The effect of single nucleotide polymorphisms on depression in combination with coronary diseases: a systematic review and meta-analysis.

Background: Depression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease. Methods: This study was designed according to the PRISMA-P guidelines. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, co-dominant model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types. Results: A total of 13 studies were included in this study, and the types of genes included are FKBP5 and SGK1 genes that act on glucocorticoid; miR-146a, IL-4-589, IL-6-174, TNF-α-308, CRP-717 genes that act on inflammatory mechanisms; eNOS genes from endothelial cells; HSP70 genes that act on the autoimmune response; ACE2 and MAS1 genes that act to mediate Ang(1-7) in the RAS system; 5-HTTLPR gene responsible for the transport of serotonin 5-HT and neurotrophic factor BDNF gene. There were three studies on 5-HTTLPR and BDNF genes, respectively, while there was only one study targeting FKBP5, SGK1, miR-146a, IL-4-589, IL-6-174, TNF-alpha-308, CRP-717, eNOS, HSP70, ACE2, and MAS1 genes. We did not perform a meta-analysis for genes reported in a single study, and meta-analysis was performed separately for studies exploring the 5-HTTLPR and BDNF genes. The results showed that for the 5-HTTLPR gene, there was a statistically significant association between 5-HTTLPR gene polymorphisms and depression in combination with coronary diseases (CHD-D) under the co-dominant model (LS vs LL: OR 1.76, 95%CI 1.20-2.59; SS vs LL: OR 2.80, 95%CI 1.45 to 5.41), the dominant model (LS+SS vs LL: OR 2.06, 95%CI 1.44 to 2.96), and the homozygous model (SS vs LL: OR 2.80 95%CI 1.45 to 5.5.41) were statistically significant for CHD-D, demonstrating that polymorphisms in the 5-HTTLPR gene are associated with the development of CHD-D and that the S allele in the 5-HTTLPR gene is likely to be a risk factor for CHD-D. For the BDNF gene, there were no significant differences between one of the co-dominant gene models (AA vs GG: OR 6.63, 95%CI 1.44 to 30.64), the homozygous gene model (AA vs GG: OR 6.63,95% CI 1.44 to 30.64), the dominant gene model (GA+AA vs GG: OR4.29, 95%CI 1.05 to 17.45), recessive gene model (AA vs GG+GA: OR 2.71, 95%CI 1.16 to 6.31), and allele model (A vs G: OR 2.59, 95%CI 1.18 to 5.67) were statistically significant for CHD-D, demonstrating that BDNFrs6265 gene polymorphisms are associated with the CHD-D development and that the A allele in the BDNFrs6265 gene is likely to be a risk factor for CHD-D. We analyzed the allele frequencies of SNPs reported in a single study and found that the SNPs in the microRNA146a gene rs2910164, the SNPs in the ACE2 gene rs2285666 and the SNPs in the SGK1 gene rs1743963 and rs1763509 were risk factors for the development of CHD-D. We performed a subgroup analysis of three studies involving the BDNFrs6265 gene. The results showed that European populations were more at risk of developing CHD-D than Asian populations in both dominant model (GA+AA vs GG: OR 10.47, 95%CI 3.53 to 31.08) and co-dominant model (GA vs GG: OR 6.40, 95%CI 1.98 to 20.73), with statistically significant differences. In contrast, the studies involving the 5-HTTLPR gene were all Asian populations, so subgroup analyses were not performed. We performed sensitivity analyses of studies exploring the 5-HTTLPR and BDNF rs6265 genes. The results showed that the results of the allele model, the dominant model, the recessive model, the homozygous model and the co-dominant model for both 5-HTTLPR and BDNF rs6265 genes were stable. Due to the limited number of studies of the 5-HTTLPR and BDNF genes, it was not possible to determine the symmetry of the funnel plot using Begg's funnel plot and Egger's test. Therefore, we did not assess publication bias. Discussion: SNPs of the microRNA146a gene at rs2910164, the ACE2 gene at the rs2285666 and the SGK1 gene at rs1743963 and rs1763509, and the SNPs at the 5-HTTLPR and BDNF gene loci are associated with the onset of comorbid depression in coronary heart disease. We recommend that future research focus on studying SNPs' impact on comorbid depression in coronary heart disease, specifically targeting the 5-HTTLPR and BDNF gene at rs6265. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229371.

Tanshinone IIA Combined With Cyclosporine A Alleviates Lung Apoptosis Induced by Renal Ischemia-Reperfusion in Obese Rats.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats.

BACKGROUND: Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. METHODS: Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined. RESULTS: TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam). CONCLUSION: We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

A study on the risk factors of coronary artery disease in patients with Takayasu arteritis.

BACKGROUND: The aim of this study was to investigate the risk factors of Takayasu arteritis (TA) involving the coronary artery. METHODS: Patients with TA involving coronary artery were included in this study. According to the patients' condition of coronary artery involvement, they were divided into two groups: group A: TA involved coronary artery disease [at least one coronary artery stenosis (≥50%)] and group B: TA did not involve coronary artery. A logistic regression model was used to analyze the risk factors of arteritis involving the patients' coronary artery lesions. RESULTS: A total of 442 TA patients were included in this study. The patients were significantly older in group A than those patients in group B (52.54±11.17 vs. 37.73±12.72, P<0.001). The age of onset in group A was significantly older than those patients in group B (42.21±11.46 vs. 32.74±13.13, P<0.001). The patients in group A had a longer course of disease (P<0.001), larger BMI (P=0.002) and higher rates of smoking, drinking, diabetes, dyslipidemia (P<0.05) when compared with group B. The level of eGFR was significantly decreased and the UA and TG levels were significantly increased in group A when compared with group B(P<0.05). Besides, the risk factors for TA involving coronary artery included the age of TA onset (OR =1.143, 95% CI: 1.007-1.298, P=0.039), course of TA (OR =1.165, 95% CI: 1.025-1.324, P=0.020), and BMI (OR =1.100, 95% CI: 1.021-1.185, P=0.013). CONCLUSIONS: The later the age of TA onset, the longer the course of TA onset and the more traditional risk factors associated with atherosclerosis, the more vulnerable patients are to coronary artery involvement and this may not be related to clinical disease activity.

Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B.

BACKGROUND: Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, and improving health-related quality of life. The Chinese herbal medicine formula Xiao Chai Hu Tang has been used to decrease discomfort and replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Xiao Chai Hu Tang formula have never been established with rigorous review methodology. OBJECTIVES: To assess the benefits and harms of Xiao Chai Hu Tang formula versus placebo or no intervention in people with chronic hepatitis B. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and seven other databases to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to 1 March 2019. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing Xiao Chai Hu Tang formula versus no intervention or placebo in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B according to guidelines or as defined by the trialists. We allowed co-interventions when the co-interventions were administered equally to all the intervention groups. DATA COLLECTION AND ANALYSIS: Review authors independently retrieved data from reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risks of bias using risk of bias domains with predefined definitions. We used GRADE methodology to evaluate our certainty in the evidence. MAIN RESULTS: We included 10 randomised clinical trials with 934 participants, but only five trials with 490 participants provided data for analysis. All the trials compared Xiao Chai Hu Tang formula with no intervention. All trials appeared to have been conducted and published only in China. The included trials assessed heterogeneous forms of Xiao Chai Hu Tang formula, administered for three to eight months. One trial included participants with hepatitis B and comorbid tuberculosis, and one trial included participants with hepatitis B and liver cirrhosis. The remaining trials included participants with hepatitis B only. All the trials were at high risk of bias, and the certainty of evidence for all outcomes that provided data for analyses was very low. We downgraded the evidence by one or two levels because of outcome risk of bias, inconsistency or heterogeneity of results (opposite direction of effect), indirectness of evidence (use of surrogate outcomes instead of clinically relevant outcomes), imprecision of results (the CIs were wide), and publication bias (small sample size of the trials). Additionally, 47 trials lacked the necessary methodological information needed to ensure the inclusion of these trials in our review. None of the included trials aimed to assess clinically relevant outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. The effects of Xiao Chai Hu Tang formula on the proportion of participants with adverse events considered 'not to be serious' is uncertain (RR 0.43, 95% CI 0.02 to 11.98; I2 = 69%; very low-certainty evidence). Only three trials with 222 participants reported the proportion of people with detectable hepatitis B virus DNA (HBV-DNA), but the evidence that Xiao Chai Hu Tang formula reduces the presence of HBV-DNA in the blood (a surrogate outcome) is uncertain (RR 0.62, 95% CI 0.45 to 0.85; I2 = 0%; very low-certainty evidence). Only two trials with 160 participants reported the proportion of people with detectable hepatitis B virus e-antigen (HBeAg; a surrogate outcome) (RR 0.72, 95% CI 0.50 to 1.02; I2 = 38%; very low-certainty evidence) and the evidence is uncertain. The evidence is also uncertain for separately reported adverse events considered 'not to be serious'. FUNDING: two of the 10 included trials received academic funding from government or hospital. None of the remaining eight trials reported information on funding. AUTHORS' CONCLUSIONS: The clinical effects of Xiao Chai Hu Tang formula for chronic hepatitis B remain unclear. The included trials were small and of low methodological quality. Despite the wide use of Xiao Chai Hu Tang formula, we lack data on all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The evidence in this systematic review comes from data obtained from a maximum three trials. We graded the certainty of evidence as very low for adverse events considered not to be serious and the surrogate outcomes HBeAg and HBV-DNA. We found a large number of trials which lacked clear description of their design and conduct, and hence, these trials are not included in the present review. As all identified trials were conducted in China, there might be a concern about the applicability of this review outside China. Large-sized, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding are lacking.

Longitudinal follow-up study of the retrobulbar and intrarenal hemodynamics in patients with T2DM.

OBJECTIVE: The primary aim of this study is to examine the hemodynamics of retrobulbar and intrarenal in the changes of early stage of type 2 diabetes mellitus (T2DM) patients from 2000 to 2015 and to assess incidence associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR). METHOD: Our study contained 60 subjects newly diagnosed of T2DM were divided into 2 groups base on the mean resistive index (RI) (≤0.7 and >0.7) of hemodynamic and to compare between-group differences of the early changes in hemodynamics of retrobulbar and intrarenal and also to conclude the incidences of diabetic kidney disease (DKD) and diabetic retinopathy (DR)subsequently with a long follow-up duration(2000-2015). First, to compare the mean RI of central retinal artery (CRA) between 2 groups. Second, to compare the mean RI of intrarenal hemodynamics in the bilateral interlobular renal arteries, renal function parameters (blood urea nitrogen (BUN), creatinine (Cr), blood glucose parameters (glycosylated hemoglobinA1c (HbA1c), fasting plasma glucose (FBG), and 2-hour postprandial blood glucose (2hPBG)), glomerular filtration rate (GFR), albumin excretion rate (AER), and urine albumin-to-creatinine ratio (UACR) between 2 groups. RESULTS: First part of our follow-up studies was to compare hemodynamic RI index of retrobulbar in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs > 0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of proliferative diabetic retinopathy (PDR) was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). Second part of our follow-up studies was to compare hemodynamic RI index of interlobular renal in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Compared data of various incidences from first part of study were coherent with second part. (Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs >0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of PDR was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). CONCLUSIONS: RIs of retrobulbar and interlobular renal which would serve as a good predictors for the hemodynamics changes in retrobulbar and intrarenal would assess incidence of DKD and DR during the preclinical stage in long-term range excluding renal function and HbA1c in T2DM patients.

Acupuncture for smoking cessation: A systematic review and meta-analysis of 24 randomized controlled trials.

INTRODUCTION: We evaluate the effectiveness and safety of transdermal acupuncture by needles for smoking cessation. METHODS: A literature search for randomized controlled trials (RCTs) was performed in seven electronic databases from inception to February 2017. Meta-analysis was conducted using Revman 5.3.0 software. We used either a random effects model (REM) or a fixed effects model (FEM) for pooling data according to the result of a heterogeneity test (defined as significant if I2>75%). Trial sequential analysis (TSA) was applied by TSA 0.9.5.10 Beta software. RESULTS: Twenty-four trials involving 3984 participants were included. The methodological quality was generally low. With regard to smoking abstinence, meta-analysis showed acupuncture was more effective compared to no intervention/waiting list for short-term (4 weeks) cessation (1 trial, RR=2.37, 95% 1.41, 3.97) and long-term (longer than 6 months) (2 trials, RR=2.66, 95% CI: 1.50, 4.70). Compared to acupuncture/auricular acupressure alone, acupuncture plus auricular acupressure showed more benefit for short-term cessation (3 trials, RR=1.52, 95% CI: 1.03, 2.25). Acupuncture plus auricular acupressure was more effective compared to sham acupuncture plus sham auricular acupressure for short-term cessation (3 trials, RR=2.50, 95% CI: 1.44, 4.33) and long-term (2 trials, RR=3.61, 95% CI: 1.37, 9.48). Acupuncture in combination with counseling, educational smoking cessation program or moxibustion had more benefit compared to acupuncture for short-term cessation (3 trials, RR=0.75, 95% 0.63, 0.91) and long-term (2 trials, RR=0.77, 95% CI: 0.56, 1.05), and TSA illustrated the cumulative Z-curve of this comparison for long-term across the traditional boundary of 5% significance and monitoring boundaries. No serious adverse events occurred. CONCLUSIONS: Acupuncture combined with counseling, educational smoking cessation program or moxibustion was more effective than acupuncture as monotherapy with regard to long-term smoking cessation. Further, high quality trials are needed to confirm the result.

Acupuncture for chronic hepatitis B.

BACKGROUND: Chronic hepatitis B is a liver disease associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming to reduce the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, as well as to improve health-related quality of life. Acupuncture is being used to decrease discomfort and improve immune function in people with chronic hepatitis B. However, the benefits and harms of acupuncture still need to be established in a rigorous way. OBJECTIVES: To assess the benefits and harms of acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B. SEARCH METHODS: We undertook electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and SinoMed to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry (ChiCTR) for ongoing or unpublished trials until 1 March 2019. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B as defined by the trialists or according to guidelines. We allowed co-interventions when the co-interventions were administered equally to all intervention groups. DATA COLLECTION AND ANALYSIS: Review authors in pairs individually retrieved data from reports and through correspondence with investigators. Primary outcomes were all-cause mortality, proportion of participants with one or more serious adverse events, and health-related quality of life. Secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered not to be serious. We presented the pooled results as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the risks of bias using risk of bias domains with predefined definitions. We put more weight on the estimate closest to zero effect when results with fixed-effect and random-effects models differed. We evaluated the certainty of evidence using GRADE. MAIN RESULTS: We included eight randomised clinical trials with 555 randomised participants. All included trials compared acupuncture versus no intervention. These trials assessed heterogeneous acupuncture interventions. All trials used heterogeneous co-interventions applied equally in the compared groups. Seven trials included participants with chronic hepatitis B, and one trial included participants with chronic hepatitis B with comorbid tuberculosis. All trials were assessed at overall high risk of bias, and the certainty of evidence for all outcomes was very low due to high risk of bias for each outcome, imprecision of results (the confidence intervals were wide), and publication bias (small sample size of the trials, and all trials were conducted in China). Additionally, 79 trials lacked the necessary methodological information to ensure their inclusion in our review.None of the included trials aim to assess all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. We are uncertain whether acupuncture, compared with no intervention, has an effect regarding adverse events considered not to be serious (RR 0.67, 95% CI 0.43 to 1.06; I² = 0%; 3 trials; 203 participants; very low-certainty evidence) or detectable hepatitis B e-antigen (HBeAg) (RR 0.64, 95% CI 0.11 to 3.68; I² = 98%; 2 trials; 158 participants; very low-certainty evidence). Acupuncture showed a reduction in detectable hepatitis B virus (HBV) DNA (a non-validated surrogate outcome; RR 0.45, 95% CI 0.27 to 0.74; 1 trial, 58 participants; very low-certainty evidence). We are uncertain whether acupuncture has an effect regarding the remaining separately reported adverse events considered not to be serious.Three of the eight included trials received academic funding from government or hospital. None of the remaining five trials reported information on funding. AUTHORS' CONCLUSIONS: The clinical effects of acupuncture for chronic hepatitis B remain unknown. The included trials lacked data on all-cause mortality, health-related quality of life, serious adverse events, hepatitis-B related mortality, and hepatitis-B related morbidity. The vast number of excluded trials lacked clear descriptions of their design and conduct. Whether acupuncture influences adverse events considered not to be serious is uncertain. It remains unclear if acupuncture affects HBeAg, and if it is associated with reduction in detectable HBV DNA. Based on available data from only one or two small trials on adverse events considered not to be serious and on the surrogate outcomes HBeAg and HBV DNA, the certainty of evidence is very low. In view of the wide usage of acupuncture, any conclusion that one might try to draw in the future should be based on data on patient and clinically relevant outcomes, assessed in large, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding.

The estrogen­like protective effect of Lycium barbarum polysaccharides in reducing oxidative stress on myocardial cells from ovariectomized rats.

Previous studies have demonstrated that ovariectomy may lead to a reduction in antioxidative biomarkers in the myocardium, thus suggesting that estrogens may serve a protective role in the suppression of oxidative stress. Lycium barbarum polysaccharides (LBP) are a well­known antioxidant Chinese traditional medicine, which appear to have a similar function to estrogens with regards to the regulation of cardiac function. In the present study, 30 Sprague­Dawley rats were randomly divided into the following groups: Sham operation group, ovariectomized (OVX) group, estradiol valerate group, high­dose LBP (LBP­H) group and low­dose LBP (LBP­L) group. All of the rats were provided tap water, estradiol valerate or LBP for 12 weeks. In addition, all rats were ovariectomized, with the exception of rats in the sham operation group, which underwent fat removal only. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH­px), catalase (CAT) and superoxide dismutase activities were subsequently examined. The protein expression levels of cleaved caspase­9, cleaved caspase­3 and phosphorylated­protein kinase B (p­Akt) were also assessed. The results demonstrated that high­dose LBP decreased the enhanced levels of ROS and MDA in OVX rats, whereas GSH­px and CAT activities were increased in the LBP­H group compared with in OVX rats. Furthermore, the expression levels of cleaved caspase­9 and cleaved caspase­3 were significantly upregulated in the OVX group, whereas high­dose LBP exerted protective effects on OVX rats by decreasing the expression of apoptotic proteins. Conversely, p­Akt expression was decreased in the OVX group and was increased in the LBP­H group. These results indicated that LBP is essentially involved in cardiac protection by inhibiting apoptosis in response to oxidative stress. In addition, improvement of antioxidant status by LBP is associated with the Akt signaling pathway in the myocardium of OVX rats.

Valproic acid attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-pyroptosis pathways.

Ischemic stroke is the third most common cause of death and the leading cause of disability worldwide in adults. The antiepileptic drug valproic acid (VPA) was reported to protect cerebral ischemia/reperfusion injury. However, the action mechanism of VPA in cerebral ischemia/reperfusion injury has not been fully understood. We explored the action mechanism of VPA in vivo and in vitro. Gerbils were subjected to transient global cerebral ischemic-reperfusion injury, and hippocampal neuron injury was treated with oxygen-glucose deprivation in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. Histopathological examinations and western blot were performed to evaluate the pyroptosis of neurons. The results showed that VPA attenuated the cognitive dysfunction, pyroptosis of the gerbils suffer from ischemic-reperfusion injury and decreased hippocampal neurons pyroptosis induced by oxygen-glucose deprivation in vitro. In addition, western blot and real-time PCR analysis revealed that VPA modulated the protein expression of apoptosis repressor with caspase recruitment domain (ARC), caspase-1 and IL-1ß/IL-18. Our results suggested that VPA alleviated ischemic/reperfusion injury-mediated neuronal impairment by anti-pyroptotic effects.

Effect of tanshinone IIA on oxidative stress and apoptosis in a rat model of fatty liver.

Oxidative stress is a crucial factor associated with fatty liver disease, which raises the possibility of using antioxidants to improve liver steatosis. Tanshinone IIA (TSIIA) is a traditional Chinese medicine that has been reported to have antioxidant effects in vitro. The present study aimed to investigate whether TSIIA possesses antioxidant effects in vivo and whether TSIIA was able to improve liver steatosis. Hence, the ability of TSIIA to protect rats from liver disease was explored, particularly in regard to antioxidant activity. Rats were fed a high-lipid diet for 90 days, causing severe liver steatosis, both morphologically and biochemically. An increase in reactive oxygen species (ROS) in the liver was exhibited in addition to significantly elevated serum lipids and malondialdehyde (MDA). Furthermore, hepatocyte apoptosis was measured by Hoechst staining, reverse transcription-quantitative polymerase chain reaction and western blot analysis and an increase in hepatocyte apoptosis rate was indicated in mice on a high-fat diet. Following intraperitoneal injection of TSIIA (10 mg/kg/day), liver steatosis was significantly inhibited. In rats receiving TSIIA treatment, less ROS were indicated in the liver and significantly decreased levels of MDA (P<0.05) in serum were exhibited, whereas significantly increased activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) were observed (P<0.05 and P<0.01, respectively). In addition, the rate of hepatocyte apoptosis was significantly decreased in the TSIIA group (P<0.01). However, TSIIA elicited no effect on serum lipid profiles. These results suggest that TSIIA attenuates oxidative stress by decreasing ROS and MDA production and enhancing the activity of T-SOD and GSH-PX, which may contribute to the inhibition of apoptosis and amelioration of liver steatosis.

Mechanism of Fructus Aurantii Flavonoids Promoting Gastrointestinal Motility: From Organic and Inorganic Endogenous Substances Combination Point of View.

BACKGROUND: Fructus Aurantii (FA) derived from the dried, and unripe fruit of Citrus aurantium L. is one of the commonly used traditional Chinese medicines to treat gastrointestinal motility dysfunction diseases. According to the literature research, FA flavonoids (FAF) are important active ingredients of FA promoting gastrointestinal motility, but the exact material basis and mechanism of action are still not very clear. OBJECTIVE: This experiment was designed to illustrate the material basis of FAF promoting gastrointestinal motility and explore the mechanism of action from an organic and inorganic combination point of view. MATERIALS AND METHODS: In this experiment, high-performance liquid chromatography (HPLC) method was used to analyze the composition and content of FAF. Based on the prominent prokinetic effect of FAF on mice, the mechanism of action was speculated through a combination of HPLC coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: With the method of HPLC, ten dominating components of FAF including neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletin accounting for more than 86% of FAF were identified. Combined HPLC-QTOF-MS with ICP-MS, the endogenous substances with difference in the blood of mice were analyzed, in which 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC(18:2 (9Z, 12Z)), and Ca2+, Mg2+, Zn2+ metal ions had significant changes, involving tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways. CONCLUSION: The results preliminarily elaborated the mechanism of FAF promoting gastrointestinal motility from an organic and inorganic point of view, which provide valuable information for researching and developing new multi-component Chinese medicine curing gastrointestinal underpower associated diseases. SUMMARY: Fructus Aurantii flavonoids are one of the main components of Fructus Aurantii that possess prominent gastrointestinal motility promoting efficacyThe mainly material basis of Fructus Aurantii flavonoids promoting gastrointestinal motility were neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletinFructus Aurantii flavonoids can regulate the content of 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC.(18:2(9Z, 12Z)) and Ca2+, Mg2+, Zn2+-metal ions, through tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways to present its gastrointestinal motility promoting efficacy. Abbreviations used: FA: Fructus Aurantii; FAF: Fructus Aurantii flavonoids; HPLC: High performance liquid chromatography; HPLC-QTOF-MS: High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; ICP-MS: Inductively coupled plasma mass spectrometry; PCA: Principal components analysis; CG: Control group; FAFLG: Low-dosage group of Fructus Aurantii flavonoids; FAFMG: Middle-dosage group of Fructus Aurantii flavonoids; FAFHG: High-dosage group of Fructus Aurantii flavonoids; DPG: Domperidone group.

Anti-ulcer effect and potential mechanism of licoflavone by regulating inflammation mediators and amino acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza is the dry root and rhizome of the leguminous plant, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., which was firstly cited in Shennong's Herbal Classic in Han dynasty and was officially listed in the Chinese Pharmacopoeia, has been widely used in China during the past millennia. Licoflavone is the major component of Glycyrrhiza with anti-ulcer activity. The present study is based on clarifying the anti-ulcer effect of licoflavone, aiming at elucidating the possible molecule mechanisms of its action for treating gastric ulcer rats induced by acetic acid. MATERIALS AND METHODS: Rats were divided into 7 groups, and drugs were administered from on the day after the onset of gastric ulcer (day 3) until day 11 of the experiment once daily continuously. The plasma were analyzed by high-performance liquid chromatography combined with time-of-flight mass spectrometry (HPLC/ESI-TOF-MS), significant different metabolites were investigated to explain its therapeutic mechanism. Furthermore, quantitative real time polymerase chain reaction (RT-PCR) analysis was performed to detect the expression of RNA in stomach tissue for verifying the above results. RESULTS: Licoflavone can effectively cure the gastric ulcer, particularly the middle dose group. According to the statistical analysis of the plasma different metabolites from each groups and the expression of genes in tissues, sixteen significant different metabolites, including histamine, tryptophan, arachidonic acid, phingosine-1-phosphate etc., contributing to the treatment of gastric ulcer were discovered and identified. In RT-PCR analysis, the results of the expression of RNA were corresponded with what we discovered. CONCLUSIONS: Our study indicated licoflavone plays the role of treating gastric ulcer by regulating inflammation mediators and amino acid metabolism. We demonstrated that metabolomics technology combined with gene technology is a useful tool to search different metabolites and to dissect the potential mechanisms of traditional Chinese medicine (TCM) in treating gastric ulcer.

[Study on Serum Metabolite Profiling in Pi-deficiency Rats Based on LC-MS Technique].

OBJECTIVE: To explore metabolite profiling changes in serum of rats with pi-qi deficiency syndrome (PQDS) and pi-yang deficiency syndrome (PYDS) based on liquid chromatograph-mass spectrometer (LC-MS) technique, and to explore the essence of Pi-deficiency syndrome (PDS) from small molecule metabolite level. METHODS: Totally 21 male SD rats of SPF grade were randomly divided into three groups, the normal control group, the PQDS group, and the PYDS group, 7 in each group. Rats in the PQDS group overate for 1 day and fasted for 2 days. They drank freely and then swam to be exhausted in water at 35 degrees C - 37 degrees C for 15 successive days. The PYDS model was established by the same method for PQDS rats plus drenching 20% Folium sennae water extract (2 mL/100 g), once in the morning and once in the evening for one successive week. After modeling, models were evaluated according to rat general state, changes in body weight and rectal temperature. Serum metabonomic profiles were detected using LC-MS technique. Difference in inter-group metabolite spectrograms was analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA). Potential biomarkers related to syndrome types in rat serum were selected via the parameter of variable importance in the projection (VIP). RESULTS: The weight of rats in the PQDS group and the PYDS group decreased more significantly after modeling. The difference in prepost weight was statistically significant from that of the normal control group (P < 0.01). It was more obviously lowered in the PYDS group than in the PQDS group (P < 0.05). Compared with the normal control group, the rectal temperature of rats in the PYDS group and the PQDS group decreased (P < 0.05, P < 0.01). It decresed more in the PYDS group than in the PQDS group (P < 0.05, P < 0.01). Compared with the normal control group, levels of PC(19:0)/PE(22:0), PC(17:0)/PE(20:0), capric acid, oleic acid, stearic acid, succinic acid, fumaric acid, malic acid, glucose increased; arachidonic acid, linolenic acid, lauric acid, androsterone, 4-heptanone, dihydroxyacetonephosphate (DHAP) (6:0), and uridine decreased in the PYDS group and the PQDS group. Compared with the PQDS group, levels of PC(22:1), PC (22:6), PE (18:0)/PC (15:0), retinol, and deoxycytidine increased significantly in the PYDS group; PC (18:1), PC(19 :3), PC (20:3), PC (17:0)/PE (20:0), PC (19:1)/PE (22:1), PC (19:0)/PE (22:0), PC (17:1)/PE (20: 1), PC (16:1)/PE (19:1), cholic acid, hippuric acid, furoic acid, undecanedicarboxylic acid, palmitoleic acid, hydroxy stearic acid, eicosatrienoic acid, phenylalanine, tyrosine, glutamic acid, serine, carbamoyl aspartic acid, palmitoyl carnitine, tetradecanoyl carnitine, acetylcarnitine, and linoleylcarnitine decreased more significantly in the PYDS group. CONCLUSIONS: Comparative contents of various serum metabolites changed significantly in PQDS and PYQS model groups. Some potential small molecular biomarkers related to PDS were preliminarily identified. These results might provide some data reference for exploring scientific connotation and pathological mechanisms of PDS.

Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol.

AIM OF STUDY: Tanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. MATERIALS AND METHODS: A model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. RESULTS: Tanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. CONCLUSION: A novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol.

[Intervention of Huayu Qutan Recipe on liver SREBP-2 signal pathway of hyperlipidemia rats of pi deficiency syndrome].

OBJECTIVE: To explore the intervention of Huayu Qutan Recipe (HQR) on liver SREBP-2 signal pathway of hyperlipidemia rats of Pi deficiency syndrome (PDS). METHODS: Totally 100 SPF grade SD rats were randomly divided into the blank control group, the hyperlipidemia group, the hyperlipidemia treatment group, the PDS hyperlipidemia group, and the PDS hyperlipidemia treatment group, 20 in each group. Common granular forage was fed to rats in the blank control group. High fat forage was fed to rats in the hyperlipidemia group and the hyperlipidemia treatment group. Rats in the PDS hyperlipidemia group and the PDS hyperlipidemia treatment group were treated with excessive labor and improper diet for modeling. They were administered refined lard by gastrogavage (3 mL each time, twice per day) and fed with high fat forage on the odd days, and fed with wild cabbage freely on even days. The modeling lasted for 30 days. Rats in the hyperlipidemia treatment group and PDS hyperlipidemia treatment group were administered with Huayu Qutan Recipe (20 mL/kg) by gastrogavage, once a day, for 30 successive days. Levels of serum cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum amylase (AMY) were detected by automatic biochemical analyzer. D-xylose excretion rate was determined using phloroglucinol method. Morphological changes of liver and the lipid deposition in liver were observed using HE stain and oil red O stain respectively, mRNA and protein expression levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase 1 (CYP7A1), LDL-R, and sterol regulatory element binding protein-2 (SREBP-2) were detected using real time RT-PCR and Western blotting. RESULTS: Compared with the blank control group, serum levels of TC (1.84 ± 0.19 mmol/L, 2.23 ± 0.43 mmol/L) and LDL-C (0.99 ± 0.24 mmol/L, 1.13 ± 0.56 mmol/L) were higher in the hyperlipidemia group and the PDS hyperlipidemia group, serum levels of HDL-C (0.41 ± 0.66 mmol/L, 0.41 ± 0.11 mmol/L) and AMY activities (351 ± 45 mmol/L, 153 ± 30 mmol/L) were lower, and urinary D-xylose excretion rates were lower (26.9 ± 2.1 ng/mL, 15.0 ± 1.7 ng/mL) (all P < 0.05). Lipid deposition occurred in liver cells. Much fat vacuoles occurred in the cytoplasm. Expression levels of HMGCR, CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver significantly decreased (P < 0.01). Compared with the hyperlipidemia group, serum levels of TC and LDL-C significantly increased (P < 0. 05), AMY activities and urinary D-xylose excre- tion rates significantly decreased in the PDS hyperlipidemia group (P < 0.01). A large amount of lipid deposition occurred in liver. The atrophy of liver cells was obviously seen. Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly lower (P < 0.01, P < 0.05). Serum levels of TC and LDL-C significantly decreased (P < 0.05), AMY activities and urinary D-xylose excretion rates significantly increased in the hyperlipidemia treatment group (P < 0.01). Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01, P < 0.05). Compared with the PDS hyperlipidemia group, serum level of TC significantly decreased (P < 0.05), HDL-C levels, AMY activities and urinary D-xylose excretion rates significantly increased in the PDS hyperlipidemia treatment group (P < 0.01),expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01). Similar changes occurred in the two treatment groups. CONCLUSIONS: Pi deficiency exacerbates abnormal serum TC level and the lipid deposition in liver. These might be related to regulating expression levels of LDL-R, HMGCR, and CYP7A1 genes in the SREBP-2 signal pathway. HQR could regulate this pathway to intervene abnormal metabolism of TC.

[Adjunctive therapy of xuezhikang capsule for coronary heart disease: a systematic review and meta-analysis of randomized controlled trials].

OBJECTIVE: To systematically evaluate the effect and safety of Xuezhikang Capsule (XZKC) for adjuvant treatment for coronary heart disease (CHD) patients accompanied with or without dyslipidemia. METHODS: China National Knowledge Infrastructure (CNKI) Database, Chongqing VIP Database (VIP), Wanfang Data base, Cochrane Library, and Medline (PubMed) were retrieved with the deadline of August 30, 2013. Randomized controlled trials (RCT) of XZKC in treating CHD patients with or without dyslipidemia were all included. Assessment of bias risk for included studies was conducted according to the Cochrane Handbook for Systematic Reviews of Intervention (Version 5.0.2): Criteria for judging risk of bias in the "risk of bias" assessment tool. Review Management (5.1.0) was employed for data statistics. If there was no significant heterogeneity, results from the random-effect model were presented. If the heterogeneity was not substantial, a meta-analysis was not performed and a narrative and qualitative summary was performed instead. RESULTS: A total of 28 RCTs (6,949 patients) were included after screening results. The methodological quality of included trial was generally lower. Results of Metaanalysis showed that XZKC was beneficial for CHD patients in decreasing cardiovascular events: when compared with the basic treatment group, the relative risk (RR) was 0.53 and 95% confidence interval (CI) was [0.35, 0.81]; when compared with the placebo + basic treatment group, RR was 0.52 and 95% CI was [0.42, 0.65]; when compared with the basic treatment group, RR for improving symptoms of angina was 1.20 and 95% CI was [1. 12, 1.30]; when compared with the basic treatment group, RR for improving abnormal ECG was 1.38 and 95% CI was [1.21, 1.57]. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the placebo + basic treatment group. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering low density lipoprotein cholesterol (LDL-C) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering LDL-C to that of the placebo + basic treatment group. A total of 18 studies describing adverse reactions (ADs) involved 61 ADs in the XZKC + basic treatment group. All suffered from mild symptoms or were improved after treatment. No severe ADs occurred. CONCLUSION: Treatment of CHD by XZKC might lower the occurrence of cardiovascular events in CHD patients accompanied with or without dyslipidemia, relieve clinical symptoms, improve ECG, lower blood lipid levels, and with less adverse reactions.

Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study.

Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.

Tanshinone IIA reduces apoptosis induced by hydrogen peroxide in the human endothelium-derived EA.hy926 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia Miltiorrhiza Bunge (also known as herb Danshen in Chinese) is a widely used Chinese herbal medicine. Tanshinone IIA (TSN IIA) is considered to be the most important bioactive ingredient in Danshen and exhibits an anti-atherosclerotic activity. AIM OF STUDY: To evaluate the protective effect of TSN IIA on the human endothelial EA.hy926 cells injured by hydrogen peroxide in vitro and its possible mechanism. MATERIALS AND METHODS: The EA.hy926 cells were incubated for 24h with different concentrations of TSN IIA (5, 10 and 20 µg/µL ) or DMEM. Subsequently, cells were treated with 300 µmol/L H(2)O(2) for another 4h. Then, the percentage of cell viability was evaluated by 3-(4, 5-di-methylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The apoptosis of EA.hy926 cells was detected by flow cytometry with AnnexinV-FITC/PI double staining and laser scanning spectral confocal technique. The generation of intracellular reactive oxygen species (ROS) generation was analyzed by flow cytometry. The mRNA expressions of caspase-3, Bcl-2 and Bax were tested by real time-reverse transcription polymerase chain reaction (real time RT-PCR). The protein expression of Bcl-2 and Bax was determined by Western blotting. MDA levels, NO production, LDH leakage, and SOD as well as caspase-3 activities were also measured using standard methods. RESULTS: Loss of cell viability and excessive cell apoptosis were observed in EA.hy926 cells after 4h of challenge with H(2)O(2) (300 µmol/L). However, cell apoptosis was attenuated in different concentrations of TSN IIA (5, 10 and 20 µg/µL) pretreated cells. Furthermore, TSN IIA markedly inhibited the elevation of ROS evoked by H(2)O(2). Real time RT-PCR and Western blotting analysis showed that TSN IIA significantly decreased the expressions of pro-apoptotic proteins (Bax and caspase-3) while significantly increased the expression of anti-apoptotic protein Bcl-2, and resulted in obvious reduction of Bax/Bcl-2 ratio in EA.hy926 cells induced by H(2)O(2). CONCLUSION: These observations provide preliminary evidence that TSN IIA protects EA.hy926 cells against H(2)O(2) damage, which is mainly associated with the ROS generation, followed by the imbalance of the Bax/Bcl-2 ratio, and caspase-3 activation leading to apoptosis.

[Measurement of health-related quality of life in coronary heart disease: a review].

This paper introduces the development and application of health-related quality of life (HRQOL) scales in research on coronary heart disease (CHD). Currently, the scales for CHD patients have been more systematically developed and widely used in foreign countries, while domestically in China, they are developed successfully but problematically; research in this field has started later and the scales introduced are limited and not suitable for the entire range of domestic CHD patients. Thus, this paper introduces 26 HRQOL scales in research on CHD, including five generic scales, ten disease-specific scales from abroad and eleven scales originating from China. With the deficiency of HRQOL scales, especially that in traditional Chinese medicine and specific scales, this paper analyzes and summarizes the problems existing in development of scales. The authors also provide solutions in order to help the development and application of scales in further studies.