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 To track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of ²⁵²Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

OBJECTIVES: This study aimed to explore the active components, potential targets, and mechanism of Cnidii Fructus in the treatment of periodontitis with osteoprosis through network pharmacology, molecular docking, and molecular dynamics simulation technology. METHODS: The main chemical constituents and targets of Cnidii Fructus were screened using the TCMSP and SwissTargetPrediction databases, as well as literature reports. Targets of periodontitis and osteoporosis were predicted using different databases. The intersection targets of Cnidii Fructus, periodontitis, and osteoporosis were obtained using Venny 2.1. The protein-protein interaction network was formed on the STRING platform. Cytoscape 3.9.1 was used to construct the active component-intersection target interaction network, perform the topological analysis, and screen key targets and core active components. Furthermore, the Metascape database was used to perform gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on the intersection targets. The top five key targets and core active components were selected as receptor proteins and ligand small molecules. Discovery Studio 2019 was used to dock ligands and receptors and visualize the docking results. Molecular dynamics simulation was conducted using Gromacs2022.3 to assess the stability of the interactions between the core active components and the main targets. RESULTS: A total of 20 potential active ingredients of Cnidii Fructus were screened, and 116 targets of Cnidii Fructus were obtained for treating periodontitis and osteoporosis. GO and KEGG analyses of the 116 targets showed that Cnidii Fructus may play a therapeutic role through the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathways. Molecular docking showed that the core constituents were well bound to the main targets. Molecular dynamics simulations confirmed the stability of the Diosmetin-AKT1 complex system. CONCLUSIONS The preliminary discovery of the potential molecular pharmacological mechanism of Cnidii Fructus extract in the targeted treatment of periodontitis with osteoporosis through a multi-component, multitarget, and multi-pathway approach can serve as a theoretical foundation for future drug-development research and clinical application.
Molecular Docking Simulation ; Molecular Dynamics Simulation ; Network Pharmacology ; Periodontitis/complications* ; Drugs, Chinese Herbal/chemistry* ; Osteoporosis/complications* ; Humans ; Protein Interaction Maps ; Cnidium/chemistry*

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:To explore the scientificity of the public hospital liability policy governance from the perspective of policy tools,and to provide evidence for the optimization and adjustment of subsequent policies.Methods:Policy texts at the national and regional levels from 2009-2022 were selected,and the coding results were statistically analyzed using Excel 2019 based on Rothwell and Zegveld's classification of policy tools.Results:A total of 128 policy texts were included in the analysis,with 29.96%,34.16%,and 35.88%of the policy tools in the policy instrument dimension being demand-based,supply-based,and environment-based,respectively.The system mechanism dimension focused primarily on compensation mechanisms.Conclusion:The use of the three policy instruments is mainly dominated by environmental policies,with a relative lack of policies from demand side.It is recommended that the use of policies from demand side could be strengthened and the internal structure of policy tools be optimized,to improve the consistency and coupling of policies.

Objective:To analyze the changes in the income structure of public hospitals at all levels in Hebei Province,evaluate the effectiveness of the compensation mechanism reform in public hospitals of Hebei Province,and provide policy recommendations for optimizing the compensation mechanism.Methods:Select some public hospitals at all levels in Hebei Province as samples,and use structural change analysis to analyze the income structure of the sample hospitals.Result:From 2016 to 2021,the proportion of medical income in tertiary and primary hospitals increased by 2.6 and 9.8 percentage points respectively,while the proportion of medical income in secondary hospitals decreased by 0.6 percentage points.The proportion of consumables revenue in hospitals at all levels has increased,and drug revenue remains the main driving factor for the growth of medical revenue in hospitals at all levels.The contribution rate of drug revenue to the growth of medical revenue in tertiary hospitals is 50％.Conclusion:The optimization of medical income structure in public hospitals in Hebei Province is significant,but the compensation mechanism still needs to be further improved,and the income structure still needs further adjustment.On the basis of consolidating and improving the policy of canceling consumable markup,it is needed to further standardize medical service behavior,improve precise and sustainable financial compensation mechanisms,adjust medical service prices,and broaden financing channels.

Objective:To explore the scientificity of the public hospital liability policy governance from the perspective of policy tools,and to provide evidence for the optimization and adjustment of subsequent policies.Methods:Policy texts at the national and regional levels from 2009-2022 were selected,and the coding results were statistically analyzed using Excel 2019 based on Rothwell and Zegveld's classification of policy tools.Results:A total of 128 policy texts were included in the analysis,with 29.96%,34.16%,and 35.88%of the policy tools in the policy instrument dimension being demand-based,supply-based,and environment-based,respectively.The system mechanism dimension focused primarily on compensation mechanisms.Conclusion:The use of the three policy instruments is mainly dominated by environmental policies,with a relative lack of policies from demand side.It is recommended that the use of policies from demand side could be strengthened and the internal structure of policy tools be optimized,to improve the consistency and coupling of policies.

Objective:To analyze the changes in the income structure of public hospitals at all levels in Hebei Province,evaluate the effectiveness of the compensation mechanism reform in public hospitals of Hebei Province,and provide policy recommendations for optimizing the compensation mechanism.Methods:Select some public hospitals at all levels in Hebei Province as samples,and use structural change analysis to analyze the income structure of the sample hospitals.Result:From 2016 to 2021,the proportion of medical income in tertiary and primary hospitals increased by 2.6 and 9.8 percentage points respectively,while the proportion of medical income in secondary hospitals decreased by 0.6 percentage points.The proportion of consumables revenue in hospitals at all levels has increased,and drug revenue remains the main driving factor for the growth of medical revenue in hospitals at all levels.The contribution rate of drug revenue to the growth of medical revenue in tertiary hospitals is 50％.Conclusion:The optimization of medical income structure in public hospitals in Hebei Province is significant,but the compensation mechanism still needs to be further improved,and the income structure still needs further adjustment.On the basis of consolidating and improving the policy of canceling consumable markup,it is needed to further standardize medical service behavior,improve precise and sustainable financial compensation mechanisms,adjust medical service prices,and broaden financing channels.

Objective:To explore the scientificity of the public hospital liability policy governance from the perspective of policy tools,and to provide evidence for the optimization and adjustment of subsequent policies.Methods:Policy texts at the national and regional levels from 2009-2022 were selected,and the coding results were statistically analyzed using Excel 2019 based on Rothwell and Zegveld's classification of policy tools.Results:A total of 128 policy texts were included in the analysis,with 29.96%,34.16%,and 35.88%of the policy tools in the policy instrument dimension being demand-based,supply-based,and environment-based,respectively.The system mechanism dimension focused primarily on compensation mechanisms.Conclusion:The use of the three policy instruments is mainly dominated by environmental policies,with a relative lack of policies from demand side.It is recommended that the use of policies from demand side could be strengthened and the internal structure of policy tools be optimized,to improve the consistency and coupling of policies.