ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Promoting the construction of a “Healthy China” is essential to building a great modern socialist country. Health workers in every era have their historical missions and they are the “benevolent doctors” of their own era. Therefore， clarifying the basic connotation and times requirements of “benevolent doctors” has become the first question to be answered in cultivating “benevolent doctors”. The basic connotation of “benevolent doctor” should reflect not only the comprehensive development of moral， intellectual， physical， aesthetic， and labor education in fostering virtue and nurturing talents， but also embody the people-centered development philosophy， promote social equity and justice， and reflect the strategic needs of building a “Healthy China.” Specifically in the practice of medical education， emphasizing both medical science spirit and medical humanities spirit has become an important path to cultivate “benevolent doctors” in the new era.

Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

As an important part of the cause of socialism with Chinese characteristics,health care plays a basic strategic support role in China's modernization drive.Deepening the reform of the medical and health system is an important part of comprehensively deepening the reform.Therefore,it is a new starting point to further deepen the reform to explore the Marx's theoretical logic of Chinese medical reform from the logic of"two combinations"and find the basis of Marx's theory and the ideological power of Chinese excellent traditional culture for the"big country medical reform".Under the guidance of the logical logic of the"two combinations",the theoretical system of Xi Jinping's important treatises on health work is built,contributing to further enrich and develop Xi Jinping's thought of socialism with Chinese characteristics in a new era.

As an important part of the cause of socialism with Chinese characteristics,health care plays a basic strategic support role in China's modernization drive.Deepening the reform of the medical and health system is an important part of comprehensively deepening the reform.Therefore,it is a new starting point to further deepen the reform to explore the Marx's theoretical logic of Chinese medical reform from the logic of"two combinations"and find the basis of Marx's theory and the ideological power of Chinese excellent traditional culture for the"big country medical reform".Under the guidance of the logical logic of the"two combinations",the theoretical system of Xi Jinping's important treatises on health work is built,contributing to further enrich and develop Xi Jinping's thought of socialism with Chinese characteristics in a new era.

Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Purpose/Significance The paper reviews the status quo of health information behavior research based on WeChat plat-form,grasps the research trends,and broadens the media perspective.Method/Process It systematically collects domestic and foreign literature,uses content analysis method to analyze the article publishing trend,research methods and research objects,summarizes and analyzes the subject category,and prospects the future development direction.Result/Conclusion Questionnaire survey and interview methods are widely used in the study of health information behavior on WeChat platform.The elderly users and the public account func-tions of WeChat platform become hot research objects.The subjects can be summarized into four categories:information using behavior,information adoption behavior,information dissemination behavior and continuous usage behavior.In the future,it is necessary to enrich research methods,subdivide research objects and clarify subject connotation and extension.