Mechanism of Aidi injection on hepatocellular carcinoma based on network pharmacology

Objective:To explore the active ingredients and potential mechanism of Aidi injection in the treatment of hepatocellular carcinoma by network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID)were used to screen the active ingredients of four traditional Chinese medicines of Renshen,Huangqi,Ciwujia,and Banmao and corresponding potential targets.Screening of hepatocellular carcinoma-related targets through the Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database platforms.The drug and disease targets are merged to obtain the intersection,and the information is imported into Cytoscape 3.7.2 to construct a network diagram of the active ingredients of Aidi injection and related targets of hepatocellular carcinoma,and the topology analysis is performed.A protein-protein interaction(PPI)network was constructed and analyzed using the STRING online analysis platform.Uses the Database for Annotation,Visualization and Integrated Discovery(DAVID)to perform GO function enrichment analysis of targets and enrichment of KEGG pathways analysis.Results:A total of 33 potential active ingredients were screened from Aidi injection for treating hepatocellular carcinoma,including quercetin,kaempferol,beta-sitosterol,isorhamnetin and other important active ingredients.There are 106 potential targets for active ingredient action,6,677 disease-related targets,and 89 drug-disease common targets.Through the network diagram,it was found that the highest degree of target is PTGS1.In the PPI graph,a total of 87 nodes.Among them,the higher degree values include IL6,CASP3,VEGFA,MAPK8,JUN,EGFR,MYC,PTGS2 and FOS.A total of 60 related signal pathways were obtained by GO enrichment analysis.It mainly involves biological processes such as inhibiting abnormal proliferation and differentiation of hepatocellular carcinoma cells,inhibiting angiogenesis of hepatocellular carcinoma,regulating cell cycle and promoting apoptosis.KEGG pathway enrichment analysis screened a total of eight significantly different signal pathways.Among them,P53,VEGF,MAPK,Toll-like receptor,ErbB signaling pathways play an important role in treatment.Conclusion:This study initially revealed the potential mechanism of multi-component,multi-target and multi-pathway treatment of Aidi injection for hepatocellular carcinoma,and provided ideas for the subsequent verification of the molecular mechanism of Aidi injection for hepatocellular carcinoma.

Effects of Aidi injection on vinorelbine plus cisplatin chemotherapy for advanced non-small cell lung cancer

Objective： To evaluate the effects of Aidi injection on vinorelbine plus cisplatin （NP） chemotherapy for advanced non-small cell lung cancer （NSCLC）. Methods： Ninety eight patients with advanced NSCLC were randomized to receive either NP alone or NP plus Aidi injection every 3 weeks. The primary endpoint was overall survival; secondary endpoints included overall response rate, time to progression, and safety. Results： The median overall survival time was 11.6 months in NP plus Aidi-treated patients and 10.1 months in NP alone-treated ones, and 1- and 2-year survival rates were higher in the former （47% and 22%） than the latter （42% and 15%）. The overall response rates in Aidi injection plus NP-treated patients tended to be higher but not statistically significant compared with NP alone-treated ones. The occurrence rates of grades 3 or 4 toxicities, e.g. fatigue, nausea, vomiting, appetite loss, leucopenia, thrombocytopenia and anemia, were lower in Aidi injec- tion plus NP-treated patients than NP alone-treated ones, although not significantly different between them. Con^lusion：Aidi injection promotes NP chemotherapeutic effects, reduces the toxicities, and improves the patients＇ tolerance to chemotherapy as well. It may be an effective adjunct to chemotherapy in patients with NSCLC.

Effect of Aidi injection-assisted intravenous chemotherapy on serum tumor markers and peripheral blood immune molecules in patients with colon cancer

Objective:To discuss the effect of Aidi injection-assisted intravenous chemotherapy on serum tumor markers and peripheral blood immune molecules in patients with colon cancer. Methods: 92 patients with colon cancer who were hospitalized in Deyang People's Hospital in Sichuan Province between October 2013 and October 2016 were collected and divided into the control group (n=50) who received intravenous chemotherapy alone and the observation group (n=42) who received Aidi injection-assisted intravenous chemotherapy after the therapies were reviewed. The differences in serum tumor markers and peripheral blood immune molecule contents before and after treatment were compared between two groups of patients.Results:Before treatment, differences in serum tumor marker levels and peripheral blood immune molecule levels were not statistically significant between two groups of patients. After treatment, serum tumor markers CEA, CA199, CA50, PTN and CCSA-2 levels of observation group were lower than those of control group, peripheral blood Th1/Th2 cytokines IL-2 and IFN-γ levels were higher than those of control group while IL-4 and IL-10 levels were lower than those of control group, and peripheral blood Th17 cytokines IL-17A and IL-22 levels were lower than those of control group.Conclusion: Aidi injection-assisted intravenous chemotherapy can effectively reduce the serum tumor marker contents and optimize the immune molecule levels in patients with colon cancer.

Effect of Aidi injection combined with FOLFOX4 chemotherapy on tumor stem cell characteristics and antitumor immune response in patients with advanced colon cancer

Objective:To study the effect of Aidi injection combined with FOLFOX4 chemotherapy on tumor stem cell characteristics and antitumor immune response in patients with advanced colon cancer.Methods:Patients with advanced colon cancer who received chemotherapy in our hospital between May 2013 and June 2016 were selected and randomly divided into the combined chemotherapy group who received Aidi injection combined with FOLFOX4 chemotherapy and the FOLFOX4 group who received FOLFOX4 chemotherapy alone. After chemotherapy, the serum was collected to determine the levels of tumor markers, tumor lesions were collected to determine the expression of tumor stem cell markers and immune cell markers, and peripheral blood mononuclear cells were collected to determine the expression of immune cell markers.Results:After 2 and 4 cycles of treatment, serum CEA, CA199, CCSA-3 and CCSA-4 levels of combined chemotherapy group were significantly lower than those of FOLFOX4 group, and the mean fluorescence intensity of CD3, CD4, CD8, CD16 and CD56 in peripheral blood mononuclear cells were significantly higher than those of FOLFOX4 group;after four cycles of chemotherapy, CD133, Musashi-1, Piwil2, Nanog and Sox-2 protein content in tumor lesions were significantly lower than those of FOLFOX4 group, and the mean fluorescence intensity of CD3, CD4, CD8, CD16 and CD56 were significantly higher than those of FOLFOX4 group.Conclusion: Aidi injection combined with FOLFOX4 chemotherapy treatment of advanced colon cancer will help reduce the tumor load, inhibit tumor stem cell characteristics and enhance antitumor immune response.

Influence of Aidi injection combined with paclitaxel and platinum drugs on malignant molecule expression in malignant ascites of patients with advanced gastric cancer

Objective: To explore the influence of Aidi injection combined with paclitaxel and platinum drugs on malignant molecule expression in malignant ascites of patients with advanced gastric cancer. Methods: A total of 80 patients with advanced gastric cancer complicated by malignant ascites who were treated in the hospital between January 2015 and December 2016 were divided into control group and observation group by random number table, each with 40 cases. Control group were treated with paclitaxel and platinum drugs, and observation group were treated with Aidi injection combined with paclitaxel and platinum drugs. The differences in the malignant molecule expression in malignant ascites were compared between the two groups of patients before and after treatment. Results: Before treatment, the proliferation, invasion and autophagy gene expression in malignant ascites were not statistically different between the two groups of patients. 1 week after treatment, EZH2, I2PP2A, Gal-1, HPA-1, MTA1, TROP2, BNIP3 and LC3 mRNA expression in malignant ascites of both groups of patients were lower than those before treatment while PTPN13, TRIM28, SOX7, Syndecan-1 and Beclin1 mRNA expression were higher than those before treatment, and EZH2, I2PP2A, Gal-1, HPA-1, MTA1, TROP2, BNIP3 and LC3 mRNA expression in malignant ascites of observation group were lower than those of control group while PTPN13, TRIM28, SOX7, Syndecan-1 and Beclin1 mRNA expression were higher than those of control group. Conclusion: Aidi injection combined with paclitaxel and platinum drugs can effectively inhibit the gastric cancer cell proliferation and invasion, and regulate cell autophagy activity in the malignant ascites of patients with advanced gastric cancer.

含奥沙利铂化疗方案联合艾迪注射液对晚期结直肠癌患者免疫功能及生活质量的影响

目的探讨含奥沙利铂化疗方案联合艾迪注射液对晚期结直肠癌(CRC)患者免疫功能及生活质量的影响。方法选取2021年3月至2023年3月江西中医药大学附属医院收治的93例CRC患者,按照随机数字表法分为对照组(47例)与试验组(46例)。对照组给予含奥沙利铂化疗方案治疗,在其基础上,试验组给予艾迪注射液治疗,比较两组临床疗效、免疫功能、肿瘤标志物水平与生活质量。结果试验组总有效率、CD4^(+)与CD3^(+)、生活质量总改善率均高于对照组,CD8^(+)、糖类抗原125(CA125)、癌胚抗原(CEA)与糖类抗原19-9(CA19-9)均低于对照组,差异有统计学意义(P<0.05)。结论含奥沙利铂化疗方案、艾迪注射液联合治疗晚期CRC疗效确切,可降低肿瘤标志物水平,增强免疫功能,提高生活质量。

艾迪注射液辅助SOX方案治疗晚期胃癌临床研究

目的:观察艾迪注射液辅助SOX方案治疗晚期胃癌的临床疗效。方法:选取64例晚期胃癌患者,按照奇偶数随机分为试验组和对照组,每组32例。对照组行SOX方案治疗,试验组在SOX方案基础上联用艾迪注射液治疗。21 d为1个疗程,2组均治疗6个疗程,随访18个月。比较2组临床疗效、肿瘤标志物[血清糖类抗原724(CA724)、糖类抗原125(CA125)、糖类抗原199(CA199)、癌胚抗原(CEA)]水平、症状积分、piper疲乏调查量表(PSR-R)评分、Karnofsky(KPS)评分、不良反应发生率、肿瘤进展时间(TTP)及中位生存时间(MST)。结果:治疗6个疗程后,试验组疾病控制率(DCR)为93.75%,疾病有效率(ORR)为68.75%,均高于对照组68.75%、40.63%,差异均有统计学意义(P<0.05);2组血清CA125、CA199、CA724、CEA水平均较治疗前降低,试验组血清CA125、CA199、CEA水平均低于对照组,差异均有统计学意义(P<0.05);2组血清CA724水平比较,差异无统计学意义(P>0.05)。2组症状积分、PSR-R评分均较治疗前降低,KPS评分均较治疗前升高,差异均有统计学意义(P<0.05);试验组症状积分及PSR-R评分均低于对照组,KPS评分高于对照组,差异均有统计学意义(P<0.05)。治疗6个疗程期间,除肝肾功能损害外,试验组血小板减少、血红蛋白减少、白细胞减少、周围神经毒性不良反应发生率均低于对照组,差异均有统计学意义(P<0.05)。随访18个月,试验组TTP和MST均长于对照组,差异均有统计学意义(P<0.05)。结论:艾迪注射液辅助SOX方案治疗晚期胃癌能够提升治疗效果,延长患者的生存期,降低不良反应发生率。

艾迪注射液联合DP化疗方案对NSCLC血清肿瘤标志物水平的影响

目的探讨艾迪注射液结合多西他赛+顺铂(DP)化疗对非小细胞肺癌(NSCLC)患者血清肿瘤标志物水平的影响。方法选取2020年10月至2022年10月在本院收治的96例NSCLC患者,使用随机数字表法将其分为艾迪联合DP组和DP组各48例,并比较两组的疗效、血清肿瘤标志物水平以及不良反应的差异。结果艾迪联合DP组有效率41.67%,明显高于DP组(22.92%)(P<0.05)。治疗后,艾迪联合DP组和DP组的CEA和CYFRA21-1水平均显著降低(P<0.05),而艾迪联合DP组的降低幅度显著低于DP组(P<0.05)。此外,两组不良反应发生率也存在显著差异(P<0.05)。结论艾迪注射剂和DP化疗的联合治疗对NSCLC疗效显著,有助于降低肿瘤标志物水平并减少不良反应发生率。

艾迪注射液辅助化疗治疗老年晚期非小细胞肺癌患者的疗效分析

目的探讨对老年晚期非小细胞肺癌患者给予艾迪注射液辅助化疗治疗的临床效果。方法62例老年晚期非小细胞肺癌患者,依据投掷硬币法分为参照组和研究组,各31例。参照组患者采用吉西他滨和顺铂(GP)化疗治疗,研究组患者在参照组基础上采用艾迪注射液治疗。比较两组患者治疗效果、免疫功能[CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)CD25^(+)调节性T细胞(Treg)]以及生存质量评分(生理层面、心理层面、社会层面、环境层面评分)。结果研究组客观有效率45.16%、疾病控制率87.10%均高于参照组的19.35%、54.84%(P<0.05)。治疗后,研究组CD3^(+)(55.65±7.86)%、CD4^(+)(36.29±5.49)%高于参照组的(50.16±8.42)%、(30.49±4.19)%,CD8^(+)(22.59±4.89)%、CD4^(+)CD25^(+)Treg(4.36±1.08)%低于参照组的(26.15±4.36)%、(8.15±1.39)%(P<0.05)。治疗后,研究组生理层面、心理层面、社会层面、环境层面评分分别为(70.33±3.12)、(71.44±3.25)、(71.64±5.22)、(71.87±4.25)分,高于参照组的(60.36±2.25)、(60.64±5.15)、(60.65±4.22)、(60.64±5.25)分(P<0.05)。结论临床对老年晚期非小细胞肺癌患者给予艾迪注射液辅助化疗治疗,可提升治疗效果以及生存质量,改善免疫功能,临床可推广应用。

艾迪注射液联合mFOLFOX6方案对晚期结直肠癌化疗患者T淋巴细胞水平及化疗安全性的影响

目的:研究艾迪注射液+mFOLFOX6方案运用于晚期结直肠癌化疗中的价值。方法:选择2022年7月—2023年3月九江市第一人民医院纳入的90例晚期结直肠癌化疗患者,按随机数字表法分为两组,各45例。研究组接受艾迪注射液+mFOLFOX6方案,对照组采取mFOLFOX6方案。比较两组毒副反应、症候积分、T淋巴细胞、糖类抗原242(CA242)、糖类抗原19-9(CA19-9)、癌胚抗原(CEA)、辅助型T细胞(Th)1、Th2、Th1/Th2、生活质量(QOL)。结果:研究组恶心呕吐、便秘、腹泻、骨髓抑制、外周神经毒性的发生率均低于对照组,差异均有统计学意义(P<0.05)。两组用药前的症候积分比较,差异均无统计学意义(P>0.05),研究组用药后的各项积分均较对照组更低,差异均有统计学意义(P<0.05)。两组用药前的T淋巴细胞水平比较,差异均无统计学意义(P>0.05),研究组用药后的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均较对照组高,但CD8^(+)低于对照组,差异均有统计学意义(P<0.05)。两组用药前的肿瘤标志物比较,差异均无统计学意义(P>0.05),研究组用药后的CA242、CA19-9、CEA均较对照组更低,差异均有统计学意义(P<0.05)。两组用药前的QOL各项评分比较,差异均无统计学意义(P>0.05),研究组用药后的QOL各项评分均较对照组高,差异均有统计学意义(P<0.05)。两组用药前的免疫指标比较,差异均无统计学意义(P>0.05),研究组用药后的Th1、Th1/Th2均较对照组更低,但Th2高于对照组,差异均有统计学意义(P<0.05)。结论:艾迪注射液+mFOLFOX6方案应用于晚期结直肠癌患者的效果更为理想,可促进患者T淋巴细胞及肿瘤标志物水平改善,减轻患者症状,并调节免疫,提高生活质量,毒副反应较少,安全性更高。

Effects of Aidi Injection(艾迪注射液)with Western Medical Therapies on Quality of Life for Patients with Primary Liver Cancer:A Systematic Review and Meta-Analysis

Objective: To evaluate the effects of Aidi Injection(艾迪注射液, AD) in combination with Western medical therapies(WMT) in patients with primary liver cancer(PLC). Methods: Randomized controlled trials(RCTs) comparing AD plus WMT with WMT alone were retrieved from inception to March 2013 by retrieving the literature database thoroughly and systematically. The extracted data from included studies were analyzed and synthesized by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg’s and Egger’s tests were used to evaluate the potential presence of publication bias. The studies were divided into 7 separate subgroups in terms of quality of life(QOL), recent chemotherapy and the incidence of leukocyte reduction. The subgroup analysis was applied to assess the heterogeneity between included researches, and the sensitivity analysis was used to weigh the stability of studies. Results: Twenty-four RCTs were included in this study. Compared with WMT used alone, AD as additional intervention was more effective on improving QOL(P<0.01), increasing short-term efficacy(P<0.01), prolonging life(P<0.05 or P<0.01), relieving clinical symptoms(P<0.01), and reducing adverse events(e.g. reduce white blood cell counts, P=0.002;reduce in platelet counts, P<0.01). Subgroup analysis showed that the hepatic artery interventions with AD was superior in improving QOL(P<0.01) and enhancing short-term response rates(P=0.007) and reducing white blood cell counts(P=0.0004) than hepatic artery interventions alone(P<0.01). The chemoembolization plus AD or the chemotherapy plus AD were both better than chemoembolization or the chemotherapy alone in improving the QOL and short-term response rate(P<0.05 or P<0.01). Conclusions: AD in combination with WMT improves QOL in patients with PLC. Considering the inherent limitations of the included studies, further well-designed, rigorously performed, high-quality, and double-blinded RCTs with large sample sizes are needed.

Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer

Background： The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin （NP chemotherapy） alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer （NSCLC）. Methods： Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIR and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses. Results： Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m2, combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency （relative risk [RR] = 1.24, 95% confidence interval [C/] [ 1.05-1.47], P = 0.010） and reducing the incidence of Grade II or above nausea and vomiting （RR = 0.49, 95% CI [0.30-0.80], P = 0.005）. Meanwhile, with cisplatin ranging from 80 to 120 mg/m2, no significant differences in efficiency （RR = 1.11, 95% CI [0.87- 1.42], P = 0.390） and Grade II or above nausea and vomiting （RR = 0.88, 95% CI [0.71-1.10], P = 0.260） were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia. Conclusions： Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

Application of Aidi Injection (艾迪注射液) in the Bronchial Artery Infused Neo-Adjuvant Chemotherapy for stage ⅢA Non-small Cell Lung Cancer before surgical Operation

Objective： To study the effect of Aidi Injection （艾迪注射液,ADI） applied in the bronchial artery infused （BAI） neo-adjuvant chemotherapy for stage ⅢA non-small cell lung cancer （NSCLC） before surgical operation.Methods： The 60 patients with NSCLC stage ⅢA underwent two courses BAI chemotherapy before tumor incision were assigned to two groups,the treatment and the control groups,using a random number table,30 in each group.ADI （100 mL） was given to the patients in the treatment group by adding into 500 mL of 5% glucose injection for intravenous dripping once daily,starting from 3 days before each course of chemotherapy,and it lasted for 14 successive days,so a total of 28 days of administration was completed.The therapeutic effectiveness and the adverse reaction that occurred were observed,and the levels of T-lymphocyte subsets,natural killer cell activity,and interleukin-2 in peripheral blood were measured before and after the treatment.Results： The effective rate in the treatment group was higher than that in the control group （70.0% vs.56.7%,P〈0.05）.Moreover,as compared with the control group,the adverse reaction that occurred in the treatment group was less and mild,especially in terms of bone marrow suppression and liver function damage （P〈0.05）.Cellular immune function was suppressed in NSCLC patients,but after treatment,it ameliorated significantly in the treatment group,showing significant difference as compared with that in the control group （P〈0.05）.Conclusion： ADI was an ideal auxiliary drug for the patients in stage ⅢA NSCLC received BAI neo-chemotherapy before surgical operation;it could enhance the effectiveness of chemotherapy,ameliorate the adverse reaction and elevate patients＇ cellular immune function;therefore,it is worthy for spreading in clinical practice.

Effects of the Aidi Dripping Pills on Immune Functions of the Tumor-bearing Mouse

Objective： To study the effects of Aidi Dripping Pills on immune functions of the tumor-bearing mouse on the basis of the previous experimental studies on its tumor-inhibiting and life-prolonging effects. Methods： By using the transplantation tumor mouse models, the effects of Aidi Dripping Pills on the lymphocyte transformation rate and the hemolysin formation in the Sis0 tumor-bearing mice, and on the phagocytic function of macrophages in the abdominal cavity of H22 tumor-bearing mice were investigated. Results： In the 2.25 g/kg and 1.125 g/kg Aidi Dripping Pills groups, the lymphocyte transformation rates in the Sis0 tumor-bearing mice were significantly higher than that of the control group （P〈0.01）. In all the Aidi Dripping Pills groups, HC50 significantly increased （P〈0.01 or P〈0.05）, carbon granular clearance significantly raised, and both the phagocytic index and phagocytic coefficient were significantly higher than those in the control group （P〈0.01 or P〈0.05）. Conclusion： The Aidi Dripping Pills can significantly increase the cellular immune function, the humoral immune function and the phagocytic function of the mononuclear- macrphages, so it may show anti-tumor effects by enhancing the function of the reticuloendothelial system.

基于网络药理学和分子对接探讨艾迪注射液治疗结直肠癌作用机制研究

目的运用网络药理学及分子对接技术探讨艾迪注射液治疗结直肠癌(CRC)的有效活性成分及潜在作用机制。方法从TCMSP、TCM-ID数据库及文献检索中提取艾迪注射液的主要活性物质,并使用SwissTargetPrediction数据库进一步确定其可能的作用靶标;从GeneCards、OMIM、DisGeNET数据库中获取CRC疾病基因靶点。运用STRING数据库及Cytoscape 3.9.1制作“药物活性成分靶点”及PPI网络图。运用Metascape数据库对交集靶点进行GO和KEGG富集分析。运用分子对接验证关键成分与疾病分子间的联系。结果共筛选出39个艾迪注射液有效成分,684个疾病分子,与CRC共有169个靶点。GO功能富集结果显示有188个分子功能、108个细胞组成、1845个生物过程。KEGG分析得到200条通路途径。分子对接结果显示,艾迪注射液核心成分华良姜素、山柰酚、槲皮素等,与疾病分子TP53、BCL2、AKT1、CCND1、CASP3对接良好。结论艾迪注射液可能通过华良姜素、山柰酚、槲皮素等活性成分调节TP53、BCL2、AKT1、CCND1、CASP3等核心靶点从而治疗CRC。

Aidi Injection (艾迪注射液) Alters the Expression Profiles of MicroRNAs in Human Breast Cancer Cells

Objective: To investigate the effects of Aidi Injection (艾迪注射液 ADI) on the MicroRNAs (miRNA) expression profiles in human breast cancer cells and explore the potential targets of the cancer treatment. Methods: MCF-7 breast cancer cells were grown in RPMI 1640 medium supplemented with different concentrations of ADI. The inhibition of cell proliferation was measured by MTT assay. MCF-7 cells were treated by ADI with above 50% inhibiting concentration (IC50) for 48 h. The expression profiles of miRNA in ADI-treated and ADI-untreated MCF-7 cells were detected with miRNA microarray chips and the array data were verified by quantitative RT-PCR. MCF-7 cells were transiently transfected with miRNA mimics by liposome method. Potential mRNA targets were predicted by informatics analysis with TargetScan and PicTar software. Results: ADI significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner. The IC50 of ADI was 55.71 mg/mL after treatment for 48 h. The 60 mg/mL ADI was used as the therapeutic drug concentration. Microarray analysis identified 45 miRNAs that were up-regulated and 55 miRNAs that were down-regulated in response to ADI treatment. Many ADI-induced miRNAs were related to breast cancers. The microarray data were validated by qRT-PCR. Ectopic expression of 100 nmol/L mir-126 mimics significantly inhibited the proliferation of MCF-7 cells. The 12 potential target genes of mir-126 were predicted by both TargetScan and PicTar software. Conclusions: The miRNA may serve as therapeutic targets, and the modulation of miRNA expression is an important mechanism of ADI inhibiting breast cancer cell growth.

基于网络药理学和细胞实验探讨艾迪注射液治疗卵巢癌的机制研究

目的利用网络药理学和细胞实验探讨艾迪注射液治疗卵巢癌的关键分子靶点及可能的作用机制。方法通过中药系统药理学数据库与分析平台(Troditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库筛选艾迪注射液中中药的活性成分及作用靶点,并筛选卵巢癌异常表达的基因,取交集后获得艾迪注射液作用于卵巢癌的可能靶点。接着对可能靶点进行蛋白质互作网络分析、构建药物-化合物-靶点网络和富集分析。进一步筛选靶点,对与卵巢癌预后相关的关键基因进行实验验证,用50mg/ml艾迪注射液处理卵巢癌细胞后利用CCK-8实验观察细胞增殖能力,实时荧光定量聚合酶链反应技术检测核心靶基因的表达。结果筛选到艾迪注射液作用于卵巢癌的可能靶点共13个。这些靶点主要富集于细胞凋亡、铂耐药和白细胞介素-17等肿瘤发生、发展密切相关的信号通路。13个基因中,与卵巢癌预后相关的关键基因为细胞间紧密连接蛋白4(claudin 4,CLDN4)、分泌性白细胞蛋白酶抑制因子(secretory leukocyte peptidase inhibitor,SLPI)和杆状病毒IAP重复序列包含5(baculoviral IAP repeat containing 5,BIRC5)。细胞实验发现,艾迪注射液能显著抑制卵巢癌细胞增殖,促进卵巢癌保护性靶点BIRC5的表达,并显著下降卵巢癌危险因素CLDN4和SLPI的水平。结论艾迪注射液可能是通过影响CLDN4、SLPI、BIRC5这3个核心靶点的表达来实现多成分、多靶点、多途径的抗卵巢癌和联合化疗的增效减毒作用。

Efficacy of Aidi Injection(艾迪注射液)on Overexpression of P-Glycoprotein Induced by Vinorelbine and Cisplatin Regimen in Patients with Non-Small Cell Lung Cancer

Objective：To investigate the efficacy of Aidi Injection（艾迪注射液） on overexpression of P-glycoprotein（P-gp） induced by vinorelbine and cisplatin（NP） regimen in patients with non-small cell lung cancer（NSCLC）, and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. Methods：Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen（2 cycles）, NP regimen（2 cycles） plus Aidi intravenous injection, or NP regimen（2 cycles） plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical efficacy was observed based on Response Evaluation Criteria in Solid Tumors（RECIST） rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progressionfree survival（PFS） was measured. Results：Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates（complete remission ＋ partial response） and the disease control rates（complete remission ＋ partial response ＋ stable disease） were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups（P〈0.05 or P〈0.01）, and the intratumor group showed better effects than the intravenous group（P〈0.05 or P〈0.01）. Compared with the control group, the occurrences of rash, nausea and leukocytopenia were significantly decreased in the intravenous and intratumor groups（P〈0.05）, but without significant difference between the intravenous and intratumor groups（P〉0.05）. Conclusion：Aidi Injection not only improves the efficacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.

Effect of Aidi injection plus chemotherapy on gastric carcinoma:a Meta-analysis of randomized controlled trials

OBJECTIVE: To conduct a Meta-analysis of studies on the effect of Aidi injectioncombined with chemotherapy versus chemotherapy alone in the treatment of gastric cancer(GC).METHODS: Nine electronic databases and six gray literature databases were comprehensively searcheduntil April 20,2013. Two reviewers independently selected and assessed included trialsaccording to the inclusion and exclusion criteria. The risk of bias tool from the Cochrane Handbook version 5.1.0was used to assess trial quality. All calculations were performed using Review Manager 5.0.RESULTS: Thirty-two studies including 1927 participants met the inclusion criteria,most of which were low quality. Compared with chemotherapy alone,Aidi injection plusthe same chemotherapy significantly improved the effective rate [OR = 1.52,95% CI(1.24,1.86),P < 0.0001],clinical beneficial rate [OR = 1.77,95% CI(1.33,2.36),P < 0.0001],and quality of life [OR = 3.02,95% CI(2.39,3.82),P <0.000 01]. There was a significant improvement in nausea and vomiting incidence [OR = 0.34,95%CI(0.24,0.47),P < 0.000 01],diarrhea [OR = 0.47,95%CI(0.33,0.69),P < 0.000 01],leukopenia( 3,0.51),P = 0.05],hemⅢ-ogⅣ)[OR = 0.34,95%CI(0.2lobin decrease(thromⅢ-boⅣ) [OR = 0.42,95%CI(0.18-1.00),P = 0.05],cytopenia(4],and Ⅲ-damⅣ) [OR = 0.46,95%CI(0.22,0.96),P = 0.0age to liver function [OR = 0.36,95%CI(0.24,0.54),P < 0.000 01].CONCLUSION: Aidi injection combined with chemotherapy significantly improved the clinical effect of chemotherapy,reducing the incidence of adverse events. Use of the CONSORT statement for randomized controlled trials is recommended for stricter reporting.

Effect of Aidi injection plus transarterial chemoembolization on primary hepatic carcinoma： a systematic review and Meta-analysis

OBJECTIVE: To assess the efficacy and safety of Aidi injection plus transarterial chemoembolization(TACE) in patients with primary hepatic carcinoma.METHODS: A comprehensive research of seven electronic databases was performed for comparative studies evaluating Aidi injection combined with TACE for primary hepatic carcinoma until September 2016. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool from the Cochrane Handbook version 5.1.0. Data was synthesized by using Rev Man 5.3 software.RESULTS: Forty-nine studies involving 3435 patients met the inclusion criteria, most of which were low methodological quality. Compared with TACE alone, Aidi injection plus TACE can significantly improve the efficiency rate [RR = 1.33, 95% CI(1.24, 1.43), P < 0.000 01], clinical beneficial rate[RR = 1.25, 95% CI(1.17, 1.33), P < 0.000 01], survival rate [6 months, RR = 1.19, 95% CI(1.09, 1.29), P <0.0001], 12 months, [RR = 1.37, 95% CI(1.24, 1.52),P < 0.000 01], 18 months, [RR = 2.00, 95% CI(1.26,3.20), P < 0.004], 24 months, [RR = 1.44, 95% CI(1.22, 1.70), P < 0.0001], 36 months, [RR = 1.50, 95%CI(1.07, 2.11), P = 0.02 < 0.05], quality of life [RR =1.84, 95% CI(1.64, 2.05), P < 0.000 01] and immune function [CD3+, MD = 11.12, 95% CI(7.93, 14.30),P < 0.000 01], CD4 +, [MD = 10.37, 95% CI(7.29,13.45), P < 0.000 01], CD4+/CD8+, [MD = 0.30, 95%CI(0.07, 0.53), P = 0.01 < 0.05], NK, [MD = 7.49, 95%CI(6.64, 8.34), P < 0.000 01]. A significant improvement was also found in improvement of symptoms[RR = 1.64, 95%CI(1.38, 1.94), P < 0.000 01], leukopenia [RR = 0.60, 95% CI(0.54, 0.66), P < 0.000 01],thrombocytopenia [RR = 0.46, 95% CI(0.34, 0.61),P < 0.000 01], nausea and vomiting incidence [RR =0.66, 95% CI(0.54, 0.81), P < 0.0001), liver damage rate [RR = 0.57, 95% CI(0.42, 0.77), P = 0.0003 <0.05), and kidney damage rate [RR = 0.18, 95% CI(0.05, 0.68), P = 0.01 < 0.05].CONCLUSION: The results suggested that Aidi injection plus TACE significantly improve the clinical effect of TACE, and reduce the incidence of adverse events. However, rigorous multicenter trials with larger size are warranted to further confirm the findings.