Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Prevention of systemic inflammation and neuroprotective effects of Qingda granules against angiotensin II-mediated hypertension.

Qingxuan Jiangya Decoction (QXJYD), prescribed by academician Ke-ji Chen, has long been used as a Traditional Chinese Medicine formula in blood pressure control and has achieved good clinical outcomes in hypertensive patients. Qingda granules (QDGs), which is a formula simplified from QXJYD, might serve as a novel anti-hypertensive pharmaceutical. However, the functional mechanism of QDGs remains unclear. This study aimed to evaluate the effect of QDGs against the elevation of blood pressure, systemic inflammation and brain injury in Ang II-mediated hypertensive mice. Ang II-mediated hypertensive mice were treated with 28.63mg QDG of per mouse every day. The blood pressure of all mice was measured on days 0, 1, 3, 5, 7, 14 and 28 by using the tail-cuff plethysmograph method. Following 28 days of treatment, the mice were sacrificed and their whole blood and brain tissues were used for analysis. The results showed that QDGs significantly decreased elevated systolic and diastolic blood pressure in Ang II-mediated hypertensive mice while body weight did not change, which demonstrated anti-hypertensive activities of QDGs without obvious toxicity. QDGs significantly attenuated the level of serum cytokines (IL-6, TNF-a) and chemokines (MCP-1, MIP-1a, RANTES) in the Ang II-mediated hypertensive mice. Moreover, pathological staining showed that QDGs significantly ameliorated cerebral histopathology changes, reduced the loss of neurons and activations of astrocytes. Additionally, QDGs inhibited neuronal apoptosis by down-regulation of Bax expression and up-regulation of Bcl-2 expression. These results suggested that QDGs exhibited excellent anti-hypertensive properties by preventing systemic inflammation and providing neuroprotective effects against Ang II-mediated hypertension.

Aloe vera for prevention and treatment of infusion phlebitis.

BACKGROUND: Up to 80% of hospitalised patients receive intravenous therapy at some point during their admission. About 20% to 70% of patients receiving intravenous therapy develop phlebitis. Infusion phlebitis has become one of the most common complications in patients with intravenous therapy. However, the effects of routine treatments such as external application of 75% alcohol or 50% to 75% magnesium sulphate (MgSO4) are unsatisfactory. Therefore, there is an urgent need to develop new methods to prevent and alleviate infusion phlebitis. OBJECTIVES: To systematically assess the effects of external application of Aloe vera for the prevention and treatment of infusion phlebitis associated with the presence of an intravenous access device. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched February 2014) and CENTRAL (2014, Issue 1). In addition the TSC searched MEDLINE to week 5 January 2014, EMBASE to Week 6 2014 and AMED to February 2014. The authors searched the following Chinese databases until 28 February 2014: Chinese BioMedical Database; Traditional Chinese Medical Database System; China National Knowledge Infrastructure; Chinese VIP information; Chinese Medical Current Contents; Chinese Academic Conference Papers Database and Chinese Dissertation Database; and China Medical Academic Conference. Bibliographies of retrieved and relevant publications were searched. There were no restrictions on the basis of date or language of publication. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised controlled trials (qRCTs) were included if they involved participants receiving topical Aloe vera or Aloe vera-derived products at the site of punctured skin, with or without routine treatment at the same site. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data on the study characteristics, description of methodology and outcomes of the eligible trials, and assessed study quality. Data were analysed using RevMan 5.1. For dichotomous outcomes, the effects were estimated by using risk ratio (RR) with its 95% confidence interval (CI). For continuous outcomes, mean differences (MD) with 95% CIs were used to estimate their effects. MAIN RESULTS: A total of 43 trials (35 RCTs and eight qRCTs) with 7465 participants were identified. Twenty-two trials with 5546 participants were involved in prevention of Aloe vera for phlebitis, and a further 21 trials with 1919 participants were involved in the treatment of phlebitis. The included studies compared external application of Aloe vera alone or plus non-Aloe vera interventions with no treatment or the same non-Aloe vera interventions. The duration of the intervention lasted from one day to 15 days. Most of the included studies were of low methodological quality with concerns for selection bias, attrition bias, reporting bias and publication bias.The effects of external application of fresh Aloe vera on preventing total incidence of phlebitis varied across the studies and we did not combine the data. Aloe vera reduced the occurrence of third degree phlebitis (RR 0.06, 95% CI 0.03 to 0.11, P < 0.00001) and second degree phlebitis (RR 0.18, 95% CI 0.10 to 0.31, P < 0.00001) compared with no treatment. Compared with external application of 75% alcohol, or 33% MgSO4 alone, Aloe vera reduced the total incidence of phlebitis (RR 0.02, 95% CI 0.00 to 0.28, P = 0.004 and RR 0.43, 95% CI 0.24 to 0.78, P = 0.005 respectively) but there was no clear evidence of an effect when compared with 50% or 75% MgSO4 (total incidence of phlebitis RR 0.41, 95% CI 0.16 to 1.07, P = 0.07 and RR 1.10 95% CI 0.54 to 2.25, P = 0.79 respectively; third degree phlebitis (RR 0.28, 95% CI 0.07 to 1.02, P = 0.051 and RR 1.19, 95% CI 0.08 to 18.73, P = 0.9 respectively; second degree phlebitis RR 0.68, 95% CI 0.21 to 2.23, P = 0.53 compared to 75% MgSO4) except for a reduction in second degree phlebitis when Aloe vera was compared with 50% MgSO4 (RR 0.26, 95% CI 0.14 to 0.50, P < 0.0001).For the treatment of phlebitis, Aloe vera was more effective than 33% or 50% MgSO4 in terms of both any improvement (RR 1.16, 95% CI 1.09 to 1.24, P < 0.0001 and RR 1.22, 95% CI 1.16 to 1.28, P < 0.0001 respectively) and marked improvement of phlebitis (RR 1.97, 95% CI 1.44 to 2.70, P < 0.001 and RR 1.56, 95% CI 1.29 to 1.87, P = 0.0002 respectively). Compared with 50% MgSO4, Aloe vera also improved recovery rates from phlebitis (RR 1.42, 95% CI 1.24 to 1.61, P < 0.0001). Compared with routine treatments such as external application of hirudoid, sulphonic acid mucopolysaccharide and dexamethasone used alone, addition of Aloe vera improved recovery from phlebitis (RR 1.75, 95% CI 1.24 to 2.46, P = 0.001) and had a positive effect on overall improvement (marked improvement RR 1.26, 95% CI 1.09 to 1.47, P = 0.0003; any improvement RR 1.23, 95% CI 1.13 to 1.35, P < 0.0001). Aloe vera, either alone or in combination with routine treatment, was more effective than routine treatment alone for improving the symptoms of phlebitis including shortening the time of elimination of red swelling symptoms, time of pain relief at the location of the infusion vein and time of resolution of phlebitis. Other secondary outcomes including health-related quality of life and adverse effects were not reported in the included studies. AUTHORS' CONCLUSIONS: There is no strong evidence for preventing or treating infusion phlebitis with external application of Aloe vera. The current available evidence is limited by the poor methodological quality and risk of selective outcome reporting of the included studies, and by variation in the size of effect across the studies. The positive effects observed with external application of Aloe vera in preventing or treating infusion phlebitis compared with no intervention or external application of 33% or 50% MgSO4 should therefore be viewed with caution.

[A system review of randomized controlled trials on treating chronic stable angina by rhodiola].

OBJECTIVE: To systematically assess the efficacy and safety of Rhodiola in treating chronic stable angina pectoris. METHODS: Our group searched the Cochrane library, PubMed, Embase, Chinese biomedical literature database (CBM), VIP database (VIP), Chinese Journal Full-text Database (CNKI) for the literature published in English and Chinese till April 2013. Randomized controlled trials (RCTs) were included on the therapeutic effect of Rhodiola or Rhodiola plus conventional Western medicine in comparison with the conventional Western medicine treatment on stable angina. Data were extracted according the data extraction form. The literature methodological quality was assessed by using the Cochrane handbook, and data analyzed by Rev-Man 5.2 Software for Meta-analysis. The effect indicators of outcomes was expressed by odds ratio (OR) and 95% CI. RESULTS: A total of 7 randomized controlled trials, 662 cases of stable angina pectoris patients met the inclusion criteria and all published in Chinese, without one scientific design and high quality literature. Compared with the conventional Western medicine treatment, combined with oral administration of Rhodiola could improve the efficiency of anti-angina (OR = 2.49, 95% CI: 1.02 - 6.09). Combined with intravenous infusion of Rhodiola could also improve the efficacy of angina pectoris (OR = 4.86, 95% CI: 2.4 - 9.82). Oral administration of Rhodiola couldn't improve ECG efficacy (OR = 1.25, 95% CI: 0.67 - 2.34). Intravenous infusion of Rhodiola could improve the clinical efficacy (OR = 2.94, 95% CI: 1.61 - 5.35). Combined with the conventional treatment, intravenous infusion of Rhodiola could improve the whole blood viscosity (low and high shear rates) and inverse variance (IV) (-1.36 and -0.99, 95% CI: -1.65 - 1.07 and -1.26 - 0.71), but could not reduce serum fibrinogen and D-dimer level. The incidence rate of adverse reactions was higher than that of the conventional treatment combined with Rhodiola (OR = 0.1, 95% CI: 0.02 - 0.51). CONCLUSIONS: On the basis of routine treatment, Rhodiola could further improve patients' symptoms. Combined with intravenous medication, Rhodiola could increase the ECG improvement rate, and reduce adverse reactions. But the methodological quality of included studies was poor, the number of samples was small, and influence factors such as the intervention period was short. This conclusion needs scientific and rational design in a larger sample, multicenter clinical trial to verify.

Xiongshao for restenosis after percutaneous coronary intervention in patients with coronary heart disease.

BACKGROUND: Percutaneous coronary intervention (PCI) with stent placement is a standard treatment for coronary heart disease (CHD). In-stent restenosis after PCI remains an important clinical problem. Xiongshao capsule has been reported to be beneficial in preventing restenosis after PCI in CHD patients. However, the strength of evidence to support its use is unclear. OBJECTIVES: To systematically assess the efficacy and safety of Chinese herbal medicine Xiongshao capsule in preventing restenosis after PCI in patients with CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3 of 2012), MEDLINE (OVID) (1948 to week 1 March 2012), EMBASE (OVID) (1980 to week 10 2012), ISI Web of Science with Conference Proceedings (1970 to 14 March 2012), LILACS (1982 to 15 March 2012), Chinese biomedical literature database (1980 to May 2012), China National Knowledge Infrastructure (1994 to May 2012), Chinese Medical Current Contents (1994 to May 2012), VIP Database for Chinese Technical Periodicals (1989 to May 2012), Chinese Master's Theses Full-Text Database (1994 to May 2012), China Doctor Dissertation Full-Text Database (1994 to May 2012), and China Proceedings of Conference Full-Text Database (1994 to May 2012). We also searched ongoing trials and research registries. SELECTION CRITERIA: All randomised controlled trials comparing Xiongshao capsule alone/plus conventional western medicine with the same conventional western medicine alone/plus placebo in participants with CHD who met the recognised diagnostic criteria and had successfully undergone a PCI procedure were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. Two review authors independently assessed the risk of bias of included trials using The Cochrane Collaboration tool, and any disagreements were resolved by discussion with a third review author. Data were pooled for meta-analysis using the fixed-effect model, and the results were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Four trials involving 649 participants were included in this review. Two of these trials (459 participants) were designed as randomised, double-blind, placebo-controlled trials with an adequate methodological description; the other two trials (190 participants) described an inadequate methodological design. All four trials with 649 participants were included in the meta-analysis. Significant differences were noted in rates of restenosis, recurrence angina pectoris, and serious cardiovascular adverse events between Xiongshao capsule plus conventional western medicine and the same conventional western medicine alone; RR values (95% CIs) were 0.41 (0.22 to 0.75), 0.47 (0.31 to 0.72), and 0.47 (0.25 to 0.90), respectively. Xiongshao capsule plus conventional western medicine showed more significant reductions in restenosis (RR 0.52, 95% CI 0.33 to 0.80), recurrence angina pectoris (RR 0.26, 95% CI 0.18 to 0.38), and serious cardiovascular adverse events (RR 0.45, 95% CI 0.28 to 0.70) than the same conventional western medicine plus placebo. Safety outcomes and adverse events of the Xiongshao capsule were reported in two trials, which reported no adverse events. AUTHORS' CONCLUSIONS: The summary estimates indicate a protective effect of Xiongshao on restenosis and suggest that Xiongshao capsule may be used to prevent restenosis after a PCI procedure in CHD patients. However, this evidence is derived from small randomised trials, all conducted in China, and two of the included trials showed important methodological limitations that undermine the validity of the findings. Additional high-quality research trials with sufficient sample size are required.

Effects of Qingda granule on patients with grade 1 hypertension at low-medium risk: study protocol for a randomized, controlled, double-blind clinical trial.

BACKGROUND: Numerous pre-clinical studies showed that Qingda granule (QDG) was effective in treating hypertension. This study aims to evaluate the efficacy and safety of QDG in reducing blood pressure among patients with grade 1 hypertension at low-medium risk. METHODS: The study is designed as a randomized, multi-center, double-blinded, non-inferiority clinical trial. Five hundred fifty-two patients with grade 1 hypertension at low-medium risk from 13 hospitals will be recruited and randomly assigned to the QDG group (n = 276, treated with valsartan capsule simulation agent and QDG) or control group (n = 276, treated with valsartan capsule and QDG simulation agent). The treatment period will be 4 weeks and the follow-up period will last 4 weeks after treatment. Primary outcome will be a decreased value of systolic blood pressure and diastolic blood pressure after treatment. And second outcome will include the decreased value of diastolic blood pressure and systolic blood pressure at the end of follow-up, the percentage of participants achieving normal blood pressure at the end of treatment and follow-up, the Hamilton Anxiety Scale and TCM syndrome scores at the end of treatment and follow-up, and levels of hypertensive hormones at end of treatment and follow-up. DISCUSSION: This study will provide initial evidence regarding the clinical efficacy and safety of QDG in treating grade 1 hypertension at low-medium risk. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033890 . Registered on 15 June 2020.

Systematic Review of Chinese Herbal Medicines for Preventing in-Stent Coronary Restenosis after Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) with stent placement is a standard treatment for coronary artery disease (CAD). In-stent restenosis after PCI remains a challenging clinical problem. In China, Chinese herbal medicines (CHMs) are widely used for preventing restenosis. This paper systematically reviewed the literature on the effectiveness and safety of CHMs in preventing restenosis after PCI in patients with CAD. Electronic databases were searched for randomized controlled trials that compared CHMs plus RWM with the same RWM plus placebo in preventing restenosis after PCI. A total of 52 trials (4905 patients) on 34 CHMs met the inclusion criteria and were analyzed. Ten trials had low risk of bias. Methodological quality of included trials was generally poor. Meta-analysis showed that at the end of at least 3 months' followup, CHMs plus RWM could significantly reduce restenosis rate, cardiac mortality, recurrence rate of angina, acute myocardial infarction, numbers of repeat PCI, and numbers of coronary artery bypass graft. Reported adverse events included gastrointestinal upset, granulocytopenia, and increased alanine transaminase (ALT). CHMs may help prevent restenosis, thus reducing cardiac mortality after PCI. Caution should be exercised in drawing a definitive conclusion due to the poor methodological quality of the trials reviewed.

Therapeutic Effects of Different Animal Bile Powders on Lipid Metabolism Disorders and Their Composition Analysis.

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS: Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia.

OBJECTIVE: To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. METHODS: Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. RESULTS: KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. CONCLUSION: KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Lipoprotein-associated phospholipase A2 gene V279F polymorphisms and coronary heart disease: a meta-analysis.

Lipoprotein-associated phospholipase A2 (LP-PLA2) may play an important role in the pathophysiology of coronary heart disease (CHD). The polymorphism of LP-PLA2 gene caused LP-PLA2 enzyme activity depressing or lost. But there is not a definite conclusion for the association of between the LP-PLA2 gene polymorphism and CHD risk. To assess the relationship between LP-PLA2 gene V279F polymorphism and CHD, a comprehensive Meta-analysis was performed. All the case-control studies evaluating the association of between the LP-PLA2 gene V279F polymorphism and CHD risk were identified. Seven case-control studies involving 3,614 patients with CHD and 4,334 controls were included. The crude odds ratios (ORs) of meta-analysis under the different gene model were not significant. But in the stratified analysis by study size, ethnicity, cases definition, and source of controls under the additive model, the association was evident in ethnicity for Japanese group (OR=1.38, 95%CI=1.22-1.56), cases definition for MI (OR=1.22, 95%CI=1.01-1.49), source of controls for the based-hospital (OR=1.42, 95%CI=1.24-1.59). These data suggested that the V279F polymorphism in LP-PLA2 gene may contribute to CHD development. But there is necessary that more well-designed large studies are required for the validation of this association.

Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-ß1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats.

OBJECTIVE: To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats. METHODS: Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- ß 1 (TGF-ß 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay. RESULTS: HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-ß 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3. CONCLUSIONS: HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-ß 1/Smad2/3 pathway.

Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice.

OBJECTIVE: To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms. METHODS: A HCC xenograft mouse model was developed by producing with huh7 cells. After 5 days following xenograft implantation, ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg•d) dose of BBP or saline for 3 weeks. Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume. Cell apoptosis, proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31), respectively. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Western blot. The mRNA and protein expressions of Bcl-2, Bax, Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining. RESULTS: BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight. In addition, BBP profoundly promoted cell apoptosis, inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05). Moreover, BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2, Bax, Cyclin D1, CDK4 and VEGF-A in HCC mice. CONCLUSION: BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.

Qingxuan Jiangya Decoction () Prevents Blood Pressure Elevation and Ameliorates Vascular Structural Remodeling via Modulating TGF-ß 1/Smad Pathway in Spontaneously Hypertensive Rats.

OBJECTIVE: To elevate the effects of Qingxuan Jiangya Decoction (, QXJYD) on hypertension and vascular structural remodeling (VSR) in spontaneously hypertensive rats (SHRs), and investigate the underlying mechanisms. METHODS: SHRs (n=8) were given intra-gastric administration with 60 mg/kg of QXJYD or saline, daily for 8 weeks, while rats in SHR-control (n=8) and WKY (n=8) groups were received equal volumes of saline solution. Systolic blood pressures (SBP), diastolic blood pressures (DBP) and mean blood pressures (MBP) were measured once a week. The levels of angiotensin II (Ang II), endothelin 1 (ET-1) and plasma renin activity (PRA) were tested by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, respectively. The effect of QXJYD on VSR was determined by examining the media thickness and the ex vivo contractility of thoracic aortic. The proliferation and fibrosis of vascular smooth muscle cells (VSMCs) were examined via immunohistochemical (IHC) staining for proliferating cell nuclear antigen (PCNA), collagen I and collagen III, respectively. The mRNA and protein expressions of transforming growth factor ß 1 (TGF-ß 1), Smad3 and phosphorylation of Smad3 in thoracic aorta tissues were determined by real-time polymerase chain reaction (PCR) and Western blot assay, respectively. RESULTS: QXJYD treatment led to a significant decrease of the elevation of blood pressure in SHRs and reduced the levels of Ang II, ET-1 and PRA in the serum (P<0.05). In addition, QXJYD treatment remarkably ameliorated VSR and vascular function in SHRs. Moreover, QXJYD inhibited VSMC proliferation and fibrosis by suppressing the expression of PCNA, collagen I and collagen III in thoracic aortic. Furthermore, QXJYD inhibited the expression of TGF-ß 1, Smad3 and the phosphorylation of Smad3, respectively (P<0.05). CONCLUSION: QXJYD reversed VSR by inhibiting VSMC proliferation and collagen deposition via regulation of TGF-ß 1/Smad signaling pathway, which may, in part, illuminate its anti-hypertensive activities.

Pien Tze Huang () Overcomes Doxorubicin Resistance and Inhibits Epithelial-Mesenchymal Transition in MCF-7/ADR Cells.

OBJECTIVE: To evaluate the effect of Pien Tze Huang (, PZH) on breast cancer chemoresistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms. METHODS: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cell viability. Adriamycin (ADR) staining observed by fluorescence microscope was performed to detect the accumulation of ADR. Transwell assay was used to analyze the cell migration and invasion. Western-blot was performed to detect the protein expression of related genes. RESULTS: MCF-7/ADR cells were resistant to ADR treatment, and PZH treatment inhibited the viability of MCF-7/ADR cells in a dose-dependent manner. PZH treatment also increased the intercellular accumulation of ADR and down-regulated the expression of ABCG2 and ABCB1 in MCF-7/ADR cells (P<0.05). In addition, PZH treatment inhibited EMT, migration and invasion of MCF-7/ADR cells (P<0.05). Moreover, PZH suppressed activation of transforming growth factor ß1 (TGF-ß) signaling in MCF-7/ADR cells (P<0.05). CONCLUSION: PZH treatment can effectively overcome chemoresistance via down regulating ABCG2, ABCB1 and inhibit EMT in ADR resistant human breast cancer cells via suppression of the TGF-ß1 pathway.

Shexiang Tongxin Dropping Pill () Protects against Na2S2O4-Induced Hypoxia-Reoxygenation Injury in H9c2 Cells.

OBJECTIVES: To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. METHODS: The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following Na2S2O4-induced hypoxia using Hoechst staining, annexin V/propidium iodide (PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis. RESULTS: STP pretreatment significantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by Na2S2O4 treatment (P<0.05). In addition, STP pretreatment attenuated Na2S2O4-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax, and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells (P<0.05). CONCLUSIONS: STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis. These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.

Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/ß-catenin signaling pathway.

OBJECTIVE: To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/ß-catenin signaling pathway in vivo and in vitro. METHODS: In vivo experiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/mL EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay, respectively. The mRNA expression of c-Myc, Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and ß-catenin as well as ß-catenin phosphorylation level were evaluated by IHC assay or Western blotting. RESULTS: EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group (P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues (P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner (P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells (P<0.05). In addition, RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of ß-catenin, c-Myc and Survivin, as well as increased APC expression and ß-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05). CONCLUSIONS: EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/ß-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.

Zika Virus Infection: Current Concerns and Perspectives.

The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

Elevated plasma platelet activating factor, platelet activating factor acetylhydrolase levels and risk of coronary heart disease or blood stasis syndrome of coronary heart disease in Chinese: a case control study: a case-control study.

The purpose of the study was to explore the association between plasma platelet activating factor (PAF) and platelet activating factor acetylhydrolase (PAF-AH) levels and risk of coronary heart disease (CHD) or blood stasis syndrome (BSS) of CHD. Questionnaire, routine clinical assays and plasma levels of PAF, PAF-AH and inflammatory factors hs-CRP and IL-6 were investigated or measured for 120 controls and 150 CHD patients (66 non-BSS and 84 BSS). Plasma PAF levels were higher in CHD patients [49.7 (34.8-73.2 pg/mL)] than in controls [23.8 (14.9-42.3 pg/mL)] (P < 0.001), and in BSS [56.0 (40.1-86.1 pg/mL)] than in non-BSS [47.4 (29.0-67.4 pg/mL)] (P = 0.027). Similarly, plasma PAF-AH levels were higher in CHD patients [11.5 (7.5-15.6 µmol/L)] than in controls [8.1 (5.4-12.6 µmol/L)] (P < 0.001), and in BSS [13.4 (8.7-18.5 µmol/L)] than in non-BSS [9.5 (7.3-14.3 µmol/L)] (P = 0.014). After adjustment for the confounded effects of inflammatory factors or conventional risk factors, plasma PAF and PAF-AH levels still had a significant difference between CHD patients and controls, but plasma PAF-AH rather than PAF levels had a significant difference between BSS and non-BSS. Elevated plasma PAF level contributed to the risk of CHD rather than BSS, and elevated plasma PAF-AH level was an independent risk factor of CHD and BSS.