[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

Abstract Recently, the Ministry of Education issued Guiding Opinions on Comprehensively Promoting the Construction of Healthy Schools hereinafter referred to as the Guiding Opinions, which systematically established the goal system, key tasks, critical measures, and safeguard mechanisms for the construction of healthy schools in the new era. Against the backdrop, comprehensively promoting the construction of healthy schools has become a core project for implementing the concept of "Health First", carrying out joint prevention and control of multiple diseases, and responding to national action plans. Based on a systematic analysis of the internal logic between healthy school construction and the "education powerhouse strategy", the study deeply expounds on its core mission as a "foundational project for talent cultivation" and a "hub for the integration of five educations". Combining the eight key tasks and three critical measures clarified in the Guiding Opinions, it constructs a multi dimensional, systematic, and operable implementation path from the aspects of concept leadership and practice internalization, data monitoring and closed loop management, team support and environmental optimization, literacy promotion and evaluation innovation, innovation drive and characteristic development,digital empowerment and smart governance. The study provides a forward looking and strategic comprehensive solution for improving the collective health literacy of students and building a comprehensive prevention and control system for common campus diseases in the new era.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To sort,summarize,and introduce key terms related to guideline reporting,evaluation,dissemination,implementation,and updating.Methods We systematically searched guideline de-velopment manuals and methodological literature from database inception to October 25,2024.Terms related to guideline reporting,updating,evaluation,and implementation were extracted,standardized,and finalized through a structured consensus process.Results A total of 13 guideline manuals and 32 methodological articles were included,yielding 14 core terms with standardized definitions.Conclusions This article introduces key terms such as reporting standards,external review,and research gaps across guideline development phases to promote concept application and deepen readers'understanding of guideline development.

Objective To analyze the development and implementation of nutritional drug treatment pathways abroad,and to provide insights for the establishment of similar pathways in China.Methods A search was conducted in international literature and guideline databases for studies on nutritional therapy pathways up until December 1st,2024.The search focused on aspects such as pathway development methods,the composition of development teams,and implementation outcomes.Results A total of 29 relevant articles were identified,including 12 clinical practice guidelines and 17 research papers.The guidelines were all issued by the European Society for Clinical Nutrition and Metabolism,while the research papers showed significant heterogeneity,spanning multiple countries,regions,and medical conditions,primarily from developed countries in Europe and North America.The analysis reveals that nutritional therapy pathways typically include components such as nutritional assessment,formulation of nutritional plans,integration with other drug therapies,development of follow-up plans,pathway implementation teams,and the reassessment and updating of pathways.Conclusions China can benefit from the practices of developed countries,particularly those in Europe and North America.Key recommendations include the establishment of multidisciplinary teams,the promotion of a tiered treatment model,and the involvement of medical associations in forming expert groups to develop and implement nutritional drug treatment pathways,thereby enhancing the quality of nutritional treatment in China.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.