OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

Objective:To explore the current situation of synergistic allocation of factors of production in China's medical research institutes,sort out the focuses and deficiencies of the existing policies,so as to provide references for the optimization of production factor and the new quality productivity formation in medical institutions.Methods:Based on the two-factor productivity theory,the index evaluation system is constructed,and the composite system synergy model is used to analyze the degree of order of production factors and the degree of synergy of the composite system,and explore the change of synergy degree of each sequential covariate;and the macro model of the health system is used in conjunction with the content analysis method to carry out the frequency counting of the policies to promote the enhancement of the capacity of each production factor of the main body of innovation of the medical scientific research institutes.Results:The synergistic degree of the production factors and the composite system of medical research institutions showed a non-synergistic development trend,with the worst synergistic level in 2021;number of personnel,number of institutions,building floor space,production factors and sequential coefficients were weakly synergized and in a state of non-synergistic development.Among the 43 policy texts,the internal submodular policy tools were used more,the external submodular policy tools were used less,and the use of internal and external policy tools is unbalanced.Conclusion:The number of personnel,institutions and building area of medical research institutions are constraints on the synergistic development of innovative entities.It is recommended to increase the training of innovative talents in medical research institutions,improve the construction of new institutions,coordinate the layout of large scientific devices and functional housing,introduce targeted systematic planning,improve the market of factors of production,and consolidate the technological foundation for future development.

Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95％.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01％,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30％.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98％of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P＜0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P＜0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.

Objective To analyse the characteristics of spatial distribution of bed resources and bed utilization efficiency of various types of medical and health institutions in Guangxi Province in 2018-2022,and to provide a reference basis for the allocation and management of bed resources of various types of medical and health institutions.Methods Spatial autocorrelation was used to analyse the status of bed allocation in various types of medical and health institutions,and the bed efficiency index and bed utilisation model were used to evaluate the efficiency of bed utilisation.Results Bed resources per 1 000 population vary considerably across types of healthcare organisations and regions.There is no spatial correlation in the overall distribution of bed resources per 1 000 population,but there are different types of aggregation,and there will be little change in the type of aggregation and the place of aggregation from 2018 to 2022.In terms of utilisation efficiency,the bed efficiency index of maternity and child healthcare hospitals is the highest,the bed efficiency index of specialist disease prevention and treatment hospitals(institutes and stations)is the lowest,general hospitals and maternity and child healthcare hospitals are operating at high efficiency,and all other healthcare institutions are operating at low efficiency;the utilisation of bed resources in various types of healthcare institutions exists in the form of efficiency-type,turn-around-type,bed-pressure-type,and unused-type hospitals at the same time.Conclusion There is an imbalance in the allocation of bed resources in various types of medical and health institutions,with large differences in the operational and utilisation efficiencies of beds;the allocation of bed resources should be continuously optimised.

Objective:To explore the current situation of synergistic allocation of factors of production in China's medical research institutes,sort out the focuses and deficiencies of the existing policies,so as to provide references for the optimization of production factor and the new quality productivity formation in medical institutions.Methods:Based on the two-factor productivity theory,the index evaluation system is constructed,and the composite system synergy model is used to analyze the degree of order of production factors and the degree of synergy of the composite system,and explore the change of synergy degree of each sequential covariate;and the macro model of the health system is used in conjunction with the content analysis method to carry out the frequency counting of the policies to promote the enhancement of the capacity of each production factor of the main body of innovation of the medical scientific research institutes.Results:The synergistic degree of the production factors and the composite system of medical research institutions showed a non-synergistic development trend,with the worst synergistic level in 2021;number of personnel,number of institutions,building floor space,production factors and sequential coefficients were weakly synergized and in a state of non-synergistic development.Among the 43 policy texts,the internal submodular policy tools were used more,the external submodular policy tools were used less,and the use of internal and external policy tools is unbalanced.Conclusion:The number of personnel,institutions and building area of medical research institutions are constraints on the synergistic development of innovative entities.It is recommended to increase the training of innovative talents in medical research institutions,improve the construction of new institutions,coordinate the layout of large scientific devices and functional housing,introduce targeted systematic planning,improve the market of factors of production,and consolidate the technological foundation for future development.

Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95％.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01％,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30％.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98％of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P＜0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P＜0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.