Objective:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

Objective To investigate the expression of Tropomyosin 4(TPM4)in thyroid cancer and its effects on the invasion and migration of thyroid cancer cells.Methods The expression level and prognostic value of TPM4 in thyroid cancer were analyzed based on bioinformatics,and its functional involvement was explored through Gene Set Enrichment Analysis(GSEA).In thyroid cancer K1 cells,lentiviral transfection was performed to establish the experimental group(TPM4 shRNA),the negative control group(empty lentiviral transfection),and the control group(untreated).Cell viability and proliferation were assessed using CCK-8 and BrdU assays.Transwell migration and invasion assays were performed to evaluate the effects of TPM4 on the migratory and invasive capacities of thyroid cancer cells.Results TPM4 expression was significantly upregulated in thyroid cancer(P<0.05)and correlated with TNM staging(P<0.05).Patients with higher TPM4 expression in advanced TNM stages exhibited poorer prognosis(P<0.05).GSEA results indicated that high TPM4 expression was enriched in gene sets associated with epithelial-mesenchymal transition,inflammatory response,P53 signaling pathway,and cell cycle.Following TPM4 knockdown in K1 cells,thyroid cancer cell growth was slowed(P<0.01),proliferative activity was decreased(P<0.001),and invasion and migration abilities were significantly impaired(P<0.001).Conclusion TPM4 is highly expressed in thyroid cancer and promotes the invasion and migration capabilities of thyroid cancer cells.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective:To analyze the regional differences and equity of the high-quality health resource allocation in primary healthcare institutions,and provide decision-making references for improving the equity of high-quality health resource allocation in primary healthcare institutions among provinces in China.Methods:The entropy weight method is used to determine the weights of indicators.Breakpoint method,Gini coefficient and grey correlation method are applied to conduct the classification,equity analysis and influencing factor analysis on the allocation levels of 31 provinces.Results:The Gini coefficients of the supply-demand ratio index in 2011,2016 and 2021 were 0.34,0.33 and 0.34,respectively.Population density,education level,education investment level,public service level,per capita GDP,regional income level and average altitude were the key influencing factors.Conclusion:There are significant differences in the high-quality health resource allocation among community-level medical and health care institutions in different provinces of China,and there are certain issues with equity.It is necessary to comprehensively consider multiple influencing factors to promote the balanced development of high-quality health resource allocation in community-level medical and health care institutions in China.

Background Diesel engines are widely used in transportation, agriculture, construction, industry, and other fields. Diesel exhaust, classified as a Group 1 carcinogen, emits particles (DEP) that can penetrate deep into the respiratory tract, posing significant health risks. DEP pollution is particularly severe in confined environments, necessitating effective control measures. Objective Under laboratory simulation conditions, to explore the spatiotemporal distribution characteristics of the mass and number concentrations of DEP as it diffuses indoors and to reveal the effects of ventilation and additional airflow on indoor DEP pollution levels. Methods A diesel engine was placed in a laboratory (length 3.39 m × width 2.85 m × height 2.4 m) with its exhaust emitted from east to west. An air purifier was installed 1 m south of the engine. Eight measurement points (1 m horizontal distance from the exhaust outlet, height: 1 m/1.5 m) were setup to monitor DEP concentrations using portable laser particle sizers. The effects of engine power (4.05 kW vs. 5.15 kW), ventilation (maximum airflow: 600 m³·h⁻¹), additional airflow intensity (low and high), and direction (forward/reverse) on DEP pollution were analyzed. DEP levels of 5 diesel vehicle models were also compared. Results The mass and number concentrations of DEP indoors increased immediately after the diesel engine started. The peak mass concentration time at the eastern measurement point (−1, 0) m opposite to the exhaust direction (17.70 min) was significantly longer than that at the western (1, 0) m (16.20 min), southern (0, -1) m (14.45 min), and northern (0, 1) m (12.70 min) points (P<0.05), with no significant differences between the other points (western, southern, and northern) (P>0.05). The northern point (0, 1) m exhibited the highest DEP mass and number concentration peaks (174.62 μg·m⁻³, 1319.85 p·cm⁻³), significantly exceeding those at the southern (0, −1) m (129.89 μg·m⁻³, 1175.24 p·cm⁻³), eastern (−1, 0) m (140.12 μg·m⁻³, 1120.53 p·cm⁻³), and western (1, 0) m (147.60 μg·m⁻³, 818.62 p·cm⁻³) points (P<0.05), and no significant differences were observed among other points (P>0.05). There were no significant differences in peak DEP mass and number concentrations by measurement heights (P>0.05). Diesel engine power, ventilation, airflow intensity, and airflow direction had no significant effect on the time of peak DEP concentration (P>0.05). However, higher engine power (5.15 kW) produced greater DEP peaks [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] than the 4.05 kW engine power [(168.41±12.65) μg·m⁻³, (1284.45±71.30) p·cm⁻³] (P<0.05). The peak mass concentration [(342.04±35.03) μg·m⁻³] and number concentration [(1886.87±57.91) p·cm⁻³] of DEP in the non-ventilated group were significantly higher than those in the ventilated group [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] (P<0.001). Forward airflow elevated DEP mass concentrations compared to reverse airflow (287.71 μg·m⁻³ vs. 243.74 μg·m⁻³, t=−2.592, P=0.009), but no effects on DEP number concentration (P>0.05). Significant differences in mass concentration were observed among selected 5 vehicle models (Z=38.109, P<0.001). Conclusion The operation of diesel engines will emit a large amount of particulate matter, causing pollution in enclosed spaces. Diesel engines with greater power have higher levels of DEP pollution emissions. Based on the spatiotemporal distribution characteristics, it is recommended to set the operation position in the reverse direction of exhaust emissions and close to air purifiers, while avoiding the use of additional air flow equipment.

Objective To sort out the management system of clinical trial drugs in our hospital,and analyze the construction and practical experience of the information system in the whole process management of clinical trial drugs,and to further improve the efficiency and quality of clinical trials.Methods Based on the original management of clinical trial drugs,an information system in line with the situation of our hospital was applied to manage the whole process of clinical trial drugs.Results Compared with the traditional management,the information system can automatically record the data of inbound and outbound storage,distribution,retrieval and return of trial drugs in real time,pre-review the prescriptions and randomized documents of clinical trial drugs,and realise paperless office.Conclusions The information system can ensure the safety,accuracy and traceability of the data of drugs used in clinical trial.The system can also save resources,improve the efficiency and quality of clinical trial management.

Objective:To evaluate the intervention effectiveness of scenario simulation teaching based on the Eilks model on the social context integration ability, critical thinking, and humanistic care of resident physicians in the department of stomatology.Methods:A total of 94 resident physicians in the department of stomatology were included in the study, with 53 in the experimental group and 41 in the control group. The control group received traditional teaching, while the experimental group received scenario simulation teaching based on the Eilks model. Through the five-link design of "text analysis, scientific background, social context, viewpoint debate, and meta reflection", the integration of social science issues (such as ethical conflicts and economic costs) and clinical decision-making was strengthened. Trainees were evaluated for clinical decision-making ability, clinical reflection ability, and doctor-patient communication ability. The data were subjected to t-test and chi-square test using SPSS 24.0. Results:In terms of clinical decision-making ability, the experimental group outperformed the control group in ethical cost balance [(7.85±1.08) vs. (6.12±1.73), t=5.68, P<0.001], multidisciplinary collaboration [(8.25±0.73) vs. (5.83±0.82), t=6.01, P<0.001)], and complication planning [(7.98±1.02) vs. (5.34±1.42), t=6.79, P<0.001]. In terms of clinical reflection ability, the experimental group scored higher in depth of cost-benefit analysis, intensity of evidence-based reflection, and cognitive upgrading (all P<0.001). In terms of doctor-patient communication skills, the experimental group demonstrated superior performance compared to the control group in information collection [(10.25±1.28) vs. (7.53±1.33)] and emotional support [(10.97±1.18) vs. (6.53±1.23)]. Conclusions:Based on the Eilks model, scenario simulation teaching effectively enhances the ability of residents in the department of stomatology to integrate social factors, optimize ethical decision-making, and perform empathetic communication through social conflict simulation (such as three-way role debate) and dual path critical thinking training. In the future, further optimization is needed in terms of personalized expression and the timeliness of basic training.

Cardiovascular disease(CVD),as one of the diseases with the highest morbidity and mor-tality rates globally,has always been a focus of med-ical research.In recent years,with a deeper under-standing of the pathogenesis of CVD,novel metabol-ic drugs have demonstrated great potential in its treatment.These novel drugs regulate multiple as-pects of cardiovascular metabolism,including reduc-ing blood glucose and lipid levels,inhibiting inflam-matory responses,and protecting vascular endothe-lial cells,thereby providing new strategies for the prevention and treatment of CVD.In terms of lower-ing blood glucose levels,SGLT2 inhibitors,GLP-1 re-ceptor agonists,DPP-4 inhibitors,and Metformin,as clinically commonly used drugs,have been prov-en to be beneficial for the prevention and treat-ment of CVD,regardless of the presence or absence of diabetes.For lipid regulation,PCSK9 inhibitors and Ezetimibe,as newly developed lipid-lowering drugs,not only reduce serum low-density lipopro-tein cholesterol levels but also directly protect the cardiovascular system from damage.The develop-ment and application of these drugs have not only improved the treatment outcomes of CVD but also provided patients with more therapeutic options.

Objective:To analyze the regional differences and equity of the high-quality health resource allocation in primary healthcare institutions,and provide decision-making references for improving the equity of high-quality health resource allocation in primary healthcare institutions among provinces in China.Methods:The entropy weight method is used to determine the weights of indicators.Breakpoint method,Gini coefficient and grey correlation method are applied to conduct the classification,equity analysis and influencing factor analysis on the allocation levels of 31 provinces.Results:The Gini coefficients of the supply-demand ratio index in 2011,2016 and 2021 were 0.34,0.33 and 0.34,respectively.Population density,education level,education investment level,public service level,per capita GDP,regional income level and average altitude were the key influencing factors.Conclusion:There are significant differences in the high-quality health resource allocation among community-level medical and health care institutions in different provinces of China,and there are certain issues with equity.It is necessary to comprehensively consider multiple influencing factors to promote the balanced development of high-quality health resource allocation in community-level medical and health care institutions in China.

Objective:To evaluate the intervention effectiveness of scenario simulation teaching based on the Eilks model on the social context integration ability, critical thinking, and humanistic care of resident physicians in the department of stomatology.Methods:A total of 94 resident physicians in the department of stomatology were included in the study, with 53 in the experimental group and 41 in the control group. The control group received traditional teaching, while the experimental group received scenario simulation teaching based on the Eilks model. Through the five-link design of "text analysis, scientific background, social context, viewpoint debate, and meta reflection", the integration of social science issues (such as ethical conflicts and economic costs) and clinical decision-making was strengthened. Trainees were evaluated for clinical decision-making ability, clinical reflection ability, and doctor-patient communication ability. The data were subjected to t-test and chi-square test using SPSS 24.0. Results:In terms of clinical decision-making ability, the experimental group outperformed the control group in ethical cost balance [(7.85±1.08) vs. (6.12±1.73), t=5.68, P<0.001], multidisciplinary collaboration [(8.25±0.73) vs. (5.83±0.82), t=6.01, P<0.001)], and complication planning [(7.98±1.02) vs. (5.34±1.42), t=6.79, P<0.001]. In terms of clinical reflection ability, the experimental group scored higher in depth of cost-benefit analysis, intensity of evidence-based reflection, and cognitive upgrading (all P<0.001). In terms of doctor-patient communication skills, the experimental group demonstrated superior performance compared to the control group in information collection [(10.25±1.28) vs. (7.53±1.33)] and emotional support [(10.97±1.18) vs. (6.53±1.23)]. Conclusions:Based on the Eilks model, scenario simulation teaching effectively enhances the ability of residents in the department of stomatology to integrate social factors, optimize ethical decision-making, and perform empathetic communication through social conflict simulation (such as three-way role debate) and dual path critical thinking training. In the future, further optimization is needed in terms of personalized expression and the timeliness of basic training.