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.Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.
Liping BAI ; Jin YANG ; Siting YU ; Zhongzheng XIANG ; Yuanyuan ZENG ; Meiling SHEN ; Xiaorong KOU ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2024;14(2):821-835
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
4.Clinical efficacy and safety of amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension
Min ZHANG ; Na ZHOU ; Xiufeng LIU ; Qunqun YU ; Guangping CHEN ; Meiling XIE ; Meihua LIU ; Xiang YANG ; Yali CHEN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(5):691-695
Objective:To investigate the clinical efficacy and safety of amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension.Methods:A total of 280 patients with primary hypertension who were treated at Shougang Shuigang Hospital between June 2022 and June 2023 were selected as study subjects. A clinical case-control study was conducted, and the RAND function method was utilized to randomly allocate the subjects into four groups, each receiving a different treatment: amlodipine besylate group (Group A, n = 70), benazepril hydrochloride group (Group B, n = 70), compound formulation amlodipine besylate and benazepril hydrochloride tablets group (Group C, n = 71), and amlodipine besylate plus benazepril hydrochloride group (Group D, n = 69). Relevant therapeutic indicators (blood pressure compliance rate, changes in blood pressure values) and safety indicators (adverse reactions, medication adherence) were observed. Results:The blood pressure compliance rates of Group C and Group D were 91.5% (65/71) and 89.9% (62/69), respectively. There was no statistically significant difference between the two groups ( χ2 = 1.24, P = 0.143), but both were higher than the rates of 77.1% (54/70) and 74.3% (52/70) in Group A and Group B, respectively ( χ2 = 5.68, 4.86, P = 0.004, 0.012). Before treatment, there was no statistically significant difference in systolic and diastolic blood pressure among the four groups of patients (all P > 0.05). After treatment, there was a statistically significant decrease in both systolic and diastolic blood pressure among the four groups compared with their pre-treatment levels (all P < 0.05). Specifically, Group C and Group D exhibited significant reductions in blood pressure following treatment ( t = 4.35, 5.12, 7.25, 5.86, all P < 0.05). Meanwhile, there was no statistically significant difference in systolic blood pressure between Group C and Group D after treatment ( P > 0.05), while diastolic blood pressure was lower in Group C than Group D after treatment ( t = 6.01, P < 0.05). There was a significant downward trend observed in total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels (all P < 0.05). Notably, Group B and Group D reported higher incidences of dry cough, with 15 and 10 cases, respectively, compared with Group A and Group C, which had 1 and 3 cases, respectively. These differences were statistically significant ( χ2 = 4.25, 5.04, both P < 0.05). Furthermore, the treatment compliance rates for Group A, Group B, and Group C were 72.9% (51/70), 71.4% (50/70), and 74.6% (53/71), respectively, all exceeding the 46.4% (32/69) compliance rate of Group D. These differences were also statistically significant ( χ2 = 4.68, 5.24, 4.98, all P < 0.05). Conclusion:The clinical efficacy and safety of the compound formulation amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension are superior to those of single tablets and combination therapy.
5.Study on molecular mechanism of Wumei-Fangfeng drug in regulating Treg/Th17 immune balance in allergic rhinitis
Zhaolan SUN ; Xia LI ; Tingting HUANG ; Meiling XIANG ; Fengying ZHANG
Chinese Journal of Immunology 2024;40(9):1908-1913,中插1
Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1β and MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.
6.Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China
Lei WANG ; Jie SHAO ; Wenhong DONG ; Shuangshuang ZHENG ; Bingquan ZHU ; Qiang SHU ; Wei CHEN ; Lichun FAN ; Jin SUN ; Yue GAO ; Youfang HU ; Nianrong WANG ; Zhaohui WANG ; Tingting NIU ; Yan LUO ; Ju GAO ; Meiling TONG ; Yan HU ; Wei XIANG ; Zhengyan ZHAO ; Meng MAO ; Fan JIANG
Chinese Journal of Pediatrics 2024;62(5):416-422
Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.
7.Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms
Xinyue WANG ; Jiqiang GUO ; Qing YU ; Luyao ZHAO ; Xiang GAO ; Li WANG ; Meiling WEN ; Junrong YAN ; Meiwen AN ; Yang LIU
Biomolecules & Therapeutics 2024;32(5):509-522
Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.
8.Prenatal imaging classification and potential diseases of fetal abnormal sylvian fissure
Yimei LIAO ; Bing WANG ; Huaxuan WEN ; Shuyuan OUYANG ; Dongming HAN ; Caiqun LUO ; Yang LIU ; Bingguang LIU ; Qing ZENG ; Yue QIN ; Dandan LUO ; Meiling LIANG ; Xin WEN ; Zhixuan CHEN ; Haishan XIANG ; Ying YUAN ; Guanxun CHENG ; Shengli LI
Chinese Journal of Ultrasonography 2023;32(3):211-219
Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.
9.Feasibility study of prenatal ultrasound in the evaluation of normal fetal sylvian fissure maturation by simplified grading
Yimei LIAO ; Huaxuan WEN ; Bing WANG ; Haishan XIANG ; Qing ZENG ; Yue QIN ; Dandan LUO ; Meiling LIANG ; Xin WEN ; Yan DING ; Mengyu ZHANG ; Zhixuan CHEN ; Ying YUAN ; Shengli LI
Chinese Journal of Ultrasonography 2022;31(1):30-36
Objective:To observe the morphological changes of the sylvian fissure on the transthalamic section of fetal brain at 20-32 weeks, and grade the fetal sylvian fissure development by means of a simple scoring system and explore its clinical feasibility.Methods:From September 2018 to June 2020, 487 normal single fetuses of 20-32 weeks were examined in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University. The sylvian fissure maturation was analyzed on the transthalamic section of fetal brain at 20-32 weeks and was graded from 0 to 5: un-visualized (grade 0), shallow arc (grade 1), obtuse-angled platform (grade 2), right-angled platform (grade 3), acute-angled platform (grade 4), and closed operculum (grade 5). The pregnancy outcomes and gestational age were recorded.Statistical analysis was performed by SPSS 20.0 software using box plot, Mann-Whitney U test, Weighted Kappa coefficient. Results:Left sylvian fissuer grades were obtained in 280 fetuses and right sylvian fissure grades were obtained in 247 fetuses. The fetal sylvian fissure maturation at 20-32 weeks was graded from 0 to 5, which increased with advancing gestation. Grade 0 only appeared in 3 fetuses at 20 weeks, and 99.4% fetuses at 20 weeks had grade ≥1. Grade 1 appeared in 20-22 weeks, grade 2 in 20-25 weeks, grade 3 in 22-26 weeks, grade 4 in 25-32 weeks, and grade 5 in 27-32 weeks. Box-plot and Mann-Whitney U test showed that gestational week distribution of sylvian fissure at all grades was symmetric on both sides ( P>0.05). The Weighted Kappa coefficients were 0.857(95% CI=0.750-0.957) and 0.939 (95% CI=0.859-1.000), respectively, with strong consistency regarding inter- and intra-observer agreements. Conclusions:Fetal sylvian fissure maturation at 20-32 weeks can be evaluated by means of a simple scoring system with symmetrical grading of both sides.
10. Survey on the stunting of children under seven years of age in nine cities of China
Yaqin ZHANG ; Hui LI ; Huahong WU ; Xinnan ZONG ; Yichen LI ; Jia LI ; Xiaomei XIANG ; Jing ZHANG ; Meiling TONG ; Zhongqiang CAO ; Suifang LIN ; Wei CHEN ; Ke ZHU
Chinese Journal of Pediatrics 2020;58(3):194-200
Objective:
To survey the children under 7 years of age in nine cities of China for a better understanding of the current situation of childhood stunting.
Methods:
According to a stratified cluster sampling design, a cross-sectional survey on children under 7 years of age was carried out in 9 cities (Beijing, Harbin and Xi′an in northern China; Shanghai, Nanjing and Wuhan in central China; and Guangzhou, Fuzhou and Kunming in southern China) from June to November in 2016. A total of 110 499 children were recruited. Height of children was evaluated using the growth standards for Chinese children (2009 edition) .Children with height less than the 3rd percentile of the growth standards were considered as stunting, and children with height between the 3rd and 10th percentiles of the growth standards were considered as relatively short stature. Chi-square test was used for comparison between data of boys and girls, urban and suburban, as well as among different ages and regions.
Results:
Totally 113 084 children under 7 years of age should be investigated and actually 110 499 children were investigated, with a rate of 97.7%. The prevalence of stunting was 1.9% (2 141/110 499) among all the children. The prevalence of stunting in urban children (1.6%, 904/55 524) was lower than that in suburban children (2.3%, 1 237/54 975, χ2=56.246,

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