1. Systematic evaluation of efficacy and safety of Xinkeshu in treatment of unstable angina pectoris
Chinese Traditional and Herbal Drugs 2020;51(18):4719-4732
Objective: To systematically evaluate the efficacy and safety of Xinkeshu combined with conventional western medicine in the treatment of unstable angina pectoris. Methods: The randomized controlled clinical trials of Xinkeshu combined with conventional western medicine for the treatment of unstable angina pectoris were searched from PubMed database, Viper database, CNKCN, Wanfang database and other databases from the establishment of the database to April 2020.The literatures were screened according to inclusion and exclusion criteria, and Rev Man5.3 software was used for Meta analysis. Results: A total of 1569 patients were included in 19 randomized controlled trials. Meta-analysis results showed that Xinkeshu combined with conventional western medicine reduced the frequency of angina attacks (SMD=-1.16, 95%CI [-1.75, -0.57], P=0.000 1), decreased the duration of angina (MD=-2.75, 95%CI [-3.77, -1.73], P < 0.000 01), reduced the dosage of nitroglycerin (MD=-0.67, 95%CI [-0.78, -0.56], P < 0.000 01), improved ECG efficacy (RR=1.26, 95%CI [1.18, 1.35], P < 0.000 01), angina pectoris efficacy (RR=1.26, 95%CI [1.20, 1.33], P < 0.000 01), decreased triglyceride (MD=-0.57, 95%CI [-1.02, -0.12], P=0.01), total cholesterol (MD=-0.78, 95%CI [-1.15, -0.41], P < 0.000 1), low-density lipoprotein cholesterol (MD=-0.58, 95%CI [-0.80, -0.36], P < 0.000 01), raised high-density lipoprotein cholesterol (MD=0.24, 95%CI [0.08, 0.40], P=0.004), decreased whole blood viscosity (MD=-1.32, 95%CI [-2.25, -0.39], P=0.005), and plasma viscosity (MD=-0.29, 95%CI [-0.38,-0.21], P < 0.000 01), fibrinogen (MD=-1.06, 95% CI [1.29, 0.83], P < 0.000 01), lower C-reactive protein (MD=-1.70, 95% CI [2.33, 1.06], P < 0.000 01), endothelin 1 (MD=-7.81, 95% CI [10.05, 5.57], P < 0.000 01), and homocysteine (MD=-2.35, 95% CI [2.63, 2.07], P < 0.000 01), improved the effect of nitric oxide (MD=8.74, 95%CI [7.00, 10.47], P < 0.000 01), which was better than that of the pure western medicine group, and subgroup analysis results showed that the treatment course was greater than or equal to three months with better treatment. There was no statistically significant difference in the incidence of adverse reactions (P=0.56), liver and kidney function were not abnormal in all the studies. Conclusion: Clinical application of Xinkeshu combined with conventional western medicine in the treatment of unstable angina pectoris is clear, which is recommended in clinical application.
2.Systematic evaluation and trial sequential analysis of Tianma Gouteng Granules combined with anti-hypertensive drugs in treatment of essential hypertension.
Meng-Lin LIU ; Gen-Hao FAN ; Huai-Liang ZHANG
China Journal of Chinese Materia Medica 2021;46(6):1511-1522
To systematically evaluate the efficacy and safety of Tianma Gouteng Granules combined with conventional anti-hypertensive drugs in the treatment of essential hypertension. The clinical randomized controlled trials(RCTs) on the treatment of essential hypertension with Tianma Gouteng Granules combined with conventional anti-hypertensive drugs were searched in PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, SinoMed since the establishment of the databases to April 2020 based on inclusion and exclusion criteria, and Meta-analysis was conducted by using RevMan 5.3 software. A total of 15 RCTs were included, involving a total of 1 508 patients. Meta-analysis results showed that Tianma Gouteng Granules combined with conventional Western medicine were supe-rior to the control group in reducing systolic blood pressure(MD=-10.24, 95%CI[-13.54,-6.95], P<0.000 01), diastolic blood pressure(MD=-5.33, 95%CI[-7.21,-3.45], P<0.000 01), improving the clinical efficacy of patients(RR=1.22, 95%CI[1.15, 1.28], P<0.000 01) and curative effect of traditional Chinese medicine syndrome(RR=1.26, 95%CI[1.02, 1.57], P=0.04), increasing nitric oxide content(MD=9.59, 95%CI[7.23, 11.96], P<0.000 01), reducing endothelin-1(MD=-10.74, 95%CI[-15.74,-5.75], P<0.000 1), tumor necrosis factor(MD=-0.28, 95%CI[-0.36,-0.19], P<0.000 01), and interleukin-6(MD=-39.71, 95%CI[-43.40,-36.03], P<0.000 01). There was no statistically significant difference between the test group and the control group in the incidence of adverse reactions. No liver and kidney dysfunction occurred. The results of the subgroup analysis showed that the effect of Tianma Gouteng Granules combined with ARB drugs was more obvious in reducing the systolic and diastolic pressure. Trial sequential analysis showed that the studies accumulatively included for clinical efficacy crossed the traditional threshold and the TSA threshold, further affirming its clinical efficacy. The clinical application of Tianma Gouteng Granules combined with conventional Western medicine in the treatment of primary hypertension and accompanying symptoms has clear efficacy and certain safety, so it is recommended for clinical application.
Angiotensin Receptor Antagonists
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Angiotensin-Converting Enzyme Inhibitors
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Antihypertensive Agents/therapeutic use*
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Drugs, Chinese Herbal
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Essential Hypertension/drug therapy*
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Humans
3.Anatomical and biomechanical characteristics of sternoclavicular joint
Kun YANG ; Tian-Hao WU ; Gen LI ; Yun-Kang YANG ; Jian-Hua GE ; Rui BAI ; Fei-Fan XIANG ; Yuan-Lin SUN
Chinese Journal of Tissue Engineering Research 2018;22(11):1695-1700
BACKGROUND: The clinical experience of the treatment of the sternoclavicular joint dislocation and peripheral fracture is relatively lacking, but its incidence is increasing yearly. At present, there are few studies on the anatomy and biomechanics of the sternoclavicular joint in and outside China, and no systematic anatomical measurements of the sternoclavicular joint are reported. OBJECTIVE: To provide a biological reference for the clinical diagnosis and treatment of sternoclavicular joint dislocation or peripheral fractures by studying the anatomy and biomechanics of the sternoclavicular joint. METHODS: (1) A total of 16 specimens (32 sides) of adult antiseptic and moist cadaveric specimens were selected. The complete manubrium, bilateral clavicle and surrounding tissues of sternoclavicular joint were anatomically separated, and repair to bone-ligament-bone specimen models. (2) The areas of manubrium articular surface and the medial clavicular articular surface of all specimens were measured by the ink pattern combined with grid counting method. (3) The morphological features of the anterior and posterior sternoclavicular ligaments of the specimens in this group were observed, and the length, width and thickness were measured and analyzed statistically. (4) The left and right sternoclavicular joints of each specimen were randomly paired into A and B groups. Group A received simply cutting of anterior sternoclavicular ligament. Group B received simply cutting of posterior sternoclavicular ligament. Before and after cuting off the ligament, the anterior and posterior load experiments were performed on the anatomical sites with the same force arm length and perpendicular to the distal clavicle. The angles of joints and load-angle regression line slopes were compared between the two groups in the anterior and posterior directions load. RESULTS AND CONCLUSION: (1) The area of articular surface of manubrium (239.00±28.78 mm2) was smaller than the area of medial articular surface of the clavicle (482.56±44.89 mm2), and the difference was statistically significant (t=-40.105, P < 0.001). (2) The length, width and thickness of the anterior sternoclavicular ligament were (17.56±1.94 mm), (15.54±1.42 mm) and (1.93±0.32 mm), and the length, width and thickness of the posterior sternoclavicular ligament were (17.21±1.86 mm), (15.97±1.17 mm), and (2.07±0.29 mm) respectively;there was no significantly statistical difference in the length, width and thickness between them (P > 0.05). (3) Before cutting the ligaments, when the loads were 2, 4, 6, 8, and 10 N, the angle backwards of joint caused by loads in the forward direction was less than the angle of forwards of joints caused by loads in the backward direction, but only when the loads were 6, 8, and 10 N, the difference between them was statistically significant (P < 0.05). The slope of the regression line of load-angle for the loads in the forward direction was less than the slope of the regression line of load-angle for the loads in the backward direction, with statistical difference (F=31.413, P < 0.001). After the ligaments were cut, when the loads were 2, 4, 6, 8 and 10 N in the forward direction in group A and group B, the backward angulation of joint in group A was less than that in group B (P < 0.05). The slope of the load-angled regression line in group A was less than that in group B (F=52.224, P <0.001). When the loads in the backward direction in group A and group B were 2, 4, 6, 8 and 10 N, the forward angulation of joint in group A was greater than that in group B (P < 0.05), and the slope of the load-angled regression line in group A was greater than that in group B (F=12.503, P=0.008). (4) These results suggest that contact area between the articular surface of the medial clavicle and the articular surface of the manubrium is narrow, which determines the instability of the joint itself. The sternoclavicular ligament is extremely important for maintaining the joint stability. The forward angulation of joint restriction effect of sternoclavicular ligament was weaker than that of the backward angulation, also because of the joint in the anatomical position of the natural forward angulation, so the sternoclavicular joint was prone to anterior dislocation. It is necessary to pay attention to the repair and reconstruction of sternoclavicular ligament when sternoclavicular joint dislocation or peripheral fractures are treated by operations.
4.Effect of FSD-C10 on modulation of inflammatory microenvironment in an Alzheimer disease double transgenic mouse model
fang Qing GU ; zhong Jie YU ; Hao WU ; hua Yan LI ; jie Hui FAN ; Zhi CHAI ; Qing WANG ; guo Bao XIAO ; gen Cun MA
Chinese Journal of Pathophysiology 2017;33(10):1729-1737
AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .
5.Systematic evaluation and trail sequential analysis of efficacy and safety of Yangxue Qingnao Granules in treatment of essential hypertension and its accompanying symptoms.
Gen-Hao FAN ; Zuo-Ying XING ; Meng-Lin LIU ; Zhao-Qi CHEN ; Yong-Xia WANG
China Journal of Chinese Materia Medica 2021;46(6):1523-1536
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.
Antihypertensive Agents/adverse effects*
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China
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Drugs, Chinese Herbal/adverse effects*
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Essential Hypertension
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Humans
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Medicine, Chinese Traditional
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Randomized Controlled Trials as Topic
6.Systematic evaluation of efficacy and safety of Songling Xuemaikang Capsules in treatment of essential hypertension.
Gen-Hao FAN ; Zuo-Ying XING ; Meng-Lin LIU ; Yan CHEN ; Yi-Pei AN ; Zhao-Qi CHEN ; Yong-Xia WANG
China Journal of Chinese Materia Medica 2021;46(2):467-477
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.
Angiotensin Receptor Antagonists
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Angiotensin-Converting Enzyme Inhibitors
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Capsules
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Drugs, Chinese Herbal
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Essential Hypertension/drug therapy*
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Humans
7.Preparation and in vitro evaluation of fused deposition modeling 3D printed verapa-mil hydrochloride gastric floating formulations.
Di CHEN ; Xiang Yu XU ; Ming Rui WANG ; Rui LI ; Gen Ao ZANG ; Yue ZHANG ; Hao Nan QIAN ; Guang Rong YAN ; Tian Yuan FAN
Journal of Peking University(Health Sciences) 2021;53(2):348-354
OBJECTIVE:
To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties.
METHODS:
Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized.
RESULTS:
SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets.
CONCLUSION
The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation
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Excipients
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Printing, Three-Dimensional
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Reproducibility of Results
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Tablets