1.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
2.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
3.Differentiation and Treatment of Polycystic Ovary Syndrome from Perspective “Deficiency Cause,Cold Accumulation, and Qi Stagnation” in Essentials from the Golden Cabinet (《金匮要略》)
Yizhuo QIAO ; Yi LI ; Yini SUN ; Yajun LI ; Yating QI ; Heqiao LI ; Xinru CHEN ; Jinghong XIE
Journal of Traditional Chinese Medicine 2024;65(7):745-749
“Deficiency cause, cold accumulation, and qi stagnation” originates from Essentials from the Golden Cabinet (《金匮要略》), which is a guiding principle for the pathogenesis of women's diseases, pioneering the differentiation and treatment of women's diseases based on patterns, and having a profound influence on future generations. Following the classical principles and simplifying the complexities, this paper explored the pathogenesis and mechanism of polycystic ovary syndrome (PCOS) from the perspective of “deficiency cause, cold accumulation, and qi stagnation”, and believed that depletion of essence and blood, long-term accumulation of internal cold, and qi constraint and blood stasis are the causes of PCOS, with depletion of essence and blood, and lack of nourishment of zang-fu (脏腑) organs as the root, and cold pathogen invasion, qi constraint and blood stasis as the branch. The main treatment principle is “treating deficiency with supplementation”, and dispelling pathogen while reinforcing healthy qi, along with “treatment of cold by warming” and “treatment of stagnation by dispersing”. This is of great significance for the treatment of polycystic ovary syndrome. Clinically, these methods can be used flexibly to guide treatment and formula selection for PCOS, with the goal of harmonizing qi and blood and regulating menstruation.
4.Sub-chronic aluminum exposure induces cognitive impairment through ALKBH5/PTEN/AKT signaling pathway in rats
Yan LIU ; Xiaoyu ZHANG ; Weitao ZHANG ; Feifan XIAO ; Ping CUI ; Binhong WANG ; Xinru CHEN ; Bin JIANG ; Huan CHEN ; Li LIN ; Jing ZHANG ; Huan LI
China Occupational Medicine 2024;51(2):144-149
ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.
5.Basic procedures and issue analysis of nursing systematic reviews
Lei FAN ; Jihong SONG ; Shaohua CHEN ; Xinru YANG ; Yaman ZHAO ; Jieling WU
Chinese Journal of Nursing 2024;59(3):281-286
Through comprehensive and systematic collection of existing evidence,systematic review adopts clinical epidemiological methods,strictly evaluates the quality of evidence,qualitatively or quantitatively combines research results,and finally provides a reliable basis for solving a focused clinical problem.The number of systematic reviews has increased rapidly.With references to the Checklist,this review discussed the typical issues with current systematic reviews in nursing,and highlighted the crucial components for reporting systematic reviews at every essential step.
6.Association of time in range with metabolic associated fatty liver disease and liver fibrosis in patients with type 2 diabetes
Danyu WANG ; Kaikun LIU ; Xinru DENG ; Xiaoyang SHI ; Junpeng YANG ; Na XU ; Yaonan CHEN ; Huijuan YUAN
Chinese Journal of Endocrinology and Metabolism 2024;40(3):198-203
Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.
7.Characteristics Evaluation and Application Analysis on Animal Models of Recurrent Spontaneous Abortion
Tiansong DING ; Jinghong XIE ; Bin YANG ; Heqiao LI ; Yizhuo QIAO ; Xinru CHEN ; Wenfan TIAN ; Jiapei LI ; Wanyi ZHANG ; Fanxuan LI
Laboratory Animal and Comparative Medicine 2024;44(4):393-404
Objective To summarize and evaluate the characteristics of current recurrent spontaneous abortion(RSA)animal models at home and abroad,and to provide reference and guidance for the standardized preparation of RSA models.Methods"Recurrent spontaneous abortion"and"animal model"were used as co-keywords in CNKI,Wanfang,VIP,PubMed and Web of Science databases to search the RSA animal experimental literature,covering the period up to January 20,2024,and a total of 1 411 articles were collected.The analysis focused on construction methods and essential elements of RSA animal models,the modeling process and result evaluation,as well as the application of these models in pharmacological and pharmacodynamic research.An Excel table was established for systematic analysis and discussion.Results A total of 138 experimental studies were obtained after screening.In constructing RSA animal models,immunological models were the most widely used in Western medicine(96.92%),with the Clark model being the main one(92.31%).In traditional Chinese medicine(TCM)models,70.00%were kidney deficiency-luteal inhibition-syndrome combination models,20.00%were kidney deficiency and blood stasis models,and 10.00%were deficiency-heat syndrome models.Most animals were selected at 6-8 weeks(33.86%)and 8 weeks(32.28%)of age.The majority of animals were paired for mating at 18:00 on the day of cage pairing.In 81.03%of literatures,vaginal plugs were checked once the following morning,with 8:00 being the most common time(17.02%).The most commonly used drug administration cycle was 14 days of continuous gavage after pregnancy.Among the tested drugs,Western drugs were mainly protein-based(29.17%),while TCM drugs were mainly TCM decoction(81.11%).The most frequently used methods for detecting indicators included visual observation of embryos(22.54%),western blot(15.96%),PCR(13.58%),ELISA(12.91%),HE staining(10.80%)and immunohistochemistry(9.39%).Conclusion The etiology of RSA is complex,and corresponding animal models should be established based on different etiologies.Clark model is commonly used in the construction of Western medicine model,while the kidney deficiency-luteal inhibition-syndrome combination model is predominant in TCM.RSA animal model is widely used in related research,but systematic evaluation needs to be strengthened.
8.Impact and Interaction of Disease Severity and Hospital Preparations Associated with 28-Day Fatality Risk in COVID-19 Hospitalizations:A Retrospective Cohort Study
Xinru HU ; Fan YANG ; Yingtian WANG ; Chen WANG ; Xirui QIU ; Fangyi CHEN ; Wei WANG ; Xiaoxiao WANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):618-627
OBJECTIVE To identify the influence factors associated with 28-day fatality among COVID-19 hospitalizations and to analyze the interaction between the disease severity at admission and the use of hospital preparations.METHODS A retrospective review of records from COVID-19 hospitalizations aged 18 to 90 who were admitted to the Jiangsu Province Hospital of Chinese Medi-cine from December 15,2022 to January 15,2023 were conducted.Patients who died or were lost to follow-up within 48 h of admis-sion were excluded.Patients were divided into survival and death groups based on their 28-day fatality status.Descriptive statistics were used to characterize the two groups and multivariate logistic regression models were employed to identify factors influencing 28-day fatality risk.The interaction between the severity of illness at admission and the use of hospital preparations was explored through cross-over analysis and hierarchical regression analysis.RESULTS Significant differences were observed between the survival and death groups in terms of severity of illness at admission,hospital preparations usage,steroid therapy,age,platelet count,lactate dehydro-genase levels,and urea(P<0.05.Crossover analysis and hierarchical logistic regression analysis revealed a significant antagonistic interaction between the severity of illness at admission and the use of hospital formulations both before adjustment(RERI=-20.678,95%CI:-33.703~-7.652;APAI=-2.301,95%CI:-4.027~-0.575 and after adjusting for gender,age,clinical characteristics and further adjusting for laboratory parameters(RERI=-5.972,95%CI:-10.564~-1.380;APAI=-2.205,95%CI:-4.131~-0.279,and it was an antagonistic interaction both before(SI=0.279,95%CI:0.157~0.493 and after adjustment(SI=0.222,95%CI:0.095~0.523.CONCLUSION The use of hospital preparations significantly reduces the 28-day fatality risk among COV-ID-19 hospitalizations and a clear antagonistic interaction was observed between the disease severity at admission and the use of hospi-tal preparations.
9.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
10.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

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