To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.
Mice ; Animals ; Male ; Ischemic Stroke ; Recovery of Function/physiology* ; Insulin-Like Growth Factor I/pharmacology* ; Mice, Inbred C57BL ; TOR Serine-Threonine Kinases/metabolism* ; Stroke/drug therapy* ; Brain Ischemia/drug therapy* ; Mammals/metabolism*

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

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 ; Mice ; Rats ; Stroke Volume ; Ventricular Function, Left ; Heart Failure/drug therapy* ; Natriuretic Peptide, Brain

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.
Humans ; Heart Failure/physiopathology* ; Natriuretic Peptide, Brain/therapeutic use* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Cardiotonic Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Recombinant Proteins/therapeutic use* ; Cardiovascular Agents/therapeutic use* ; Drug Therapy, Combination

INTRODUCTION: Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use. METHODS: A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE. RESULTS: We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046). CONCLUSION Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.
Humans ; Male ; Aged ; Female ; Coronary Artery Disease ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Myocardial Perfusion Imaging/methods* ; Calcium ; Stroke Volume ; Brain Ischemia ; Risk Factors ; Ventricular Function, Left ; Stroke ; Prognosis

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.
Humans ; Bayes Theorem ; Cardiomyopathy, Dilated/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Natriuretic Peptide, Brain ; Network Meta-Analysis ; Nonprescription Drugs/therapeutic use* ; Stroke Volume ; Ventricular Function, Left

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.
Animals ; Spinal Cord Injuries/therapy* ; Motor Neurons/physiology* ; Brain ; Stroke ; Recovery of Function/physiology*

Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.
Adolescent ; Child ; Female ; Humans ; Young Adult ; Heart Failure/surgery* ; Longitudinal Studies ; Natriuretic Peptide, Brain ; Peptide Fragments ; Retrospective Studies ; Stroke Volume ; Takayasu Arteritis/surgery* ; Ventricular Function, Left/drug effects* ; Heart Ventricles/drug effects* ; Male ; Cardiovascular Agents/therapeutic use* ; Angioplasty, Balloon ; Stents ; Blood Vessel Prosthesis Implantation

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO₂peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO₂peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO₂peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO₂ slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO₂peak in patients with HFmrEF.
Aged ; Benzhydryl Compounds ; Glucosides ; Heart Failure/drug therapy* ; Humans ; Male ; Natriuretic Peptide, Brain ; Oxygen/therapeutic use* ; Peptide Fragments ; Stroke Volume/physiology* ; Ventricular Dysfunction, Left ; Ventricular Function, Left