1.GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension
Liangyu CUI ; Yukun LI ; Tianyue JING ; Yu WANG ; Cong REN ; Tong YIN ; Zhiwei ZHAO ; Jiaheng WANG ; Chenge SUN ; Dasheng LIU ; Zhizheng XING ; Xuejie HAN ; Liying WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):106-115
ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension, synthesize and update the evidence, form expert consensus, and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform (WanFang), Vip Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (Sinomed), National Library of Medicine (PubMed), Cochrane Library, Web of Science, and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31, 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment, Development, and Evaluation profiler (GRADEprofiler) 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included, and the results of literature quality evaluation and risk of bias showed that 70.31% (45/64) of the studies indicated some risks, and 29.69% (19/64) indicated high risks. Compared with conventional western medicines, the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure (SBP) and diastolic pressure (DBP), increase the effective rate of antihypertensive, reduce the incidence of adverse reactions, endothelin-1, and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive, and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive, without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive, and Xinmaitong capsules decreased DBP, with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally, four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension, antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety, but they are mostly weak recommendations in terms of efficacy, and more high-quality evidence is needed.
2.Preliminary Proteomics-based Investigation of Inhibitory Effect and Mechanism of BD-77 by Nebulized Inhalation on Respiratory Viral Infections
Lei BAO ; Zihan GENG ; Shanshan GUO ; Lirun ZHOU ; Ronghua ZHAO ; Jing SUN ; Yanyan BAO ; Xing LI ; Cigang HUANG ; Kun JIANG ; Feiyan PENG ; Zhou XU ; Chenggang HUANG ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):52-59
ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group, model group, Tamiflu group, and BD-77 groups of 75 and 37.5 g·L-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group, model group, chloroquine phosphate group, and BD-77 groups of 75, 37.5, 18.75, and 9.375 g·L-1, with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect related inflammatory factors in lung tissue, and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group, the lung index of mice in each infection group was significantly increased (P<0.01), and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) in the lung tissue of mice infected with human coronavirus 229E were all significantly increased (P<0.01). BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 (P<0.05, P<0.01), cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 (P<0.01), and lower the contents of IL-6, IL-10, and TNF-α in the lung tissue of mice infected with human coronavirus 229E (P<0.01). Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway, TNF signaling pathway, NOD-like signaling pathway, IL-17 signaling pathway, Forkhead box protein O (FoxO) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism, enhancing the immune function of the host, and attenuating inflammatory responses.
3.Prevalence of comorbidity of hypertension, diabetes and dyslipidemia and the association between comorbidity and cardiovascular mortality in population aged 40 years and over in Liaoning Province
Li JING ; Yuanmeng TIAN ; Han YAN ; Qun SUN ; Shubao LI ; Shimin CUI ; Jixu SUN ; Lei SHI ; Yuyao MA ; Guangxiao LI ; Shuang LIU ; Liying XING
Chinese Journal of Cardiology 2024;52(11):1311-1316
Objective:To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality.Methods:This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk.Results:A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P<0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI: 1.63-3.99). Conclusion:The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.
4.Genetic diversity of Ixodes persulcatus in parts of Inner Mongolia
Meng-Yu CUI ; Si SU ; Li-Li XING ; Lan MU ; Rui-Juan GAO ; Qi-Qi GUO ; Hong REN ; Dong-Dong QI ; Jing-Feng YU
Chinese Journal of Zoonoses 2024;40(4):295-301
The aim of this study was to clarify the genetic diversity and population history of Ixodes persulcatus in some ar-eas of Inner Mongolia in order to provide accurate data for effective vector control programs and reveal the transmission mecha-nism.Samples were collected in 10 areas of Inner Mongolia during the active tick season(April 2021-July 2023)using the flag-dragging and manual sampling methods.The 16S rRNA and COI gene were sequenced to clarify genetic diversity of I.per-sulcatus.The positivity rates for the COI gene and 16S rRNA were 90.00%and 98.33%respectively.Overall,18 and 15 haplotypes were identified for the COI gene and 16S rRNA,respectively,with a total haplotype diversity>0.762 and total nucleotide diversity<0.005.The Tajima's values and Fu's Fs were negative for significance.A nucleotide mismatch map was shown as a single peak.The genetic differentiation index FST of the population indicates a small degree of genetic differ-entiation of the population,while analysis of molecular vari-ance indicates that the variation within populations was greater than between populations.Phylogenetic tree and haplotype network plots showed confounding distributions between hap-lotypes.I.persulcatus from the Hinggan League and Hulun-buir regions can adapt to environmental changes and possess abundant genetic diversity.Genetic differentiation is mainly concentrated within the population and no geographical isolation was observed.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Evaluation of the report quality of Chinese and English randomized controlled trials of acupuncture based on CONSORT statement and STRICTA checklist.
Wen-Cui XIU ; Xing MENG ; Xiang-Yu HU ; Lan-Jun SHI ; Wei-Juan GANG ; Xiang-Hong JING
Chinese Acupuncture & Moxibustion 2023;43(3):355-361
OBJECTIVE:
To evaluate the report quality of Chinese and English randomized controlled trials (RCTs) of acupuncture based on the CONSORT statement and STRICTA checklist.
METHODS:
The Chinese and English RCTs of acupuncture published from January 1, 2015 to December 31, 2019 were searched in 7 databases including PubMed. The report quality of the included RCTs was evaluated with the CONSORT 2010 statement and STRICTA checklist.
RESULTS:
A total of 506 Chinese RCTs and 76 English RCTs were included. According to the CONSORT statement, in Chinese RCTs, the items with report rate less than 50% accounted for 78.38% of all items, and the report rate of 25 items, such as background and reason, study design, outcome index, and sample size, was less than 10%. In English RCTs, the items with report rate less than 50% accounted for 35.14% of all items, and 5 items had a report rate of less than 10%. The difference of the report rate of 15 items, such as background, reason and study design, was more than 50% between Chinese and English RCTs. The report rate of all items of STRICTA checklist was relatively high in both Chinese and English RCTs. In Chinese RCTs, the items with report rate less than 50% accounted for 29.41% of all items, which included acupuncture rationale and depth of insertion. In English RCTs, only two items had a report rate less than 50%, which were acupuncture rationale, setting and context of treatment. The report rate of five items, including needle retention time, frequency and duration of treatment sessions, details of other interventions administered to the acupuncture group, setting and context of treatment, and precise description of the control or comparator in Chinese RCTs, were higher than in English RCTs.
CONCLUSION
The report quality of Chinese acupuncture RCT needs to be improved urgently, and corresponding measures should be taken to further standardize the writing and reporting of acupuncture clinical research.
Humans
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Acupuncture Therapy
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Checklist
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Randomized Controlled Trials as Topic/standards*
7.Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb.
Jing Jing JIANG ; Xin ZHENG ; Ming Sheng MA ; Xing Ge CUI ; Shan JIAN ; Xiao Yan TANG ; Xu Dong BAO ; Si Min ZHANG ; Jing Ran MA ; Hong Mei SONG ; Zheng Qing QIU
Chinese Journal of Pediatrics 2023;61(6):515-519
Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans
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Child
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Child, Preschool
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Adolescent
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Prospective Studies
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Glycogen Storage Disease Type I/drug therapy*
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Neutropenia
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Abdominal Pain
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Diarrhea/drug therapy*
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Hypoglycemia
8.Analysis of changes in plasma endothelin-1 concentrations in patients with acute respiratory distress syndrome
Shan FENG ; Yunpeng WANG ; Xiyue CHENG ; Dandan LI ; Ru CUI ; Boya JING ; Haibin LI ; Xing Ming FANG ; Zhiyong WANG
Chinese Journal of Anesthesiology 2023;43(4):441-444
Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.
9.Astragaloside IV for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis.
Xing-Xing LI ; Dong LI ; Xiao-Yun CUI ; Kun ZHOU ; Jing LIU ; Jin-Jin LU ; Yang WU ; Qian LIN ; Yan LI
Chinese journal of integrative medicine 2023;29(7):626-633
OBJECTIVE:
To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).
METHODS:
PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.
RESULTS:
Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).
CONCLUSIONS
AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.
Animals
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Mice
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Rats
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Stroke Volume
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Ventricular Function, Left
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Heart Failure/drug therapy*
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Natriuretic Peptide, Brain
10.Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.
Zekai WU ; Yuan SHI ; Yueli CUI ; Xin XING ; Liya ZHANG ; Da LIU ; Yutian ZHANG ; Ji DONG ; Li JIN ; Meijun PANG ; Rui-Ping XIAO ; Zuoyan ZHU ; Jing-Wei XIONG ; Xiangjun TONG ; Yan ZHANG ; Shiqiang WANG ; Fuchou TANG ; Bo ZHANG
Protein & Cell 2023;14(5):350-368
Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans
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Mice
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Rats
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Cell Proliferation
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Heart/physiology*
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Mammals
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Myocardial Infarction/metabolism*
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Myocytes, Cardiac/metabolism*
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Pericardium/metabolism*
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Single-Cell Analysis
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Zebrafish/metabolism*

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