Objective: To investigate the current status and related factors of human papillomavirus (HPV) vaccination intention among male college students in Shanghai, so as to provide references for promoting HPV vaccination among males. Methods: From January to February 2025, a stratified random cluster sampling method was used to select 548 male college students in 10 universities from Shanghai for a self questionnaire survey. The survey included socio demographic characteristics, vaccine hesitancy, vaccine beliefs (complacency, confidence, convenience), HPV knowledge level, health status, social support, and information acquisition channels. Latent class analysis (LCA) was used to identify latent classes of vaccine beliefs, and multinomial Logistic regression was used to analyze the related factors of vaccination intentions. Results: The acceptance, hesitancy, and refusal rates of HPV vaccine among college students in Shanghai were 39.4% ( n =216), 35.2% ( n =193), and 25.4% ( n =139), respectively. LCA identified four vaccine belief groups: low complacency high confidence (21.4%), high complacency high confidence (36.1%), low complacency low confidence (18.8%), and high complacency low confidence (23.7%). Multinomial Logistic regression showed that vaccine belief category was an important factor affecting vaccination intentions among college students in Shanghai. Compared with the low complacency high confidence group, high complacency low confidence group had the highest risk of vaccine refusal ( OR =24.80， P <0.05). Medical majors ( OR =0.13), participation in basic medical insurance ( OR =0.37), and recommendations from relatives, friends ( OR =0.39) or healthcare professionals ( OR =0.33) reduced the risk of vaccine refusal among male college students in Shanghai (all P <0.05). The Internet (70.6%) was the main source of HPV related information for male college students, and recommendations from healthcare professionals were associated with more positive vaccination intentions. Conclusions HPV vaccine hesitancy and refusal are common among male college students in Shanghai, with significant heterogeneity in vaccine belief structures. Targeted health education based on belief categories should be conducted to improve the vaccination intentions of male college students.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective:To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed.Results:The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2.Conclusion:UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.

Objective:To analyze the experiences of implementing coverage with evidence development for cell and gene therapy products in the UK.to provide references for the future access of cell and gene therapy products in China.Methods:By systematically combing the strategies of coverage with evidence development adopted by National Health Service(NHS)in the UK.,and summarizing the four links of assessment,payment,further evidence collection and final decision-making,the implementation experience of coverage with evidence development of cell and gene therapy products was analyzed by taking the reimbursement of four typical cell gene therapy products as an example,and suggestions were made for the access of this type of products in China.Results:Access to cell and gene therapy products in the UK.is cautious,with assessment focused on clinical utility.Management access agreement is used to control the risk of overspending during specialized fund reimbursement,while a unified data collection system has been established.Conclusion:China could learn from the experience of the UK.and promote the admission of cell gene therapy products from three aspects:exploring the evidence-based reimbursement model for universal commercial medical insurance;developing a targeted data collection framework based on actual data needs;establishing a unified data collection platform to provide the support for product access decision.

Objective: To explore the treatment plan for severe papillary defects in the aesthetic zone caused by severe periodontitis, providing a reference for clinical practice. Methods : A patient with severe periodontitis leading to severe papillary defects in the upper anterior teeth from 12 to 23 was treated using interdental tunnel technique combined with personalized connective tissue grafting for periodontal plastic surgery, and stable soft tissue augmentation was achieved. Resin restoration was conducted to modify the crown shape of the aesthetic zone teeth, reconstruct white aesthetics, guide the shaping of the gingival papillae, reduce “black triangles,” and enhance the patient’s confidence in smiling. Results : The patient’s periodontal condition and the regeneration of soft tissues in the aesthetic zone were good, and the smile aesthetics were restored. After a 3-year follow-up, the gingival morphology, color, and texture were good, and the effect was stable. The literature review indicates that for papillary defects in the aesthetic zone, analysis should be conducted based on the following aspects: whether a defect is present in periodontal hard and soft tissues, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest. Based on the analysis of aesthetic defects and surgical indications, a personalized treatment plan should be designed. Conclusion For patients with obvious papillary defects in the aesthetic zone due to the reduction of periodontal support tissues caused by severe periodontitis, factors such as periodontal hard and soft tissue defects, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest should be fully considered, and a personalized treatment plan should be formulated after multidisciplinary joint consultation.

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 evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

The US.is the first country to establish a systematic and comprehensive rare disease protection mechanism to provide protection for patients with rare diseases.Based on the perspective of the whole process,it systematically comprehends the rare disease protection mechanism and its operation from five aspects:rare disease legislation,therapy R&D and marketing support,screening and treatment,medical insurance reimbursement,patient registration and information sharing,so as to provide useful references for China to improve the protection mechanism for rare diseases.

The US.is the first country to establish a systematic and comprehensive rare disease protection mechanism to provide protection for patients with rare diseases.Based on the perspective of the whole process,it systematically comprehends the rare disease protection mechanism and its operation from five aspects:rare disease legislation,therapy R&D and marketing support,screening and treatment,medical insurance reimbursement,patient registration and information sharing,so as to provide useful references for China to improve the protection mechanism for rare diseases.

Objective:To analyze the experiences of implementing coverage with evidence development for cell and gene therapy products in the UK.to provide references for the future access of cell and gene therapy products in China.Methods:By systematically combing the strategies of coverage with evidence development adopted by National Health Service(NHS)in the UK.,and summarizing the four links of assessment,payment,further evidence collection and final decision-making,the implementation experience of coverage with evidence development of cell and gene therapy products was analyzed by taking the reimbursement of four typical cell gene therapy products as an example,and suggestions were made for the access of this type of products in China.Results:Access to cell and gene therapy products in the UK.is cautious,with assessment focused on clinical utility.Management access agreement is used to control the risk of overspending during specialized fund reimbursement,while a unified data collection system has been established.Conclusion:China could learn from the experience of the UK.and promote the admission of cell gene therapy products from three aspects:exploring the evidence-based reimbursement model for universal commercial medical insurance;developing a targeted data collection framework based on actual data needs;establishing a unified data collection platform to provide the support for product access decision.