1.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
2.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
3.Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020
Wenji ZHUO ; Ran WEI ; Yanmei CHEN ; Xunxun CHEN ; Meiling YU ; Huixin GUO ; Hongdi LIANG ; Jing LIANG ; Xiaoyu LAI
The Journal of Practical Medicine 2024;40(5):702-707
Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.
4.Effects of Qiangxin decoction on myocardial mitochondrial homeostasis and energy metabolism in chronic heart failure rats
Yan PANG ; Meiling MAO ; Jianqi LU ; Jiayong CHEN ; Meiling TANG ; Puwei HUANG
China Pharmacy 2024;35(15):1831-1836
OBJECTIVE To investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure (CHF) based on mitophagy. METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery. The successful modeling rats were divided into model group, Qiangxin decoction group [12.25 g/(kg·d), calculated by crude drug], captopril group [10.38 mg/(kg·d)], and Qiangxin decoction+captopril group (the same usage and dosage as single drug group) according to a random number table method, with 8 rats in each group. Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group. Starting from the second day after successful modeling, the rats in administration groups were given relevant drug intragastrically, twice a day, for consecutive 28 days. After the last medication, the levels of adenosine triphosphate (ATP), adenosine monophosphate (AMP) and free fatty acid (FFA) in infarcted myocardial tissues were detected, the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed, as well as the protein expressions of B cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), TANK-binding kinase 1 (TBK1), p62 were detected in each group. RESULTS Compared with the sham operation group, the infarcted myocardial tissue fibrosis was changed evidently, with a large number of mitochondrial swelling and fusion, and internal cristae rupture; the levels of AMP and FFA, the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue, while the level of ATP, and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly (P<0.05). Compared with the model group, the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved; the levels of AMP and FFA, and the protein expressions of Bax and p62 in infarcted myocardial tissue were significantly decreased or down-regulated in administration groups, while the level of ATP, and the protein expressions of Bcl-2 and TBK1 were increased or up-regulated significantly (P<0.05). And the effect of Qiangxin decoction+captopril group was better than that of single drug group. CONCLUSIONS Qiangxin decoction can alleviate myocardial fibrosis and mitochondrial swelling in CHF rats, and improve their myocardial energy metabolism, which may be related to regulating the expression of Bcl-2, Bax, TBK1 and p62 proteins and promoting myocardial mitophagy.
5.Application of whole exome sequencing in patients with primary ciliary dyskinesia
Ke CHEN ; Jing SHI ; Lijuan HU ; Li ZHANG ; Minlu CAO ; Wei GUO ; Meiling JIN
Chinese Journal of Clinical Medicine 2024;31(6):1006-1010
A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.
6.Reference values for inspiratory muscle related indexes of preschool children in Nanjing
Yanlu HE ; Zhiyong YANG ; Weiding CHEN ; Xia CHI ; Meiling TONG
Chinese Journal of Child Health Care 2024;32(5):507-510
【Objective】 To generate reference values for inspiratory muscle of preschool children in Nanjing, so as to provide a reference index for evaluating children′s lung function and exercise performance. 【Methods】 A total of 236 preschool children were selected from the main urban area of Nanjing by stratified cluster sampling.The inspiratory muscles were evaluated by breath link respiratory function evaluation system to obtain the maximum inspiratory pressure (MIP) and inspiratory peak flow rate.Pearson analysis was used to determine the correlation of MIP and inspiratory peak flow rate with gender, age, height and weight.Multiple linear stepwise regression analysis was used to obtain the formula of MIP and inspiratory peak flow rate. 【Results】 Differences in MIP and peak inspiratory flow rate were not significant between boys and girls (P>0.05), but were statistically significant among different age groups and showed an increasing trend with age (F=13.660, 33.581, P<0.001).MIP and peak inspiratory flow rate were positively correlated with children′s age, height and weight (P<0.001).The regression model, proved to be statistically significant(F=12.913、22.398, P<0.08), indicated that height was the best predictor of MIP and age was the best predictor of inspiratory peak flow rate. 【Conclusions】 This study is the first study on the predicted value of inspiratory muscle in preschool children in China.The predicted value formula can provide a reference for clinical inspiratory muscle evaluation.
7.Efficacy and safety of omalizumab in the treatment of allergic bronchopulmonary aspergillosis:a real-world study
Jing SHI ; Zilinuer ABUDUXUKUER ; Hui CAI ; Jian WANG ; Yu CHEN ; Ke CHEN ; Ling YE ; Meiling JIN
Chinese Journal of Clinical Medicine 2024;31(2):161-168
Objective To explore the efficacy and safety of omalizumab in the treatment of allergic bronchopulmonary aspergillosis(ABPA).Methods The clinical data of 26 ABPA patients treated with omalizumab in Zhongshan Hospital,Fudan University from November 2018 to December 2023 and 24 ABPA patients treated with prednisone combined with itraconazole in the same period were analyzed retrospectively.The primary outcomes were exacerbation times and oral corticosteroid-sparing effect.The secondary outcomes were respiratory symptoms,circulating eosinophil count,total immunoglobin E(IgE)level,specific IgE for aspergillus,pulmonary function(the percentage value of forced expiratory volume in one second predicted[FEV1%pred]),fraction of exhaled nitric oxide(FeNO),thoracic computed tomography(CT)manifestation and adverse reactions.Results In omalizumab group,the exacerbation times of ABPA after 6 and 12 months of treatment were 0(0,0)times/6 months and 0(0,1)times/6 months,there was no significant difference(P=0.157),which were significantly lower than those of the baseline(1[1,2]times/6 months,P<0.001).The oral dose of prednisone decreased from 10(5,15)mg/d(before treatment)to 3.125(0,5)mg/d(6 months after treatment,P<0.001).After 12 months of treatment,the oral dose of prednisone was 0(0,3.125)mg/d,which was significantly lower than that of the baseline dose(P=0.003).After treatment with omalizumab for 12 months,the FeNO level decreased significantly(26[13,36]×10﹣9 vs 30[18,56]×10﹣9,P=0.049).There was no significant difference in blood eosinophil count,total IgE level,specific IgE for aspergillus and FEV1%pred before and after omalizumab treatment.After 6 months of treatment with omalizumab,respiratory symptoms were relieved in 23 patients(88.5%)and radiographic improvement was achieved in eight out of sixteen patients(50%)with mucus plugs.More patients successfully discontinued oral prednisone when treated with omalizumab for 12 months than those in control group(P=0.035).During the treatment of omalizumab,4(15.4%)patients had a slight increase in alanine aminotransferase(ALT),and 1 patient was complicated with hepatocellular carcinoma during follow-up.Conclusions Omazumab treatment can effectively reduce the number of acute episodes of ABPA,reduce the dosage of oral glucocorticoids,improve FeNO,facilitate the absorption of mucus plugs,and has high safety.
8.Effects of Electroacupuncture Preconditioning on Local Inflammation and DNA-PK/Rictor/Myc Signaling Pathway in Myo-cardium of Acute Myocardial Ischemia Mice
Minjiao JIANG ; Rou PENG ; Yuhang YAN ; Xiaoer LIU ; Danying QIAN ; Xiaohan LU ; Liyao CHEN ; Meiling YU ; Shengfeng LU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):589-597
OBJECTIVE To observe the changes of cardiac function,local inflammation level and macrophage M2 polarization in mice with acute myocardial infarction(AMI after electroacupuncture preconditioning at the Neiguan point,and to explore the possible mechanisms from the perspective of regulating the DNA-PK/Rictor/Myc signaling pathway.METHODS Male C57BL/6J mice were randomly divided into sham group,model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group received bilateral electroacupuncture interventions at the Neiguan points,sparse-dense wave,2/15 Hz,1 mA,20 min/time,once a day for 3 consecutive days,and AMI models were performed 0.5 h after the electroacupuncture interventions.The myocardial ischemia model was prepared by ligating the left anterior descending branch.Echocardiography was used to detect cardiac ejection frac-tion(EF and fractional shortening(FS to evaluate cardiac function;HE and TUNEL staining were used to observe the pathological morphology of myocardium and apoptosis of cardiomyocytes,and immunohistochemistry and ELISA were used to detect IL-1β,TNF-α and NLRP3 in infarcted myocardium and peripheral blood to evaluate the level of inflammation;flow cytometry was used to detect cardiac macrophage polarization status,and Western blot method to detect the protein expression levels of DNA-PK,p-DNA-PK,Rictor and Myc in infarcted myocardium.RESULTS Compared with the sham group,the model group showed significantly lower EF and FS(P<0.000 1,significant inflammatory cell infiltration,significantly higher cardiomyocyte apoptotic index(P<0.001,up-regulated expression of IL-1β,NLRP3 and TNF-α in the myocardium and serum(P<0.01,P<0.001,a significant increase in the percentage of macrophages(P<0.001,a decrease in the percentage of cardiac M2-type macrophages(P<0.000 1,and a significant decrease in the expression levels of p-DNA-PK,Rictor and Myc proteins in myocardium(P<0.05,P<0.000 1.Compared with the model group,EF and FS were significantly higher in the electroacupuncture group(P<0.000 1,inflammatory cell infiltration was re-duced,cardiomyocyte apoptotic index was decreased(P<0.01,and the expression of IL-1β,NLRP3 and TNF-α was down-regula-ted in myocardium and serum(P<0.05,P<0.01,P<0.001;the macrophage percentage was decreased(P<0.05,cardiac M2-type macrophage percentage was increased(P<0.01,and p-DNA-PK,Rictor and Myc protein expression was enhanced in myocardium(P<0.05,P<0.01,P<0.000 1.CONCLUSION Electroacupuncture preconditioning may promote macrophage M2 polarization,attenuate local inflammation,and reduce cardiomyocyte apoptosis by modulating the DNA-PK/Rictor/Myc signaling pathway,thus im-proving cardiac function and achieving myocardial protective effects.
9.Mechanism of leukemia stem cells immune escape by Traditional Chinese Medicine intervention
Meiling ZHANG ; Yaru CUI ; Shupeng CHEN ; Junyun LUO ; Yingjian ZENG
Chinese Journal of Comparative Medicine 2024;34(2):137-143
Leukemia is a critical disease with a high incidence and extremely high fatality rate.Immune escape by leukemia stem cells(LSC)is the main factor for recurrence and progression after remission.Clinical diagnosis and treatment by Traditional Chinese Medicine(TCM)have distinct advantages of syndrome differentiation and treatment.Based on the purpose of diagnosis and treatment,leukemia treatment by TCM emphasizes the harmony of yin and yang to restore human functions,which is conducive to improve autoimmunity and conforms to the mechanism of intervention for tumor cell immune escape.This article discusses the mechanism and research progress of TCM interventions in LSC immune escape based on literature and TCM theory.
10.Study on the curative effect of Huoluoxiaolingdan formula combined with ginkgolide injection in treatment of blood stasis and collateral obstruction syndrome in convalescent period of cerebral infarction
Le ZHAO ; Lin CHEN ; Meiling JIANG ; Fangfang LIU
China Pharmacist 2024;27(1):125-134
Objective To investigate the efficacy and safety of Huoluoxiaolingdan formula combined with ginkgolide injection in the treatment of ischemic stroke patients with blood stasis blockage syndrome.Methods The ischemic stroke patients with blood stasis blockage syndrome who were treated in Suzhou First People's Hospital from June 2017 to August 2019 were randomly divided into test group and control group.The control group was given ginkgolide injection,and the test group was given Huoluoxiaolingdan formula additionally.Both groups were treated for 2 weeks.The efficacy and adverse drug reactions of the two groups were evaluated,and the changes of clinical scores,hemorheology,blood lipids and inflammatory factors before and after treatment were compared between the two groups.Results A total of 194 patients were included,there were 97 cases in each group.The total effective rate of test group was 91.75%,which was significantly higher than that of control group(79.38%)(P<0.05),and the incidence of adverse reactions was significantly lower than that in the control group(P<0.05).After treatment,NIHSS,CSS and ASS in both groups were lower than before treatment(P<0.05),while BI was higher than before treatment(P<0.05).The levels of ηp,ηb,Fib and EEP in test group were significantly lower than those in control group(P<0.05).HDL-C level of test group was significantly higher than that of control group,TC,LDL-C and TG levels were lower than that of control group(P<0.05).The levels of IL-4 in test group were significantly higher than those in control group,and the levels of IL-1 β,IL-8 and TNF-α were lower than those in control group(P<0.05).The above indexes in the test group was significantly better than that in control group(P<0.05).Conclusion Huoluoxiaolingdan formula combined with ginkgolide injection can significantly improve the efficacy of patients with blood stasis blockage syndrome during the recovery period of ischemic stroke,improve clinical symptom score,correct abnormal hemorheology,reduce blood lipid level,inhibit the progression of inflammation,and alleviate adverse reactions,which has high clinical application value.

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