BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Purpose/Significance The paper systematically reviews the application and research progress of large language models(LLMs)in the medical field,analyzes the key challenges and opportunities,and provides references for related research.Method/Process The systematic literature review method is adopted to comprehensively review the relevant literature published in recent years,fo-cusing on the latest progress of medical LLMs.The application results,research status and challenges of LLMs in medical natural lan-guage processing(NLP)tasks are analyzed.Result/Conclusion The application of LLMs in the medical field has a broad prospect,and the future research should focus on the technical progress and the improvement of ethical norms.On the one hand,the pace of technologi-cal innovation should be accelerated,and on the other hand,strict compliance with ethical standards should be ensured to jointly promote the sustainable development of LLMs technology in the medical field.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the ‘H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project’ among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01–1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22–6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04–3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

Objective:To analyze the prognostic risk factors of patients with traumatic pancreatitis (TP) and establish an early combined prediction of multiple indicators model for TP.Methods:Patients admitted to the ICU of the First Affiliated Hospital of Zhengzhou University from June 2017 to June 2022 were collected retrospectively. Based on their prognosis, the patients were divided into two groups: the good prognosis group and the poor prognosis group. The general data such as sex, age, underlying diseases, Glasgow Coma Scale (GCS), acute physiology and chronic health evaluationⅡ (APACHEⅡ), injury severity score (ISS), bedside index for severity in acute pancreatitis (BISAP), and clinical test indices such as blood routine, blood coagulation, blood gas analysis, and liver and kidney function at admission were compared between the two groups. Univariate analysis and multivariate logistic regression analysis were used to screen the early independent predictors of poor prognosis of TP, and the prediction model of TP was established by combining all of the independent indicators. The receiver operating characteristic (ROC) curve of each independent predictor and prediction model was drawn, and the area under the curve (AUC), sensitivity, specificity, and optimal cut-off value were calculated to examine the diagnostic impact of each independent predictor and the combined prediction model.Results:There were statistically significant differences in the complication rate of mental disorders, GCS, APACHE II, combined craniocerebral injury, combined chest injury, activated partial thromboplastin time, fibrin(pro)degradation products, lactate, aspartate aminotransferase, glomerular filtration rate, amylase, lipase, NT-proBNP, myoglobin, procalcitonin, ISS, and BISAP between the good and poor prognosis groups (all P<0.05). Multivariate logistic regression analysis showed that lactate ( OR=1.636, 95% CI: 1.046-2.559), lipase ( OR=1.005, 95% CI: 1.001-1.008), and ISS ( OR=1.161, 95% CI: 1.064-1.266) were independent risk factors influencing the prognosis of patients with TP. Based on the risk factors listed above, a prediction model was created: Logit P=-9.260+0.492×lactate+0.005×lipase+0.149×ISS, and the ROC curve was plotted. The AUC curve of the prediction model was 0.96 (95% CI: 0.91-1.00). Conclusions:Lactate, lipase, and ISS are early independent risk factors associated with the prognosis of TP. Their combined multi-indicator prediction model has an excellent clinical prediction effect, which can provide a clinical reference for early prediction and treatment of TP.

Objective:To explore the effect of job insecurity on work engagement, and examine the mediating role of job satisfaction and the moderating role of occupational proactive behavior.Methods:Using the convenient sampling method, nurses from Southern University of Science and Technology Hospital and Jiangyou Second People's Hospital were selected as the research objects in July 2022. General information questionnaire, Occupational Insecurity Scale, Occupational Satisfaction Scale, Work Engagement Scale and Occupational Proactive Behavior were used for questionnaire investigation. A total of 598 valid questionnaires were collected. Model 4 and Model 7 in the SPSS 22.0 Process were used to test the mediating effect and the moderated mediating effect respectively.Results:Occupational insecurity was negatively correlated with occupational satisfaction and work engagement ( r=-0.202, -0.165, P<0.01) , while occupational satisfaction was positively correlated with work engagement ( r=0.549, P<0.01) . Work satisfaction played a completely mediating role in the effect of job insecurity on work engagement (mediating effect value: -0.090 9, 95% confidence interval: -0.14 - -0.04) , accounting for 65.30% of the total effect. Occupational active behavior positively moderated the relationship between job insecurity and job satisfaction (β=0.07, P<0.01) . Conclusions:Nurses' work engagement is at a high level, but occupational insecurity will reduce nurses' job satisfaction and thus reduce their work engagement. Nurses with high occupational proactive behavior can alleviate the weakening of job insecurity on job satisfaction.

ObjectiveTo conduct a systematic review of the susceptibility gene polymorphism sites of primary knee osteoarthritis (PKO). MethodsThe literature on genetic susceptibility and gene polymorphisms of PKO were retrieved from PubMed, Web of Science, CNKI, Wanfang Data, and China Biomedical Literature Database from establishment of the library to December, 2020, and systematically reviewed. ResultsA total of 42 papers on the polymorphism sites of human PKO susceptibility genes were included, involving cellular signaling pathways related to PKO pathogenesis, including inflammatory response, receptor signaling pathway, transcription factor signaling pathway, bone-related signaling pathway, etc. Multiple gene polymorphism sites located in inflammatory factor genes, chemokine genes, Toll-like receptor genes, transcription factor genes, obesity-related genes, and bone-related genes. ConclusionInflammatory factor genes and bone-associated allele polymorphisms are likely to be related to PKO susceptibility.

ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules （JWZX） based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology，the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study，the average degree （AD） of the nodes in the modules was used as an index to screen the main modules of the disease，and the intervention of the sovereign drugs，minister drugs，and assistant drugs on the main modules was explored. Finally，the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment，JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor （P<0.05，P<0.01）. The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor （TNF），epidermal growth factor receptor （EGFR），vascular endothelial growth factor A （VEGFA），transcription factor （JUN），tumor protein p53 （TP53），and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8，and the minister drugs such as Centipeda Herba jointly intervened in modules 1，3，5，8，10，and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3，5，10，and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules，and the pathway functions involved 12 categories including cancer，signal transduction，immune system，endocrine system，and amino acid metabolism. The functions of the four major modules involved cancer，signal transduction，and immune system. According to the results of literature verification，the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） and hypoxia-inducible factor-1 （HIF-1） signaling pathways，reduction of the immunosuppressive effect in the tumor microenvironment，and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer，and the therapeutic efficacy was achieved through the multiple targets，multiple modules，and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer，which provides a new idea for interpreting the complex mechanism of prescription compatibility.