Study on a job competence evaluation system for resident physicians (including integrated postgraduates) receiving standardized training.

BACKGROUND: Standardized training for resident physicians is the primary form of postgraduate medical education, and it plays a pivotal role in healthcare safety and industry stability. Currently, it has garnered significant attention from healthcare institutions. METHODS: By conducting a comprehensive literature review and a Delphi consultation in June 2022 for which 40 experts in clinical medicine, public health, and other related fields in China were invited. The indicators were adjusted according to the results of the consultation, and the final indicator weights were determined through an analytic hierarchy process. RESULTS: The response rate was 100%, and the expert authority coefficient was 0.879. The consistency among the experts on the tertiary indicators, as measured by Kendall's W, was 0.675 (χ2 = 42.516, p < 0.001). Based on the results of the expert consultation, a job competence evaluation system for resident physicians (including integrated postgraduates) receiving standardized training was established, which included 6 primary indicators, 18 secondary indicators, and 116 tertiary indicators. The weights for the primary indicators, namely professional quality, skills and knowledge, patient care, communication and collaboration, teaching skills, and lifelong learning, were 0.313, 0.248, 0.181, 0.083, 0.066, and 0.110, respectively. The top three secondary indicators in terms of combined weights were clinical skills (0.122), professional ethics (0.120), and professional dedication (0.109). The three tertiary indicators with the highest scores were "maintains collaboration with peers and colleagues in patient treatment," "has clinical thinking skills, makes diagnosis and treatment decisions based on analysis of evidence, and has the ability to administer suitable treatments," and "abides by laws and discipline and refuses to seek personal gains in medical practice"; their combined weights were 0.035, 0.028, and 0.027, respectively. CONCLUSION: This study has established a concrete, objective, and quantifiable competency assessment index system for standardized training of clinical resident physicians (including integrated postgraduates). This system provides a foundation for the quantitative evaluation of the competency of clinical resident physicians (including integrated postgraduates) undergoing standardized training.

Loss of TRIM24 promotes IL-10 expression via CBP/p300-dependent IFNß1 transcription during macrophage activation.

BACKGROUND: As an anti-inflammatory cytokine, interleukin 10 (IL-10) plays a vital role in preventing inflammatory and autoimmune pathologies while also maintaining immune homeostasis. IL-10 production in macrophages is tightly regulated by multiple pathways. TRIM24, a member of the Transcriptional Intermediary Factor 1 (TIF1) family, contributes to antiviral immunity and macrophage M2 polarization. However, the role of TRIM24 in regulating IL-10 expression and its involvement in endotoxic shock remains unclear. METHODS: In vitro, bone marrow derived macrophages cultured with GM-CSF or M-CSF were stimulated with LPS (100ng/ml). Murine models of endotoxic shock were established by challenging the mice with different dose of LPS (i.p). RTPCR, RNA sequencing, ELISA and hematoxylin and eosin staining were performed to elucidate the role and mechanisms of TRIM24 in endotoxic shock. RESULTS: The expression of TRIM24 is downregulated in LPS-stimulated bone marrow-derived macrophages (BMDMs). Loss of TRIM24 boosted IL-10 expression during the late stage of LPS-stimulation in macrophages. RNA-seq analysis revealed the upregulation of IFNß1, an upstream regulator of IL-10, in TRIM24 knockout macrophages. Treatment with C646, a CBP/p300 inhibitor, diminished the difference in both IFNß1 and IL-10 expression between TRIM24 knockout and control macrophages. Loss of TRIM24 provided protection against LPS-induced endotoxic shock in mice. CONCLUSION: Our results demonstrated that inhibiting TRIM24 promoted the expression of IFNß1 and IL-10 during macrophage activation, therefore protecting mice from endotoxic shock. This study offers novel insights into the regulatory role of TRIM24 in IL-10 expression, making it a potentially attractive therapeutic target for inflammatory diseases.

Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study.

BACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60-69 years of age to elucidate the underlying mechanisms using a multi-omics approach. METHODS: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3-kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. DISCUSSION: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896.

Imperatorin inhibits LPS-induced bone marrow-derived macrophages activation by decreased NF-κB p65 phosphorylation.

BACKGROUND: Imperatorin (IMP) is a secondary metabolite of plants and is the most abundant in Angelica dahurica. Previous studies showed that IMP exhibited anti-inflammatory activity in RAW264.7 cell line. Here, we aim to investigate the roles and mechanisms of IMP in bone marrow-derived macrophages (BMDMs), in view of the difference between primary macrophages and cell lines. METHODS: BMDMs were stimulated with LPS for the inflammation model. Flow cytometry was performed with BMDMs treated with different doses of IMP (0-20mg/L) within staining Annexin V-APC for 5 min. The cytokines and inflammatory mediators were detected by RT-PCR or ELISA. RNA-seq was performed in IMP-treated BMDMs or control, stimulated with LPS for 6h. Western blotting is carried out to determine the phosphorylation of p65, ERK1/2, JNK1, p38, and Akt. RESULTS: Our results showed that IMP inhibited IL-12p40, IL-6, TNF-α and IL-1ß in LPS-stimulated BMDMs. RNA-seq analysis suggested that IMP inhibits Toll-like receptor signaling pathway (KEGG), TNF signaling pathway (KEGG), NF-κB signaling pathway (KEGG), Inflammatory Response (GO). In addition, IMP inhibited myd88, tpl2, cxcl1, ptgs2(COX-2) expression in mRNA level. Finally, we found decreased phosphorylation of NF-κB p65 in IMP-treated BMDMs, after stimulated with LPS. CONCLUSION: IMP inhibits IL-12p40, IL-6, TNF-α, and IL-1ß expression in LPS-stimulated BMDMs. IMP inhibits macrophage activation, which maybe resulted in decreased phosphorylation of NF-κB p65. Furthermore, IMP may protect against the progress of inflammatory-related diseases.

Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide.

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from Corydalis edulis, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.

Knowledge, Practice of Personal Hygiene, School Sanitation, and Risk Factors of Contracting Diarrhea among Rural Students from Five Western Provinces in China.

BACKGROUND: Diarrhea is a global public health issue and a leading cause of childhood malnutrition, growth disturbances, and mortality. The spread of diarrhea is closely linked to the knowledge and maintenance of personal hygiene and quality of drinking water and sanitation facilities. However, there are few such investigations and analysis in rural areas of China. This study aims to determine the association between the risk of contracting diarrhea and knowledge and practices of personal hygiene and school sanitation among rural students as well as provide a scientific basis for preventing the spread of diarrhea and other infectious diseases. A stratified cluster sampling method was used to randomly select 12 rural primary schools in each of 5 counties where the Water, Sanitation and Hygiene (WASH) Plus Program has been implemented. The counties are located in the Guangxi Zhuang autonomous region, Chongqing municipality, Guizhou province, Yunnan province, and Xinjiang Uygur autonomous region. A single fourth-grade class was randomly chosen from each of the 60 schools for observation and a questionnaire survey. The study involved a total of 2330 students. The logistic regression method was adopted to determine the factors contributing to diarrhea in rural students. The results show that male students accounted for 49.40% (n = 1151) of the 2330 research subjects; the average age of the students was 9.9 ± 0.3 years. Approximately 33.09% of the students suffered from diarrhea in the three months leading up to the survey. The odds ratios (ORs) of students who did not know that "diarrhea can be prevented by washing fruits before eating them raw and not drinking untreated water" (OR: 1.303, 95% confidence interval [CI]: 1.063, 1.597) and that "the disease can be prevented by washing hands before meals and after going to the toilet" (OR: 1.522, 95% CI: 1.207, 1.920) were higher than those who knew the above stated facts. Students who "have drunk untreated water at school" (OR: 1.584, 95% CI: 1.268, 1.978), "have drunk untreated water at home" (OR: 1.643, 95% CI: 1.319, 2.048), and "did not wash hands before every meal" (OR: 1.490, 95% CI: 1.120, 1.983) were at a higher risk of contracting diarrhea than those who drank treated water at school and at home and washed their hands before every meal. Diarrhea was more likely to affect students who attended schools with unclean and poorly maintained toilets (OR: 1.586, 95% CI: 1.261, 1.995) or toilets with flies (OR: 1.383, 95% CI: 1.114, 1.717) and without adequate drinking water facilities (OR: 1.407, 95% CI: 1.009, 1.962). The knowledge of methods to maintain personal hygiene, general hygiene practices, and school sanitation are the three major risk factors that account for the spread of diarrhea among rural students from five western provinces (municipalities and autonomous regions) of China. Therefore, to prevent such diseases and maintain health, it is important to provide students with health education, help them develop good hygiene habits, ensure the provision of clean water at schools, and improve the overall school environments.

Research on the Establishment and Application of the Environmental Health Indicator System of Atmospheric Pollution in China.

To understand the health impact represented by exposure to current atmospheric pollution in China, an environmental health indicators (EHIs) system of atmospheric pollution was established. The EHIs were based on comprehensive consideration of environment, population, economy and diseases associated with atmospheric pollution. An EHIs evaluation system of atmospheric pollution, based on corresponding EHIs data collection and weighting coefficients determined using principal component analysis, was applied to major provinces and regions in China to evaluate the environmental health status. Results showed that the EHIs of atmospheric pollution in Central and East China were low, indicating a serious environmental health condition. Prevention and management of atmospheric pollution in these regions should be strengthened and protective measures taken to improve human health. Compared with other methods, the EHIs evaluation system was more intuitive, which facilitated users to identify the environmental health status and provided support for health management and pollution prevention.