左旋门冬酰胺酶在儿童急性淋巴细胞白血病临床应用的安全性分析

左旋门冬酰胺酶(L-ASP)作为儿童急性淋巴细胞白血病治疗联合化疗方案中的最基本药物之一,在对维持患儿长期处于带病生存状态中起着极为重要的作用。但长期以来其在儿童临床应用的安全性也一直是人们关注的重点。就近些年L-ASP在国内外儿童临床应用引起不良反应的类型、原因以及发展方向等方面的研究进展进行综述。     

临床药师参与盆腔脓肿腹腔镜术后抗感染会诊

目的: 通过参与妇科盆腔脓肿腹腔镜术后抗感染来增强临床药师的临床药学服务能力。方法: 了解病例基本资料情况, 分析术后感染的致病菌, 选择适当抗感染药, 并跟踪患者用药情况至出院。结果: 通过分析, 得出此病例为厌氧菌及革兰阴性杆菌(包括大肠埃希菌、铜绿假单胞菌等)感染为主, 选用哌拉西林舒巴坦及替硝唑治疗后, 血常规正常, 体温正常, 出院。结论: 临床药师可运用药物相关知识给临床提供有价值的药学服务。     

Therapeutic effects of total alkaloids of Tripterygium wilfordii Hook f. on collagen-induced arthritis in rats

Ethnopharmacological relevance

Tripterygium wilfordii Hook f. is one of Traditional Chinese Medicines which is commonly used to treat rheumatoid arthritis (RA). The total alkaloids were the main constituent part of Tripterygium wilfordii Hook f. It has a great significance to study the effects of the total alkaloids of Tripterygium wilfordii Hook f. (ATW) on RA.

Aim of the study

This paper aims at investigating the therapeutic effect of ATW on RA and its possible mechanism, and providing a theoretical and experimental basis for the clinical use of ATW.

Materials and methods

The model of wistar rats of type II collagen-induced arthritis (CIA) was made, and the rats were perfused a stomach with ATW for 4 weeks continuously. Then the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-<alpha>, in the serum of CIA rats were detected by enzyme linked immunosorbent assay (ELISA), and the joint pathological section of CIA rats was observed by hematoxylin and eosin (HE) staining method and the expression of IL-6, IL-8, nuclear factor kappa B (NF-κB), TNF-α were measure by immunohistochemistry staining method.

Results

Compared with model group, ATW could significantly reduce paw swelling and suppresse articular cartilage degenerated. The results also found that there was significant reduction levels of IL-6, IL-8 and TNF-α in serum of CIA rats treated with ATW and ATW inhibited the expression of IL-6, IL-8, NF-κB, TNF-α in synovial tissue.

Conclusion

ATW not only could inhibit the symptom of CIA rats significantly but also could inhibit the production of IL-6, IL-8, TNF-α in serum and the expression of IL-6, IL-8, NF-κB and TNF-α in synovial tissue targeting the inflammatory. ATW would be a drug as a novel botanical drug for the treatment of RA.     

Evaluation of protective effects of Chi-Zhi-Huang decoction on Phase I drug metabolism of liver injured rats by cocktail probe drugs

AIM OF THE STUDY: Chi-Zhi-Huang decoction (PGR) is one of the traditional Chinese medicine (TCM) preparations with unique effect on withdrawing jaundice and has been used to treat icteric patients in China for many years. In this research, we aim at to evaluate the potential activity of PGR in restoring hepatic drug metabolism in a damaged liver. MATERIALS AND METHODS: A cocktail approach with caffeine (10mg/kg), dapsone (10mg/kg) and chlorzoxazone (20mg/kg) respectively as probe drug of cytochrome P450 (CYP) isoform of CYP 1A2, 3A4 and 2E1 was used to evaluate its possible effects on Phase I oxidative metabolism. Pretreated with three dosages of PGR water extract (0.75, 1.5 and 3g/kg, po) for 5 days, male Wistar rats (220-240 g) were intoxicated by phenylisothiocyanate (PITC, 100mg/kg, po) 24h before probes intravenous injection. The pharmacokinetics of the probes in the blood was determined simultaneously by HPLC, and their non-compartmental parameters were used to evaluate the metabolic difference among the groups. Moreover, the levels of liver enzymes (ALT, AST, ALP) and bilirubins were also measured for insight of liver function. RESULTS: The findings in this study suggest that PGR induces CYP 3A4, does not have much effect on CYP 2E1, and inhibits CYP 1A2 at high dosage. CONCLUSION: The current pharmacokinetic approach allowed the protective effects of PGR on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the explanation of synergistic effect of the composites formula.     

三联疗法与序贯疗法根除长期服用非甾体类抗炎药人群幽门螺旋杆菌的疗效观察

目的 观察长期服用非甾体类抗炎药(NSAID)人群采用三联疗法与序贯疗法根除幽门螺旋杆菌(Hp)的疗效.方法 选取于2012年6月至2014年6月期间来我院接受治疗的84例感染Hp的患者作为研究对象.据随机数表法将患者分成观察组和对照组各42例,对照组患者采用三联疗法治疗,观察组患者则采用序贯疗法,观察两种不同治疗方式根除Hp感染的效果.结果 对照组患者治疗后Hp转阴率为76.20%,观察组为80.95%,两组比较差异无统计学意义(P>0.05).两组患者治疗后,对照组不良反应发生率为11.90%,观察组为9.52%,两组比较差异无统计学意义(P>0.05).对照组患者治疗后总有效率为71.43%,观察组为92.86%,两组比较差异有统计学意义(P<0.05).结论 序贯疗法能有效抑制幽门螺旋杆菌对非甾体药物产生耐药性,增强药物药效,同时降低非甾体药物对患者胃部黏膜损害,提高药物有效治愈率,值得广泛使用.     

Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drugs treatment: a multicenter prospective study in China

Background::Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic dr...     

萸黄连的炮制研究进展

萸黄连为“相反为制”改变饮片药性的代表性炮制品之一,首载于《韩氏医通》,炮制方法为吴茱萸汁与净黄连拌匀闷润后炒干即得,即通过吴茱萸制黄连在保留黄连泻火解毒功效的基础上降低了黄连的苦寒之性,使黄连寒而不滞,可清气分湿热,对肝气犯胃、呕吐吞酸等病症有良好疗效。作为相反为制、药汁制的代表品种,萸黄连饮片收录于2020年版《中华人民共和国药典》和多个地方炮制规范中,其炮制工艺研究及优选一直备受关注。现代研究表明,萸黄连除含有小檗碱、药根碱、巴马汀等黄连中的成分外,还含有吴茱萸碱、吴茱萸次碱、柠檬苦素等吴茱萸中的成分,具有抗炎、抗菌、抗肿瘤等药理活性。该文对近20年萸黄连相关的研究报道进行整理归纳,从萸黄连的炮制历史及工艺、药效药性、质量评价和临床应用等方面进行综述,发现萸黄连在各省市炮制规范收载的炮制方法及标准差异较大,主要涉及吴茱萸汁的制备方法、吴茱萸汁的用量和炮制终点的判断标准等方面;此外,不同研究期间萸黄连炮制前后主要成分的变化情况差异较大,推测与萸黄连的炮制工艺和质量标准不同有关。该综述可为完善萸黄连的质量评价体系提供参考。     

Point-of-care hepatitis C screening with direct access referral to improve linkage to care among halfway house residents: a pilot randomised study

INTRODUCTIONLinkage to care among individuals with substance misuse remains a barrier to the elimination of the hepatitis C virus (HCV). We aimed to determine whether point-of-care (PoC) education, screening and staging for liver disease with direct access to hospitals would improve linkage to care among this group.METHODSAll participants were offered PoC education and HCV screening. HCV-positive participants were randomised to standard care (controls) or direct access, which provided a direct pathway to hospitals. Linkage to care was determined by reviewing electronic medical records. Linkage of care cascade was defined as attendance at the specialist clinic, confirmation of viraemia by HCV RNA testing, discussion about HCV treatment and initiation of treatment.RESULTS351 halfway house residents were screened. The overall HCV prevalence was 30.5% (n = 107), with 69 residents in the control group and 38 in the direct access group. The direct access group had a significantly higher percentage of cases linked to specialist review for confirmatory RNA testing (63.2% vs. 40.6%, p = 0.025), HCV treatment discussion (p = 0.009) and treatment initiation (p = 0.01) compared to the controls. Overall, only 12.6% (n = 13) had treatment initiation during follow-up. PoC HCV screening with direct access referral had significantly higher linkage to HCV treatment initiation (adjusted odds ratio 9.13, p = 0.005) in multivariate analysis.CONCLUSIONPoC HCV screening with direct access improves linkage to care and simplifies the HCV care cascade, leading to improved treatment uptake. PoC education, screening, diagnosis and treatment may be an effective strategy to achieving HCV micro-elimination in this population.     

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

PurposeTriple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC.MethodsA kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation.ResultsThe significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively).ConclusionComprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.     

High-Throughput Screening of FDA-Approved Drug Library Reveals Ixazomib Is a Broad-Spectrum Antiviral Agent against Arboviruses

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome β5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses’ life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.