Reversal of P‐glycoprotein‐mediated multidrug resistance of human hepatic cancer cells by Astragaloside II

Objectives Chemoresistance is the main obstacle encountered in cancer treatment and is frequently associated with multidrug resistance (MDR). Astragaloside is a saponin which is widely used in traditional Chinese medicine. It has been reported that Astragaloside has antitumour effects on hepatocellular carcinoma Bel‐7402 cells in vitro and in vivo. The purpose of this study was to examine the effects of Astragaloside II on the reversal of MDR and its molecular mechanism in vitro. Methods In this study, Bel‐7402 and Bel‐7402/FU cell lines were used as the experimental model. Drug sensitivity was determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay, accumulation and efflux of Rh123 were analyzed by flow cytometer, the mRNA level of mdr1 was determined by RT‐PCR and the protein levels of P‐glycoprotein (P‐gp) and mitogen‐activated protein kinase were determined by Western blot. Key findings Astragaloside II (0.08 mg/ml) showed strong potency to increase 5‐fluorouracil cytotoxicity toward 5‐fluorouracil‐resistant human hepatic cancer cells Bel‐7402/FU. The mechanism of Astragaloside II on P‐gp‐mediated MDR demonstrated that Astragaloside II significantly increased the intracellular accumulation of rhodamine 123 via inhibition of P‐gp transport function. Based on the analysis of P‐gp and mdr1 gene expression using Western blot and RT‐PCR, the results revealed that Astragaloside II could downregulate the expression of the P‐gp and mdr1 gene. In addition, Astragaloside II suppressed phosphorylation of extracellular signal regulated kinase 1/2, p38 and c‐Jun N‐terminal kinase. Conclusions The results suggested that Astragaloside II is a potent MDR reversal agent and may be a potential adjunctive agent for hepatic cancer chemotherapy.     

Acupuncture for the treatment of sudden sensorineural hearing loss: A systematic review and meta-analysis: Acupuncture for SSNHL

BackgroundAcupuncture as an alternative treatment method is widely used in the treatment of sudden sensorineural hearing loss(SSNHL) in China. We performed a systematic review and meta-analysis to assess the clinical efficacy of acupuncture for the management of SSNHL patients.Materials and MethodsThe PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and WanFang databases were searched. Searches were performed on April 27, 2018 and without language and publication year restrictions. We collected and analyzed the randomized controlled trials (RCTs) of acupuncture for the treatment of SSNHL patients to assess its efficacy and safety. The RevMan5.3 software was used for analysis. The fixed-effects model can be applied to calculate the risk ratio (RR) or weighted mean difference (WMD) if the chi-square test shows there was no significance of heterogeneity (p > 0.10, I²<50%). Otherwise, the random effects mode was used.ResultsTwenty randomized controlled trials met our inclusion criteria. The electroacupuncture(EA), manual acupuncture(MA) plus western medicine(WM) and EA plus WM groups lead to significantly better pure tone audiometry(PTA) than WM alone in cured rate (P = 0.01; P < 00,001; P < 0.006, respectively). However, no significant differences were observed between MA and WM (p = 0.27). In terms of total effective rate, all of them showed significant improvement compared to WM alone (MA: P = 0.03; EA: P = 0.01; MA + WM: P < 0.00001; EA + WM: P = 0.04). In addition, no significant difference was found between the MA plus WM and WM alone groups in the improvement of tinnitus (P = 0.37). No trials reported serious adverse events.ConclusionAcupuncture could be a valid treatment option for SSNHL, especially for patients who could not be cured by drugs alone. However, the outcome was limited temporarily due to the lack of high-quality research support. High-quality evidence is needed to clarify the future efficacy and safety of acupuncture for SSNHL.     

Inhibition of acid-sensing ion channels in articular chondrocytes by amiloride attenuates articular cartilage destruction in rats with adjuvant arthritis

Objective  

The aim of this study was to examine whether drugs such as amiloride that block acid sensing ion channels (ASICs) could attenuate articular cartilage destruction in adjuvant-induced arthritis (AA).     

MiRNA-based model for predicting the TMB level in colon adenocarcinoma based on a LASSO logistic regression method

Some patients with advanced colon adenocarcinoma (COAD) are not sensitive to radiotherapy and chemotherapy, and as such, immunotherapy has become the most popular option for these patients. However, different patients respond differently to immunotherapy. Tumor mutational burden (TMB) has been used as a predictor of the response of advanced COAD patients to immunotherapy. A high TMB typically indicates that the patient''s immune system will respond well to immunotherapy. In addition, while microRNAs (miRNA) have been shown to play an important role in treatment responses associated with the immune system, the relationship between miRNA expression levels and TMB has not been clarified in COAD.We downloaded miRNA data and mutational files of COAD from the Cancer Genome Atlas database. Differentially expressed miRNAs were screened in the training group, and miRNAs used to construct the model were further identified using the LASSO logistic regression method. After building the miRNA-based model, we explored the correlation between the model and TMB. The model was verified by a receiver operating characteristic curve, and the correlation between it and 3 widely used immune checkpoints (programmed death receptor-1, programmed death-ligand 1, and cytotoxic T-lymphocyte associated protein-4) was explored. Functional enrichment analysis of the selected miRNAs was performed, and these respective miRNA target genes were predicted using online tools.Our results showed that a total of 32 differentially expressed miRNAs were used in the construction of the model. The accuracies of the models of the 2 datasets (training and test sets) were 0.987 and 0.934, respectively. Correlation analysis showed that the correlation of the model with programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein-4, as well as TMB, was high, but there was no correlation with programmed death receptor-1. The results of functional enrichment analysis indicated that these 32 miRNAs were involved in many immune-related biological processes and tumor-related pathways.Therefore, this study demonstrated that differentially expressed miRNAs can be used to predict the TMB level, which can help identify advanced COAD patients who will respond well to immunotherapy. The miRNA-based model may be used as a tool to predict the TMB level in patients with advanced COAD.     

姜黄素增加 U937细胞对 TRAIL 的敏感性的凋亡机制研究

目的：观察姜黄素增敏肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis-inducing ligand,TRAIL）对人白血病 U937细胞株的细胞毒作用,探讨其凋亡机制。方法取对数生长期的白血病 U937细胞,MTT 法检测不同浓度的姜黄素和 TRAIL对 U937细胞的增殖抑制率及杀伤率,流式细胞术检测凋亡。结果姜黄素对白血病细胞 U937有明显抑制作用,且呈剂量依耐性,与 TRAIL 联用后可显著促进 U937的凋亡率。不同浓度的姜黄素作用24 h 后,可显著上调死亡受体5（Death receptor 5, DR5）的表达。结论姜黄素增敏 TRAIL 对白血病 U937的抑制作用明显,其凋亡机制可能是与上调 DR5有关。     

清胰汤治疗重症急性胰腺炎的临床疗效的Meta分析

目的:系统评价清胰汤辅助治疗重症急性胰腺炎的临床疗效。方法:采用Meta分析方法,制定原始文献的纳入标准、排除标准及检索策略,计算机检索中国知网(1979—2014年),万方数据知识服务平台(1990—2014年),中国生物医学文献数据库(1978—2014),pubmed(1966—2014)等中英文数据库,按照Cochrane评价标准评价文献质量。结果:共纳入19项研究。清胰汤辅助治疗组首次排便时间[WMD=-2.098,95%CI(-2.739,-1.456),P0.01)],腹痛缓解时间[WMD=-3.008,95%CI(-3.689,-2.326),P0.01],住院时间[WMD=-7.633,95%CI(-8.449,-6.756),P0.01],病死率[OR=2.719,95%CI(1.717,4.306),P0.01]均优于对照组,有统计学意义。结论:清胰汤辅助治疗重症急性胰腺炎可显著降低患者病死率,并可缩短患者首次排便时间、腹痛缓解时间及住院时间。     

基底节损伤患者视—空间工作记忆反应时间研究

目的探讨基底节损伤患者视—空间工作记忆反应时间的改变。方法对25例基底节损伤患者及25例与其人口学资料相匹配的健康对照者,采用视觉面孔和视觉空间的延迟匹配任务,并对上述2组进行视—空间工作记忆测试。结果基底节损伤组患者的视觉面孔及空间工作记忆反应时间分别为（2 314.9±400.4）、（1 844.2±381.9）m s,对照组分别为（1 871.8±621.2）、（1 389.6±368.2）m s,2组比较差异均有统计学意义（P均〈0.01）。结论基底节在工作记忆环路中承担着重要的连接功能,基底节损伤可表现为工作记忆执行障碍,且左、右侧基底节均参与了执行过程。