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.

Research on Incentive Policies for Chinese Innovative Drug R&D - Taking Innovative Anti-tumor Drugs as an Example

Objective To provide reference for improving Chinese innovative drug research and development incentive policies.Methods Based on investigating the incentive policies for innovative drug research and development in clinical research,evaluation and approval in China,anti-tumor drugs were taken as the research object to discuss relevant policies from the perspective of clinical trials and registration approval based on data statistics and current situation analysis.Results and Conclusion Driven by a series of incentive policies for innovative drug R&D,great achievements have been made on anti-tumor drugs.However,there are problems such as concentration of drug targets,homogenization of clinical trials,and gaps in some drugs with large clinical needs.To improve incentive policies for innovative drug R&D,China should adhere to the orientation of clinical value,focusing on basic research and translational research,improving evaluation and approval capabilities,and establishing a sound ecosystem for innovative drugs.

An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs

Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.

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.

A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs

Suppression of cellular O-linkedβ-N-acetylglucosaminylation(O-Glc NAcylation)can repress proliferation and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-Glc NAcylation in HEK293 T cells.The fluorescent reporter mainly consists of a reporter(green fluorescent protein(GFP)),an internal reference(red fluorescent protein),and an operator(neuronal differentiation 1),which serves as a"sweet switch"to control GFP expression in response to cellular OGlc NAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular OGlc NAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-Glc NAcylation in He La and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for conducting gene transcription studies.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature

Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

Research Progress on Dimension and Indicators of Comprehensive Value Assessment of Anti-Tumor Drugs

Objective To sort out the dimension and indicators of comprehensive value assessment of anti-tumor drugs abroad,and provide a reference for constructing a similar system in China.Methods The keywords such as anti-tumor drugs,value,assessment,method,and framework were used to search CNKI,WanFang database,VIP database,Embase,PubMed and Web of Science.Results and Conclusion According to the research on the value framework of anti-tumor drugs,6 first-level dimensions and 8 second-level indicators with common characteristics were summarized.In view of China’s national conditions,this study summarizes the available value judgment dimensions of anti-tumor drugs at home and abroad,so as to learn from international experience and their mature methodologies,and provide ideas for constructing a multi-dimensional value system of anti-tumor drugs in China.

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。

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。

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。

Therapeutic drug monitoring in patients with inflammatory bowel disease

Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients&#x02019; pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated.Starting from fifteen structurally diverse natural products,a focused library featured by Michael acceptors is constructed with IBX mediated oxidation.Biological assay on five tumor cell lines indicates that four Michael acceptors,8a,11a,12a,14a,are with improved cytotoxicity(3-10 folds more potent than the parent compounds),which merit further investigations.Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor.The results suggest that the strategy is not only effective and relatively high discovery rate(28%),but also resource saving.

Overview of Research and Development for Anticancer Drugs

Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

Anti-tumor Effects of Aspirin: Progress in Clinical and Basic Studies

Beyond the antipyretic analgesic and anti-inflammatory effects for which aspirin has historically been used,studies have shown that aspirin also plays an important role in the prevention or treatment a variety of diseases.The anti-tumor effects of aspirin have received increasing attention during the past decade.Many studies have explored the molecular mechanisms underlying these anti-tumor effects in vitro and in vivo,and abundant discoveries have been made through observational or interventional clinical studies.In terms of its molecular function,aspirin has been shown to prevent tumor cell growth through inhibiting the signal transduction of the COX,tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),NFκB/IκB,and Bcl-2/Bax pathways.Under certain conditions,aspirin can also induce autophagy,which is an inhibitory mechanism for some tumors.This article provides a comprehensive overview of the anti-tumor effects of aspirin and discusses the concrete mechanisms underlying aspirin’s anti-tumor effects that have been discovered in the past 30 years.

癌因性疲乏作为肿瘤辅助治疗中药新药研发临床定位的思考与分析

癌因性疲乏通常发生于恶性肿瘤化放疗患者身上,对患者的生存质量造成了一定程度的不良反应,因此如何积极干预一直是临床的关注重点。现有研究通常认为癌因性疲乏的发生可能受到肿瘤病变、化放疗、手术、合并症、心理问题等多种机制复杂作用。由于患者本身的病情严重,目前关于该病在西医治疗方面尚无积极、有效的对策。传统中医药用于肿瘤患者的辅助治疗时,在改善患者生活质量方面具有一定的特色与优势,对癌因性疲劳的缓解也有积极作用。因此,本研究以癌因性疲乏作为临床定位,进一步探索中药新药研发在肿瘤辅助治疗中的意义的重要性,以期能促进传统中医药更好的为广大肿瘤患者服务。

兽用疫苗中药佐剂发展与管理研究

本文聚焦兽用疫苗中药佐剂的研究与产业化发展,总结兽医领域在单味药与中药组份佐剂,以及配合疫苗使用的“免疫增强剂”效用,从现代免疫与中兽医理论两个角度分析作用机理,推动兽用疫苗中药佐剂在提高免疫效果、提高疫苗免疫应答方面的应用,提出产业发展对策与管理建议。

国家医保谈判对公立医院抗肿瘤药物采购费用、数量及结构的影响:以EGFR-TKI靶向药物为例

目的分析国家医保药品目录准入谈判(以下简称“国谈”)政策对某省公立三级医院非小细胞肺癌EGFRTKI靶向药物采购费用、数量及结构的影响,为相关政策制定提供依据。方法收集2018年1月—2020年12月某省公立三级医院EGFR-TKI靶向药物每月采购数据,利用中断时间序列模型分析采购费用、数量、药品结构及日均费用的变化趋势。结果阿法替尼、奥希替尼、吉非替尼、埃克替尼、厄洛替尼5种EGFR-TKI靶向药物总体采购量及费用以稳定为主,2018年国谈准入品种采购量及费用上升。5种EGFR-TKI靶向药物药品结构变化明显,呈即刻上升趋势;各品种日均费用出现不同程度的下降。结论国谈政策的实施增加了靶向药物的使用,国谈准入药物品种逐步进入临床,患者的用药负担进一步减轻。

临床药师参与抗肿瘤辅助用药管理效果评价

目的促进临床抗肿瘤辅助药物的合理使用。方法通过医院信息系统(HIS)调取医院肿瘤内科2个病区2019年2月至2021年1月收治的1000例肿瘤患者的一般资料及用药相关信息,各500例;A9病区的患者纳入对照组,未进行临床药师干预;A10病区的患者纳入干预组,均接受临床药师干预至化学药物治疗(简称化疗)结束。比较两组患者抗肿瘤辅助药物的用药频度(DDDs)、限定日费用(DDC)、药品利用指数(DUI)、药品费用及药品不良反应(ADR)。结果干预组联合用药种数与对照组有显著差异(P<0.05)。干预组和对照组患者参麦注射液、还原型谷胱甘肽、康艾注射液使用率较高(>50%),两组均以参芪扶正注射液使用率最低;干预组DDC值以香菇多糖注射液最高,黄芪多糖注射液最低,对照组分别以还原型谷胱甘肽最高,香菇多糖注射液最低;干预组DUI值以香菇多糖注射液、参芪扶正注射液最佳,对照组DUI值以参芪扶正注射液最佳。干预组各项人均费用均显著低于对照组(P<0.05)。干预组ADR总发生率显著低于对照组(P<0.05)。结论临床药师参与抗肿瘤辅助用药管理,可促进药物合理使用,明显减少患者的医疗费用及ADR。