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 generate heterozygous TRAF2 knockout mice, the CRISPR/Cas9 technology was successfully employed. These mice were served as a valuable model to explore the pathological mechanisms underlying inflammatory and immune disorders mediated by abnormal TNF-α-TRAF2 signaling and to develop new therapeutic targets. Methods : A vector targeting the knockout of the TRAF2 gene was constructed. Lead RNA and Cas9 Mrna were introduced into the fertilized eggs of C57BL/6JGpt mice through microinjection to mediate the TRAF2 gene mutation in mice. The mouse tail protein was extracted and the genotype of the F0 generation was determined by PCR and Western blot. TRAF2+/- mice were successfully obtained. F0 generation mice were backcrossed with C57BL/6JGpt wild-type mice to obtain stable TRAF2+/- mice for propagation and subsequent experiments. The body weight of TRAF2+/- mice was detected; Western blot was used to detect the expression of TRAF2 in the spleen, liver and kidney tissues of TRAF2+/- mice. The development of spleen, liver and kidney tissues in TRAF2+/- mice was detected by HE staining. Results : PCR identification using specific primers demonstrated that TRAF2+/- mice exhibited a target band at 679 bp. Western blot analysis results indicated that, compared with the WT group, the expression of TRAF2 in the tail protein of TRAF2+/- mice was significantly reduced(P+/- mice had a lower body weight compared to their littermate WT mice(P+/- mice was decreased(P+/- mice and WT mice. Conclusion The successful construction of TRAF2+/- mice has provided an important animal model for exploring the role of TRAF2 in developmental regulation, revealing the mechanism of inflammatory immune diseases mediated by abnormal TNF-α-TRAF2 signaling, and screening related drug targets.

Objective To investigate knowledge,attitude and practice towards the fertility preservation of female cancer patients among clinical nurses in a cancer hospital,and to analyze influencing factors,so as to provide references for clinical implementation of related nursing services.Methods A self-designed questionnaire was delivered to 336 nurses working at a tertiary oncology hospital in Tianjin.Univariate analysis and multiple linear regression were used to analyze the factors influencing the knowledge,attitude,and practice level of female fertility preservation among nurses in a cancer hospital.Results In October 2022,a total of 291 nurses completed the questionnaires.The score of the knowledge,attitude and practice were(46.13±8.66),31.00(29.00,33.00),12.00(8.00,14.00),respectively,and the total score was(88.08±12.78).Multiple logistic regression analysis showed that education level,position,department types and whether or not getting the knowledge about fertility preservation of female cancer patients were the influencing factors for the total scores of knowledge,attitude and practice(P＜0.05).Conclusion Nurses who work at the cancer hospital have a positive attitude towards fertility preservation for female cancer patients,while their knowledge and practice level need be improved.Nursing administrators should attach importance to improving the knowledge level and practical ability of nurses in cancer hospitals to protect the fertility of female cancer patients,so as to promote the development of onco-fertility nursing in the future.

The 18th National Postgraduate Symposium on Environmental and Occupational Medicine, co-sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and the School of Public Health of Sun Yat-sen University, was successfully held on August 22 to 25, 2024 in Guangzhou, Guangdong Province, China. Adhering to the theme of “Research and practice: Healing the schism”, the symposium aims to enliven academic thinking, expand research horizons, encourage innovation, enhance inter-university exchanges, and strengthen talent cultivation, especially to promote the close integration of academic research and public health practice. A total of 105 papers were received from 38 universities. The symposium also gathered about 160 participants, mainly authors postgraduates from universities and experts and professors in the field of environmental and occupational medicine. All the participants discussed the latest research advances and future development trends of environmental and occupational medicine, and endeavor to apply the research results in public health practice.

Objective To understand the experience of oncology nurses participating in fertility preservation services,and to provide a reference for oncology nurses to formulate targeted training courses and management measure.Methods From September to November 2023,phenomenological research methods were used to select 14 oncology nurses in a tertiary A cancer hospital in Tianjin for semi-structured interviews.Colaizzi 7-step analysis method was used to analyze the interview data and summarize the themes.Results 3 themes and 10 sub-themes were extracted:①The driving forces for participating in fertility preservation services(long-term benefits of fertility preservation,individual conditions of cancer patients,self-conscious cognition of role responsibilities,and internal drivers of empathy);②Oncology nurses are hampered by the lack of professional quality(knowledge system has not been built,ideological deviation needs to be corrected,communication skills need to be strengthened);③ The practical difficulties of oncology nurses participating in fertility preservation services(lack of targeted education and training,lack of multidisciplinary team contact channels,and lack of normative institutional guarantee).Conclusion Oncology nurses play an indispensable role in fertility preservation services.Hospitals need to pay attention to the unique role of oncology nurses and develop targeted training courses to improve their professional quality,so as to promote the implementation of fertility preservation services in China.

Objectives To develop a multi-stage and multi-epitope vaccine, which consists of epitopes from the early secretory and latency-associated antigens of Mycobacterium tuberculosis (MTB). Methods The B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes of 12 proteins were predicted using an immunoinformatics. The epitopes with antigenicity, without cytotoxicity and sensitization, were further screened to construct the multi-epitope vaccine. Furthermore, the proposed vaccine underwent physicochemical properties analysis and secondary structure prediction as well as 3D structure modeling, refinement and validation. Then the refined model was docked with TLR4. Finally, an immune simulation of the vaccine was carried out. Results The proposed vaccine, which consists of 12 B-cell, 11 CTL and 12 HTL epitopes, had a flexible and stable globular conformation as well as a thermostable and hydrophilic structure. A stable interaction of the vaccine with TLR4 was confirmed by molecular docking. The efficiency of the candidate vaccine to trigger effective cellular and humoral immune responses was assessed by immune simulation. Conclusion A multi-stage multi-epitope MTB vaccine construction strategy based on immunoinformatics is proposed, which is expected to prevent both active and latent MTB infection.
Mycobacterium tuberculosis/metabolism* ; Molecular Docking Simulation ; Toll-Like Receptor 4 ; Epitopes, T-Lymphocyte/chemistry* ; Epitopes, B-Lymphocyte/chemistry* ; Vaccines, Subunit/chemistry* ; Computational Biology/methods*

Objective:To investigate the predictive value of serum C-type lectin-like receptor 2 (CLEC-2) combined with insulin resistance in the outcome of patients with acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with AIS received alteplase intravenous thrombolytic therapy in the Department of Neurology, the Second Affiliated Hospital of Nantong University from October 2019 to March 2021 were enrolled retrospectively. According to the modified Rankin Scale score at 90 d after onset, they were divided into good outcome group (0-2) and poor outcome group (>2). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Person correlation analysis was used to determine the correlation between CLEC-2 and HOMA-IR. Multivariate logistic regression analysis was used to determine the correlation between serum CELC-2, HOMA-IR and the outcome after intravenous thrombolysis. Receiver operating characteristic (ROC) curve was used to determine the predictive value of serum CLEC-2 combined with HOMA-IR for poor outcome after intravenous thrombolysis. Results:A total of 100 patients were enrolled (56 males, 56.0%; aged 70.6±10.86 years, range 49-83 years). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 10.00±6.36. Senenty-four patients (74.0%) had a good outcome and 26 (26.0%) had a poor outcome. Person correlation analysis showed that there was a significant positive correlation between serum CLEC-2 and HOMA-IR ( r=0.523; P<0.001). Multivariate logistic regression analysis showed that after adjusting for confounding factors (C-reactive protein, baseline NIHSS score, onset-to-needle time), the highest quartile of serum CLEC-2 (compared with the lowest quartile: odds ratio [ OR] 4.836, 95% confidence interval [ CI] 1.105-21.169; P=0.036) and the highest quartile of HOMA-IR (compared with the quartile 1-3: OR 15, 95% CI 2.647-30.722; P=0.002) were the independent risk factors for the poor outcome in patients with AIS after intravenous thrombolysis. ROC curve analysis showed that the area under the curve for serum CLEC-2 combined with HOMA-IR to predict poor outcome was 0.785 (95% CI 0.688-0.883; P<0.001), the optimal cut-off value was 0.72, and the sensitivity and specificity were 76.0% and 95.0%, respectively. Conclusion:CLEC-2 combined with insulin resistance has a certain predictive value for the poor outcome of patients with AIS after intravenous thrombolysis.

OBJECTIVE：To e xplore the health economic burden of hypertension patients at county-level areas and its influential factors in China. METHODS ：A questionnaire survey was conducted on hypertension patients in 7 county-level public hospitals from 6 provinces as Hebei ，Shandong，Shanxi provinces by using a convenient sampling method. Catastrophic health expenditure was defined by the standard of “medical and health expenditure exceeding 10％ of household income ”. The incidence ， average gap and relative gap of catastrophic health expenditure were analyzed. A multi-factor Logistic regression model analysis was used to analyze the influential factors that lead to catastrophi c health expenditure. RESULTS ：A total of 1 378 questionnaires were sent out ，and 925 valid questionnaires were collected with effective rate of 67.13％ . The incidence of catastrophic health expenditure，average gap and relative gap among hypertension patients were 23.03％，19.37％ and 84.12％，respectively. At different income levels ，the incidence of catastrophic health expenditure，average gap and relative gap were 72.67％ ， 96.79％ and 133.18％ in the poorest household group ，and were 1.94％ ，0.47％ and 24.23％ in the richest household group. Among different types of medical insurance ，the incidence of catastrophic health expenditure in patients covered by “New Rural Cooperative Medical Scheme （NRCMS）”the highest （31.30％）. The household income ，complications and the type of health insurance had significant impacts on the incidence of catastrophic health expenditure in hypertension patients （P＜0.05）. CONCLUSIONS：The incidence of catastrophic health expenditure in hypertension patients with different income levels is different. As the income level raised ，the incidence of catastrophic health expenditures continued to decrease. But the protection of household health expenditure by NRCMS is weak. It is suggested that a certain policy preference should be given to families with low income and patients with chronic diseases ，so as to ensure the rights and interests of patients with hypertension .

Objective: To compare the treatment effect and adverse reaction of oxaliplatin and tiggio and paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer. Methods: From January 2015 to April 2018, 60 patients with advanced gastric cancer were selected from Department of Oncology of the First Affiliated Hospital of Anhui Medical University.The patients were randomly divided into two groups according to the principle of simple randomization, with 30 cases in each group.The control group was treated with oxaliplatin + tiggio.The observation group was given paclitaxel (or docetaxel) combined with oxaliplatin (or cisplatin) and fluorouracil.The incidence of adverse reactions(hematotoxicity and non-hematologic toxicity), the efficacy(CR, PR, SD, PD) of the two groups were compared. Results: The RR level of the observation group was 66.7%, which was significantly higher than 40.0% of the control group (χ²=4.286, P<0.05). There were no statistically significant differences between the two groups in incidence of adverse reactions such as thrombocytopenia, impaired liver function, anemia, oral mucositis, nausea and vomiting and neurotoxicity(all P>0.05). Conclusion Treatment of advanced gastric cancer with FLOT or DCF can improve efficacy without increasing side effects.

Objective To investigate thermal degradation kinetic characteristics of Cefmenoxime Hydrochloride in infusion solutions, and predict its thermal stability. Methods The HPLC was applied to determine the contents of Cefmenoxime Hydrochloride. Classical isothermal kinetic method and multivariate linear model were used to predict the expiration date of the injection. Results It was found that the thermal degradation kinetics of Cefmenoxime Hydrochloride in two infusion solutions corresponded with the first-order kinetics. The expiration dates of Cefmenoxime Hydrochloride in 0. 9%sodium chloride injection calculated by two different methods were 2. 20 days and 1. 52 days,and in 5% glucose injection were 2. 09 days and 1. 53 days,respectively. Conclusion The thermal stability of Cefmenoxime Hydrochloride in infusion solutions is poor and its expiration dates are the same calculated by two different methods.