Current situation and policy suggestion of adjuvant drugs management

通过调查我国11个省（区）、市的辅助用药政策与管理现状,分析发现我国辅助用药仍存在概念不明晰、评估不合理等主要问题,提出了统一辅助用药的概念界定、有效发挥临床药师的作用和发挥信息化建设的 管理支撑作用等具体政策建议.

Gem-Diphosphonates： The Motif of Diverse Biological and Medicinal Importance

The introduction of gem-diphosphonates （known as bisphosphonates, BPs） in oncology has dramatically changed the management of patients with metastatic bone disease. In this manuscript, we thoroughly scrutinize the available body of clinical trials supporting the use of bisphosphonates in this setting and review new and ongoing research. Additionally, we summarize the data showing the benefits of BP-use in the prevention of treatment-induced bone loss and the intriguing emerging evidence on the antitumor potential of some of these agents when used in the adjuvant setting. Finally, we address the need for a careful consideration of potential benefits of BPs therapy and the risk for osteonecrosis, a recently recognized late-toxicity of their use.

Chemotherapy as a component of multimodal therapy for gastric carcinoma

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase Ⅲ trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced （T2-stage） cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase Ⅱ trials using active drug combinations. In 2005, a large phase Ⅲ trial testing preand postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase Ⅲ studies testing this strategy may be warranted in the near future.

Locally advanced rectal cancer:The importance of a multidisciplinary approach

Rectal cancer accounts for a relevant part of colorectal cancer cases,with a mortality of 4-10/100000 per year.The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients.In the last two decades,new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival.Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates.The employment of neoadjuvant treatment,delivered before surgery,also achieved an improved local control and an increasedsphincter preservation rate in low-lying tumors,with an acceptable acute and late toxicity.This review describes the multidisciplinary management of rectal cancer,focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

The Adverse Event Profile in Patients Treated with Transferon^TM(Dialyzable Leukocyte Extracts): A Preliminary Report

Background: Dialyzable leukocyte extracts (DLE) are heterogeneous mixtures of peptides less than 10 kDa in size that are used as immunomodulatory adjuvants in immune-mediated diseases. TransferonTM is DLE manufactured by National Polytechnic Institute (IPN), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of TransferonTM is induction of a Th1 immunoregulatory response. Despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human DLE or TransferonTM. Objective: To assess the safety of TransferonTM in a large group of patients exposed to DLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the Unit of External Services and Clinical Research (USEIC), IPN. Analysis was performed from January 2014 to November 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with TransferonTM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with TransferonTM (MD 1.9, IQR 1.7 - 2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with TransferonTM, and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: TransferonTM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

The Regulatory Action of the Modified Yu Ping Feng Tang on Cellular Immunity in Mice under Amputation-Induced Stress

To approach the action of modified Yu Ping Feng Tang ([symbol: see text] Jade-Screen Decoction) on cellular immunity, an experiment was conducted in mice under amputation-induced stress. On the 3rd day after amputation, acute atrophy was found in the thymus, the reactivities of T- and B-lymphocytes to Con-A and LPS were decreased, the IL-2 content and its activity reduced and the activity of NK cells lowered. The high, moderate and low concentrations of the modified Yu Ping Feng (YPF) Decoction all have antagonistic action on the above manifestations of immune inhibition.

Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.

Clinical Observation in 31 Cases of Chronic Bronchitis at Remission Stage Treated with Bufei Keli

To observe the therapeutic effects of a Chinese drug Bufei Keli (补肺颗粒 granules for invigorating the lung) in the treatment of chronic bronchitis at remission stage, 62 cases were randomly divided into a treatment group (treated with Bufei Keli) and a control group (treated with Yupingfeng Keli 玉屏风颗粒). The results turned out to be that the short-term clinically controlled and markedly effective rate was 77.42% and the long-term relapse-resisting markedly effective rate was 74.2% in the treatment group, which were obviously higher than 45.16% and 38.71% respectively in the control group (P<0.05). And the increase in contents of SOD and CD_3 and the decrease in LPO content in the treatment group were also bigger than that in the control group (P<0.01). It is therefore concluded that Bufei Keli can improve qi deficiency syndrome and raise the immunity of patients with chronic bronchitis, hence its effect of resisting relapse of chronic bronchitis.

基于“药辅合一”理念的厚朴挥发油纳米乳制备及其抗氧化性能研究

目的:采用Box-Behnken响应面法优化厚朴挥发油纳米乳处方的制备工艺并初步评价其稳定性及抗氧化效果。方法:以粒径为评价指标,筛选乳化剂、K_(m)值、厚朴挥发油用量三个因素的最佳比例,考察离心稳定性、稀释稳定性、储存温度稳定性以评价厚朴挥发油纳米乳的稳定性,并用1,1-二苯基-2-三硝基苯肼(1,1-Diphenyl-2-picrylhydrazyl,DPPH)自由基和2,2’-联氮-双(3-乙基苯并噻唑啉-6-磺酸)(2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid),ABTS^(+))阳离子自由基的清除能力为指标评价其抗氧化性能。结果:厚朴挥发油纳米乳的最优处方为厚朴挥发油15.05%,K_(m)值2.5,乳化剂32.9%,所制得的纳米乳外观澄清、透明、微泛蓝光、稳定性良好,厚朴挥发油和纳米乳均具有清除DPPH自由基和ABTS^(+)自由基能力,且厚朴挥发油纳米乳在DPPH和ABTS^(+)自由基的清除能力上更佳。结论:制备所得的厚朴挥发油纳米乳工艺可行、理化性质稳定,具有良好的抗氧化效果,为厚朴挥发油的开发利用提供一种新思路。

云南元江诺丽果汁对正常大鼠血压与糖尿病模型小鼠血糖的影响

为了探究云南元江诺丽果汁与其他种类诺丽果汁对正常大鼠血压与糖尿病模型小鼠血糖的影响,以正常大鼠和糖尿病模型小鼠为研究对象,观察试验前后正常大鼠血压和糖尿病模型小鼠血糖的变化。正常大鼠麻醉后经十二指肠灌注药或果汁,采用直接测压法测定血压,读取试验前后的血压值并进行数据分析;采用腹腔注射四氧嘧啶建立糖尿病小鼠模型,并分别给予造模成功的小鼠相对应的药物或果汁,每日给药或果汁1次,连续给药或果汁9 d,并在第10天采集小鼠血液测定其空腹血糖数值进行研究对比分析。分析大鼠血压发现,云南元江高剂量组在注射云南元江诺丽果汁前后血压值无显著差异;中剂量组在注射90 min前后血压值差异极显著;低剂量组在注射240 min前后血压值差异显著;中剂量组降血压效果最佳。分析糖尿病模型小鼠血糖发现,注射云南元江诺丽果汁的低、中、高3个剂量组均可不同程度地降低血糖,且低剂量组的降血糖效果最佳;大溪地诺丽果汁降糖率为0.00%。云南元江诺丽果汁具有降血糖和降血压的双重功效,且低剂量组降血糖的效果最显著;诺丽由美国夏威夷引种至云南西双版纳和元江,对其降血糖的功效并无显著影响。

基于“药辅合一”的辛夷油亚微乳的制备及评价

目的 基于“药辅合一”理念优化辛夷油亚微乳的处方与制备工艺,并对其进行表征和体外释放动力学研究。方法 以离心稳定性常数Ke、粒径、ζ电位的综合评分为指标,采用Box-Behnken效应面法优化辛夷油亚微乳处方工艺,透析法研究其体外释放桉油精的情况。结果 辛夷油亚微乳的最优处方:辛夷油5%、大豆磷脂1.2%、泊洛沙姆188 1.8%、油酸1.3%,最佳制备工艺条件:乳化时间10 min,乳化温度60℃,超声时间10 min。辛夷油亚微乳的桉油精含量为(2.43±0.04)mg·mL^(-1),粒径为(156.93±1.53)nm,多分散指数(PDI)为(0.16±0.02),ζ电位为(-24.87±1.67)mV,体外释放符合一级动力学方程特征,释放机制为Fick扩散。结论 成功制备辛夷油亚微乳并优化了处方工艺,所得制剂的稳定性良好,并且具有缓释作用。

肿瘤专科医院辅助药品监测指标构建与探讨

目的构建灵敏、稳定且导向性强的肿瘤专科医院辅助药品比值比监测指标。方法以专科技术服务收入为分子,辅助药品收入为分母,首治率、专科率为校正因素分别构建外科、内科、放疗系统辅助药品比值比指标体系并进行效果评价。结果校正后月辅助药品比值比和药占比的变异系数显著低于校正前(p<0.05)。指标纳入科室考核后,外科、内科系统辅助药品比值比水平显著高于考核前(p<0.05)。结论通过首治率、专科率校正后的辅助药品比值比稳定、灵敏,可作为一项医院管理监测指标。

Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer （NSCLC）. But this doublet has considerable toxicity and unfavorable tolerability, and results in poor compliance. The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC, but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting. Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin （75 mg/m2） and gemcitabine （1250 mg/m2） between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results A total of 132 patients met the criteria and were included in the study, 96 were male （72.7%） and 36 were female （27.3%）. Median age was 60.5 years old, range 29-75 years, and 41.7% of patients were 〉65 years old. Overall, 68.2% patients received all four planned cycles, and the cumulative dose delivered for gemcitabine was 8333 mg （83.3% of the planned dose） and cisplatin 248 mg （82.7% of the planned dose）. There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 patients （35.6%） and was the predominant hematologic toxicity. Common grade 3/4 non- hematologic toxicities were nausea/vomiting （22.0%）, infection （12.3%）, and febrile neutropenia （11.4%）. Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerabilitv compared with Dublished data on cisDlatin and vinorelbine.

绒毛膜下血肿的病因及诊疗进展

绒毛膜下血肿(SCH)指胚胎周围绒毛膜下出血,发生时孕妇常出现阴道出血和腹痛。无症状SCH常在超声检查时偶然发现。随着超声技术在产科检查中的广泛应用,临床医师对SCH的重视程度也随之提高。早孕期SCH是早孕异常出血的常见原因之一。近年来,SCH对妊娠结局的影响成为研究焦点。尽管目前积累了丰富的SCH临床处理经验,但仍缺乏明确的指南。因此,未来需要进一步研究SCH的病因和发病机制,以更好地预防和控制SCH的发生和进展,并有效评估患者预后。

Recent advances on vaccines against malaria: A review

This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.

细菌外膜囊泡在疫苗领域的应用研究进展

细菌外膜囊泡(outer membrane vesicles,OMVs)是一种由革兰阴性菌在生长过程中分泌的纳米球状颗粒,通过释放毒力因子、调控宿主免疫反应、外排抗生素等途径参与细菌感染性疾病的发生过程。由于OMVs携带大量细菌组分,如蛋白质、脂质、遗传物质等,可以有效激活免疫系统,具有作为疫苗、疫苗佐剂以及优良外源抗原载体的潜力,可用于传染性疾病预防疫苗和肿瘤免疫治疗疫苗的开发研制过程中。随着医药和生物技术等高新产业的迅速发展,现有疫苗都被发现存在不同的缺陷,亟需一种能够同时保证安全性与有效性的疫苗,由此可见,外膜囊泡疫苗具有良好的应用前景。本文就细菌外膜囊泡的生物合成、结构组分、生物学作用及其在疫苗领域的应用等各个方面的研究进行综述分析,为进一步推动细菌外膜囊泡疫苗的研发提供了一定的理论基础和借鉴价值。

我院辅助用药合理使用的管控实践

目的:为加强辅助用药的管控、促进医院合理用药提供参考。方法:介绍我院对辅助用药的管理措施,引入"辅助用药使用强度"至考核管理中,收集我院实施辅助用药管理前后的相关数据,以药占比、辅助用药使用强度、辅助用药使用金额等为指标进行比较以评价管理效果。结果:通过加强对辅助用药的管理,采取量化指标、考核到组、监测预警、超限停药、限量采购、医师培训等信息技术与行政干预等措施,我院辅助用药管理成效显著,2016年5月(开始实施管控)与2017年6月辅助用药金额分别为1 943.92、540.57万元,药占比分别为39.90%、33.76%;与管控前比较,管控后各科室辅助用药使用强度下降比例达12.86%～86.32%,不合理用药问题数从639例(在535份病历中)下降到147例(在538份病历中)。结论:我院采取的加强辅助用药管控的措施,不仅减少了辅助用药的费用、降低了药占比,还促进了临床合理用药。

辅助用药分类方法探索

目的:对辅助用药的范围、分类进行界定。方法:利用PubMed,CNKI,万方等数据库及《临床用药须知》、《新编药物学》、《马丁代尔药物大典》等药学专著对辅助用药定义、分类的解释进行查询探索辅助用药的范围和分类的界定方法。结果:对辅助用药的定义、范围及分类方法有了初步定论,将辅助用药分为十类,对我院辅助用药进行监管。结论:辅助用药范围的界定及分类有待进一步探讨及规范,以促进对辅助用药临床应用的规范管理。

云南省医疗机构辅助治疗药品重点监控品种使用情况调查分析

目的:调查云南省医疗机构辅助治疗药品中重点监控品种使用情况,为制定相关政策及促进临床合理用药提供依据。方法:调查云南省医疗机构2015年1月1日-3月31日重点监控品种使用相关数据,对相关数据进行统计分析。结果:上报数据有效率最高的是三级医院,为93.94%;销售金额排名前10位药品中重点监控品种所占的品种数最高的是三级医院,平均为(5.50±2.12)种;住院重点监控品种销售金额占住院药品总销售金额比例最高的是三级医院,平均为(31.94±16.99)%,二级医院和一级医院分别为(26.13±11.93)%和(22.14±16.39)%;销售金额排名前10位药品中重点监控品种的销售金额占住院重点监控品种总销售金额比例最高的是二级医院,平均为(50.34±26.87)%,其中最高可达98.53%;三级医院的平均比例是(39.13±22.55)%,一级医院的平均比例是(27.38±27.75)%。住院销售金额排名前5位的重点监控品种中,各级医院均包括红花黄色素和奥美拉唑。结论:云南省医疗机构使用辅助治疗药品情况普遍存在,重点监控品种以中药注射剂以及质子泵抑制剂为主,可采取有效措施,制订相应的监管制度并加以落实,以促进临床合理使用药物。

中药免疫调节作用的研究进展

研究表明中药具有免疫促进和免疫抑制的双向免疫调节作用,本文就中药免疫调节作用的相关研究进行总结,从中药对免疫细胞、细胞因子、免疫器官发育的促进作用及其抗肿瘤的功效,到中药在炎症反应、超敏反应、自身免疫性疾病以及移植排斥反应中所起的免疫抑制作用进行论述,并对中药在免疫调节中的应用前景进行了展望。