Study on the effects and mechanism of luteolin on osteogenic repair of bone defects / 中国药房

OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.

KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.

Meta-analysis of the Efficacy of Gongliuqing Capsules Combined with Mifepristone in the Treatment of Uterine Leiomyoma / 中国药房

OBJECTIVE：To systematically evaluate therapeutic efficacy of Gongliuqing capsules combined with mifepristone in the treatment of uterine leiomyoma ，in order to provide evidence-based reference for clinical medication. METHODS ：Retrieved from Cochrane Library ，PubMed，Embase，CJFD，VIP，CBM and Wanfang database ，randomized controlled trials （RCTs）about Gongliuqing capsules combined with mifepristone （trial group ）versus mifepristone alone （control group ）in the treatment of uterine leiomyoma were collected. After literature screening and data extraction ，the quality of included literatures was evaluated with modified Jadad scale. Meta-analysis was conducted by using Stata 14.0 software，and trial sequential analysis （TSA）was performed by using TSA 0.9 software. RESULTS ：A total of 12 RCTs were included ，involving 1 210 patients. The results of Meta- analysis showed that the total response rate of trial group [RR ＝1.12，95％CI（1.00，1.26），P＜0.05] was significantly higher than that of control group ；maximum uterine leiomyoma volume after treatment [SMD ＝－1.08，95％CI（－1.21，－0.95），P＜0.05]，uterine volume after treatment [SMD ＝－0.80，95％CI（－1.14，－0.45）， P＜0.05]，follicle stimulating hormone （FSH）level [SMD ＝ － 0.28，95％ CI（－ 0.45，－ 0.19），P＜0.05]，luteinizing hormone（LH）level [SMD ＝－0.44，95％CI（－0.52，－0.12）， 020-38076311。E-mail：867203217@qq.com P＜0.05]，E2 level [SMD ＝－2.69，95％CI（－3.08，－1.49）， P＜0.05] and progesterone （P）level [SMD ＝－1.27，95％CI（－1.69，－0.71），P＜0.05] of trial group were significantly lower or better than those of control group. Results of subgroup analysis showed that except for the level of FSH in 5 and 10 mg mifepristone groups （P＞0.05），maximum uterine leiomyoma volume after treatment ，uterine volume after treatment ，the levels of FSH，LH，E2 and P in trial group were significantly lower than control group. The results of TSA showed that there were definite evidences for total response rate of Gongliuqing capsules combined with mifepristone being better in the treatment of hysteromyoma. CONCLUSIONS ：Total response rate of Gongliuqing capsules combined with mifepristone in the treatment of hysteromyoma is better than mifepristone alone ，which can effectively decrease the volume of maximum uterine leiomyoma volume and uterine vilume ，and reduce the level of serum hormone.

Comparison of postoperative bowel function between patients undergoing transanal and laparoscopic total mesorectal excision / 中华胃肠外科杂志

OBJECTIVE@#To compare the effects of transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laparoscopic TME) on patients' postoperative long-term bowel function.@*METHODS@#A retrospective cohort study was used in this study. We analyzed the clinical data of 134 patients with locally advanced mid-low rectal cancer, who underwent transanal TME or laparoscopic TME in the TaLaR randomized controlled trial at the Sixth Affiliated Hospital, Sun Yat-sen University from April 2016 to November 2017. Inclusion criteria included age of 18 to 80 years old, distance from tumor low margin to anal edge ≤10 cm, preoperative staging of T1-3NxM0, and single rectal adenocarcinoma. Exclusion criteria included local recurrence, distant metastases, abdominoperineal resection, unreduced stoma, new stoma, less than 1 year after protectomy or stoma reduction, or preoperative poor anal function or incontinence. Patients were divided into taTME group and laparoscopic TME group. The taTME group received hybrid transanal and transabdominal approach performed simultaneously. The effects of surgical procedures on postoperative bowel function were evaluated with LARS (low anterior resection syndrome) scale, where 0-20 was defined as " no LARS" , 21-29 as " minor LARS" , and 30-42 as " major LARS" . Univariate and multivariate logistic regression analyses were performed to determine the risk factors associated with major LARS, with surgical approach as a pre-selected variate.@*RESULTS@#A total of 107 patients were included. Of the 54 patients in the taTME group, 35 were male, median age was 57.2 (26.0-77.0) years old, and 22 cases had a tumor less than 5 cm from anal verge. Of the 53 patients in the laparoscopic TME group, 35 were male, median age was 62.0 (33.0-73.0) years old, and 25 cases had a tumor less than 5 cm from anal verge. All baseline clinical data including age, gender, preoperative staging, and tumor height were comparable between the two groups (all P>0.05). All operations in both groups were performed successfully. The operation time, intra-operative blood loss, postoperative anastomotic complication, postoperative hospital stay were comparable between the two groups (all P>0.05), except for a lower diverting stoma rate in the taTME group [37.0% (20/54) vs. 64.2% (34/53), χ²=7.866, P=0.005]. Of the 107 patients, 27 (25.2%) had no LARS, 32 (29.9%) had minor LARS, and 48 (44.9%) had major LARS, after a median follow-up of 17.2 (12.1-30.4) months. No significant difference was found between the two groups in overall bowel function [major LARS: 48.1% (26/54) vs. 41.5% (22/53), Z=-0.994, P=0.320]. Compared with the laparoscopic TME group, the taTME group experienced worse clustering of stools [68.5% (37/54) vs. 45.3% (24/53), Z=-2.354, P=0.019]. However, there were no significant differences between the two groups in terms of gas incontinence, liquid stool incontinence, frequency of defecation, and urgency (all P>0.05). Multivariate analysis identified preoperative radiotherapy (OR=5.073, 95% CI: 1.336 to 19.259, P=0.017) and anastomotic height (OR=3.633, 95% CI: 1.501 to 8.802, P=0.004) as independent risk factors for major LARS, but no impact of taTME on LARS (OR=1.442, 95% CI: 0.638 to 3.261, P=0.379).@*CONCLUSIONS@#Compared with laparoscopic TME, taTME has similar outcomes of postoperative long-term bowel function. Preoperative radiotherapy and anastomotic height, but not surgical approach, are independent risk factors for postoperative bowel function.

Research on the Functional Mechanism of Couplet Medicine of “Bupleuri Radix- Atractylodis macrocephalea Rhizoma”on Mammary Hyperplasia Based on Network Pharmacology / 中国药房

OBJECTIVE： To screen the active component， target and pathway of couplet medicine of “Bupleuri Radix- Atractylodis macrocephalea Rhizoma”， and to comprehensively explore its potential mechanism. METHODS： Based on the method of network pharmacology， main active componets and potential targets of  couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” were retrieved from TCMSP， DRAR-CPI， Genecards and OMIM database. The active component-potential target network and interaction network of potential targets were established by Cytoscape 3.6.0 software. Five potential core targets were screened， and its affinity with active components were validated with molecule docking method. GO classified enrichment analysis and KEGG pathway enrichment analysis of potential targets were carried out to obtain key pathway so as to construct active component-potential target-key pathway network. RESULTS： Totally 17 active components and 47 active component-potential targets were obtained from couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma”. Five core targets were obtained， including AKT1， PRKCA， PRKCE， HRas， and PIK3CA. Five signaling pathways were involved， including MAPK pathway， PI3K/AKT pathway， RAS pathway， Estrogen pathway， BMP pathway. CONCLUSIONS： The couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” not only act on multiple targets through multiple components for mammary hyperplasia， but also play a complex network regulation role through the interaction between potential targets.

Meta-analysis of Efficacy and Safety of Endostar Combined with Gemcitabine and Cisplatin in the Treatment of Advanced Non-small Cell Lung Cancer / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of Endostar combined with gemcitabine and cisplatin in the treatment of non-small cell lung cancer （NSCLC）， and to provide evidence-based reference for clinical drug use. METHODS： Retrieved from Cochrane Library， PubMed， Embase， ClinicalTrials， CNKI， Wanfang and VIP database， randomized controlled trials （RCT） about Endostar combined with gemcitabine and cisplatin（trial  group） vs. gemcitabine combined with cisplatin （control group） for NSCLC were collected. After literature screening， data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale， Meta-analysis was performed by using Rev Man 5.3 software. RESULTS： A total of 27 RCTs were included， involving 1 646 patients. Results of Meta-analysis showed that response rate [RR＝1.67， 95％CI（1.48，1.89），P＜0.000 01] and clinical benefit rate [RR＝1.26， 95％CI （1.20， 1.33），P＜0.000 01] of trial group were significantly higher than those of control group. There was no statistical significance in the incidence of leucopenia [RR＝0.98，95％CI（0.88， 1.11），P＝0.79]， thrombocytopenia [RR＝1.07， 95％CI（0.91， 1.26），P＝0.39] and gastrointestinal reaction [RR＝1.01， 95％CI（0.90， 1.14），P＝0.85] between 2 groups. CONCLUSIONS： Endostar combined with gemcitabine and cisplatin can improve therapeutic efficacy of NSCLC patients， without increasing the incidence of ADR.

Meta-analysis and Trial Sequential Analysis of Therapeutic Efficacy of Compound Xuanju Capsules Combined with Chemical Medicine versus Chemical Medicine Alone in the Treatment of Polycystic Ovarian Syndrome / 中国药房

OBJECTIVE： To systematically evaluate the efficacy of Compound xuanju capsules combined with chemical medicine versus chemical medicine alone in the treatment of polycystic ovarian syndrome （PCOS）， in order to provide evidence-based medicine guidelines for clinical medication. METHODS： Retrieved from PubMed， Embase， Cochrane library， CBM， VIP， CJFD and Wanfang database from database establishment to Apr. 5， 2019， randomized controlled trials （RCTs） about therapeutic efficacy （total response rate， ovulation rate， pregnancy rate， FSH level， LH level， testosterone level， degree of endometrial thickening） of Compound xuanju capsules combined with chemical medicine （trial group） versus chemical medicine alone （control group） in the treatment of PCOS were collected. After data extraction and quality evaluation of included studies with modified Jadad scale， Meta-analysis was conducted by using STATA 14.0 software. Trial sequential analysis （TSA） was conducted by using TSA 0.9 software. RESULTS： A total of 15 RCTs were included， involving 1 259 patients. The results of Meta-analysis showed that the total response rate [RR＝1.27，95％CI（1.13，1.44），P＜0.001]， ovulation rate [RR＝1.18，95％CI（1.03，1.37），P＜0.001]， pregnancy rate [RR＝1.34，95％CI（1.11，1.61），P＜0.001]， serum hormone level {FSH [SMD＝－0.66，95％CI （－0.51，  －0.82），P＜0.001]， 95％CI（－1.76，－1.41），P＜0.001]， LH [SMD＝－1.24，95％CI（－1.39， －1.08），P＜0.001]， testosterone [SMD＝－1.59，95％CI（－1.76，－1.41），P＜0.001]} and endometrial thickness [SMD＝1.20，95％CI（1.04，1.37），P＜0.001] of the trial group were better than those of the control group， with statistical significance. The results of TSA were reliable. CONCLUSIONS： In the treatment of PCOS， Compound xuanju capsules combined with chemical medicine is better than chemical medicine alone in improving total response rate， pregnancy rate， ovulation rate and endometrial thickness， and reducing serum hormone levels.

Meta-analysis and Trial Sequential Analysis of Therapeutic Efficacy of Modified Cangfu Daotan Decoction Combined with Chemical Medicine versus Chemical Medicine Alone in the Treatment of Polycystic Ovarian Syndrome / 中国药房

OBJECTIVE： To systematically evaluate therapeutic efficacy of modified Cangfu daotan decoction （MCDD） combined with chemical medicine versus chemical medicine alone in the treatment of polycystic ovarian syndrome （PCOS）， and to provide evidence-based reference for clinical decision. METHODS： Retrieved from PubMed， Embase， Cochrane Library， CJFD， Wanfang database， VIP and CBM， randomized controlled trials （RCTs） about MCDD combined with chemical medicine [ethynestradiol cycloprogesterone （Diane-35）， clomiphene， metformin] （trial group） versus chemical medicine alone （control group） in the treatment of PCOS were collected. After data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale， Meta-analysis was conducted for total response rate， serum hormone level （FSH， LH， LH/FSH， testosterone）， BMI， ovulation rate and physical signs （hirsutism， acne） by using Stata 14.0 software. Trial sequential analysis（TSA）was conducted by using TSA 0.9 software. RESULTS： A total of 20 RCTs were included， involving 1 484 patients. Results of Meta analysis showed that total response rate [RR＝1.13，95％CI （1.02，1.24），P＜0.05]， serum hormone level {FSH [WMD＝－0.59，95％CI（－0.98，－0.20），P＜0.05]，LH [WMD＝－0.95，95％CI（－1.41， －0.52），P＜0.05]，LH/FSH [WMD＝－1.04，95％CI（－1.78，－0.33），P＜0.05]，testosterone [WMD＝－0.93，95％CI（－1.38，－0.28），P＜0.05]}， BMI [SMD＝－1.01，95％CI  （－1.76，－0.27），P＜0.05]， ovulation rate [RR＝1.17，95％CI（1.02，1.34），P＜0.05] and physical signs {hirsutism [WMD＝－0.48，95％CI（－0.86， －0.10），P＜0.05]， acne [WMD＝－1.16，95％CI（－1.56，－0.75），P＜0.05]} of trial group were all better than those of control group， with statistical significance. TSA showed that there are reliable evidences for MCDD combined with chemical medicine in the treatment of PCOS. CONCLUSIONS： Versus chemical medicine alone in the treatment of PCOS， MCDD combined with chemical medicine can improve total response rate and ovulation rate， reduce serum hormone levels， BMI and physical signs.

Study on the Mechanism of Prunus persica -Carthamus tinctorius Couplet Medicine in the Treatment of Osteonecrosis of the Femeral Head Based on Network Pharmacology / 中国药房

OBJECTIVE： To study the mechanism of Prunus persica-Carthamus tinctorius couplet medicine in the treatment of osteonecrosis of the femoral head （ONFH）. METHODS： The network pharmacology was adopted. The active components of P. persica -C. tinctorius couplet medicine and ONFH target were screened through TCM systematic pharmacological analysis platform target （TCMSP）， DRAR-CPI， hnuman gene database （GeneCards） and online medelian inheritance in man （OMIM） using oral availability of compounds （OB）＞30％ and drug like （DL）＞0.18 as standard. Network topology attribute analysis software Cytoscape 3.6.0 was utilized to construct the active components-ONFH targets network. Target protein interaction network was established on the basis of STRING database， and top 5 target proteins in the list of connectivity were screened， and molecular docking server was used to predict the combination activity of active components from P. persica -C. tinctorius couplet medicine. The biological processes of target gene ontology （GO） and metabolic pathways in Kyoto encyclopedia of genes and genomes （KEGG） were enriched and analyzed by DAVID. RESULTS： A total of 44 active components were screened from P. persica -C. tinctorius couplet medicine， including baicalin， quercetin， etc.， and 78 targets related to ONFH including VEGF， VEGI， CRP， etc. Through analysis of molecular docking server， binding activity of active components of P. persica -C. tinctorius couplet medicine to target protein was strong. GO and KEGG pathway enrichment analysis showed that biological process of P. persica -C. tinctorius couplet medicine for ONFH was related with negative regulation of apoptosis process and positive regulation of nuclear factor-κB transcription factor， mainly through regulating secretory glycoprotein signaling pathway， melanogenesis signaling pathway， VEGF signaling pathway， signaling pathway of basal cell carcinoma， adenosine-activated protein kinase signaling pathway. CONCLUSIONS： This study preliminarily validates the major targets and pathways of P. persica -C. tinctorius couplet medicine for ONFH， which lay a foundation for further study on their pharmacological action.

Meta-analysis of Efficacy and Safety of TCM Compound Preparation for Tonifying Kidney and Activating Blood Circulation in the Treatment of Postmenopausal Osteoporosis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of TCM compound preparation for tonifying kidney and activating blood circulation， and to provide evidence-based reference for rational drug use in the clinic. METHODS： By retrieving Cochrane library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about TCM compound preparation for tonifying kidney and activating blood circulation （trial group） versus calcium or non-calcium agents （control group） in the treatment of postmenopausal osteoporosis were included. After literature screening， data extraction and quality evaluation with bias risk evaluation tool and Jadad scale of Cochrane system evaluator manual 5.1.0， Meta-analysis was conducted by using Stata 12.0 software， and trial sequential analysis （TSA） was conducted by using TSA 0.9 software. RESULTS： Totally 18 RCTs were included， involving 1 408 patients. The results of Meta-analysis showed that total response rate [RR＝1.35，95％CI（1.17，1.54），P＜0.000 1] and bone density[SMD＝0.24，95％CI（0.16，0.32），P＜0.000 1] of trial group were significantly higher than those of control group； blood calcium [SMD＝－0.05，95％CI（－0.09，0.00）， P＝0.033] of trial group was significantly lower than that of control group. There was no statistical significance in the levels of urine creatinine [SMD＝－1.60，95％CI（－5.94，2.74），P＝0.470]， urinary calcium/urine creatinine ratio [SMD＝－0.05，95％CI（－0.14，0.04），P＝0.295]， urinary hydroxyproline/urine creatinine ratio [SMD＝－0.16，95％CI（－1.04，0.72），P＝0.726]， ALT [SMD＝0.51，95％CI（－3.26，4.28），P＝0.790]， AST [SMD＝0.23，95％CI（－5.22，4.77），P＝0.929]， serum alkaline phosphatase [SMD＝－0.22，95％CI（－0.68，0.25），P＝0.361]， serum phosphate [SMD＝－0.02，95％CI（－0.11，0.07），P＝0.639]， urea nitrogen [SMD＝－0.19，95％CI（－0.70，0.31），P＝0.453]， estradiol [SMD＝0.62，95％CI（－0.28，1.52），P＝0.177]， IL-6 [SMD＝－1.78，95％CI（－4.86，1.30），P＝0.258] or VAS [SMD＝0.55，95％CI（－1.03，2.13），P＝0.496] between 2 groups. No server ADR was found in 2 groups. TSA showed that there were extract evidences for total response rate of TCM compound preparation in the treatment postmenopausal osteoporosis. CONCLUSIONS： TCM compound preparation for tonifying kidney and activating blood circulation shows significant therapeutic efficacy for postmenopausal osteoporosis， and can improve serum calcium and bone density with good safety.

Study on the Effects and Its Mechanism of Calcium Phosphate Bone Cement Loading Total Flavonoids of Davallia mariesii on Osteoblast Differentiation in Induced Membrane of Bone Defect Model Rats / 中国药房

OBJECTIVE： To investigate the effects and its mechanism of calcium phosphate bone cement （CPC） loading total flavonoids of Davallia mariesii on osteogenic differentiation of induced membrane in rats. METHODS： Drug-loading CPC and drug-loading polymethyl methacrylate （PMMA） cement were prepared with the contents of Qianggu capsules （total flavonoids of D. mariesii as active ingredient） using CPC and PMMA cement as carrier. Totally 64 male SD rats were randomly divided into drug-loading CPC group， drug-loading PMMA cement group， no-drug CPC group， no-drug PMMA cement group， with 16 rats in each group. The femur of rats was separated and osteotomized to prepare bone defect model， and then the corresponding bone cement was implanted. Four weeks after modeling， the induced membranes of rats were cut and protected. Bone cement was taken out and autogenous cancellous bone was implanted. At the 4th week after modeling， X-ray photographs were taken on the hind limb bones of rats. At the 4th week after modeling and 6th week after bone grafting， induced membranes and new bone were taken from the bone defect area of rats respectively. HE staining was used to observe the morphology of induced membrane， and the width of bone rabecular and the number of osteoblasts of new bone tissue were measured. Immunohistochemistry was used to detect the protein expression of BMP-2 and VEGF in induced membrane. Western blotting assay was used to detect the protein expression of Smad1， Smad4 and Smad7 in new bone. RESULTS： Compared with other 3 groups， the degradation of bone cement in drug-loading CPC group was more obvious in the bone defect areas， which showed that the formation of induced membrane was observed and the bone defect areas were smaller； capillary endothelial cells were abundant and orderly arranged in the induced membranes， and the width of bone trabeculae and the number of osteoblasts in the new bone tissue increased significantly （P＜0.05）； the protein expression of BMP-2 and VEGF in the induced membrane， the protein expression of Smad1， Smad4 and Smad7 in new bone were increased significantly （P＜0.05）. CONCLUSIONS： CPC loading total flavonoids of D. mariesii promotes the formation of induced membrane osteoblast in bone defect model rats， which may be associated with regulating osteoblast differentiation by activating BMP-2/Smad pathway； at the same time， it can promote bone healing by promoting the differentiation of vascular endothelial cells， accelerating the formation of capillary network and increasing the expression of vascular endothelial cells.

Study on the Mechanism of “Astragalus membranaceus -Draba nemorosa ”Couplet Medicine for Heart Failure Based on Network Pharmacology / 中国药房

OBJECTIVE： To explore potential mechanism of “Astragalus membranaceus-Draba nemorosa” couplet medicine for heart failure. METHODS： By network pharmacology， based on drug-like and oral bioavailability， the active components of “A. membranaceus-D. nemorosa” for chronic heart failure were screened and the targets of treating chronic heart failure were predicted by using TCMSP，GeneCards database， OMIM database and DRAR-CPI. The active component-chronic heart failure target network was established by Cytoscape 3.6.0 software. The protein-protein interaction network was constructed by utilizing STRING database. Then top 5 targets in the list of connectivity were screened and performed a molecular docking in molecular docking server. Finally， GO bioprocess analysis and KEGG pathway enrichment analysis were performed in DAVID database. RESULTS： The study predicted 28 active components in total， including 20 A. membranaceus and 12 D. nemorosa， such as kaempferol and quercetin， there were four components in common. Totally 92 target gene of active components were obtained， including heat shock protein 90α （HSP90AA1）， tyrosine protein kinase SRC gene， etc. Results of GO bioprocess analysis showed an association with mitochondrial electron transport， mitochondrial intima， cytoplasmic sol， extracellular body， mitochondrial matrix and drug response. KEGG pathway enrichment analysis showed a link with MAPK signal pathway， TGF signal pathway， PI3K signal pathway， cAMP signal pathway， protein kinase B signal pathway， EPK1 signal pathway and NF-κB signal pathway. CONCLUSIONS： “A. membranaceus-D. nemorosa” couplet medicine exerts therapeutic effects on heart failure from multiple targets as HSP90AA1， SRC and mitochondrial electron transport and MAPK signaling pathway. The study can provide reference for further researches on its material basis and mechanism.

Analysis of the Literature Quality of Systematic Evaluation/Meta-analysis of Oral Administration of Traditional Chinese Medicine in the Treatment of Lumbar Disc Herniation Based on Radar Plot / 中国药房

OBJECTIVE： To evaluate the literature quality of systematic reviews/Meta-analysis of oral administration of traditional Chinese medicine （TCM） in the treatment of lumbar disc herniation （LDH） using radar plot， and to provide scientific and effective evidence for clinical use of medicine. METHODS： Retrieving CNKI， VIP， Wanfang database， CBM， PubMed， Cochrane library and Embase during the establishement of database to Oct. 1st， 2018， the literatures about systematic reviews/Meta-analysis of oral administration of TCM in the treatment of LDH were collected. After data extraction of literatures met inclusion criteria， the quality literatures were evaluated from 6 aspects of radar plot （year of publication， design type， AMSTAR methodological quality evaluation， PRISMA reprot quality evaluation， homogeneous， publication bias risk）. The average score of rank number was calculated. Moreover， Excel 2010， Adobe Illustrator CC and other software were used to draw and optimize the radar plot. RESULTS： A total of 6 qualified literatures were included； average score of rank number of 6 aspects were 3.83， 4.67， 3.83， 3.67， 6.00， 4.67， scoring 4.56 in average. Multivariate evaluation of radar plot showed that 2 studies had higher qualities and only 1 study had lower qualities relatively. However， problems could be found such as information selection bias， inclusion and exclusion criteria， publication situation， limitations， project registration. CONCLUSIONS： The literature quality of systematic review/Meta-analysis of oral administration of TCM in the treatment of LDH need to be improved， starting with strengthening methodological quality and reporting quality. Radar plot is a visual and effective method of graphic evaluation， which is worth popularizing and applying in the future.

Investigation on Anti-atherosclerosis Mechanism of Tiaopi Huxin Prescription Based on Cav- 1/NF-κB Pathway / 中国药房

OBJECTIVE： To study the effects of Tiaopi huxin prescription （TPHXP） on the atherosclerosis （AS） of ApoE－/－ mice， and to investigate its mechanism. METHODS： Forty male ApoE－/－ mice were divided into blank group， model group， simvastatin group （positive control， 5 mg/kg） and TPHXP low-dose and high-dose groups （50， 150 mg/kg）， with 8 mice in each group. Except that blank group was given common diet， other groups were given high-lipid diet to induce AS model. After modeling， administration groups were given relevant medicine intragastrically， and blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 12 weeks. After last medication， the serum levels of TC， TG， LDL-C and HDL-C were determined by spectrophotometry. The serum level of NO was detected by nitrate reduction method. The serum levels of IL-6 and VCAM-1 were determined by ELISA. After separating thoracic aorta， HE staining was used to observe the formation of plaque in the thoracic aorta of mice in each group， and the corrected plaque area was calculated. Western blotting was conducted to determine the expression of NF-κB p65， Cav-1 and eNOS. RESULTS： Compared with blank group， the serum levels of TC， TG， LDL-C， IL-6 and VCAM-1 were increased significantly in model group， while the levels of HDL-C and NO were decreased significantly （P＜0.01）. The plaque of thoracic aorta was obvious and the corrected plaque area were increased significantly （P＜0.01）. The relative expression of NF-κB p65 and Cav-1 were increased significantly， while the relative expression of eNOS was decreased significantly （P＜0.01）. Compared with model group， the serum levels of TC， TG and LDL-C in administration groups， the serum levels of IL-6 and VCAM-1 in simvastatin group and TPHXP high-dose group were decreased significantly， while the serum levels of HDL-C and NO were increased significantly in administration groups （P＜0.05 or P＜0.01）. In administration groups， the plaques of thoracic aorta were reduced and the corrected plaque area was decreased significantly （P＜0.05 or P＜0.01）； the relative expression of NF-κB p65 and Cav-1 were decreased significantly， while the relative expression of eNOS was increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： TPHXP can regulate the level of blood lipid， decrease the level of inflammatory factors and inhibit the formation of AS plaque， the mechanism of which may be associated with inhibiting Cav-1/NF-κB pathway.

Meta-analysis and Trial Sequential Analysis of Efficacy and Safety of Toutongning Combined with Flunarizine versus Flunarizine in the Treatment of Migraine / 中国药房

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of Toutongning combined with flunarizine vs. flunarizine in the treatment of migraine,and to provide evidence-based reference in clinic. METHODS:Retrieved from PubMed,Cochrane library,Embase,Chinese Journal Full-text Database,Chinese Sci-tech Periodicals Database,Wanfang database and CBM,randomized controlled trials(RCTs)about therapeutic efficacy(total response rate,VAS score,blood potassium and blood magnesium concentration,CGRP level)and safety(the incidence of ADR)of Toutongning combined with flunarizine(trial group)vs. flunarizine in the treatment of migraine(control group)were collected. Meta-analysis of included trials meet inclusion criteria was conducted by using Stata 14.0 software,and trial sequential analysis(TSA)was conducted by using TSA 0.9 software after data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale. RESULTS:Totally 16 RCTs were included,involving 1 726 patients. Results of Meta-analysis showed that total response rate [RR=1.21,95%CI(1.16, 1.26),P<0.05],the decrease of VAS score [WMD=-1.04,95%CI(-1.42,-0.66),P<0.001],the decrease of blood potassium [WMD=-2.05,95%CI(-0.32,-0.18),P<0.001],the increase of blood magnesium [WMD=0.09,95%CI(0.04,0.14),P<0.001] and the decrease of CGRP [WMD=-2.22,95%CI(-3.25,-1.18),P<0.001] in trial group were better than control group,with statistical significance. The incidence of ADR in trial group was 2.27% in trial group and 2.89% in control group, without statistical significance(P>0.05). TSA showed that there were extract evidences for total response rate of Toutongning combined with flunarizine in the treatment migraine. CONCLUSIONS:Therapeutic efficacy of Toutongning combined with flunarizine is better than flunarizine in the treatment of migraine,and the ADR is not increased.

Meta-analysis of Shenqi Fuzheng Injection Combined with Chemotherapy for Colorectal Cancer / 中国药房

OBJECTIVE:To evaluate the clinical efficacy and safety of Shenqi fuzheng injection combined with chemotherapy in the treatment of colorectal cancer.METHODS:Retrieved from PubMed,EMBase,Clinical Trials,Cochrane Library,CJFD,CBM,Wanfang database and VIP,RCTs about Shenqi fuzheng injection combined with chemotherapy (trial group) vs.chemotherapy alone (control group) in the treatment of colorectal cancer were included.Meta-analysis was performed by Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual.RESULTS:A total of 25 RCTs were included,involving 1 987 patients.Results of Meta-analysis showed that objective remission rate of trial group was significantly higher than control group [RR=1.19,95％ CI (1.02,1.39),P=0.02];the improvement of survival quality was significantly better than control group [RR=1.72,95％CI(1.49,1.99),P＜0.001];CD4VCD8+ was significantly higher than control group [MD=0.40,95％ CI (0.29,0.50),P＜0.001];the incidence of gastrointestinal reaction was significantly higher than control group [RR=0.59,95％CI(0.52,0.68),P＜0.001];the incidence of liver and renal injury was significantly lower than control group [RR=0.52,95％CI(0.41,0.67),P＜0.001],with statistical significance.CONCLUSIONS:Shenqi fuzheng injection combined with chemotherapy can improve objective remission rate of colorectal cancer patients,survival quality and immune function,and reduce the occurrence of toxic reation.

Nickel-titanium memory-shape compression anastomosis clip for gastrointestinal anastomosis: a Meta-analysis and sequential analysis / 中国组织工程研究

BACKGROUND:Nickel-titanium memory-shape compression anastomosis clip (Ni-Ti CAC) has been used in gastrointestinal anastomosis, but its efficacy and safety still remain controversial.OBJECTIVE:To evaluate the efficacy and safety of Ni-Ti CAC in gastrointestinal anastomosis.METHODS:A computer-based online research of PubMed, EMbase, Cochrane Library, CBM, CNKI, and VIP databases was performed for articles published before January 15th, 2017 using the keywords of nickel-titanium, compression anastomosis clip, anastomosis, gastric, jejunum, ileum, small intestine, colon, rectum, and large intestine in English and Chinese, respectively. The randomized controled trials about Ni-Ti CACversus conventional methods for gastrointestinal anastomosis were included. Meta-analysis of the anastomosis time, time of exsufflation, and hospitalization time was performed, and sequential analysis was conducted on TSA v0.9 software.RESULTS AND CONCLUSION:A total of 18 eligible randomized controlled trials were enroled, involving 1860 patients. Ni-Ti CAC could reduce the anastomosis time [MD=-3.83, 95%CI(-6.48,-1.19),P=0.004] and time of exsufflation [MD=-0.14, 95%CI(-0.22,-0.05),P=0.002], but there was no significant difference in the hospitalization time [MD=-0.83, 95%CI(-1.82, 0.16), P=0.10]. The quality was ranked as low level based on GRADE system. The time of exsufflation of Ni-Ti CAC was superior to that of conventional method, which was confirmed by sequential analysis. One case of death was reported and incision infection was the most common adverse effects; additionaly, pulmonary embolism and abdominal pain occurred. To conclude, Ni-Ti CAC can facilitate gastrointestinal anastomosis, accelerate the time of exsufflation, and holds a good safety. However, more multicenter and high-quality randomized controlled trials are needed.