男性肝豆状核变性生殖激素水平临床观察

目的:观察男性肝豆状核变性患者体内生殖激素水平,为男性肝豆状核变性患者合并生殖损害提供依据。方法:对2018年2—8月就诊于安徽中医药大学第一附属医院脑病科的男性肝豆状核变性患者进行生殖激素系列检查,得出生殖激素结果,进行统计学分析。结果:此次参与观察的100位男性肝豆状核变性患者,总体生殖激素异常率在78%,其中雌二醇、泌乳素、睾酮、孕酮、卵泡刺激素是此次临床观察主要异常指标,此次观察中无黄体生成素异常,其异常率分别是41.3%,13.7%,27.5%,34.5%,10.3%。结论:雌二醇、泌乳素、睾酮、孕酮、卵泡刺激素指标的异常可表现在生殖损害中,在一定程度上可体现出患者的生殖功能水平,相关分泌的不足或过量可导致生殖损害,此次观察为男性肝豆状核变性患者合并生殖损害提供临床依据。     

不同领域现实世界临床研究证据转化的应用策略

参考已发布的政策法规指导意见，通过文献检索现实世界研究相关的专家共识指南，总结国内外现实世界临床研究不同领域的研究现况，归纳不同领域现实世界临床研究证据转化的观点，结合典型案例，为现实世界数据转化为现实世界证据的应用提供策略支持。     

银离子抗菌凝胶配合艾灸治疗带状疱疹疗效观察

目的:观察银离子抗菌凝胶配合艾灸治疗带状疱疹的临床效果。方法:选取符合标准的34例带状疱疹患者并随机分为2组。对照组17例,仅接受常规的抗病毒药物和涂抹喷昔洛韦乳膏治疗;观察组17例,在接受常规方法治疗的同时,采用银离子抗菌凝胶并配合艾灸辅助治疗。15d为1个疗程。结果:通过治疗前后2组患者的恢复情况比较,观察组痊愈率为82.35%,对照组痊愈率为47.06%,观察组治愈率明显优于对照组(P<0.05),总有效率上观察组亦优于对照组(P<0.05)。2组症状消退时间存在显著差异(P<0.05),而不良反应差异比较无明显统计学意义(P>0.05)。观察组后遗神经痛发生率(0.00%)明显低于对照组(23.53%),比较具有统计学意义(P<0.05)。结论:在接受常规抗病毒药物和涂抹喷昔洛韦乳膏的基础上附以银离子抗冻凝胶配合艾灸治疗能够有效提高带状疱疹患者的治疗效果,值得临床推广应用。     

PM2.5 induced lung injury through upregulating ROS-dependent NLRP3 Inflammasome-Mediated Pyroptosis

The main cause of air pollution is PM_2.5, which directly causes lung injury through respiration. Oxidative stress and inflammation are considered to be the key mechanism of cell damage. Pyroptosis is a process of the programmed death of inflammatory cells and as a dangerous endogenous signal, it is widely involved in different inflammatory diseases. However, few studies have been conducted on PM_2.5 exposure and cell pyroptosis. In this study, we aimed to investigate the effect of PM_2.5 on apoptosis, pyroptosis and cell cycle arrest regulated by reactive oxygen species production. Balb/c mice were exposed to PM_2.5 dynamically and verified by the RAW264.7 cells in vitro. The results showed the activation of NF-κB and NLRP3 inflammasome and the release of IL-1β and reactive oxygen species were caused by exposure to PM_2.5. The maturation of IL-1β relied on Caspase-1, and the active Caspase-1 was related to cell pyroptosis. Oxidative stress, inflammation, apoptosis and pyroptosis all affected the cell cycle. This study describes a potentially important mechanism of PM_2.5-induced lung damage that PM_2.5 promotes lung injury via upregulating ROS-NLRP3-mediated the RAW264.7 cells pyroptosis.     

Antiproliferation and apoptosis induction of paeonol in HepG2 cells

AIM To investigate the antiproliferative effect of paeonol (Pae) used alone or in combination with chemotherapeutic agents [cisplatin (CDDP), doxorubicin (DOX) and 5-fluorouracil (5-FU)] on human hepatoma cell line HepG2 and the possible mechanisms.METHODS The cytotoxic effect of drugs on HepG2 cells was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay.Morphologic changes were observed by acridine orange (AO) fluorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry (FCM). Drug-drug interactions were analyzed by the coefficient of drug interaction (CDI).RESULTS Pae (7.81-250 mg/L) had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of (104.77 7.28) mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae (15.63, 31.25, 62.5 mg/L) was combined with CDDP (0.31-2.5 mg/L), DOX (0.16-1.25 mg/L), or 5-FU (12.5-100 mg/L) at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae (P ＜0.01). Of the three different combinations, the sensitivity of cells to drugs was considerably different.CONCLUSION Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2,which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.     

柱前衍生化-HPLC法测定患者体内丙戊酸钠的血药浓度

目的建立反相高效液相色谱法测定人血清中丙戊酸钠血药浓度。方法血清用环己烷提取,以环已烷羧酸为内标,2-溴苯乙酮为衍生化试剂,用高效液相色谱法测定丙戊酸钠血药浓度。采用Symmetry C18(4.6 mm×250 mm,5μm)色谱柱;流动相为甲醇-水(82∶18);检测波长为248 nm;流速为1.0 ml.min-1;柱温:30℃。结果血清中丙戊酸钠线性范围为12.5～150mg.L-1,平均回收率98.74%,日内RSD<5%。结论该法快速、灵敏、准确,适用于临床常规监测需要。     

Renal tubular acidosis and associated factors in patients with primary Sjögren’s syndrome: a registry-based study

Clinical Rheumatology - To investigate the clinical features and factors associated with primary Sjögren’s syndrome (pSS)–associated renal tubular acidosis (RTA). This...     

Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing

IntroductionBy implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.MethodsIn a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.ResultsA total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.ConclusionsOur study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.     

Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm,Multicenter Phase 2 Study

IntroductionSome ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC.MethodsThe exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %.ConclusionsEnsartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.