cm×4 cm to 22 cm×12 cm, and the flap size ranged from 15 cm×6 cm to 28 cm×14 cm. Twenty-five patients had the complication of chronic osteomyelitis. The boundaries of a modified MGMF were as follows: the anterior boundary was the anterior border of the tibia, where the posterior boundary at 3.0 cm lateral to the posterior midline, the proximal boundary at the popliteal fossa crease, and the distal boundary at the plane 2.0 cm above the tip of medial malleolus. The anterior edge of the modified MGMF was designed running along the medial edge of the defect and its curved extension line. Pretibial skin was equally divided into 9 zones, with the 1st to 9th zones from proximal to distal in sequence. Postoperative routine anti-infection treatment was offered. All patients were included in the postoperative follow-up through outpatient visits, telephone or WeChat interviews. Flap viability and wound healing in both donor and recipient sites were evaluated. Function of the affected limb was assessed using the evaluation criteria established by Punor et al.Results:All patients were included in the follow-up for 1 to 169 (median duration: 9)months. The 33 modified MGMFs included MGMFs with extended boundary of anterior ( n=18), inferior ( n=5), anterior combined with inferior ( n=6), posterior combined with anterior ( n=2), and posterior combined with inferior ( n=2) boundaries. Twenty-nine (87.9%) flaps survived completely. Partial necrosis occurred in 4 flaps(12.1%)(2 flaps with extended anterior boundary and 2 flaps with extended inferior boundary). The anterior margins of 26 flaps (78.7%) with extended anterior boundary alone or in combination with extended inferior or posterior boundary exceeded the medial edge of the tibia by 1.0-4.5 (mean, 2.1) cm, and 3 of them reached the anterior edge of tibia. Fourteen (42.4%) modified MGMFs were used to reconstruct the defects involving 1/3 of distal calf, and the distal ends of these defects were located in the 7th ( n=8) or 8th ( n= 6) zone. All the skin grafts in the donor sites survived. During follow-up, 31 patients (93.9%) showed no sign of infection, and 2 patients (6.1%) who had recurrence of chronic osteomyelitis. Functions of the affected limbs were excellent ( n=25), good ( n=6) and fair ( n=2) by Punor et al. Conclusion:Modified MGMF with extended anterior, posterior and (or) inferior boundaries is clinically feasible. It offers advantages of easier design and operation. It can be used to reconstruct a more distal, wider and larger defect as well as broadens the application of the MGMF.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.