克拉屈滨治疗经典型毛细胞白血病致间质性肺炎一例报道并文献复习

毛细胞白血病（HCL）是一种以脾大、全血细胞减少、骨髓组织增生等为临床表现的罕见慢性B淋巴细胞增殖性疾病。克拉屈滨作为其一线药物，对HCL的完全缓解率很高。本文报道了2017-09-04绍兴市人民医院收治的1例经典型HCL患者在克拉屈滨治疗期间，出现严重粒细胞缺乏伴高热，合并全身皮疹及间质性肺炎，经大剂量激素等治疗后好转的诊疗过程。并结合文献回顾了HCL的诊断及治疗方法，简述了克拉屈滨治疗HCL致间质性肺炎这一少见并发症的诊疗思路，以提高临床医师对该毒副作用的认识，为临床工作提供帮助。     

中低度近视SMILE术后超早期视觉质量变化的研究

目的观察飞秒激光小切口角膜基质透镜取出术(SMILE)术后超早期患者视觉质量变化,探讨其变化发生的可能原因。方法选取中低度近视患者23例46眼行SMILE术,术前及术后24 h超早期行主观视觉质量问卷,测量最佳矫正视力的全程视力(远视力5 m,中视力60 cm,近视力33 cm)、对比敏感度(CS)、眩光敏感度(GS)及集合近点(NPC)和调节幅度(AA)。结果视觉质量主观问卷显示术后超早期主观视觉质量较术前下降(P=0.001)。术后裸眼视力(UCVA)明显提高(P=0.0001)。术前与术后最佳矫正视力(BCVA)中远视力没有变化(P=0.096),而中视力和近视力均较术前下降(P=0.039,0.003)。术后CS、GS降低(PCS=0.0001,PGS=0.04),NPC、AA较术前无明显变化(P=0.68,0.13)。结论SMILE术后超早期患者可获得预期理想远视力,但中、近视力尚未恢复。超早期中出现的异常视觉质量改变可能与对比敏感度和眩光敏感度的改变有关。     

针刺干预对肌萎缩侧索硬化症模型小鼠脑及脊髓中IBA-1和TNF-α表达的影响

目的:探讨电针治疗肌萎缩侧索硬化症(ALS)的机制。方法:将SOD1^G93A转基因小鼠随机分为正常组、模型组、针刺组及利鲁唑治疗组,每组各8-10只。小鼠日龄30 d后,针刺组选取双侧天枢穴(ST25)及足三里穴(ST36)予以电针治疗。利鲁唑治疗组按照30 mg/(kg·d)的剂量予以90 d日龄小鼠灌胃治疗,1次/d。模型组及对照组常规饲养,不予干预。于小鼠电针治疗前及治疗后分别对4组进行体质量记录及行为学观察。采用免疫组化法检测各组小鼠脑干及脊髓中IBA-1和TNF-α表达变化。结果:正常组小鼠精神状态及运动功能良好,针刺组及利鲁唑组小鼠较模型组精神状态及运动功能明显改善; 转棒实验结果显示针刺组及利鲁唑组小鼠潜伏期较模型组延长; 免疫组化检测结果表明在模型组脑干IBA-1阳性细胞表达高于正常组(P<0.05); 而利鲁唑组IBA-1阳性细胞表达虽有降低,但组间无统计学差异(P>0.05)。该结果与IBA-1阳性细胞在脊髓L_4-5节段表达趋于一致(P<0.05)。针刺治疗后脊髓中促炎因子TNF-α表达明显减少(P<0.05),但利鲁唑组较模型组无统计学差异(P>0.05)。结论:电针治疗及利鲁唑灌胃治疗均可以改善小鼠运动功能及生存质量,但早期针刺干预明显减少脑干及脊髓中小胶质细胞的活化,抑制促炎因子TNF-α释放,表明电针治疗ALS有效,其机制可能与针刺抑制神经炎症产生有关。     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

Two new bisamides from the leaves of Aglaia perviridis

Two new bisamides, aglaiamides A (1) and B (2), along with three known ones (3–5), were isolated from the leaves of Aglaia perviridis. Their structures were established on the basis of detailed spectroscopic analyses.