1.Effect of atractylenolide I on myocardial mitochondrial function in mice with dilated cardiomyopathy by regulating cGAS/STING pathway
Hongxing WANG ; Huichao ZHANG ; Zhiwei LI ; Xiaofang YU
Journal of China Pharmaceutical University 2026;57(1):90-97
This study aimed to investigate the effect of atractylenolide I (Atr-I) on myocardial mitochondrial function in mice with dilated cardiomyopathy (DCM) by regulating the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. Sixty SPF-grade male cTnT R141W transgenic DCM mice were randomly divided into the DCM group, Atr-I low-dose group (60 mg/kg), Atr-I high-dose group (240 mg/kg), captopril group (0.01 g/kg), and Atr-I high-dose+cGAS/STING pathway activator 5,6-dimethylxanthenone-4-acetic acid (DMXAA) group, with 12 mice in each group. Additionally, 12 male C57BL/6J mice were used as the control group. All mice were administered via oral gavage once daily for 8 weeks. Cardiac function was assessed using the Vevo 770 ultrasound system; myocardial pathology was examined via HE staining; mitochondrial ultrastructure in cardiomyocytes was observed using transmission electron microscopy; the proportion of cardiomyocytes without reduced mitochondrial membrane potential was detected using JC-1 staining; reactive oxygen species (ROS) content in myocardial tissue was measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining; adenosine triphosphate (ATP) content in myocardial tissue was determined using a commercial kit; and Western blot was performed to detect the protein expression levels of mitofusin-2 (MFN2), dynamin-related protein 1 (DRP1), cGAS, STING, interferon-β (IFN-β), CXC chemokine ligand 10 (CXCL10), and interleukin-6 (IL-6) in myocardial tissue. The aim was to observe the effect of Atr-I on myocardial mitochondrial function in DCM mice. The results showed that low- and high-dose Atr-I (60 mg/kg, 240 mg/kg) intervention improved cardiac function, alleviated cardiomyocyte hypertrophy and disordered muscle fiber arrangement, ameliorated mitochondrial ultrastructure in cardiomyocytes, reduced ROS content and the protein expression levels of DRP1, cGAS, STING, IFN-β, CXCL10, and IL-6 in myocardial tissue, and increased the proportion of cardiomyocytes without reduced mitochondrial membrane potential, as well as ATP content and MFN2 protein expression in myocardial tissue. However, DMXAA attenuated the beneficial effects of high-dose Atr-I on myocardial mitochondrial function in DCM mice. In conclusion, Atr-I may improve myocardial mitochondrial function in DCM mice by inhibiting the cGAS/STING pathway.
2.Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system.
Jizhuang MA ; Keda ZHANG ; Wenhan LI ; Yu DING ; Yongfeng CHEN ; Xiaoyu HUANG ; Tong YU ; Di SONG ; Haoran NIU ; Huichao XIE ; Tianzhi YANG ; Xiaoyun ZHAO ; Xinggang YANG ; Pingtian DING
Acta Pharmaceutica Sinica B 2025;15(6):3291-3304
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEOx-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEOx) by ester bonds. AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEOx-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEOx-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.
3.Development of a standard for the accreditation of community training teacher in hospice care for general practitioners
Huichao ZHENG ; Ying YU ; Hua YANG ; Zhijie YU ; Yuezhong TANG ; Qiong ZHU ; Sunfang JIANG ; Shanzhu ZHU
Chinese Journal of General Practitioners 2025;24(2):169-175
Objective:To formulate a community teacher standard for the training of general practitioner program (direction in hospice care).Methods:This was a qualitative study. Twenty-nine experts in general practice and hospice care from various teaching hospitals and community health service centers were invited to participate in two rounds of Delphi consultation from April to August 2022. Based on the results of the consultation, a standard for community faculty training in comprehensive care and end-of-life care for general practitioners was formulated, and the weight coefficients of the indicators were calculated.Results:Of the 29 experts, 11 (37.9%) were male, their age was (52.9±8.9) years, and their working life was (17.0±7.2) years. In the two rounds of expert consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.789 and 0.851, and the expert opinion coordination coefficient W of the importance of all indicators was 0.124 and 0.131, respectively ( χ2=123.01, 131.71, P<0.05). Finally, a set of community-based teacher standard for general practitioner specialty training (direction in hospice care) was established, which consisted of 4 first-level indicators and 30 second-level indicators. The four first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, and scientific research ability, all with the weight coefficients of 0.254, 0.254, 0.252 and 0.240, respectively. Conclusion:The standard of teachers in the community base of general practitioner specialty training (direction in hospice care) established in this study is more scientific, which is conducive to the comprehensive evaluation of teachers in the community training base.
4.Development of accreditation standards for clinical teaching faculty in hospice care training of general practitioners
Ying YU ; Huichao ZHENG ; Hua YANG ; Zhijie YU ; Yuezhong TANG ; Qiong ZHU ; Sunfang JIANG ; Shanzhu ZHU
Chinese Journal of General Practitioners 2025;24(4):420-425
Objective:To develop accreditation standards for clinical faculty in general practitioner specialized training of hospice care.Methods:This was a qualitative study. Twenty nine experts in fields of general practice and hospice care were invited for two rounds of Delphi consultation from April 2022 to August 2022. Based on the consultation results, the accreditation standards for clinical faculty in general practitioner training bases of hospice care specialty was preliminarily developed.Results:The mean age of the consulting experts was (52.9±8.9) years with a mean working year of (17.0±7.2), and 69.0% (20/29) of them held senior professional titles. In the two rounds of consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.765 and 0.813, and the expert opinion coordination coefficient W for the importance of all indicators was 0.112 and 0.196, respectively. The expert opinions tended to be consistent. Finally, a set of clinical base faculty standards for general specialty training was developed, which consisted of 4 first-level indicators and 24 second-level indicators. The 4 first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, scientific research ability, with the weight coefficients of 0.253, 0.255, 0.254 and 0.241, respectively. Conclusion:The standards for clinical teaching faculty in general practitioner specialty training base of hospice care has been established in this study, which is conducive to the comprehensive quality evaluation for training faculty.
5.Study on the construction of admission evaluation indicators for terminal patients in community hospice wards
Huichao ZHENG ; Ying YU ; Xiaopan LI ; Ming LIU ; Yuezhong TANG ; Zhijie YU ; Qiong ZHU ; Sunfang JIANG
Chinese Journal of General Practitioners 2025;24(9):1106-1113
Objective:To construct a set of admission evaluation indicators for terminal patients in community hospice wards.Methods:This qualitative study employed a mixed-methods approach. From January to June 2023, 10 physicians working in community hospice wards in Shanghai participated in one-on-one, semi-structured, in-depth interviews. Based on the interview findings and literature review, a preliminary set of admission evaluation indicators was drafted. Subsequently, from July to December 2023, 18 national experts in hospice/palliative care were selected for a two-round Delphi expert consultation to refine the indicators. The final indicator system was established based on the consultation results, and the weight coefficients for each indicator were determined.Results:Sixteen experts completed both rounds of consultation. The experts had a mean age of (52.0±8.3) years and a mean working experience of (14.4±6.8) years. The response rates for the two rounds were 88.9% and 100.0%, respectively. The authority coefficients were 0.875 and 0.894, and the Kendall′s W coordination coefficients were 0.338 (χ2=471.737, P<0.001) and 0.349 (χ2=398.230, P<0.001), respectively. After two rounds of Delphi consultation, a final admission evaluation indicator system was established, comprising 4 first-level indicators and 63 second-level indicators. The first-level indicators and their weight coefficients were: Underlying Disease (0.256 7), Survival Prognosis (0.256 7), Holistic Needs (0.256 6), and Social Environment (0.240 0). Conclusion:The admission evaluation indicator system for terminal patients in community hospice wards developed in this study facilitates the standardized development of community hospice/palliative care services and contributes to providing high-quality care for patients and their families.
6.1,25-dihydroxyvitamin D3 regulates the Th17/Treg cell balance and improves sepsis-induced acute kidney injury via mediating VDR-NLRP6
Xin LUO ; Yudong MA ; Mingjin LÜ ; Huichao YU
Journal of China Medical University 2025;54(8):690-696
Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.
7.1,25-dihydroxyvitamin D3 regulates the Th17/Treg cell balance and improves sepsis-induced acute kidney injury via mediating VDR-NLRP6
Xin LUO ; Yudong MA ; Mingjin LÜ ; Huichao YU
Journal of China Medical University 2025;54(8):690-696
Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.
8.Development of a standard for the accreditation of community training teacher in hospice care for general practitioners
Huichao ZHENG ; Ying YU ; Hua YANG ; Zhijie YU ; Yuezhong TANG ; Qiong ZHU ; Sunfang JIANG ; Shanzhu ZHU
Chinese Journal of General Practitioners 2025;24(2):169-175
Objective:To formulate a community teacher standard for the training of general practitioner program (direction in hospice care).Methods:This was a qualitative study. Twenty-nine experts in general practice and hospice care from various teaching hospitals and community health service centers were invited to participate in two rounds of Delphi consultation from April to August 2022. Based on the results of the consultation, a standard for community faculty training in comprehensive care and end-of-life care for general practitioners was formulated, and the weight coefficients of the indicators were calculated.Results:Of the 29 experts, 11 (37.9%) were male, their age was (52.9±8.9) years, and their working life was (17.0±7.2) years. In the two rounds of expert consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.789 and 0.851, and the expert opinion coordination coefficient W of the importance of all indicators was 0.124 and 0.131, respectively ( χ2=123.01, 131.71, P<0.05). Finally, a set of community-based teacher standard for general practitioner specialty training (direction in hospice care) was established, which consisted of 4 first-level indicators and 30 second-level indicators. The four first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, and scientific research ability, all with the weight coefficients of 0.254, 0.254, 0.252 and 0.240, respectively. Conclusion:The standard of teachers in the community base of general practitioner specialty training (direction in hospice care) established in this study is more scientific, which is conducive to the comprehensive evaluation of teachers in the community training base.
9.Development of accreditation standards for clinical teaching faculty in hospice care training of general practitioners
Ying YU ; Huichao ZHENG ; Hua YANG ; Zhijie YU ; Yuezhong TANG ; Qiong ZHU ; Sunfang JIANG ; Shanzhu ZHU
Chinese Journal of General Practitioners 2025;24(4):420-425
Objective:To develop accreditation standards for clinical faculty in general practitioner specialized training of hospice care.Methods:This was a qualitative study. Twenty nine experts in fields of general practice and hospice care were invited for two rounds of Delphi consultation from April 2022 to August 2022. Based on the consultation results, the accreditation standards for clinical faculty in general practitioner training bases of hospice care specialty was preliminarily developed.Results:The mean age of the consulting experts was (52.9±8.9) years with a mean working year of (17.0±7.2), and 69.0% (20/29) of them held senior professional titles. In the two rounds of consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.765 and 0.813, and the expert opinion coordination coefficient W for the importance of all indicators was 0.112 and 0.196, respectively. The expert opinions tended to be consistent. Finally, a set of clinical base faculty standards for general specialty training was developed, which consisted of 4 first-level indicators and 24 second-level indicators. The 4 first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, scientific research ability, with the weight coefficients of 0.253, 0.255, 0.254 and 0.241, respectively. Conclusion:The standards for clinical teaching faculty in general practitioner specialty training base of hospice care has been established in this study, which is conducive to the comprehensive quality evaluation for training faculty.
10.Study on the construction of admission evaluation indicators for terminal patients in community hospice wards
Huichao ZHENG ; Ying YU ; Xiaopan LI ; Ming LIU ; Yuezhong TANG ; Zhijie YU ; Qiong ZHU ; Sunfang JIANG
Chinese Journal of General Practitioners 2025;24(9):1106-1113
Objective:To construct a set of admission evaluation indicators for terminal patients in community hospice wards.Methods:This qualitative study employed a mixed-methods approach. From January to June 2023, 10 physicians working in community hospice wards in Shanghai participated in one-on-one, semi-structured, in-depth interviews. Based on the interview findings and literature review, a preliminary set of admission evaluation indicators was drafted. Subsequently, from July to December 2023, 18 national experts in hospice/palliative care were selected for a two-round Delphi expert consultation to refine the indicators. The final indicator system was established based on the consultation results, and the weight coefficients for each indicator were determined.Results:Sixteen experts completed both rounds of consultation. The experts had a mean age of (52.0±8.3) years and a mean working experience of (14.4±6.8) years. The response rates for the two rounds were 88.9% and 100.0%, respectively. The authority coefficients were 0.875 and 0.894, and the Kendall′s W coordination coefficients were 0.338 (χ2=471.737, P<0.001) and 0.349 (χ2=398.230, P<0.001), respectively. After two rounds of Delphi consultation, a final admission evaluation indicator system was established, comprising 4 first-level indicators and 63 second-level indicators. The first-level indicators and their weight coefficients were: Underlying Disease (0.256 7), Survival Prognosis (0.256 7), Holistic Needs (0.256 6), and Social Environment (0.240 0). Conclusion:The admission evaluation indicator system for terminal patients in community hospice wards developed in this study facilitates the standardized development of community hospice/palliative care services and contributes to providing high-quality care for patients and their families.

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