1.Gut microbiota analysis and its significance in vasovagal syncope in children.
Wei BAI ; Selena CHEN ; Chao-Shu TANG ; Jian-Guang QI ; Qing-Hua CUI ; Ming XU ; Jun-Bao DU ; Hong-Fang JIN
Chinese Medical Journal 2019;132(4):411-419
BACKGROUND:
Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance.
METHODS:
Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test.
RESULTS:
No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P < 0.05), and LEfSe analysis revealed Ruminococcaceae as a discriminative feature (linear discriminant analysis [LDA] score > 4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients.
CONCLUSION
Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.
Adolescent
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Child
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Child, Preschool
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Fatty Acids, Volatile
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metabolism
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Female
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Gastrointestinal Microbiome
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Humans
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Male
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Ruminococcus
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isolation & purification
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physiology
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Syncope, Vasovagal
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etiology
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microbiology
2.Research advances in endogenous neural stem cells promoting neural repair after ischemic stroke.
Chang-Yun FANG ; Xu-Sheng WU ; Hang ZHANG ; Yan-Ling GU ; Shi-Bing WANG ; Hui-Wen REN ; Ke CHEN ; Hui ZHANG ; Bao-Hua CHENG ; Yang GAO
Acta Physiologica Sinica 2019;71(3):454-462
Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases. It is noteworthy that some stroke patients showed an ability to repair brain several months after the stroke happened, suggesting an existence of endogenous nerve repair in these patients. The research advances in functions of endogenous neural stem cells in neural regeneration and the related regulators after ischemic stroke are summarized in this review to provide new views of the mechanism of neural functional recovery after ischemic stroke.
Brain Ischemia
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therapy
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Humans
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Nerve Regeneration
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Neural Stem Cells
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cytology
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Stroke
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therapy
3.Therapeutic effect of different doses of atorvastatin on patients with diabetic cardiomyopathy and its influence on blood lipids and cardiac diastolic function
Yue-Hua WANG ; Fang-Xia ZHAO ; Xue-Li WANG ; Long BAO
Chinese Journal of cardiovascular Rehabilitation Medicine 2018;27(1):46-50
Objective: To explore therapeutic effect of different doses of atorvastatin on patients with diabetic cardiomyopathy (DCM) and its influence on levels of blood lipids, glycosylated hemoglobin A1c (HbA1c), advanced glycosylation end product (AGEs) and cardiac diastolic function. Methods: A total of 96 DCM patients treated in our hospital were selected, randomly and equally divided into routine dose group (received atorvastatin of routine dose, 20mg/d) and double dose group (received atorvastatin of double dose, 40mg/d), and both groups were treated for four weeks. Levels of blood glucose, blood lipids, HbA1c, AGEs and cardiac diastolic function were measured and compared between two groups before and after treatment, and clinical therapeutic effect and safety were assessed. Results: After treatment, total effective rate of double dose group was significantly higher than that of routine dose group (91. 67% vs. 72. 92%, P=0. 032); compared with routine treatment group after treatment, there were significant reductions in levels of blood glucose, blood lipids [except high density lipoprotein cholesterol (HDL-C)], HbA1c [(7. 58±1. 47) % vs. (6. 18±1. 35) %], AGEs [(12. 45±2. 36) μg/ml vs. (7. 62±1. 54) μg/ml]and mitral early diastolic peak flow velocity/early mitral annulus diastolic peak velocity [E/Ea: (7. 54±1. 36) vs. (5. 27± 1. 09)], and significant rise in HDL-C level and mitral early diastolic peak flow velocity/mitral late diastolic peak flow velocity [E/A: (1. 25±0. 32) vs. (1. 57±0. 41)] in double dose group, P=0. 001 all. There was no significant difference in incidence rate of adverse reactions between two groups, P=0. 712. Conclusion: In DCM patients, double dose atorvastatin can more effectively regulate blood lipid level, reduce serum levels of HbA1c and AGEs, and improve cardiac diastolic function with more significant therapeutic effect.
4.Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial.
Xu-Dong TANG ; Bin LU ; Zhen-Hua LI ; Wei WEI ; Li-Na MENG ; Bao-Shuang LI ; Zhi-Peng TANG ; Rui GAO ; Feng-Yun WANG ; Fang LU ; Li-Qun BIAN ; Ying-Pan ZHAO ; Ping WANG ; Yin-Qiang ZHANG
Chinese journal of integrative medicine 2018;24(9):645-652
OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D).
METHODA multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests.
RESULTSA total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant.
CONCLUSIONChang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).
5.The correlation between STAT3 phosphorylation and the activity of Behcet's disease
Hua-Fang BAO ; Jian-Fei CAI ; Yong CHEN ; Dan LUO ; Yan SHEN ; Jun ZOU ; Jian-Long GUAN
Fudan University Journal of Medical Sciences 2018;45(2):169-176
Objective To explore the role of signal transducer and activator of transcription 3 (STAT3) phosphorylation in the pathogenesis of Behcet's disease (BD),and to investigate the association between STAT3 phosphorylation and disease activity in BD patients.Methods Peripheral blood mononuclear cell (PBMC) was isolated from 15 mL peripheral boood of 10 active BD patients (BD-A),10 BD patients in remission (BD-R) and 10 healthy controls (HC) respectively.The blockade of STAT3 phosphorylation was performed by Stattic.The PBMC was divided into Stattic subgroup (treated with 2.5 μmol/L stattic and 1 640 medium,5 mL) and blank control subgroup (treated with 5 mL 1 640 medium),respectively.The protein levels of phosphorylated STAT3 (pSTAT3) and STAT3 were examined by flow cytometry and Western blot.The protein and mRNA levels of TNF-α,IFN-γ and IL-17 were tested by RT-PCR and ELISA.Two-way ANOVA and Bonferroni post hoc test were used to analyze the results.Results Compared with HC,the BD patients showed higher protein levels of pSTAT3 and STAT3,and higher protein and mRNA levels of TNF-α,IFN-γ and IL-17;compared with blank control subgroup,the protein levels of pSTAT3 and STAT3,and protein and mRNA levels of TNF-α,IFN-γ and IL-17 decreased in Stattic subgroup.In the BD-A group,the protein level of pSTAT3,and protein and mRNA levels of TNF-α,IFN-γ and IL-17 were significantly higher than those in the BD-R group.Conclusions An increased activation of the STAT3 pathway may contribute to the pathogenesis of BD and relate to disease activity in BD patients by inducing TH1 and Th17 cells activation.
6.Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy.
Qing-You ZHANG ; Hong-Fang JIN ; Selena CHEN ; Qing-Hua CHEN ; Chao-Shu TANG ; ; Jun-Bao DU ; Ya-Qian HUANG
Chinese Medical Journal 2018;131(7):839-844
ObjectiveHydrogen sulfide (HS), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that HS regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that HS targets cardiomyocyte autophagy to regulate cardiovascular function.
Data SourcesThis review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases."
Study SelectionOriginal articles and critical reviews on HS and autophagy were selected for this review.
ResultsWhen autophagy plays an adaptive role in the pathogenesis of diseases, HS restores autophagy; otherwise, when autophagy plays a detrimental role, HS downregulates autophagy to exert a cardioprotective function. For example, HS has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. HS postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy.
ConclusionsHS exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of HS therapy for cardiovascular diseases.
Animals ; Autophagy ; drug effects ; Cardiovascular Diseases ; prevention & control ; Cardiovascular System ; cytology ; drug effects ; Humans ; Hydrogen Sulfide ; therapeutic use ; Myocytes, Cardiac ; cytology ; drug effects
7.Total flavonoids of bugloss limits left ventricular remodeling after myocardial infarction in mice
Shou-Bao WANG ; Dan-Shu WANG ; Yi-Huang LIN ; Rong-Rong WANG ; Lian-Hua FANG ; Yang LYU ; Guan-Hua DU
Chinese Journal of Pharmacology and Toxicology 2018;32(4):306-306
OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.
8.Evaluation of ventricular systolic function in fetuses with congenital heart disease by spatio-temporal image correlation with M-mode display
Hua YUAN ; Bowen ZHAO ; Zuoping XIE ; Li XIONG ; Qiqi HUA ; Linhua WANG ; Jiamei ZHOU ; Min FANG ; Lei BAO
Chinese Journal of Ultrasonography 2018;27(9):766-770
Objective To evaluate the effectiveness of spatio-temporal image correlation with M-mode display ( STIC-M ) in monitoring fetal left ventricular systolic function in fetuses with congenital heart disease(CHD) . Methods Five hundred and thirty-six normal fetuses and 34 fetuses with CHD( 29 without hydrops and 5 with hydrops) were involved in the study . Left ventricular fractional shortening ( LVFS) was measured using STIC-M . The data of normal fetuses was used to construct reference ranges of LVFS for assessment of fetuses with CHD . Results The LVFS of the normal fetuses [ range :26 .8% - 42 .9% , mean :( 34 .9 ± 4 .1) % ] was negatively correlated with gestational age ( r = - 0 .16 , P < 0 .001) . Compared with the normal controls ,LVFS was significantly decreased in CHD fetuses with hydrops ( P < 0 .001) . However ,there was no significant difference in LVFS between normal controls and CHD fetuses without hydrops ( P > 0 .05) . Conclusions STIC-M is a new method that can be used to measure LVFS to evaluate fetal ventricular systolic function . The fetal ventricular contractile function of CHD fetuses without hydrops may not be damaged or is in compensation stage . The fetuses with cardiac hydrops generally become lower .
9.Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study.
Wei QIU ; De-Hui HUANG ; Shi-Fang HOU ; Mei-Ni ZHANG ; Tao JIN ; Hui-Qing DONG ; Hua PENG ; Chao-Dong ZHANG ; Gang ZHAO ; Yi-Ning HUANG ; Dong ZHOU ; Wei-Ping WU ; Bao-Jun WANG ; Ji-Mei LI ; Xing-Hu ZHANG ; Yan CHENG ; Hai-Feng LI ; Ling LI ; Chuan-Zhen LU ; Xu ZHANG ; Bi-Tao BU ; Wan-Li DONG ; Dong-Sheng FAN ; Xue-Qiang HU ; Xian-Hao XU ; TOWER Trial Chinese Group
Chinese Medical Journal 2018;131(23):2776-2784
Background:
Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.
Methods:
TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).
Results:
Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.
Conclusions:
Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.
Trial Registration
ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China
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Crotonates
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administration & dosage
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adverse effects
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therapeutic use
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Double-Blind Method
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Drug Administration Schedule
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Humans
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Immunosuppressive Agents
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administration & dosage
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adverse effects
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therapeutic use
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Multicenter Studies as Topic
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Multiple Sclerosis
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drug therapy
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metabolism
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Proportional Hazards Models
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Toluidines
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administration & dosage
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adverse effects
;
therapeutic use
10.Expert consensus on the design and implementation of clinical safety centralized monitoring study of Chinese medical injection.
Jun-Hua ZHANG ; Jing-Tian REN ; Jing-Qing HU ; Yan-Ming XIE ; Hai-Bo SONG ; Ming-Jun ZHU ; Rui GAO ; Zhong WANG ; Wen-Ke ZHENG ; Xue-Lin LI ; Meng JIANG ; Yu-Hong HUANG ; Fang LU ; Li-Yun HE ; Wei-Xiong LIAN ; Zhong-Qi YANG ; Wei-An YUAN ; Si-Yuan HU ; Bao-He WANG ; Wei-Liang WANG ; De-Quan REN ; Bo-Li ZHANG ; null ; null
China Journal of Chinese Materia Medica 2017;42(1):6-9
Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

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