Systematic evaluation and trail sequential analysis of efficacy and safety of Yangxue Qingnao Granules in treatment of essential hypertension and its accompanying symptoms / 中国中药杂志

To systematically evaluate the efficacy and safety of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms. PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, and China biomedical database(CBD) were searched to screen out from the establishment of the database to April 2020 about the clinical randomized controlled trials of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and accompanying symptoms. The articles were selected according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. TSA 0.9.5.10 Beta software was used for sequential analysis, and GRADE 3.6 was used for evidence quality evaluation. A total of 4 532 patients were included in 34 randomized controlled trials. Meta-analysis results showed that: Yangxue Qingnao Granules combined with conventional anti-hypertensive agents reduced systolic blood pressure(MD=-10.56, 95%CI[-13.63,-7.50], P<0.000 01) and diastolic blood pressure(MD=-8.21, 95%CI[-10.84,-5.59], P<0.000 01), improved total effective rate(RR=1.21, 95%CI[1.14, 1.29], P<0.000 01), improved patients dizziness(RR=1.29, 95%CI[1.21, 1.37], P<0.000 01), insomnia(RR=1.66, 95%CI[1.44, 1.91], P<0.000 01), headache(RR=1.32, 95%CI[1.21, 1.43], P<0.000 01), chest distress(RR=1.26, 95%CI[1.12, 1.42], P=0.000 1), memory loss(RR=1.24, 95%CI[1.10, 1.40], P=0.000 4), palpitation(RR=1.28, 95%CI[1.17, 1.41], P<0.000 01), and improved traditional Chinese medicine symptom scores(MD=-4.24, 95%CI[-5.25,-3.23], P<0.000 01) and headache symptom improvement scores(MD=-2.02, 95%CI[-2.51,-1.53], P<0.000 01) as compared with Western medicine group alone. Subgroup analysis results showed that Yang-xue Qingnao Granules combined with ACEI drug had more obvious effects in lowering systolic blood pressure and diastolic blood pressure. There was no statistically significant difference in the incidence of adverse reactions, and no abnormal liver and kidney function was observed in each study. Trial sequential analysis showed that the total effective rate was cumulative across the traditional and TSA thresholds, further confirming its clinical efficacy. The evidence level was mostly low or extremely low in GRADE evaluation. The clinical application of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms is clear and safe, so it is recommended for clinical application.

Systematic evaluation of efficacy and safety of Songling Xuemaikang Capsules in treatment of essential hypertension / 中国中药杂志

To evaluate the efficacy and safety of Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. PubMed, VIP, CNKI, Wanfang and other databases were retrieved from the establishment of the database to February 2020 for clinical randomized controlled trial(RCT) about Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. The literatures were screened out according to the inclusion criteria, and RevMan 5.3 software was used for Meta-analysis. A total of 3 100 patients in 27 RCTs were enrolled. According to Meta-analysis, Songling Xuemaikang Capsules combined with conventional Western medicine could effectively reduce systolic blood pressure(MD=-7.88,95%CI[-9.68,-6.08],P<0.000 01) and diastolic blood pressure(MD=-7.85, 95%CI[-9.07,-6.62], P<0.000 01), triglyceride(MD=-0.46, 95%CI[-0.66,-0.26], P<0.000 01) and total cholesterol(MD=-0.92, 95%CI[-1.49,-0.35], P=0.001), but increase HDL cholesterol(MD=0.51, 95%CI[0.28, 0.73], P<0.000 01), with a better effect than the Western medicine group alone. The results of LDL-C analysis showed that there was no significant difference between the two groups(MD=-0.91, 95%CI[-1.82, 0.01], P=0.05). The subgroup analysis suggested that reduced systolic blood pressure may be related to the use of ARB. There was a close correlation between CCB drugs and the decrease of diastolic blood pressure. In addition, there was no significant difference in the compliance and the incidence of adverse reactions. Clinical application of Songling Xuemaikang Capsules combined with Western medicine in the treatment of patients with essential hypertension has clear efficacy and certain safety. More clinical randomized controlled trials are needed for verification in the future.

Olmesartan Reduces New-onset Atrial Fibrillation and Atrial Fibrillation Burden after Dual-chamber Pacemaker Implantation in Atrioventricular Block Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial fibrillation (AF) is the most frequent tachyarrhythmia in patients with a permanent pacemaker. Angiotensin II receptor antagonists have a protective effect against the occurrence of AF in patients with heart diseases. This study aimed to assess the effectiveness of olmesartan in the prevention of new-onset AF and AF burden in atrioventricular block (AVB) patients with dual-chamber (DDD) pacemaker implantation.</p><p><b>METHODS</b>This was a single-center, prospective, randomized, single-blind, controlled clinical study. A total of 116 AVB patients, who received DDD pacemakers implantation with the percentage of ventricular pacing (VP%) ≥40% from April 22, 2011 to December 24, 2012, were prospectively randomized to olmesartan group (20 mg per day; n = 57) or control group (n = 59). Patients were followed up using pacemaker programming, 12-lead electrocardiography in the intrinsic sinus rhythm, laboratory examinations, and transthoracic echocardiography at 24 months. Atrial high rate events (AHREs) were defined as 180 beats/min over a minimum of 5 min. AF burden was calculated by the number of hours with AHREs divided by the number of measurement hours.</p><p><b>RESULTS</b>Ten (17.5%) patients in the olmesartan group and 24 patients (40.7%) in the control group occurred new-onset AF, and the difference between two groups was statistically significant (P = 0.04). AF burden was lower in olmesartan group than that in control group (8.02 ± 3.10% vs. 13.66 ± 6.14%, P = 0.04). There were no significant differences in mean days to the first occurrence of AHREs and mean cumulative numbers of AHREs between two groups (P = 0.89 and P = 0.42, respectively). Moreover, olmesartan group had smaller values of maximal P-wave durations and P-wave dispersion (PD) after 24 months follow-up compared with the control group (109.5 ± 7.4 ms vs. 113.4 ± 7.1 ms, P = 0.00; and 40.6 ± 4.5 ms vs. 43.3 ± 4.4 ms, P = 0.02, respectively). Left ventricular end-diastolic diameter and left ventricular ejection fraction were not significantly different between two groups (both P > 0.05).</p><p><b>CONCLUSION</b>This study suggested that 24-month of olmesartan therapy could reduce new-onset AF and AF burden in patients with DDD pacemakers.</p><p><b>CLINICAL TRIAL REGISTRATION</b>ChiCTR-TRC-12004443; http://www.chictrdb.org.</p>

Intravenous injection of nicardipine changed the distribution of coronary artery endothelial shear stress and fluid dynamics in patients with unstable angina / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coronary endothelial shear stress (ESS) triggered the development of atherosclerosis. However, the effect of calcium channel antagonist on the distribution of ESS remained unclear.</p><p><b>METHODS</b>Twenty consecutive patients with acute coronary syndrome (ACS) 48 hours after maximal medication with single left anterior descending artery stenosis < 50% were studied. Nicardipine was intravenously injected at 1 µg/kg after a bolus of 10 mg in order to achieve mean blood pressure (MBP) reduced by 10% or more, or the heart rate increased by 10 - 15 beats/min. Hemodynamic variables and angiogram at baseline and during injection of nicardipine were recorded, respectively. Coronary artery 3-D reconstruction was used for the analysis of ESS.</p><p><b>RESULTS</b>Distal reference-vessel-diameter and minimal lumen diameter decreased significantly from (2.42 ± 0.41) mm and (1.47 ± 0.49) mm at baseline to (2.22 ± 0.35) mm and (1.35 ± 0.49) mm at maximal drug-dosage (P = 0.018 and 0.020, respectively). Nicardipine did not change blood velocity. Lowest mean shear stress at segments 2-mm distal to plaque increased significantly from (0.034 ± 0.519) Pa at baseline to (0.603 ± 0.728) Pa (P = 0.013) at peak effect of drug.</p><p><b>CONCLUSIONS</b>Nicardipine was associated with the constriction of diseased vessel segment that adapted to the reduction of blood pressure, without dynamic change of blood velocity at each stage of whole cardiac cycle. Increased ESS value at segments distal to plaque reflected the cardioprotection by nicardipine (ChiCTR-TRC-10000964).</p>

Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1:1:1 ratio to receive either adenosine 50 µg×kg(-1)×min(-1) (low-dose group, n = 31), or 70 µg×kg(-1)×min(-1) (high-dose group, n = 32), or saline 1 ml/min (control group, n = 27) for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG), and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram (ECG) and their ratio (STsum-post/STsum-pre) were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure.</p><p><b>RESULTS</b>A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 (35.5%) patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group (both P = 0.001). STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group (low-dose group vs. control group, P = 0.003 and high-dose group vs. control group, P = 0.001), without a dose-dependent pattern (P = 0.238). The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group (P = 0.024). Compared to the left ventricular ejection fraction (LVEF) in control group, LVEF in the low-dose group increased by 5.8% at 24 hours (P = 0.012) and by 10.9% at 6 months (P = 0.007), LVEF in the high-dose group increased by 9.5% at 24 hours (P = 0.001) and by 10.0% at 6 months (P = 0.001), respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups (P = 0.008). There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly (P = 0.013, P = 0.016).</p><p><b>CONCLUSION</b>Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.</p>

Hemodynamic change in wall shear stress in patients with coronary bifurcation lesions treated by double kissing crush or single-stent technique / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fluid dynamic mechanisms attributed to coronary bifurcation lesions remain a subject of study. The present study aimed at investigating the hemodynamic change of wall shear stress (WSS) in patients with coronary bifurcation lesions treated by double kissing (DK) crush or one-stent with final kissing balloon inflation (FKBI).</p><p><b>METHODS</b>Eighty-one patients with bifurcation lesions treated by stenting who had 3-D model reconstruction were studied. The bifurcation vessels were divided into main vessel (MV), main branch (MB), side branch (SB), and polygon of confluence (POC). MB and SB were classified by internal- and lateral-subsegments, respectively.</p><p><b>RESULTS</b>The baseline magnitude of WSS in proximal MV, POC-MV, POC-MB, POC-SB and MB-internal segments increased significantly, compared to MB-lateral, SB-internal and SB-lateral. DK crush had the potential of uniformly reducing WSS, turbulent index and the WSS gradient. The WSS value at the POC-SB and SB in the one-stent group remained higher. The turbulent index and WSS gradient between the POC-SB minus the SB-lateral had equal predictive values for in-stent restenosis (ISR).</p><p><b>CONCLUSION</b>Fluid dynamic results favor the use of DK crush over the one-stent technique.</p>

Effect of anti-oncogene PTEN on cell proliferation in breast cancer cell BT549 / 中国医师杂志

ObjectiveTo investigate the effect of PTEN on cell proliferation in human breast cancer cell BT549.MethodsThe plasmid pcDNA3-PTEN was used to transfect the PTEN - null breast cancer cell BT549 by lipo - transfection.After G418 selection,BT549 cells which stably expressed PTEN were obtained and amplified.Western blot were used to determine the target protein expression,the cell viability was tested by MTT assay.Results(1)Compared with the control,PTEN-BT549 cells demonstrated high expression of PTEN protein ;(2)The proliferation speed of PTEN-BT549 was obviously slower than BT549 and pcDNA3-BT549 cells( P ＜ 0.05 ).ConclusionAnti-oncogene PTEN suppresses the growth of breast cancer cell BT549.

On-line Glucose Concentration Prediction and Control for Improving Glutamate Fermentation Performance / 微生物学通报

In industrial glutamate fermentation, intermitted feeding glucose with the help of off-line glucose measurement is generally necessary. This kind of feeding strategy could cause large variations in glucose concentration so that it is not favorable for the achievement of efficient and stable glutamate fermentation. Glutamate fermentation is characterized with typical non-growth association behavior, and during glutamate production phase glucose consumption is closely correlated with ammonia consumption. In this study, glucose concentration was controlled at various pre-determined levels by predicting glucose consumption amount and thus its concentration with the aid of on-line monitoring ammonia consumption. When glucose concentration was controlled around a lower level of 5 g/L~10 g/L, the final glutamate concentration could reach a relatively higher level of 80 g/L. In this way, the huge osmotic stress change due to the large glucose concentration variation with the intermitted feeding method could be avoided and the glutamate fermentation performance enhancement be expected.

Left ventricular endocardial pacing predicts the reduction of left ventricular outflow tract pressure gradient immediately after percutaneous transseptal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy refractory to medication / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertrophic obstructive cardiomyopathy (HOCM) carries an increased risk for sudden cardiac death. No data regarding the percutaneous transseptal myocardial ablation (PTSMA) and epicardial left ventricular pacing (LVP) were reported.</p><p><b>METHODS</b>Seven patients with recurrent symptoms and increased resting left ventricular outflow tract pressure gradient (LVOTG) after PTSMA and another 14 patients with HOCM without history of PTSMA were studied. Both resting and dobutamine stress echocardiography, PTSMA and LVP were routinely performed.</p><p><b>RESULTS</b>In patients without previous PTSMA procedure, mild reduction of resting LVOTG was detected at 5 minutes after left ventricular pacing, and this reduction became significant at 10 minutes. All patients were divided into successful and unsuccessful groups according to their response to LVP. In contrary to patients in unsuccessful group, resting and R-S2 stimuli-induced LVOTG during PTSMA procedure were decreased dramatically ((9 +/- 5) mmHg vs (58 +/- 12) mmHg, (12 +/- 2) mmHg vs (113 +/- 27) mmHg, P < 0.001). Analysis of Logistic regression demonstrated that only LVOTG level during left ventricular pacing was an independent factor predicting the reduction of LVOTG immediately after PTSMA (odds ratio (OR), 0.59; 95% CI 2.67 to 5.82; P = 0.0002).</p><p><b>CONCLUSION</b>Left ventricular endocardial temporary pacing plays a critical role in predicting acute effect on the reduction of LVOTG immediately after PTSMA procedure.</p>

The analysis of heterogeneity of HWTX-I expressed in Pichia pastoris / 生物工程学报

To seek the reason of heterogeneity of recombinant HWTX-I (rHWTX-I) expressed in Pichia pastoris. We expressed HWTX-I gene of interest in Pichia pastoris GS115/HWTX-I. The heterogenous product expressed was separated, purified and identified by using Ion exchange HPLC, reverse HPLC, Tricine SDS-PAGE and MALDI-TOF Mass Spectrometry and then sequenced in both N-terminus and C-terminus. These results show that the heterogeneity of rHWTX-I results from the incomplete processing of signal peptide of N-terminus and the internal degradation of C-terminus. Biological activity assay shows that the activity of the heterogenous rHWTX-I only showed 30% activity compared with the native HWTX-I. The Solutions to how to avoid the heterogeneity are also discussed.

Purification and characterization of glutamate dehydrogenase. from Corynebacterium glutamicum S9114 / 生物工程学报

Glutamate dehydrogenase (GDH) is a key enzyme in the biosynthesis of glutamate. The GDHs from Corynebacterium glutamicum S9114 the most commonly used strain in glutamate fermentation, were purified and their molecular structures and properties characterized. The coenzymes were also studied in the hope to increase glutamate production. Cells were harvested at mid-exponential phase by centrifugation and washed with Tris-HCl buffer containing DTT and EDTA (pH 7.5). The cells were then disrupted using a French pressure cell press and the supernatant was collected by centrifugation. The extract was concentrated by 70-fold using the AKTA-100 FPLC system employing a DEAE-cellulose ion exchange column, a hydrophobic interaction chromatography (HIC) and Sephadex G-200 gel filtration. The purified extracts contained NADPH-dependent GDH and NADH-dependent GDH. Both of the enzymes were highly specific for the coenzymes. The molecular masses of the NADPH-dependent GDH and its subunit were 188kD and 32kD respectively, suggesting the enzyme is a homo-hexamer. Our data reported for the first time the presence of NADH- dependent GDH in Corynebacterium glutamicum S9114, similar to other microorganisms containing both GDHs. The NADPH-dependent and NADH-dependent GDH in Corynebacterium glutamicum S9114 may participate in the assimilation and dissimilation of ammonia respectively. The absorptions of NADPH-dependent GDH was very weak at 280nm but very high at 215nm, suggesting a low phenylalanine and tyrosine content in the enzyme.