Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme that plays a crucial role in the development and progression of diabetes and its complications. Studies have reported that increased HDAC3 activity is associated with pancreatic β-cell dysfunction in type 1 diabetes, while in type 2 diabetes, HDAC3 affects insulin resistance and signaling by regulating the metabolism of the liver, adipose tissue, and muscle. Additionally, HDAC3 plays a key role in diabetic complications such as cardiomyopathy, retinopathy, and nephropathy. Selective inhibition of HDAC3 has the potential to improve insulin sensitivity, reduce chronic inflammation, and enhance pancreatic cell function, offering a promising new therapeutic strategy for diabetes and its complications.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.

Objective:To explore whether acupuncture can affect intestinal barrier and visceral pain of rats with irritable bowel syndrome(IBS)by regulating brain-derived neurotrophic factor(BDNF)and its downstream tyrosine kinase receptor B(TrkB),and to explore the possibility of BDNF/TrkB signaling pathway as a new target for acupuncture treatment.Methods:Sixty SD rats were ran-domly grouped into healthy group,IBS group,acupuncture group,positive control group and acupuncture+TrkB activation group,with 12 rats in each group.An IBS rat model was established,abdominal withdrawal reflex(AWR)was used to detect visceral pain of rats in each group;levels of TNF-α and IL-1β in colon of rats in each group were measured;expression levels of colonic mucosal cyto-plasmic Claudin 1(ZO-1)and occludin were measured with immunohistochemistry;expression levels of BDNF and TrkB mRNA and protein in colon of rats in each group were measured with fluorescence quantitative PCR and Western blot.Results:Compared with healthy group,colonic mucosa of rats in IBS group was damaged,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phos-phorylation were significantly increased(P<0.05);compared with IBS group,colon mucosa of acupuncture group and positive control group gradually recovered,expressions of ZO-1 and occludin were significantly increased,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly re-duced(P<0.05);compared with acupuncture group,colonic mucosa of rats in acupuncture+TrkB activation group still had lesions,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly increased(P<0.05).Conclusion:Acupuncture can regulate BDNF/TrkB pathway,inhibit expression of related proteins,improve intestinal barrier function,reduce vis-ceral pain,inflammation and relieve IBS.

Objective To investigate the relationship between the changes of serum human surfactant pro-tein D(SP-D)and vascular cell adhesion molecule-1(sVCAM-1)levels and postoperative fracture healing and short-term prognosis in patients with traumatic rib fractures.Methods A total of 102 patients with traumatic rib fractures who were treated in Banan Hospital Affiliated to Chongqing Medical University from January 2020 to December 2021 were selected as the research objects.After 8 months of treatment,the healing status of the patients was analyzed and divided into non-healing group(21 cases)and healing group(81 cases).Ac-cording to the pulmonary contusion,the patients were divided into pulmonary contusion group(19 cases)and non-pulmonary contusion group(83 cases).The serum levels of SP-D and sVCAM-1 were compared between the healing group and the non-healing group,and between the pulmonary contusion group and the non-pulmo-nary contusion group.The relationship between the changes of serum SP-D and sVCAM-1 levels and postop-erative fracture healing and short-term prognosis in patients with traumatic rib fractures were studied.Results The levels of SP-D and sVCAM-1 in the healing group were lower than those in the non-healing group(P＜0.05).The levels of SP-D and sVCAM-1 in the non-pulmonary contusion group were lower than those in the pulmonary contusion group(P＜0.05).Serum SP-D and sVCAM-1 levels were independent risk factors for postoperative fracture healing and short-term prognosis.Conclusion The changes of serum SP-D and sVCAM-1 levels in patients with traumatic rib fractures are related to fracture healing and short-term prognosis,which can be used as an important reference for prognosis evaluation.

Objective:To explore the talent cultivation model of nursing professional group under the 1+X certificate system, to build a talent cultivation system for nursing professional groups with "three progressions, four integrations, and five cocultivation"Methods:From 1 July 2021 to 31 December 2023, built a professional group course system of "mutual sharing of foundations, mutual generation of majors, mutual selection of positions, and progressive improvement of abilities". Aligned course content with X certificate content. Deepen the reform of the three education systems, create a "dual teacher" teaching team that combines full-time and part-time work, and build teaching resources that connect the cloud and the ground. The application effect of this model was evaluated in 2021 nursing majors in Cangzhou Medical College by cluster sampling.Results:There were 748 students majoring in nursing in class of 2021, 150 boys aged 19-22(20.00 ± 1.23), 598 girls, aged 19-21(19.00 ± 2.57). There were 118 students majoring in midwifery in class of 2021, all of them were girls, aged 18-20(18.00 ± 2.11). There were 128 students majoring in rehabilitation therapy technology in class of 2021, 66 boys aged 19-21(19.00 ± 2.11), 62 girls aged 19-21(19.00 ± 2.54). Nursing professional group completed the "Basic Nursing Technology Training Guidance", "Elderly Care" and other 5 self-compiled textbooks, 730 students had participated in the X certificate assessment, 729 students e passed the assessment, the passing rate was 99.9%.Conclusions:The talent cultivation model of "three progressions, four integrations, and five co cultivation" in the nursing professional group can cultivate students′ professional abilities, and cultivate a composite technical and skilled talent with multiple abilities and interconnections in one job.

Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.

Large-scale gene expression profiling generates or integrates massive data of gene expression under drug induction and employs artificial intelligence algorithms for pattern matching and association analysis. This approach facilitates the identification of complex relationships and functional networks between drugs, genes, and diseases, thereby significantly advancing drug research. Traditional Chinese medicine(TCM), with its characteristic multi-component, multi-target, and multi-pathway mechanisms, poses challenges to conventional methodologies in the comprehensive elucidation of its biological effects. The drug discovery strategy that combines large-scale gene expression profiling with artificial intelligence offers distinct advantages since it does not need the prior knowledge of specific drug targets or mechanisms. This article comprehensively reviews the innovative applications of large-scale gene expression profiling in TCM research as well as the recent advancements in the development of these technologies, the optimization of pattern matching algorithms, and the construction of related databases. In summary, the integration of large-scale gene expression profiling with artificial intelligence provides a powerful hypothesis-generating tool for the modern application and theoretical innovation of TCM.
Medicine, Chinese Traditional/methods* ; Gene Expression Profiling/methods* ; Humans ; Artificial Intelligence ; Drugs, Chinese Herbal/pharmacology* ; Algorithms ; Animals