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.

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.

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.

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.

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.

Effects of two novel sugar drug candidates on CYP450 isoforms in different sexed Chinese human liver microsome in vitro

The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.

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.

Novel therapeutic agents in the treatment of metastatic colorectal cancer

Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.

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’ 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.

A novel nanogel delivery of poly-α,β-polyasparthydrazide by reverse microemulsion and its redox-responsive release of 5-Fluorouridine

To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.

Complex structure of human Hsp90~N and a novel small inhibitor FS5

Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.

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.

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.

CRISPR accelerates the cancer drug discovery

Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients,such as gene mutation,amplification,or deletion,with the overall survival prognosis,underscoring patients’genetic background may directly regulate drug sensitivity/resistance during chemotherapies.Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery.The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research,providing a precise and simplified genome editing tool with unlimited editing possibilities.Furthermore,it presents a powerful tool in cancer drug discovery,which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance.Herein,we summarized the application of CRISPR/Cas9 in drug screening,with the focus on CRISPR/Cas9 mediated gene knockout,gene knock-in,as well as transcriptional modification.Additionally,this review provides the concerns,cautions,and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.

四种抗新型冠状病毒药物对肝功能影响的临床观察

目的 观察阿兹夫定、奈玛特韦、莫诺拉韦、先诺特韦对新型冠状病毒感染患者肝功能的影响。方法 回顾性收集196例应用口服小分子抗病毒药物的新型冠状病毒感染患者的临床资料,根据所用药物不同将患者分为阿兹夫定组(92例)、奈玛特韦组(41例)、莫诺拉韦组(42例)、先诺特韦组(21例)。阿兹夫定组接受阿兹夫定治疗,奈玛特韦组接受奈玛特韦/利托那韦治疗,莫诺拉韦组接受莫诺拉韦治疗,先诺特韦组接受先诺特韦/利托那韦治疗。比较四组患者治疗前后肝功能指标水平,分析四组患者治疗后肝功能异常例数及占比,分析四组治疗后肝功能异常患者年龄及基础疾病。结果 阿兹夫定组治疗7 d后的谷丙转氨酶(47.24±13.86)U/L、谷草转氨酶(48.59±16.71)U/L高于治疗前的(38.87±19.14)、(40.18±22.33)U/L(P<0.05),碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,无统计学差异(P>0.05)。奈玛特韦组治疗5 d后的谷丙转氨酶(61.71±27.74)U/L高于治疗前的(44.95±20.55)U/L(P<0.05),谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,无统计学差异(P>0.05)。莫诺拉韦组、先诺特韦组治疗5 d后的谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,均无统计学差异(P>0.05)。阿兹夫定组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为28例(30.4%)、9例(9.8%)、4例(4.3%)、0、4例(4.3%)。莫诺拉韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为7例(16.7%)、7例(16.7%)、1例(2.4%)、1例(2.4%)、1例(2.4%)。奈玛特韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为14例(34.1%)、11例(26.8%)、5例(12.2%)、1例(2.4%)、1例(2.4%)。先诺特韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为4例(19.0%)、2例(9.5%)、0、0、0。四组治疗后肝功能异常患者共63例,其中男44例(69.8%),女19例(30.2%)。年龄23~90岁,平均年龄73.06岁。无基础疾病14例(22.2%),合并高血压31例(49.2%),合并冠状动脉相关疾病16例(25.4%),合并脑血管病15例(23.8%),合并糖尿病11例(17.5%),合并肿瘤5例(7.9%),合并慢性肺疾病4例(6.3%)。结论 对新型冠状病毒感染患者,口服阿兹夫定显著升高谷丙转氨酶和谷草转氨酶,口服奈玛特韦显著升高谷丙转氨酶,口服莫诺拉韦、先诺特韦后肝功能无显著变化。对口服小分子抗病毒药物患者,需要监测肝功能。

新型抗炎药游离甾体化合物伐莫洛酮的研究进展

伐莫洛酮是一种新型抗炎药,结构与糖皮质激素相似,相关动物及临床实验发现其在很多动物疾病模型中具有与泼尼松类似的抗炎作用,但副作用明显减少。临床研究发现其对Duchenne型肌营养不良症(duchenne muscular dystrophy,DMD)有同糖皮质激素一样的疗效,但安全性明显提高及不良事件明显减少,且伐莫洛酮治疗不会导致皮质类固醇引起的生长迟缓。本文就伐莫洛酮的药物结构及药理作用、临床试验及不良反应等研究进展进行综述,以期为其临床应用提供更多参考。

雷公藤多苷纳米粒的制备及其对关节炎大鼠的治疗作用

目的 制备雷公藤多苷纳米粒,探究其对胶原诱导型(collagen-induced arthritis, CIA)关节炎大鼠的治疗作用。方法 运用薄膜分散法制备雷公藤多苷纳米粒,对其进行质量评估。构建CIA模型,进行药物干预,称量大鼠体质量、测定足趾肿胀度和关节炎指数;观察大鼠脏器、膝、踝关节滑膜的病理改变;检测大鼠血清中肝肾功能水平和炎症因子表达。结果 制备的雷公藤多苷纳米粒在电镜下呈圆粒状且分布均匀,性质稳定。相较于模型组,给药组大鼠左右足趾肿胀度均明显下降(P<0.01),关节炎指数明显降低(P<0.01)。其中TG-NPs组的疗效优于TG组。与正常组相比,大鼠心脏、脾、肾、睾丸指数均明显降低(P<0.05,P<0.01)。TG-NPs组膝踝关节软骨病理损伤明显减轻,凋亡的滑膜细胞增加;与模型组相比,TG-NPs组大鼠血清中的ALT、BUN、CRE水平均明显降低(P<0.05),IL-1β、TNF-α和IL-6含量下降明显(P<0.05)。结论 TG-NPs通过诱导滑膜细胞凋亡和降低炎性细胞因子的表达对CIA有较好的治疗作用,通过静脉注射血液循环,可实现药物的缓、控释,避免口服药物造成的首过效应,减轻脏器的毒性,为治疗类风湿关节炎的新型纳米制剂的开发提供了实验依据。

冠心病合并2型糖尿病患者的血糖管理专家共识

我国冠心病合并糖尿病患者的比例较高,即使接受降压、降脂、抗栓等常规治疗仍存在残余心血管风险。近年的研究证明,一些降糖药物对2型糖尿病患者具有明确的心血管获益。但调研显示,目前心内科医师对2型糖尿病筛查时机、指标和诊断标准仍不熟悉,对具有明确心血管获益的新型降糖药物如胰高糖素样肽-1受体激动剂/钠-葡萄糖共转运蛋白2抑制剂的认知程度不够、规范应用率低。在此背景下,根据国内外指南/共识和最新的循证医学证据,本共识旨在规范急性冠状动脉综合征、慢性冠状动脉综合征以及经皮冠状动脉介入治疗围术期冠心病患者的血糖管理方案,不涉及糖尿病急性并发症,对冠心病患者中2型糖尿病的筛查和诊断、心血管风险综合管理等内容总结了要点,明确具有心血管获益的降糖药物的临床应用实践,促进上述药物在心血管及其他相关专业领域规范应用,同时也关注患者的非降糖治疗,以全面降低其心血管风险。

精神分裂症的药物治疗进展

精神分裂症是导致严重精神残疾的重性疾病之一,给社会、患者及其家属带来了重大负担。随着科技进步,不仅传统药物有了新的用法,而且新型药物的涌现也提供了更个体化和有效的治疗选择,如占诺美林-曲司氯铵(xanomeline-trospium,KarXT)、Emraclidine和微量胺相关受体1(trace-amine-associated receptor 1,TAAR1)调节剂等。本文将深入研究这些药物的临床应用疗效及治疗机制,以及新药物引入也带来治疗领域的挑战,如药物的停药时间、不良反应和药物预测动物模型的建立等,并在最后提出这些挑战并展望未来研究方向。本文旨在探讨精神分裂症药物治疗方面的最新进展,为研究者和临床医生提供最新的参考。

613例抗肿瘤药物的不良反应分析

目的 分析抗肿瘤药物的药品不良反应(adverse drug reaction,ADR)的特征与规律,为日间化疗的安全用药提供参考。方法 收集202l年1月1日至2022年12月31日某院613例抗肿瘤药物ADR报告,并对数据进行统计和分析。结果 613例抗肿瘤药物ADR报告中60.03%发生在医院内,男性患者的ADR发生率多于女性,年龄分布以51~70岁为主(51.23%)。静脉滴注是引发ADR的主要给药途径(72.49%),严重ADR占14.68%,经停药或治疗未好转占4.24%。细胞毒类抗肿瘤药物的ADR占81.23%,其中以奥沙利铂最常见(18.65%)。ADR主要累及血液或造血系统(17.68%)。结论 应加强细胞毒类抗肿瘤药ADR的监测,关注特殊人群及重点药物。在日间化疗中心使用抗肿瘤药物时应评估ADR风险并制定相应治疗方案,确保患者用药安全。