OBJECTIVE To systematically evaluate the effectiveness and safety of safflower yellow for injection(SYI)in acute ischemic stroke(AIS).METHODS Computer searches were conducted on CNKI,Wanfang Database,VIP.com,Chinese Biomedical Literature Database,PubMed,Embase,Web of Science and Cochrane Library for randomized controlled trials(RCTs)of SYI combined with conventional Westem medicine treatment as experimental group(EG)and conventional Western medicine treatment as control group(CG).The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of included studies.Statistical analysis was performed using R4.3.1 software.RESULTS A total of 29 RCTs were included.Meta-analysis results showed that compared with the CG group,the total effective rate of the EG group was higher(P＜0.000 1),the patients'NIHSS,Barthel,IL-8,IL-6,plasma viscosity,and hematocrit indexes were improved(P＜0.05);while in terms of NO and FIB indexes,there was no statistically significant difference between the two groups(P＞0.05).In terms of safety,the total incidence of adverse drug reactions in the EG group was lower than that in the CG group(P=0.001 8).The results of sensitivity analysis and publication bias analysis showed that except for the fact that the incidence of adverse reactions reversed to a point had no statistically significant difference between the two groups(P=0.173 4),the results obtained in the study were basically stable,and the possibility of publication bias was small.CONCLUSION Compared with conventional treatment,SYI combined with conventional treatment is generally more effective in terms of effectiveness and does not increase the risk of adverse reactions.
Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. In the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optical regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regard to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and approaches according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.
The liver cancer has microenvironmental features such as low pH, M2 tumor-associated macrophage enrichment, low oxygen, rich blood supply and susceptibility to hematotropic metastasis, high chemokine expression, enzyme overexpression, high redox level, and strong immunosuppression, which not only promotes the progression of the disease, but also seriously affects the clinical effectiveness of traditional therapeutic approaches. However, nanotechnology, due to its unique advantages of size effect and functionalized modifiability, can be utilized to develop various responsive nano-drug delivery system (NDDS) by using these characteristic signals of the liver cancer microenvironment as a source of stimulation, which in turn can realize the intelligent release of the drug under the specific microenvironment, and significantly increase the concentration of the drug at the target site. Therefore, researchers have designed a series of stimuli-responsive NDDS based on the characteristics of the liver cancer microenvironment, such as hypoxia, weak acidity, and abnormal expression of proteases, and they have been widely investigated for improving anti-tumor therapeutic efficacy and reducing the related side effects. This paper provides a review of the current application and progress of NDDS developed based on the response and regulation of the microenvironment in the treatment of liver cancer, compares the effects of the microenvironment and the NDDS, and provides a reference for building more advanced NDDS.
OBJECTIVE To review systematically the population pharmacokinetic（PPK） study of levetiracetam（LEV） and explore the affecting factors of LEV pharmacokinetic parameters. METHODS The PPK studies using nonlinear mixed effect model method were collected by searching CNKI, Wanfang, VIP, Embase and PubMed. RESULTS A total of 17 studies were included, among which 15 studies characterized LEV pharmacokinetics as a one-compartment model structure. The two most frequently identified significant covariates influencing LEV pharmacokinetics included weight and renal function. For model verification, only 4 studies used external evaluation. CONCLUSION Pharmacokinetic variability of LEV is dependent on the weight and renal function. The generalizability of these PPK models should be externally assessed. Existing studies are insufficient to evaluate the pharmacokinetic behavior of LEV in special populations such as enhanced renal clearance, neonatal and gestational epilepsy patients using PPK method, and further research is needed.
目的 探讨和分析碘对比剂致对比剂相关性脑病(contrast-associated encephalopathy,CAE)的发生情况和特点,为临床安全用药提供参考.方法 检索建库至2022年2月收录在PubMed、Embase、中国知网、万方和维普期刊数据库有关碘对比剂致CAE的病例报道并对其进行整理和分析.结果 共纳入80篇文献合计110例患者,男67例(60.9％),女43例(39.1％),平均(65.2±13.4)岁,其中≥60岁80例(72.7％).CAE的发生时间主要集中在术中至术后24 h内(81.8％),其临床表现以皮质盲最为常见(25.5％),其次是烦躁(23.6％)和意识障碍(20.0％),经水化和糖皮质激素等对症治疗后整体(97.3％)预后良好.结论 虽然CAE较为罕见且预后良好,但在患者应用过程中及之后的至少24 h内仍应密切关注,尤其是对于存在高危因素的患者,一旦出现CAE的相关症状应及时予以水化等对症处理,避免引起不可逆的损害.
目的 探讨基于知信行干预理论(knowledge-attitude-practice,KAP)的分级药学服务模式在系统性红斑狼疮(systemic lu-pus erythematosus,SLE)患者中的实施效果.方法 收集2019年1月～2022年2月在我院风湿免疫科门诊就诊并自愿参与研究的SLE患者,将符合纳入标准的530例患者随机分为对照组和干预组.对照组患者仅接受常规的用药交代,干预组患者依据分级药学服务标准接受不同级别的药学服务.对2组患者不同时间点的分级评分及KAP水平进行统计分析.干预9个月后,评价干预前后2组患者风险感知水平、疾病控制效果和预后情况.结果 干预组患者KAP各维度在预设时间点的得分均低于对照组(P＜0.05);9个月后,干预组较对照组一级和二级服务比例分别下降8.98％和5.38％,急性发作和不良反应发生率分别下降了 12.88％和11.89％,风险感知水平、疾病活动度、器官损伤和临床检验指标均显著改善,差异具有统计学意义(P＜0.05).结论 基于KAP干预理论为SLE患者提供分级药学服务,有利于药师快速筛选出需要重点干预的患者和采取针对性的干预措施,从而提高药学服务质量和疾病控制效果.
高端药物制剂是一类能够提高药效,增强用药安全的高技术含量制剂,它的发展是衡量一个国家药物制剂水平的指标.高端药物制剂的研发常依赖于具有特殊功能性的新型辅料.近十年来,高端药物制剂用辅料的研制和生产发展迅速.本研究围绕辅料的作用以及辅料在中药现代化发展、化学药品高端制剂创新和生物制品生产中的应用,对功能性辅料研究进展的文献追踪,结合对相关领域国际技术水平进行综合分析,提出我国高端药物制剂用功能性辅料的未来发展方向,以期对我国高端药物制剂用辅料的开发和应用提供启发和参考.
目的 以对照制剂为随行对照,对6个厂家28批复方鲜竹沥液质量进行评价.方法 采用高效液相色谱法(HPLC)建立复方鲜竹沥液指纹图谱,并测定原儿茶酸、糠酸、对羟基苯甲酸、2,6-二甲氧基苯酚、水杨酸、(+)-南烛木树脂酚-3α-O-β-D-吡喃葡萄糖苷的含量;以对照制剂作为随行对照,并结合聚类分析(CA)和正交-偏最小二乘法判别分析(OPLS-DA),对样品质量进行评价.结果 标定了复方鲜竹沥液指纹图谱的16个共有峰,指认了 13个成分;6个厂家28批样品中,只有9批样品与对照制剂的相似度大于0.75.含量测定结果显示,28批样品均未检测到2,6-二甲氧基苯酚,2～4批样品的原儿茶酸、糠酸、对羟基苯甲酸含量与对照制剂相应含量的比值大于60％,1批样品的水杨酸含量与对照制剂相应含量比值大于50％,15批样品的(+)-南烛木树脂酚-3α-O-β-D-吡喃葡萄糖苷含量与对照制剂对应含量比值大于80％,复方鲜竹沥液整体质量不稳定;CA分析将对照制剂和F厂家样品聚为一类,B厂家样品聚为一类,其他4个厂家样品聚为一类;OPLS-DA分析筛选出(+)-南烛木树脂酚-3α-O-β-D-吡喃葡萄糖苷、原儿茶酸等6个差异性成分.结论 所建方法简便、准确,可用于复方鲜竹沥液的质量控制与评价.
神经肽(neuropeptide)作为一种特殊的信息物质,具有含量低、活性高、作用广泛而复杂的特点,在体内对多种生理功能具有调节作用.以食欲素、胃动素和胆囊收缩素等10种神经肽为例,总结神经肽的生理功能及检测方法.结果显示,目前放射免疫法、酶联免疫法、免疫组织化学法和RNA印迹试验等是常用检测已知神经肽的方法,但这些方法容易受到蛋白质、无机盐和寡糖等影响,并且不能较好区分结构相似的神经肽,使得神经肽检测结果并不理想.随着液质联用技术(LC-MS)和样品前处理技术的发展和应用,提高了神经肽检测的灵敏度和专属性,同时可以检测到未知神经肽,使得神经肽检测得到改善.
OBJECTIVE To explore the protection of soy isoflavones（SIF） on ovarian tissue damage in polycystic ovary syndrome（PCOS） rats based on the nuclear factor E2-related factor 2（Nrf2）/heme oxygenase 1（HO-1） pathway. METHODS Female SD rats were treated with letrozole(1 mg·kg -1 ) to establish PCOS model, and the experiment rats were divided into control group, PCOS group, low-concentration SIF group(L-SIF group, 50 mg·kg -1 ), and high-concentration SIF group(H-SIF group, 100 mg·kg -1 ) and SIF+ML385 group(SIF 100 mg·kg -1 +Nrf2 inhibitor ML385 30 mg·kg -1 ), 12 rats per group. Each group was given corresponding drugs for intervention, once a day, for 4 weeks in total. The body weight, fasting blood glucose（FBG） and fasting insulin（FINS） levels of the rats were measured, and the insulin resistance index（HOMA-IR） was calculated; the serum testosterone（T）, estradiol（E2）, follicle-stimulating hormone（FSH） and luteinizing hormone（LH） levels, ovarian tissue glutathione peroxidase（GPx）, superoxide dismutase（SOD） and catalase（CAT） activity were measured to calculate the LH/FSH ratio; the pathological changes of ovarian tissue were observed by HE staining, and the number of cystic follicles and corpus luteum was counted; the apoptosis of ovarian tissue cells was observed by TUNEL staining, and the apoptosis index（AI） was calculated; the expression of Nrf2 and HO-1 proteins in ovarian tissue was measured by Western blot. RESULTS Compared with the PCOS group, the body weight, levels of FBG, FINS, HOMA-IR, T, LH, LH/FSH ratio, the number of cystic follicles, and AI in the L-SIF and H-SIF groups were decreased, the level of E2, ovarian tissue GPx, SOD, CAT activities, corpus luteum number, and the protein levels of Nrf2 and HO-1 were increased, and the H-SIF group was better than the L-SIF group; ML385 was able to inhibit the activation of Nrf2/HO-1 pathway and obviously attenuate the protective effect of SIF on ovarian tissue damage in PCOS rats. CONCLUSION SIF may inhibit oxidative stress and reduce ovarian tissue damage in PCOS rats by activating the Nrf2/HO-1 pathway.
目的 建立了基于核基因内部转录间隔区(ITS2)序列及二级结构鉴别维吾尔药材黑加仑及其混伪品(黑加仑葡萄和异果小檗)的方法.方法 对维吾尔药材黑加仑及其混伪品的ITS2序列进行聚合酶链式反应(PCR)扩增并双向测序,Codon Code Aligner软件对测序峰图进行序列拼接,用MEGA 6.0软件对拼接后的序列进行多重比对.计算种内、种间遗传距离,构建邻接法(Neighbor-Joining,N-J)系统聚类树,预测其ITS2二级结构.结果 经PCR扩增测序后,黑加仑药材ITS2序列长度均为238 bp,GC含量为57.14％～57.98％,A1为主体单倍型;黑加仑葡萄药材序列长度均为226 bp,GC含量为47.79％,仅为一个单倍型;异果小檗药材序列长度均为223 bp,GC含量为53.36％,仅为一个单倍型.并且维吾尔药材黑加仑的种内遗传距离明显小于种间遗传距离.二级结构表明黑加仑及混伪品其螺旋区的茎环数目、大小、位置以及螺旋角度均有明显差异.结论 ITS2序列可以作为鉴定维吾尔药材黑加仑及其混伪品的DNA条形码,为维吾尔药材黑加仑的用药安全提供有效的科学技术手段.
目的 研究木贼麻黄二氯甲烷萃取部位的化学成分.方法 运用各种色谱技术对木贼麻黄二氯甲烷部位的化学成分进行系统分离,并依据其波谱数据鉴定化合物的结构.结果 从木贼麻黄二氯甲烷部位中分离得到23个化合物,分别为黑麦草内酯(1)、异黑麦草内酯(2)、3,9-二羟基-猕猴桃内酯(3)、洋川芎内酯Ⅰ(4)、paeoveitol B(5)、α-松油醇-8-0-β-D-吡喃葡萄糖苷(6)、桃金娘烯醇-β-D-葡萄糖苷-6'-0-乙酸酯(7)、cheonnyunchol A(8)、布卢姆醇B(9)、(6R,7Z)-9,10-二羟基-4,7-巨豆二烯-3-酮(10)、(6S,9R)-2-hydroxy-4-(2,6,6-trimethyl-4-oxo-cyclohex-2-enyl)-butyric acid methyl ester(11)、蚱蜢酮(12)、3,5,6-trihydroxy-7-megastigmen-9-one(13)、菜豆酸(14)、脱落酸(15)、楝叶吴萸素B(16)、苜蓿素(17)、柯伊利素(18)、异鼠李素(19)、herbacetin 7-methyl ether(20)、二氢芹菜素(21)、甘草素(22)以及 salcolin A(23).结论 化合物 1～5、7～16 以及23 为首次从麻黄属植物中分离得到,其余化合物均为首次从木贼麻黄中分离得到.
OBJECTIVE To investigate the protective effect of Qinglongyi on rat gastritis model, and explore the potential targets and molecular mechanisms of Qinglongyi′s anti-inflammatory and immune effects by using network pharmacology and molecular docking methods. METHODS A rat model of gastritis was established and the effects of the ethanol extract of Qinglongyi was investigated on the morphological changes and biochemical parameters of gastric tissue in rats, and the active ingredients, action targets and disease targets of Qinglongyi were searched and summarized by using TCMSP database, Swiss Target Prediction database, GeneCards database, DisGeNET database and OMIM database, and the component target network diagram was constructed by Cytoscpe software. The main core targets were identified by DAVID database, GO function analysis and KEGG pathway enrichment analysis were carried out, and finally the molecular docking validation was carried out using AutoDock software. RESULTS It was found that the ethanol extract of Qinglongyi could improve the gastritis of rats, increase the antioxidant activity and reduce the level of inflammatory factors. Forty-six active ingredients of Qinglongyi were further screened and 156 potential targets were identified. GO function analysis and KEGG pathway enrichment analysis show that the mechanism of Qinglongyi′s anti-gastritis effects may be through regulating signal transduction, changing nuclear receptor activity and binding with protein, and anti-gastritis effects by regulating PI3K-AKT pathway, TNF signal pathway and FoxO signal pathway. Molecular docking results show that the binding energy of ligand and receptor is less than-20.9 kJ·mol -1 , indicating that ligand and receptor have good binding. CONCLUSION Qinglongyi has a good anti-gastritis effect and its main active ingredients are flavonoids and naphthoquinones. The main targets involved are AKT1, SRC, MAPK14 and MAPK1. Following the characteristics of multi-component, multi-target and multi-channel of traditional Chinese medicine, it provides references for the follow-up study on the anti-gastritis effect of Qinglongyi.
OBJECTIVE Bovis Calculus is a valuable Chinese medicine in China. The identification of Bovis Calculus and its substitutes is one ofthe difficulties in the research of traditional Chinese medicine. In view of this, we aim to establish and evaluate the identification methods of succession medicinal substances of Bovis Calculus with infrared spectrum information data based on techniques of data handling and data analysis. METHODS Two ranges of infrared spectra data were selected and preprocessed by first derivative, standard normal variatetransformation（SNV） and auto-scale before analysis. In the analytical process, principal component analysis（PCA）, hierarchical cluster analysis（HCA）,K-nearest neighbors（KNN）, partial least squares-discrimination analysis（PLS-DA）, and support vector machines-discrimination analysis（SVM-DA） were used.Based on the loading plot in PCA and the relationship between the structure of chemical composition and the infrared spectrum absorption band, the infrared spectrum characteristic bands of various Bovis Calculus were analyzed and discussed.RESULTS PCA and HCA indicated that the infrared spectra of samples had good characteristics for identification and the cluster of samples was correct. As for KNN, PLS-DA, and SVM-DA, the prediction accuracies of test setall were 100%.CONCLUSION Infrared spectrum has good characteristics, which can realize the accurate identification of succession medicinal substances of Bovis Calculus.
OBJECTIVE To establish an LC-MS/MS method with good accuracy and sensitivity for determination of insulin single chain precursor in insulin glargine, and provide reference for the development of determination method of single chain precursors of insulin and its analogues. METHODS ACQUITY UPLC peptide CSH C 18 coulumn（2.1 mm×150 mm, 130 ?, 1.7 μm）was adopted. The mobile phase A was 0.1% formic acid/water and the mobile phase B was 0.1% formic acid/acetonitrile, gradient elution program was conducted at the flow rate of 0.3 mL·min -1 , with column temperature of 60 ℃ and detection wavelength of 214 nm. Orbitrap Exploris 480 was used, and parallel reaction monitoring was carried out by ESI + scanning and quantification ion pair 1155.6/1 151.5. RESULTS Good linearity between peak area and concentration of insulin glargine single chain precursor was achieved in the range of 1-1 00 ng·mL -1 （r=0.999 2）. The average recovery of single chain precursor was 97%（n=9）. CONCLUSION This method is suitable for the determination of insulin single chain precursor in recombinant insulin glargine, with good accuracy, repeatability, precision, and durability.
目的 探索建立基于循证医学的药品目录遴选方法,并修订北京市医疗机构抗菌药物临床使用分级管理目录,为科学形成药品目录和合理应用抗菌药物提供支持.方法 北京市卫生健康委员会建立多学科的目录工作组根据目录计划书,整合药品数据、药品证据和专家意见,按照纳入排除标准,通过德尔菲法对北京市医疗机构抗菌药物临床使用分级管理目录形成专家共识.结果 遴选的目录共纳入99种药品,与上版目录相比,新增10种抗菌药物,调出38种抗菌药物;另有5种和13种抗菌药物分别上调和下调了管理级别.结论 以循证医学思想和方法为指导,通过全面的证据和数据支持、结合多学科专家的经验、科学的共识方法,可以提高药品目录修订的科学性和合理性.
目的 通过对已上市化药制剂生产场地变更政策解读和常见问题进行分析,为国内制药企业开展相关场地变更研究与质量管理工作提供参考.方法 对近年来出台的系列变更法规、技术指南进行深入解读,对已上市化药制剂生产场地变更中常见问题进行汇总分析.结果 上市药品变更贯穿于药品上市全生命周期,随着科学技术的进步,新原料、新工艺、新分析方法、新设备等新的科技成果都有可能被应用于药品的生产.其中药品生产场地变更是药品上市后变更的重要内容,是上市药品质量风险管理最具挑战性的一部分.结论 药品上市许可持有人作为药品上市后生产场地变更管理的责任主体,应当主动按照相关法规、指导原则的要求,开展药品上市后研究,实现全生命周期管理.
细胞移植疗法方兴未艾,其中干细胞因其分化替代、旁分泌滋养能力、天然炎症归巢能力和低免疫原性优势可促进细胞和组织再生,在再生医学领域具有巨大的潜能.缺血性脑卒中是脑卒中的主要类型,发病后常伴随着不可逆转的神经功能损失和组织坏死.干细胞移植疗法在脑部疾病的治疗中表现出色,除自身的修复作用外,还可以利用干细胞作为药物/基因的靶向递送载体,调节卒中发生后的疾病微环境,促进神经再生.笔者对干细胞的炎症归巢能力及机理、干细胞的药物/基因携载方法和移植干细胞用于缺血性脑卒中的治疗等方面研究进行综述,讨论干细胞移植疗法在临床转化中存在的问题,为基于干细胞的基因传递和缺血性脑卒中的靶向治疗提供参考和新思路.
OBJECTIVE To investigate the effect of cryptotanshinone on tumor microenvironment（TME） and its possible molecular mechanism in mice with diffuse large B cell lymphoma（DLBCL） based on STAT3 phosphorylation. METHODS The model of xenograft tumor was established by SUDHL-4 cell line（DLBCL） in NOD-SCID mice. The model mice were divided into model group, cryptotanshinone low-dose group and high-dose group. The tumor volumes were measured twice a week, and the mice were killed after 17 days, the weights of the mice and the tumor were measured, the expression of inflammatory factors and CCL2 in peripheral blood were detected by Elisa, the levels of STAT3 protein and its phosphorylation in the xenograft tumor were detected by Western blot, the expression of VEGF was observed by immunohistochemistry, and the mRNA levels of E-cadherin, MMP9 and Vimentin were detected by real-time PCR. RESULTS The results showed that the volume and weight of the xenograft tumors in the low and high-dose groups were significantly lower than model group, while the effect was more pronounced in the high-dose group（P＜0.001,P＜0.01 or P＜0.05）, and the expressions of IL-6, IL-10, TGF-β and CCL2 in the low and high-dose groups were significantly lower than model group, while IL-12 showed the opposite trend, also the high-dose group was more pronounced（P＜0.001, P＜0.01 or P＜0.05）. The expressions of p-STAT3, VEGF and the most of EMT markers in the low and high-dose group were significantly lower than model group, and the high-dose group still has the best effect（P＜0.001, P＜0.01 or P＜0.05）. CONCLUSION Cryptotanshinone can inhibit the growth of xenograft tumor in DLBCL mice, which may be related to the changes of TME, including suppression of STAT3 phosphorylation and subsequent down-regulation of tumor-associated inflammatory cytokines, chemokine CCL2, VEGF expression, and EMT markers.
OBJECTIVE To evaluate the efficacy, safety, and economy of dihydropyrimidine dehydrogenase（DPYD） gene testing before chemotherapy with fluorouracil by rapid health technology assessment（HTA）and investigate the necessity of individualized fluorouracil therapy based on genetic testing and provide efficient and convenient evidence-based evidence for clinicians and policymakers. METHODS PubMed, the Cochrane Library, Wanfang, CNKI and other databases were searched, two researchers independently screened the literature, extracted data, and evaluated the quality according to inclusion and exclusion criteria, and conducted qualitative analysis of the results.RESULTS A total of 1HTA,5 systematic reviews/meta-analyses and 5pharmacoeconomic studies were included. The results showed that the incidence of adverse reactions in patients with DYPD*2A, 2846A ＞ T, *13 and 1236G ＞ A gene mutations was significantly higher than that in wild type（P＜0.05）. DPYD gene testing and genotype-guided administration before chemotherapy with fluorouracil could significantly reduce patients′ adverse reactions and reduce treatment costs. CONCLUSION For cancer patients with fluorouracil-based chemotherapy, DPYD genotype testing is recommended before medication. If patients have gene mutations, it is recommended to appropriately reduce the dose or switch to other drugs. It is necessary to carry out economic research in China in the future.
