(1) Background: As prescribers, physicians play a decisive role in applying and promoting pharmacogenomic (PGx) testing in clinical practices. So far, little is known about physicians' perspectives on PGx testing in China. The aim of this study was to assess physicians' knowledge of, attitude towards, and experience of PGx testing in China. (2) Methods: A 39-question online survey was developed. Participants were physicians recruited through two platforms, MEDLINKER and "Dazhuanjia". (3) Results: A total of 450 respondents completed the survey and 366 questionnaires were eligible for analysis based on the inclusion criteria. Among all included physicians, 275 (75.1%) had heard of PGx testing before. More than half rated their knowledge of PGx testing as "Fair" (61.5%) while 20.0% chose "Excellent" or "Good" and 18.6% chose "Poor" or "Terrible". "Guidelines, consensus, and treatment paths for disease diagnosis and treatment" (72.7%) were the most preferred sources of information about PGx testing. Respondents were confident in their personal capacity to conduct PGx, with an average score of 3.30 ± 0.09 (out of 5.00). Most respondents (75.6%) believed that PGx could "help to improve efficacy and reduce the incidence of adverse reactions". Targeted cancer therapy (score 78.95 ± 1.26 out of 100) was considered the field where PGx testing had its highest value. Lack of professionals and knowledge (n = 186, 67.6%), high costs of testing (n = 170, 61.8%), and lack of hospitals to offer PGx testing (n = 166, 60.4%) were identified as the primary obstacles to increasing the uptake of PGx testing in China. Academic conference (n = 213, 72.4%) was considered the most efficient way for physicians to obtain information about PGx testing. (4) Conclusions: Physicians in China have poor knowledge about PGx testing; nonetheless, they generally had confidence in their capacity to order PGx testing and positive attitudes towards the use of PGx testing in routine clinical practices. Future efforts to promote the uptake of PGx testing should focus on foundational education and practical training.
ObjectiveThe aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.Materials and methodsThree databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.ResultsPatients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.ConclusionCML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
Background T-cell immunoreceptor with Ig and ITIM domains (TIGIT) participates in tumor immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the prognostic value of TIGIT and its immunological function in solid cancers. Methods Three databases were searched for relevant articles. The main endpoints were overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Hazard ratios (HR) were pooled by using fixed-effects or random-effects models. Pancancer analysis of TIGIT was performed based on public online databases, mainly The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UCSC Xena. The possible relationships between TIGIT expression and the tumor microenvironment (TME), infiltration of immune cells, immune-related genes, tumor mutation burden (TMB), and microsatellite instability (MSI) were revealed in this article. Results Sixteen studies met the inclusion criteria. High expression of TIGIT was associated with worse OS [HR= 1.73, 95% confidence interval (CI) 1.50, 1.99], PFS (HR = 1.53, 95% CI [1.25, 1.88]), RFS (HR = 2.40, 95% CI [1.97, 2.93]), and DFS (HR= 6.57, 95% CI [0.73, 59.16]) in East Asian patients with solid cancers. TIGIT expression was positively correlated with immune infiltration scores and infiltration of CD8 T lymphocytes in all of the cancers included. TIGIT was found to be coexpressed with the genes encoding immunostimulators, immunoinhibitors, chemokines, chemokine receptors, and major histocompatibility complex (MHC), especially in gastroesophageal cancer. TMB and MSI were also associated with TIGIT upregulation in diverse kinds of cancers. Conclusion High expression of TIGIT is associated with poorer prognosis in East Asian patients with solid cancers. TIGIT is a novel prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumorigenesis.
(1) Background: Uptake of pharmacogenomic testing in routine clinical practices is currently slow in China. Pharmacists might play an important role in leveraging care through applying pharmacogenomics, therefore, it is important to better understand clinical pharmacists' knowledge of and attitudes toward pharmacogenomic testing, which has not been well-studied. (2) Methods: A self-administered survey was developed based on previous knowledge of pharmacogenomic testing and its uptake in China. Participants were recruited through the Committee of Pharmaceutical Affairs Management under the Chinese Hospital Association. (3) Results: A total of 1005 clinical pharmacists completed the questionnaire, among whom 996 (99.10%) had heard of pharmacogenomic testing before participation. More than half of respondents (60.0%, n = 597) rated their knowledge of pharmacogenomic testing as "average", while 25% rated it "good" or "excellent". "Guidelines, consensus and treatment paths for disease diagnosis and treatment" (78.7%) were the most preferred sources of information about pharmacogenomic testing. Most respondents (77.0%) believed that pharmacogenomics could "help to improve efficacy and reduce the incidence of adverse reactions". Our participants also believed that patients would benefit most from pharmacogenomic testing through better prediction of individual drug responses and thus informed treatment decisions. The top challenge for the uptake of pharmacogenomic testing was its high cost or lack of insurance coverage (76.7%). (4) Conclusions: Most Chinese clinical pharmacists who participated in our study had a positive attitude toward pharmacogenomic testing, while the knowledge of pharmacogenomic testing was generally self-assessed as average.
Antiarrhythmic drugs (AADs) have a therapeutic effect on atrial fibrillation (AF) by regulating the function of ion channels. However, several adverse effects and high recurrence rates after drug withdrawal seriously affect patients’ medication compliance and clinical prognosis. Thus, safer and more effective drugs are urgently needed. Active components extracted from natural products are potential choices for AF therapy. Natural products like Panax notoginseng (Burk.) F.H. Chen, Sophora flavescens Ait., Stephania tetrandra S. Moore., Pueraria lobata (Willd.) Ohwi var. thomsonii (Benth.) Vaniot der Maesen., and Coptis chinensis Franch. have a long history in the treatment of arrhythmia, myocardial infarction, stroke, and heart failure in China. Based on the classification of chemical structures, this article discussed the natural product components’ therapeutic effects on atrial fibrillation by regulating ion channels, connexins, and expression of related genes, in order to provide a reference for development of therapeutic drugs for atrial fibrillation.
目的:为提高我国医院药学服务水平、推动我国医疗机构O2O药学服务模式的不断转型升级提供参考.方法:以"互联网""网络""O2O""药学服务""用药教育""慢病管理""用药咨询""科普宣教"等为关键词检索中国知网、维普、万方等中文数据库,收集发表时间为2012年1月-2020年3月的相关文献,对我国O2O药学服务模式的发展历程、特点、服务内容、优势、不足进行分析汇总,并提出相关建议.结果与结论:我国医院O2O药学服务内容涵盖了处方审核与调剂、药品配送以及就诊后的用药咨询、用药教育、慢病管理、科普宣教、药学门诊等部分,实现了全过程的闭环管理.目前我国医院O2O药学服务已经逐步从1.0向2.0阶段迈进,人工智能技术也开始广泛融入药学服务的各个环节,辅助医院药师更好地践行"以患者为中心"的服务理念,不仅更加高效精准地提升了药师的药学服务质量和价值,还促进了优质药学资源下沉并服务基层.我国O2O药学服务具有优化药学资源配置、扩大药学服务范围、改善医患关系、分流不同需求患者、促进分级诊疗的落实等优势,但还存在未能有效覆盖农村患者、患者隐私泄露风险、缺乏专门的质量管理标准等问题,阻碍了医院O2O药学服务的进一步发展与完善.建议相关机构进一步完善平台药学服务功能、扩大消费人群,尽快出台相关法规,根据基层地区患者需求针对性地开展药师继续教育培训,并建立健全相关法律法规,完善O2O药学服务质量管理标准,以进一步促进我国医院O2O药学服务模式的发展.
Aim: The aim of this study was to assess the association between PEAR1 polymorphisms and ischemic clinical outcomes. Materials & methods: We searched the electronic database for articles on the relationship of PEAR1 SNPs and ischemic events in patients with coronary artery disease (CAD) up to October 2020. Results: A total of 9914 patients with CAD from six studies focusing on 12 SNPs of PEAR1 were included in this study. The A allele of rs12041331 were associated with ischemic events (odds ratio: 1.40; 95% CI: 1.04-1.88; p = 0.03). The AA homozygotes of rs2768759 was related to a higher risk of ischemic events than carriers of the C allele (odds ratio: 2.08; 95% CI: 1.09-3.97; p = 0.03). Conclusion: PEAR1 rs12041331 and rs2768759 are significantly associated with ischemic events in patients with CAD.
目的:在现阶段我国医疗卫生体制改革背景下,通过抽样调查研究全国各地区医院药学服务的发展现状,分析我国药师队伍建设情况、发展趋势及医院药事管理机制改革现状,为进一步深化医疗卫生体制改革提出相关建议.方法:在政策及文献分析的基础上,采用实地调查法与集体访谈法相结合的调研方式对全国7地市医疗机构执行药师制度改革后的发展现状进行抽样调研.结果:在医疗卫生体制改革不断深化的背景下,我国医院药学事业发展取得了长足进步,新的药学服务模式探索日益活跃,但仍存在以患者为中心的药学服务人员配备不足,医院药师队伍建设仍不完善;基础药学服务内容未能完全实现规范和标准化,医疗机构药学服务价值没有得到科学体现,绩效考核分配体系尚不完备;医院药学部门信息系统建设仍不完善,临床专科建设方向仍需调整等方面的问题,医院药学事业的发展仍需进一步的规范和引导,不断完善医院药事管理体系建设.结论:建议完善药事管理体制建设,明确药学部门职能定位;探索规范药学服务模式,加强药学服务能力建设;建立医疗保险激励机制,加强药事管理信息化建设.
目的:通过对现阶段我国医疗卫生体制改革背景下药师队伍的发展趋势进行分析,结合我国医院药事管理事业发展经验,为推动药师制度改革的不断深化,提升药师服务水平提出相关建议.方法:在文献研究的基础上从法律法规及相关政策、医药健康事业及社会发展趋势以及国内外发展趋势3个角度分析我国医院药师队伍管理模式与发展趋势.结果:我国药师队伍服务模式逐渐向"以患者为中心"的药学服务模式转型,药师配备数量仍然未能满足药学服务需求,目前仍存在药师立法缺位、管理培训制度不完善以及药学服务价值难以体现的问题.结论:进一步完善药师法律法规体系,明确药师职业权利义务;建立药师绩效评价体系和价值导向薪酬体系;完善药师继续教育体系,加强药师队伍质量建设.
目的 调查中国三甲医院药学门诊开设情况.方法 通过医院线上挂号平台和医院官网获取药学门诊开设情况,包括专业方向、收费情况以及出诊药师资质等.结果 1326家三甲医院中开设药学门诊的医院共有172家,占所调查医院总数的12.97%;其中药学门诊开设数量排名前5的省份分别为广东、北京、浙江、江苏和上海.药学门诊开设专业主要包括妊娠/哺乳期用药管理、抗凝/抗栓、慢病管理、疼痛管理及儿童用药管理等.结论 目前多地医疗机构对开设药学门诊进行了初步探索,但在药学门诊发展过程中仍存在一些问题,需要完善管理规范以保证其健康发展.
Background As the spectrum of ophthalmic diseases keeps changing, uveitis has gradually become one of the major blinding eye diseases in the world. In recent years, it has become a research hotspot to select effective components for uveitis treatment from natural drugs. Methods We searched PubMed and EMBASE databases for studies written in English as well as Chinese National Knowledge Infrastructure (CNKI), CQVIP, and Wan Fang database for studies written in Chinese (inception through 30 December 2020). Results Eight kinds of natural product ingredients were included in this article. They were found to not only regulate the expression of cytokines, proliferation, and differentiation of T help cells but also inhibit the damage of cytokines and inflammatory cells to uvea, blood aqueous barrier, and blood retinal barrier. Conclusion Natural product ingredients have their unique advantages in the treatment of uveitis. They have good anti-inflammatory effects without causing serious adverse reactions, which enables them to be promising choices for preventive and therapeutic strategy of uveitis.
Parkinson’s disease (PD) is a common neurodegenerative disease in middle-aged and older adults. Abnormal proteins such as α-synuclein are essential factors in PD’s pathogenesis. Autophagy is the main participant in the clearance of abnormal proteins. The overactive or low function of autophagy leads to autophagy stress. Not only is it difficult to clear abnormal proteins but also it can cause damage to neurons. In this article, the effects of natural products ingredients, such as salidroside, paeoniflorin, curcumin, resveratrol, corynoxine, and baicalein, on regulating autophagy and protecting neurons were discussed in detail to provide a reference for the research and development of drugs for the treatment of PD.
植物类中药长期以来被认为安全有效、无严重毒副作用,但是近年来随着马兜铃、关木通等植物类中药导致肾脏严重不良事件的报道,植物类中药的肾脏毒性引发了国内外学者的关注.本文将按植物类中药化学成分进行分类,对有机酸、苷类、毒性蛋白、生物碱、萜类、木脂素、黄酮、蒽醌等8类植物类中药成分肾脏毒性的临床表现、病理变化、发病机制以及对中毒的预防和治疗措施进行逐一阐述.
目的:为治疗新型冠状病毒肺炎的中成药选择提供参考依据.方法:以"中成药"、"药理学"、"机理"、"临床研究"、"新型冠状病毒肺炎(COVID-19)"等为关键词,组合检索2000年1月?2020年2月在中国知网、万方、维普、PubMed、Web of Science、Embase等数据库中有关《新型冠状病毒肺炎诊疗方案(试行第六版)》中推荐的连花清瘟颗粒、热毒宁注射液等12种中成药的基础研究和临床试验的文献报道,进行系统归纳、总结.结果:共查阅到相关文献264篇,其中有效文献73篇.12种中成药通过不同的机理发挥治疗作用,藿香正气胶囊解表散寒、芳香化湿;连花清瘟颗粒、金莲清热颗粒、疏风解毒颗粒、热毒宁注射液、痰热清注射液、喜炎平注射液疏散风热、清热解毒;血必净注射液活血通络、清热化瘀;参麦、生脉注射液补气养阴;参附注射液回阳救逆;醒脑静注射液醒脑开窍.结论:今后应不断完善参附注射液、喜炎平注射液、热毒宁注射液等中成药用于治疗新型冠状病毒肺炎的临床试验,进一步探讨对该病有效、安全、经济的防治策略.
目的:为抗新型冠状病毒药物的研发和新型冠状病毒肺炎(COVID-19)患者的临床治疗提供参考.方法:以"新型冠状病毒肺炎"、"2019-nCov"、"COVID-19"、"Novel Coronavirus Pneumonia"等为关键词,组合检索2000年1月至2020年2月在中国知网、万方、维普、Pubmed、Web of Science、Embase等数据库中有关对新型冠状病毒肺炎有潜在治疗作用的文献,进行系统归纳、总结.结果与结论:共查阅到相关文献261篇,其中有效文献65篇,涉及西药18种.其中,《新型冠状病毒感染的肺炎诊疗方案(试行第六版)》和《重症新型冠状病毒感染肺炎诊疗与管理共识》中推荐试用的抗病毒药物有洛匹那韦/利托那韦、α-干扰素、利巴韦林、阿比多尔、磷酸氯喹等5种.而体外实验对新型冠状病毒有效的药物有达芦那韦考比司他、瑞德西韦、法匹拉韦、萘莫司他、硝唑尼特等5种.文献(基于机理)推测有效的药物有氨溴索、巴瑞替尼和Galidesivir(BCX4430)、卡瑞利珠单抗、ASC09/利托那韦等5种.文献提出需要严格控制适应症使用的是糖皮质激素(甲泼尼龙),未能证明临床有效的是奥司他韦、巴洛沙韦.今后,相关研究者需不断筛选出更多对COVID-19有潜在治疗效果的抗病毒药物,完善瑞德西韦、氯喹、法匹拉韦等抗病毒药物的临床试验,进一步探讨治疗新型冠状病毒肺炎有效、安全、经济的防治策略.
As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications.
As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications.
In recent years, as the infertility rate in China has been increasing year by year and semen quality decreasing, male reproductive toxicity of drugs attracts more and more attention. There are many factors that cause male reproductive toxicity, among which Chinese materia medica is an important aspect. This article will introduce the male reproductive toxicity of Chinese materia medicas grouped by different effectivenesses such as immunosuppressant, evacuant, diuretic, cardiotonic, anti-infective drug and analgesic.
Objective To compare the effectiveness and safety of acupuncture versus intramuscular injection of neostigmine. Methods Databases including CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, and clinicaltrials.gov database were retrieved for relevant literature, with the retrieval deadline being November 2017. Two reviewers independently screened, selected, and extracted data and validated the results. The methodological quality was evaluated with the “Risk of Bias” tool, and the meta-analysis was performed by using the RevMan 5.3.5 software. Results Totally 953 patients with postpartum urinary retention from 15 randomized controlled trials entered the meta-analysis. 12 articles compared the clinical cure rate of acupuncture alone versus intramuscular injection of neostigmine and found the cure rate in the acupuncture group was 2 times that in the neostigmine group (RR, 1.91; 95% CI: 1.66–2.19). 15 articles compared the clinical effectiveness rate of acupuncture alone with that of intramuscular injection of neostigmine and found the clinical effectiveness rate was 28% higher in the acupuncture group than in the neostigmine group (RR: 1.28; 95% CI: 1.16–1.42). No adverse event was reported in the acupuncture group. Conclusion Acupuncture alone is more effective in treating postpartum urinary retention than intramuscular injection of neostigmine, with good safety profile. Therefore, it is a feasible and valuable technique in clinical settings.