ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Background Depressive symptoms have become a significant factor affecting the physical and mental health of the occupational population, and workers in petroleum refining enterprises face multiple stressors in their work environment. Objective To explore the impact of occupational noise exposure on depressive symptoms among workers in a petroleum refining enterprise. Methods This cross-sectional study was conducted in July 2024 using a questionnaire survey among workers of a petroleum refining enterprise in Hainan Province. Basic information of the subjects was collected. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality, and the Chinese version of the Effort-Reward Imbalance (ERI) scale was used to evaluate occupational stress. Chi-square test was employed to compare the differences in reporting depressive symptoms among populations with different characteristics. Binary logistic regression models were used to analyze the impact of occupational noise exposure and other factors on depressive symptoms. Results The overall positive rate of depressive symptoms in the study population was 42.7%. The results of the multifactor analysis indicated that compared with the control group, employees in both the low-exposure and high-exposure groups had elevated odds of depressive symptoms, with OR (95%CI) of 2.244 (1.131, 4.454) and 1.970 (1.009, 3.850), respectively. This association remained robust after adjusting for potential confounders, including gender, age, work tenure, and other occupational exposures. Additionally, female [OR (95%CI)=1.483 (1.039, 2.118)], exposure to benzene, toluene, or xylene [OR (95%CI)=1.621 (1.208, 2.174)], sleep disturbance [OR (95%CI)=3.772 (2.942, 4.838)], and occupational stress [OR (95%CI)=2.018 (1.575, 2.585)] were also significantly associated with higher odds of depressive symptoms. Conclusion The positive rate of depressive symptoms is relatively high among employees in this petrochemical enterprise, and occupational noise exposure may be a risk factor for depressive symptoms.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Soil cadmium pollution can adversely affect the cultivation of the ornamental plant, Coleus scutellarioides. Upon cadmium contamination of the soil, the growth of C. scutellarioides is impeded, and it may even succumb to the toxic accumulation of cadmium. In this study, we investigated the effects of arbuscular mycorrhizal fungi (AMF) on the adaptation of C. scutellarioides to cadmium stress, by measuring the physiological metabolism and the degree of root damage of C. scutellarioides, with Aspergillus oryzae as the test fungi. The results indicated that cadmium stress increased the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the content of malondialdehyde (MDA) and proline (Pro) within the cells of C. scutellarioides, but inhibited mycorrhizal infestation rate, root vigour and growth rate to a great degree. With the same cadmium concentration, the inoculation of AMF significantly improved the physiological indexes of C. scutellarioides. The maximum decrease of MDA content was 42.16%, and the content of secondary metabolites rosemarinic acid and anthocyanosides could be increased by up to 27.43% and 25.72%, respectively. Meanwhile, the increase of root vigour was as high as 35.35%, and the DNA damage of the root system was obviously repaired. In conclusion, the inoculation of AMF can promote the accumulation of secondary metabolites, alleviate root damage, and enhance the tolerance to cadmium stress in C. scutellarioides.
Cadmium/toxicity* ; Mycorrhizae/physiology* ; Plant Roots/drug effects* ; Soil Pollutants/toxicity* ; Stress, Physiological ; Superoxide Dismutase/metabolism*

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Background Light gradient boosting machine (LightGBM) has become a popular choice in prediction models due to its high efficiency and speed. However, the "black box" issues in machine learning models lead to poor model interpretability. At present, few studies have evaluated the severity of occupational injuries from the perspective of LightGBM model and model interpretability. Objective To evaluate the application value of LightGBM models and model interpretability methods in occupational injury prediction. Methods The Mine Safety and Health Administration (MSHA) occupational injury data set of mining industry workers from 1983 to 2022 was used. Injury severity (death/fatal occupational injury and permanent/partial disability) was used as the outcome variable, and the predictor variables included the month of occurrence, age, sex, time of accident, time since beginning of shift, accident time interval from shift start, total experience, total mining experience, experience at this mine, cause of injury, accident type, activity of injury, source of injury, body part of injury, work environment type, product category, and nature of injury. Feature sets were screened using least absolute shrinkage and selection operator (Lasso) regression. A LightGBM model was then employed to predict occupational injury, with area under curve (AUC) of the model serving as the primary evaluation metric; an AUC closer to 1 indicates better predictive performance of the model. The interpretability of the model was evaluated using Shapley additive explanations (SHAP). Results Through Lasso regression, 7 key influencing factors were identified, including accident time interval from shift start, experience at this mine, cause of injury, accident type, body part of injury, nature of injury, and work environment type. A LightGBM model, constructed based on feature selection via Lasso regression, demonstrated good predictive performance with an AUC value of 0.9941 (95%CI: 0.9917, 0.9966), accuracy of 0.9743, specificity of 0.9781, and sensitivity of 0.9640. The predicted probability of fatal occupational injuries showed high consistency with the actual probability of fatal occupational injuries. In the occupational injury prediction model, the importance of each indicator was analyzed through its SHAP value, and it was found that the body part of injury and the nature of injury were the two main features that affected the prediction results of the model, and the impacts of other features were relatively small. The distribution of SHAP values across body part of injury was broad, with significant impacts on the model's prediction of fatal risk, particularly for injuries to the head and neck, as well as multi-part injuries. The nature of injury also exerted influences on the model in different directions, with suffocation/drowning, crushing, and multi-part injuries having a greater impact on the risk of fatal occupational injuries. Conclusion LightGBM model is capable of efficiently processing large-scale data and providing high-precision prediction results. Research on model interpretability aids in more accurately exploring and analyzing various key risk factors for fatal occupational injuries among mining workers, and further reveals the complex interactions among these factors. This, in turn, enables better preventive intervention and protection measures, as well as optimal resource allocation for labor workers.

Diabetic retinopathy(DR)is a late-stage peripheral micro-neurovascular complication of chronic hyperglycemia, leading to blood-retinal barrier impairment and retinal dysfunction. Recent studies have found that diabetic neuroretinopathy(DN)may be one of the earliest events in diabetic retinal alterations. The main features include defective electroretinographic responses in newly diagnosed patients, early self-activation of microglia and Müller cells, reduced activity of neurotransmitters(e.g., DOPA/GABA), and early mitochondrial dysfunction, such as persistent Drp1-Fis1 fission and mtDNA methylation mismatches. Understanding the molecular basis of DN is essential for elucidating its pathogenesis and developing early treatments. This review summarizes pathological changes and mechanisms of retinal function, glial cells, neurotransmitters, mitochondria, and other factors in early diabetes mellitus, in order to provide a theoretical foundation for investigating early DN mechanisms and developing targeted therapies.