BackgroundFatty acid metabolic reprogramming is critically implicated in tumorigenesis and progression. However, the role and prognostic significance of fatty acid metabolism-related genes (FMGs) in diffuse large B-cell lymphoma (DLBCL) remain largely unexplored.MethodsWe analyzed transcriptomic data from the Gene Expression Omnibus (GEO) database to identify key prognostic FMGs. Through an integrative machine learning pipeline, we developed a prognostic signature termed the FAMscore. The association of the FAMscore with tumor immunity was assessed. Furthermore, we validated the dysregulation of multiple FMGs using quantitative real-time PCR and single-cell RNA sequencing data. Among these FMGs, we further investigated the role of CPT1A in DLBCL cell proliferation and apoptosis.ResultsThe FAMscore effectively distinguished between high- and low-risk DLBCL patients and served as an independent prognostic factor. A higher FAMscore was associated with poorer overall survival (OS). A nomogram integrating the cell-of-origin (COO) subtype, the International Prognostic Index (IPI) score, and the FAMscore was developed and demonstrated reliable predictive performance. Tumors in the high-FAMscore group exhibited higher tumor purity and an immune infiltration profile conducive to an immunosuppressive microenvironment. Functional assays revealed that knockdown of CPT1A significantly inhibited DLBCL cell proliferation and induced apoptosis.ConclusionsOur study highlights fatty acid metabolism as a key prognostic indicator and immune regulator in DLBCL. These findings advance the framework for personalized treatment strategies in this malignancy.

CD4(+) T cells are indispensable for CD8(+) T cells-mediated anti-tumor immunity, while little is known about how CD4(+) T cells coordinate with other cells to promote CD8(+) T cells activity. In this study, by coupling single-cell RNA sequencing (scRNA-seq) with multiplex immunohistochemistry staining (mIHC), CXCL13-expressing CD4(+) T cells were explored to recruit CXCR5(+) B cells to form CXCL13(+)CD4(+) T cells:: CXCR5(+) B cells:: CD8(+) T cells triad, promoting the anti-tumor immunity and heralding a favorable prognosis. A CXCL13-expressing subset of CD4(+) T cells was identified to be associated with better prognosis and tumor-reactive hallmarks. The further cell types interaction analysis revealed a specific interaction between CXCL13(+)CD4(+) T cells and CXCR5(+) B cells in comparison with other cell types. The mIHC verified that an elevated level of CXCR5(+) B cells infiltration in the proximity of CXCL13(+)CD4(+) T cells. The subsequent Entropy analysis, which characterizes the colocalization among more than two cell types, was employed to reveal the spatial distribution pattern. The results revealed that CXCL13(+)CD4(+) T cells and CXCR5(+) B cells co-localized with cytotoxic CD8(+) T cells, forming a functional lymphocyte triad, whose existence heralded a better prognosis. Collectively, by integrating scRNA-seq with mIHC, we demonstrated that the recruitment of CXCR5(+) B cells by neoantigen reacting to CXCL13(+)CD4(+) T cells through CXCL13-CXCR5 signaling contributed to the lymphocyte triad, leading to an enhanced anti-tumor immunity and heralding a favorable prognosis in non-small-cell lung cancer (NSCLC).

Purpose:Previous small-sample study suggested that fecal calprotectin (FC) combined with blood inflammatory biomarkers may aid in Crohn's disease (CD) diagnosis. This study aimed to validate the FC's diagnostic and mucosal healing assessment value of FC and a noninvasive composite index in pediatric CD. Patients and Methods:Patients aged 2-17 years who underwent ileocolonoscopy for suspected or established CD were enrolled. Based on endoscopy, participants were classified into three groups: controls (functional gastrointestinal disorders), MH (mucosal healing, SES-CD <3, indicating minimal or absent visible inflammation), and ML (mucosal lesions, SES-CD ≥3). Fecal and blood samples were collected before endoscopy. Group differences were assessed using Kruskal-Wallis/Dunn's tests; correlations were evaluated via Spearman coefficients; ROC analysis was used to assess diagnostic performance. A composite index was constructed by weighting CRP, ESR, and IL-6 based on their correlations with FC. Results:Among 123 participants, FC levels significantly differed across groups (P < 0.001), highest in patients with mucosal lesions. For distinguishing CD from controls, FC showed limited accuracy (AUC = 0.651), while the composite index improved performance (AUC = 0.754). In established CD, FC alone showed strong ability to differentiate mucosal healing from active disease (AUC = 0.888), with a slight improvement using the composite index (AUC = 0.921). Conclusion:The composite index integrating FC with inflammatory markers improves diagnostic performance over FC alone for distinguishing CD from controls and slightly enhances mucosal healing assessment, supporting its potential utility as a practical noninvasive tool for clinical monitoring in pediatric CD.

Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.

This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8

Background: Iron metabolism related genes participate in cell proliferation, cell growth, and redox cycling in multiple cancers. Limited studies have revealed the roles and clinical significance of iron metabolism in the pathogenesis and prognosis of lung cancer. Methods: A total of 119 iron metabolism related genes were extracted from MSigDB database and their prognostic values were determined in The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) dataset and the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. Immunohistochemistry technique and correlations with immune cell infiltration, gene mutation and drug resistance were used to identify the potential and underlying mechanisms of STEAP1 and STEAP2 as prognostic biomarkers of LUAD.Results: The expression of STEAP1 and STEAP2 are negatively associated with the prognosis of LUAD patients both at the mRNA and protein level. The expression of STEAP1 and STEAP2 was not only negatively correlated with the trafficking degree of CD4+ T immune cells and positively related to most immune cells' trafficking degree, but also significantly associated with gene mutation status, particularly with mutations on TP53 and STK11. Four types of drug resistance showed significant correlation with the expression level of STEAP1 while 13 types of drug resistance were associated with the expression level of STEAP2.Conclusion: Multiple iron metabolism related genes including STEAP1 and STEAP2 are significantly associated with the prognosis of LUAD patients. STEAP1 and STEAP2 might affect the prognosis of LUAD patients partially through immune cell infiltration, gene mutation and drug resistance, which indicated they were independent prognostic factors for LUAD patients.

Backgrounds The widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection. Objective This study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time. Methods We summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022. Results In this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients. Conclusion This is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.

Nuclear Factor Erythroid 2 -Related Factor 2 (NRF2) is important for the expression of genes associated with oxidative stress. The levels of NRF2 are controlled by Kelch-like ECHassociated protein 1 (KEAP1)-dependent degradation. Although oxidative stress is known to suppress KEAP1 activity to stabilize the levels of NRF2, the mechanism for this control is unclear. Here, we identify that KEAP1 is modified by SUMO1 at the lysine residue position 39 (K39). Arginine replacement of this lysine (K39R) in KEAP1 did not affect its stability, subcellular localization, or dimerization but promoted the formation of the Cullin 3 ubiquitin ligase and increased NRF2 ubiquitination. This was accompanied by decreased NRF2 expression. Gene reporter assays showed that the transcription of antioxidant response elements was heightened in KEAP1-WT cells compared to cells expressing the KEAP1-K39R SUMO1 substrate mutant. Consistent with this, chromatin immunoprecipitation assays revealed higher NRF2 binding to the promoter regions of antioxidant genes in cells expressing the KEAP1-WT compared to the KEAP1-K39R mutant protein in H1299 lung cancer cell. The significance of this suppression of KEAP1 activity by its SUMOylation was tested in a subcutaneous tumor model of H1299 lung cancer cell lines that differentially expressed the WT and K39R KEAP1 constructs. This model showed that mutating the SUMOylation site on KEAP1 altered the production of reactive oxygen species and suppressed tumor growth. Taken together, our study recognizes that NRF2dependent redox control is regulated by the SUMOylation of KEAP1. These findings identify a potential new therapeutic option to counteract oxidative stress.

ObjectivesBy the end of 2022, China had made a pivotal decision to optimize the COVID-19 policy. The dominant Omicron variant in China at that time was highly transmissible. In this study, we aimed to evaluate the real-world safety and efficacy of tixagevimab and cilgavimab against this background in China.MethodsParticipants were enrolled if they were over 12 years old and were planning to receive tixagevimab or cilgavimab. All participants received intramuscular administration of tixagevimab (150 mg) and cilgavimab (150 mg). Data were collected on demographics, underlying illness, prior infection, vaccination, adverse events, and COVID-19 outcomes (e.g., infection rate, hospitalization rate, and severe disease).ResultsDuring the study period, 168 (37.9%) of 443 who received tixagevimab/cilgavimab were diagnosed with SARS-CoV-2 infection. All infected patients had mild COVID-19. Two patients (0.5%) were hospitalized for COVID-19, but none of them were admitted to the ICU. None of the patients died during this study. 4 (0.9%) reported mild local adverse events, and no severe systemic adverse reactions were reported.ConclusionTixagevimab/cilgavimab may have protected high-risk populations against infection with the Omicron variant, hospitalization and severe disease during the China COVID-19 pandemic.

Purpose:Vitamin D, an essential nutrient and a pleiotropic steroid hormone, has been reported to be associated with the risk and severity in patients infected with Coronavirus Disease-2019 (COVID-19). The role of vitamin D in predicting clinical outcome for COVID-19 patients is unknown. Here, we aimed to determine the prognostic value of plasma 25(OH)D level in COVID-19 patients.Patients and Methods:A total of 158 patients infected with novel COVID-19 Omicron variants in Shanghai were recruited in this study and were categorized into three groups by the tertile levels of plasma 25(OH)D. Plasma 25(OH)D level was determined along with routine blood tests related to liver and renal functions in newly diagnosed COVID-19 patients at admission. The nucleic acid negative conversion time of throat swab samples was evaluated as the primary clinical outcome. The prognostic value of clinical characteristics and plasma 25(OH)D level was assessed using the Kaplan-Meier plot and Cox proportional hazards regression tests.Results:Higher level of plasma 25(OH)D level in COVID-19 patients was independently associated with shorter nucleic acid negative conversion time from COVID-19 infection (multivariate adjusted HR: 0.54, 95%CI: 0.35-0.82, P=0.004, tertile 2 vs 1; multivariate adjusted HR: 0.60, 95%CI: 0.39-0.90, P=0.014, tertile 3 vs 1).Conclusion:Plasma 25(OH)D level may serve as an independent prognostic factor in COVID-19 patient. Our findings indicate the protective roles of vitamin D supplementation in the regiment of patients with COVID-19.

本论文通过分析临床急需进口药品当前在上海交通大学医学院附属瑞金医院海南医院申请及审批环节的现状,探讨临床急需进口药品资料在申请审批环节中存在的问题.研究发现,在临床急需进口药品的首次申请中,审批无驳回的申请耗费时间会大大缩短.通过分析临床急需进口药品申请资料,发现其中主要问题为基本资料信息缺失、不全,信息不一致等,建议加强业务培训,提高申请资料质量,加强沟通,提高审批效率,从而达到缩短药品审批环节的消耗时长,加快国际创新临床药品落地乐城先行区.

社会捐赠体系是国家应急物资保障的重要组成部分.物资捐赠作为疫情防控期间物资保障的一种重要形式和补充,其响应速度对解决疫情特殊时期医疗物资匮乏问题起到了至关重要的作用.该文通过在国家会展中心(上海)方舱医院物资捐赠管理工作实践中反复总结、积累实践,以分配公平性、效用优化性、信息透明性为目标,制定了大型方舱医院物资捐赠制度,创建了相关流程,形成了大型方舱医院物资捐赠管理体系,在确保国家会展中心(上海)方舱医院正常运行中发挥了重大作用.

探索在新型冠状病毒（新冠）感染疫情防控中的大型方舱医院药品保障管理模式。根据方舱医院规模及收治新冠感染者特征，成立应急药品管理团队，搭建药品管理组织架构、建立规章制度；根据方舱医院的运行特点，制定和调整药品目录，规范申领、调拨流程，并加强特殊药品的管理；依据感染者的需求，开展多元化药学服务，指导患者用药。本团队建立了针对大型方舱医院运行的特色药品保障体系，分为中心药库及二级药库进行药品保障管理，在做到保障基本医疗药品供应的同时，提供药学服务以确保患者的用药安全。本团队建立的方舱药品保障管理模式，可为应对突发公共卫生事件时药品保障及完善服务患者提供参考。

社会捐赠是指自然人、法人或其他社会团体出于爱心,自愿无偿地向公益性社会团体、公益性非营利单位、某个群体或个人进行捐赠财产的救助活动.针对方舱医院的社会捐赠不是一般意义上的慈善捐助行为,而是捐赠者自愿、主动支持方舱医院救治工作(包括方舱医院建设、感染者救治、医护生活改善)的意识体现.本文分析社会捐赠对国家会展中心(上海)方舱医院物资保障的作用及成因,提出推进社会捐赠事业发展的建议,以期为弘扬抗疫精神、慈善精神,凝聚慈善共识提供借鉴.

Hospital culture plays an important role in the orderly operation of large shelter hospitals as well as epidemic prevention and control.From April to May 2022, the shelter hospital of the National Convention and Exhibition Center(Shanghai) had created the large shelter hospital culture co-built by doctors and patients with a greater sense of belonging by taking measures such as joint party building between doctors and patients, giving play to the vanguard force of party members, carrying out various forms of cultural, sports and science popularization activities, encouraging enthusiastic patients to participate in activity planning, focusing on key groups, formulating shelter " residents convention", and so on. These measures ultimately formed cultural adaptation, cultural synchronization and cultural shaping, which were conducive to enhancing the empathy of doctors and patients, improving the effectiveness of medical implementation, and promoting the standardization of shelter management system. This harmonious, warm and autonomous culture co-built by doctors and patients effectively ensures the safe and orderly operation of the shelter hospital, and provides reference for the construction of the cultural system of large shelter hospitals in China.

目的 探讨医疗装置配置在超大型方舱医院运行保障中的作用。方法 从医疗装置基本情况、面临挑战、建议对策等方面，总结瑞金医院方舱医院管理团队在国展中心(上海)方舱医院医疗装置配备工作中的经验，为超大型方舱医院的运行保障提供借鉴。结果 自2022年3月以来，上海紧急启动建设市区两级方舱医院，用于收治轻症及无症状感染者，以快速阻断疫情传播。国展中心(上海)方舱医院瑞金医院方舱医院规模最大，总床位近5万张，收治患者174 308例。瑞金医院方舱医院管理团队全程参与了该方舱医院的开仓和运行，并为方舱医院正常运行提供医疗装置保障。结论 瑞金医院方舱医院管理团队保障了国展中心(上海)方舱医院医疗装置配置，为其正常运行提供条件，但战时状态下快速部署、灵活机动地装备方舱医院应对重大突发公共卫生事件仍需探索。

大型方舱医院作为一个突发公共事件或灾害救援中的特殊医疗空间,受到社会广泛关注.探索方舱医院文化体系建设,通过党建文化、精神文化、制度文化、行为文化和社群文化建设,形成文化合力,营造和谐医院氛围,提升医疗执行效能,为方舱医院管理目标的实现,提供文化保障.