Network pharmacology to predicting therapy targets of traditional Chinese medicine Kang’ai injection on breast cancer

Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology database was used to predict the effective components of the Chinese patent medicine Kang’ai injection,and GeneCards database,Online Mendelian Inheritance in Man database and the Therapeutic Target Database were used to predict the therapeutic targets of breast cancer.Cytoscape 3.7.2 was used to construct active ingredient-disease-target network.String database and Cytoscape 3.7.2 software were used to draw the protein-protein interaction network and obtain the core target.Bioconductor and R language were used to analyze the effective action target for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:There were 42 effective active ingredients in the Chinese patent medicine Kang’ai injection,which acted on 105 targets,and it had 32 components that acted on 96 targets associated with breast cancer.The target regulates various biological processes such as inflammation,angiogenesis,apoptosis and cell proliferation,and regulates pathways such as PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications and thyroid hormone signaling pathway through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Conclusion:The treatment of breast cancer with the Chinese patent medicine Kang’ai injection is a complex mechanism process with multiple targets,multiple pathways,and multiple choices,which provides a theoretical basis for the further extraction of effective components in the treatment of breast cancer.

Clinical Observation on the Improved Short-Term Effects of Anti-Tumor Purified Chinese Medicine Injection Ai-Jing for 138 Cases with Malignant Tumors

The subjects of this study were to observe the improved short-term effects of anti-tumor purified Chinese medicine injection Ai-Jing for 138 cases with malignant tumors. This was a multi-center clinical study, and a total of 138 patients included 96 males and 42 females, with the age from 60 to 76 years. Ai-Jing has obtained the Chinese invention patent since 2008 (ZL991-03528.3). A novel technique acupoint injection method was adopted. Except for lung cancer, patients with other malignant tumors were injected once every other day, 2 ml each time. A course of treatment needs 6 Ai-Jing injections, lung cancer patients need 10 - 20 Ai-Jing injections. At the same time, patients were treated with traditional medicine decoction. Due to the limited number of cases, cure rate, recovery rate and remission rate were calculated as a whole, respectively 18.12%, 44.20% and 32.15%. All the invalid patients were lung cancer, accounting for 16.67% of the patients treated with lung cancer, and the total treatment inefficiency was 6.52%. Conclusion: Chinese Medicine Injection Ai-Jing extracts the effective components of anti-cancer and tumorigenesis, and has the effects of anti-cancer and tumorigenesis, anti-inflam-matory and analgesic, and repairing body damage, with small toxic and side effects and low cost.

Efficacy and safety of Kang’ai injection adjunct with TP chemotherapy for the treatment of non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Background:Combination therapy with traditional Chinese medicine and chemotherapy was proposed as a therapeutic strategy for non-small cell lung cancer patients.Therefore,we performed a systematic review and metaanalysis of randomized controlled trials to assess effects of this combination therapy on non-small cell lung cancer.To evaluate the efficacy and safety of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the treatment of non-small cell lung cancer.Methods:A randomized controlled study of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the databases of China National Knowledge Infrastructure Database,WanFang Database,VIP Database,Sino-Med Database,PUBMED,EMBASE and Cochrane library was searched by computer.The literatures published from the database establishment to July 1,2020 were included in the search scope.After 2 evaluators independently evaluated and cross checked the quality of the study,Revman 5.3 was used to meta analyze the clinical effect of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy on patients with non-small cell lung cancer.Results:A total of 1,370 lung cancer patients were included in 20 RCTs.The results of meta-analysis showed that there were significant differences between the 2 groups in clinical efficacy(RR=1.32,95%CI(1.20,1.44)),quality of life(RR=1.44,95%CI(1.32,1.57)),immune function(MD=0.53,95%CI(0.23–0.83)),adverse reactions(RR=0.49,95%CI(0.41,0.58)).Conclusion:The Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy is effective and safe in the treatment of non-small cell lung cancer,and has great prospects for further development.However,the quality of evidence was very low-to-moderate.Considering the poor quality of evidence,we are not very confident in the results.We look forward to more research and update results in the future and improve the evidence quality.

Effect of Kang Ai injection + conventional chemotherapy on tumor markers, apoptotic molecules and immune response in patients with advanced NSCLC

Objective: To study the effects of Kang Ai injection + conventional chemotherapy on tumor markers, apoptotic molecules and immune response in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients diagnosed as advanced NSCLC in our hospital during March 2015 - October 2017 were randomly divided into the experimental group receiving Kang Ai injection + conventional chemotherapy and the control group receiving conventional chemotherapy. The contents of tumor markers, apoptotic molecules and immunologic cytokines in serum and the contents of immune cells in peripheral blood were determined before and after chemotherapy. Results: after chemotherapy, the content of CEA, CYFRA21-1, SCC-Ag, GDF15 and Livin in the serum of the two groups decreased significantly, and the content of PDCD5, P53 and Bax increased significantly, and the content of CEA, CYFRA21-1, SCC-Ag, GDF15, Livin in the serum of the experimental group were lower than those of the control group, and the content of PDCD5, P53 and Bax were higher than those of the control group;the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of control group significantly decreased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly increased after chemotherapy;while the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of experimental group significantly increased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly decreased after chemotherapy. Conclusion: Kang Ai injection + conventional chemotherapy in the treatment of advanced NSCLC can more significantly decrease the serum tumor markers, regulate the secretion of apoptotic molecules and anti-tumor immune response than conventional chemotherapy.

Meta-analysis of therapy of Kang’ai injection combined with chemotherapy in the treatment of non-small cell lung cancer

Objective:To compare the safety and efficacy of Kang’ai injection combined with chemotherapy and chemotherapy alone in the treatment of non-small cell lung cancer.Methods:The related control and randomized studies from 1966 to October 01,2022,were retrieved in the following databases:China National Knowledge Infrastructure,Wanfang databases,Value In Paper,SinoMed,PubMed,Embase and Cochrane Library.A comprehensive literature search was conducted in 7 electronic databases identifying all the relevant randomized controlled trials.Cochrane handbook 5.2.3 was applied to evaluate the quality of included trials,and the RevMan 5.3 software was used to analyze data and assess the publication bias.Results:From the 16 studies reviewed,a total of 1,398 patients were included.Compared with docetaxel+cis-platinum chemotherapy alone,Kang’ai injection combined with docetaxel+cis-platinum chemotherapy showed significant effects in improving clinical response rate(RR:1.40,95%confidence interval(CI)(1.25,1.58)),quality of life score(Karnofsky score)(RR:1.53,95%CI(1.32,1.78)),traditional Chinese medicine syndrome(RR:2.01,95%CI(1.43,2.83))and safety(RR:0.62,95%CI(0.54,0.71)),the differences were statistically significant.Conclusion:Kang’ai injection may increase the therapeutic effectiveness,improve the quality of life,and reduce the toxicity of chemotherapy in patients with non-small cell lung cancer.These results require confirmation by further rigorously designed randomized controlled trials(PROSPERO registration number:CRD42020176917).

PFI/DI喷射对分层火焰引燃的SI-CAI混合燃烧的影响

针对均质SI-CAI混合燃烧存在循环波动大、较高负荷下最大压力升高率过高等问题,提出一种基于分层火焰引燃(stratified flame ignition,SFI)的SI-CAI混合燃烧技术.并在一台直喷(DI)四缸汽油机上,采用内部废气重压缩策略配合进气道喷射(PFI)方式实现了SFI燃烧.探索了PFI/DI喷射对SFI燃烧特性的影响规律.研究结果表明,随着直喷时刻在压缩冲程初期的推迟,直喷燃油的物理冷却作用使得燃烧始点推迟,同时分层的稀释混合气使得最大压力升高率大幅下降,但指示平均有效压力IMEP略微恶化;过晚的直喷时刻将导致自燃燃烧提前,放热变快,最大压力升高率迅速增大,IMEP恶化显著,循环变动变大.直喷比例的增大能大大降低最大压力升高率,同时能够保持稳定的燃烧.点火时刻在不同的喷油策略下都能有效控制SFI燃烧过程.相比均质混合燃烧,SFI燃烧可以较好地缓和混合燃烧中最大压升率与燃烧稳定性的矛盾,能同时保证较低循环波动和较小压升率.

Study and Analysis of Defect Amplification Index in Technology Variant Business Application Development through Fault Injection Patterns

Software reliability for business applications is becoming a topic of interest in the IT community. An effective method to validate and understand defect behaviour in a software application is Fault Injection. Fault injection involves the deliberate insertion of faults or errors into software in order to determine its response and to study its behaviour. Fault Injection Modeling has demonstrated to be an effective method for study and analysis of defect response, validating fault-tolerant systems, and understanding systems behaviour in the presence of injected faults. The objectives of this study are to measure and analyze defect leakage;Amplification Index (AI) of errors and examine “Domino” effect of defects leaked into subsequent Software Development Life Cycle phases in a business application. The approach endeavour to demonstrate the phasewise impact of leaked defects, through causal analysis and quantitative analysis of defects leakage and amplification index patterns in system built using technology variants (C#, VB 6.0, Java).

亮剑企业服务 携DI和AI双引擎勇闯智能财税之海

说起＂噼里啪＂,大多数人很容易就会联想到噼里啪啦的算盘声,而在国内恰好有一家基于智能财税系统为中小微企业提供一站式标准化财税服务的公司——噼里啪智能·财税。算盘是古代劳动人民发明的计算工具,具有灵便、准确的特点,噼里啪智能·财税,也同时兼具灵便与准确的优势。

AI智能注塑成型的分析研究

本文提出了AI注塑成型的理念,分析了融入AI注塑成型的AI的模块及性能;研究了AI注塑成型技术提升注塑成型性能;论述了AI注塑成型应用现状;提出了AI注塑成型技术研究领域拓展和深化的几个方面;阐述了AI注塑机高动态性能运行机构的开发。指出AI注塑成型预示着未来注塑成型将朝着自主学习、数据驱动和智能化服务的方向发展,推动行业向更高水平的智能化迈进。

冷EGR对DME PCCI-DI发动机燃烧和排放特性影响的试验研究

PCCI-DI是一种部分预混充量压缩着火和燃料直接喷射燃烧的组合工作方式,可有效降低发动机的NOx排放,但其在高负荷工作时易受到爆震影响,导致发动机功率下降,排放恶化。为此,开展了冷EGR对DME PCCI-DI发动机燃烧和排放特性影响的试验研究。结果表明:随着EGR率的增加,缸内最高燃烧压力下降,主燃烧期推迟并略有延长,NOx排放下降,但较大的EGR率会导致PCCI-DI发动机HC和CO排放迅速升高。采用冷EGR在一定程度上可以改善PCCI-DI发动机的燃烧过程,拓宽发动机的工作范围。

赛莱乐对多梗死性痴呆患者CD_(62)P、CD_(63)P、P_(10)、DI的变化影响

目的 :观察赛莱乐治疗对多梗死性痴呆 (MID)患者CD6 2 P、CD6 3、P10 、DI变化的影响。方法 :将禁用阿司匹林及尼莫地平的 78例MID患者分 2组 ,治疗组 4 8例 ,应用赛莱乐 15 0mg静滴 ,1次 /日× 15天 ;对照组 30例 ,复方丹参 2 0ml静滴 ,1次 /日× 15天 ,观测治疗前、后CD6 2 P、CD6 3、P10 及DI变化。结果 :治疗后治疗组CD6 2 P、CD6 3、P10表达明显降低 ,DI明显增强 (P <0 0 1)与对照组比差异显著 (P <0 0 5 )。CD6 2 、P10 与DI呈负相关 (P <0 0 5 ) ,CD6 3与DI无相关。结论 :赛莱乐可降低CD6 2 P、CD6 3、P10 表达 ,抑制血小板活化 ,增强红细胞变形能力 ,对MID恢复有益。

Effect of Kang’ai Injection (康艾注射液) on Serum Level of Soluble Interleukin-2 Receptor and Vascular Endothelial Growth Factor in Patients with Esophageal Carcinoma during Radiotherapy

Objective： To observe the effect of Kang＇ai Injection （康艾注射液, KAI） on serum level of soluble interleukin-2 receptor （sIL-2R） and vascular endothelial growth factor （VEGF） in patients with esophageal carcinoma （EC） during radiotherapy （RT）, and to investigate its synergistic effect with RT and its influence on immunological function of the body. Methods： One hundred and seventy patients with EC, who had missed the chance of surgical operational therapy, were assigned to the treated group （90 cases） and the RT group （80 cases）, and at the same time a control group consisting of 80 inpatients without tumors was set up. Patients in the RT group were treated with RT alone but KAI was given additionally to those in the treated group, with 50 ml given once per day via intravenous dripping, 15 days as one course, and 2 courses administered in total. The immediate therapeutic efficacy and changes of serum slL-2R and VEGF levels were observed, and the effect of KAI on patients＇ quality of life （QOF） was evaluated by Karnofsky scoring. Results： In 16 patients of the treated group it was completely remission （OR）, in 54 partially remission （PR）, in 18 it was stabilized disease （SD） and in 2 progressive disease （PD）, with the total effective rate （CR ＋ PR） as 77.8%, while in those of the control group it was 12, 46, 18, 4 and 72.5%, respectively, the immediate therapeutic efficacy in the treated group was somewhat better than that in the RT group, but showed no statistical significance （P〉0.05）. Serum levels of slL-2R and VEGF in all the patients before treatment were higher than those in the control group, which were decreased after treatment in both groups （P〈0.05）, but the improvement in the treated group was better than that in the RT group, showing significant difference （P〈0.05）, and patients＇ QOF improved more significantly in the former as well （62.2 % vs 40.0%, P〈 0.05）. Conclusion： KAI in combination with RT in treating patients with EC could enhance the immunological function of patients, improve their QOF and enhance their sensitivity to RT.

氯吡格雷与丹参川芎嗪注射液联合亚低温对急性缺血性脑卒中（AIS）患者神经功能等方面的影响

目的评价探究氯吡格雷与丹参川芎嗪注射液联合亚低温对急性缺血性脑卒中(acuteischemicstroke,AIS)患者神经功能等方面的影响。方法选取该院于2017年12月—2019年3月收治的急性缺血性脑卒中(AIS)患者64例进行观察研究,按照治疗方式的不同分成两组,每组32例,接受氯吡格雷联合亚低温治疗的患者作为对照组,对照组基础上联合丹参川芎嗪注射液治疗的为观察组,比较两组患者的神经功能评分、治疗效果、生活能力及残障程度情况。结果治疗后观察组的临床总有效率(96.88%)显著高于对照组(75.00%),差异有统计学意义(χ^2=6.3354,P=0.0118),相比治疗前,治疗后两组患者的神经功能评分和残障程度显著下降,其生活活动能力评分显著提升,并且观察组患者的NIHSS评分(9.79±2.11)分、mRS评分(1.11±0.56)分以及BI指数(68.95±6.88)与对照组[(13.87±3.22)分、(1.89±0.77)分、(51.29±6.11)]相比较差异有统计学意义(t=5.9952、4.6343、10.8570,P<0.05)。结论临床治疗急性缺血性脑卒中采用氯吡格雷与丹参川芎嗪注射液联合亚低温的疗效更确切,可有效提升患者的神经功能,值得应用借鉴。

艾迪注射液联合常规化疗对肺癌脑转移患者的临床疗效

目的观察艾迪注射液联合化疗对肺癌脑转移患者认知障碍的缓解情况。方法回顾性分析2018年6月至2020年6月在浙江省丽水市人民医院就诊的80例肺癌脑转移患者的临床资料,按照不同治疗方法分为常规化疗组和艾迪组,常规化疗组患者采用顺铂联合多西他赛的化疗方案,艾迪组在常规化疗组基础上予以艾迪注射液。观察2组患者的近期疗效、认知功能以及毒副作用,评价联合艾迪注射液治疗的有效性和安全性。结果常规化疗组患者近期有效率50%,艾迪组患者近期有效率73%,2组差异有统计学意义(χ^(2)=4.266,P=0.039)。治疗开始前,常规化疗组和艾迪组患者的蒙特利尔认知评估量表(MoCA)评分和简易智能量表(MMSE)评分差异无统计学意义。治疗后2周,与常规化疗组比较,艾迪组患者的MoCA评分和MMSE评分均增加,差异具有统计学意义(t=-3.462、-2.507,P=0.001、0.047);治疗后2周艾迪组患者的Karnofsky评分和生活质量量表(QOL)评分升高,差异具有统计学意义(t=-4.634、-4.050,P<0.01)。与常规化疗组比较,艾迪组患者骨髓抑制和眩晕情况减轻,差异具有统计学意义(χ^(2)=4.126、4.050,P=0.042、0.044),恶心呕吐等胃肠道反应和脱发情况差异无统计学意义(P>0.05)。80例患者均因本病死亡。常规化疗组患者平均生存期为(15±3)个月,艾迪组患者的中位生存期为(18±4)个月,2组差异无统计学意义(χ^(2)=17.752,P<0.01)。结论艾迪注射液联合常规化疗方案治疗肺癌脑转移患者可提升近期疗效,缓解认知障碍,减轻化疗的毒副作用,但对于患者的生存期无明显影响。

康艾注射液联合化疗及贝伐珠单抗对晚期结直肠癌患者疗效及生存的影响

目的:探讨康艾注射液联合化疗及贝伐珠单抗对晚期结直肠癌(mCRC)患者疗效及生存的影响。方法:回顾性分析2018年6月~2021年12月芜湖市第一人民医院诊治的mCRC患者68例,分为A、B两组,A组34例给予康艾注射液联合CAPEOX方案(奥沙利铂+卡培他滨)及贝伐珠单抗一线方案治疗,B组34例予化疗及贝伐珠单抗一线方案治疗(方案同A组)。5周期治疗后,两组肿瘤未进展的患者,改为卡培他滨维持治疗至疾病进展。比较两组患者的疗效、血清肿瘤标志物的变化,采用生存分析比较两组患者的中位无进展生存期(mPFS)。结果:A组客观缓解率(67.6%)高于B组(41.2%)(P<0.05)。A组和B组5周期治疗后的CEA及CA199水平较治疗前均下降(P<0.001),且A组治疗前后的CEA及CA199水平下降幅度均高于B组(P<0.05)。A组的mPFS长于B组(P<0.05),两组病人骨髓抑制、恶心呕吐等不良反应发生率差异均无统计学意义(P>0.05)。结论:与CAPEOX方案联合贝伐珠单抗相比,mCRC患者行康艾注射液联合CAPEOX方案及贝伐珠单抗治疗,可以提高临床疗效、降低血清肿瘤标志物水平和延长mPFS,且未增加不良反应。

燃烧室形状及喷油策略对柴油机排放的综合影响

通过数值模拟的方法研究了活塞凹坑几何形状及喷油策略对柴油机排放的综合影响。活塞凹坑几何形状及不同喷油策略是影响直喷式柴油发动机油气混合、燃烧以及排放的重要因素。在保证活塞凹坑容积、发动机压缩比、总喷油量、总喷油持续时间不变的前提下,本文对三种不同的喷油策略及四种不同的活塞几何形状相结合的方案进行了研究,结果表明多次喷油及改变燃烧室形状对柴油机排放有着显著的影响。

消癌平注射液对多西紫杉醇在大鼠体内的药代动力学及体外CYP450酶活性的影响研究

目的探讨消癌平注射液(XAP)对大鼠体内多西紫杉醇(DOC)药代动力学与体外细胞色素P450(CYP450)酶活性的影响。方法对24只SD雄性大鼠实施体内研究,随机分为A组(DOC对照组)、B组(XAP+DOC组)、C组[(咪达唑仑(MDZ)对照组)]、D组(XAP+MDZ组)共4组。借助超高效液相色谱串联质谱法检测给药后5、10、20、30 min和1、2、3、4、6、8、12、24 h大鼠血清中DOC/MDZ浓度,计算药代动力学参数。通过重组CYP450酶3A4(CYP3A4)的体外反应体系展开研究,制备人肝微粒体,以MDZ为底物探究XAP对CYP450酶活性的抑制作用,考察XAP对DOC代谢的影响。结果体内药代动力学结果显示,XAP可使DOC的C max和AUC 0→t分别增加150%(P<0.01)和60%(P<0.05);t 1/2和MRT分别为(4.24±1.78)h、(3.92±1.14)h,较DOC对照组显著延长;XAP可使MDZ的消除延长,半衰期t 1/2延长至(0.962±0.19)h,MRT延长至(1.008±0.13)h,药时曲线下面积(AUC 0→∞)为(1510.078±242.11)ng·h/ml,均显著高于MDZ对照组(P<0.05)。以MDZ为底物进行的体外抑制实验表明,XAP(10~100 mg/ml)和C 21总甾体提取物(10~50μg/ml)能明显抑制人肝微粒体CYP3A4活性。结论XAP与DOC联合使用后,DOC的血药浓度升高,DOC的多个药代动力学参数明显改变,XAP对DOC的消除有抑制效能,同时其作用机制可能与CYP3A4受抑制有关。

黄芪颗粒和黄芪注射液对CYP1A2、CYP2D、CYP2C亚酶活性影响的实验研究

目的通过体内和体外实验研究黄芪颗粒和黄芪注射液对CYP1A2、CYP2D、CYP2C亚酶的活性影响。方法建立体外"cocktail"反应体系,利用LC/MS/MS法测定酶代谢产物,计算黄芪颗粒和黄芪注射液对CYP1A2、CYP2D6、CYP2C9和CYP2C19亚酶活性的影响;大鼠随机分为对照组和实验组,不同浓度黄芪颗粒和黄芪注射液连续灌胃10 d,制备肝微粒体并进行"cocktail"反应,评价两种药物体内对大鼠CYP1A2、CYP2D1、CYP2C6和CYP2C11亚酶活性影响。结果在体外"cocktail"实验中,黄芪颗粒和黄芪注射液明显地抑制了CYP2D6、CYP2C19和CYP1A2亚酶活性,而二者对于CYP2C9亚酶活性无影响。在大鼠灌胃给药实验中,黄芪颗粒在剂量32、160和800 mg.kg-1.d-1提高CYP1A2亚酶活性2.13、3.23和2.20倍,黄芪注射液在剂量0.16、0.8、4 g.kg-1.d-1提高CYP1A2亚酶活性1.65、2.26和2.89倍,而二者均未诱导CYP2D1、CYP2C6和CYP2C11亚酶活性增加。结论黄芪颗粒和黄芪注射液对CYP2D6、CYP2C19活性有抑制作用,对大鼠CYP1A2活性有诱导作用。

康艾注射液联合化疗对胃癌疗效的Meta分析

目的:探讨康艾注射液联合化疗治疗胃癌在临床疗效方面是否优于单独化疗方案。方法:全面收集2005-2012年PubMed、中国期刊全文数据库、中文科技期刊全文数据库、中国生物医学文献光盘数据库发表的康艾注射液联合化疗治疗胃癌的临床随机对照试验(randomized controlled trial,RCT),采用Stata软件进行数据处理和Meta分析。结果:共有14项RCT纳入Meta分析,与单用化疗相比,康艾注射液联合化疗在改善胃癌患者生活质量(P=0.000)、白细胞降低(P=0.000)、肠胃反应(P=0.000)、肝功损害(P=0.047)、周围神经系统损伤(P=0.000)、体质量降低(P=0.002)及疼痛(P=0.017)方面作用明显,而在临床有效率(P=0.093)及其他不良反应方面的差异无统计学意义。结论:基于现有临床证据,康艾注射液联合化疗治疗胃癌可提高患者生活质量、减轻化疗的部分不良反应。