空间统计学在食品污染物分布研究中的应用

目的 以2017年某省食品安全监测大米中砷含量数据为例，探讨空间统计学方法在食品污染物分析中的应用价值。方法 采用空间点模式估计、核密度分析，全局以及局部自相关性分析等空间统计学方法，在县级空间尺度下，对某省大米中砷含量进行探索性空间数据分析。结果 空间点模式分布图显示，该省大米砷污染的空间分布比较分散，核密度分析结果显示污染热点区域主要在该省中东部地区。全局自相关Moran''s I指数值为0.11，有统计学意义，大米样品中砷污染呈现出低度空间聚集性。有1个"高-高"聚集区，2个典型的"低-低"聚集区。结论 空间统计学运用于食物污染物分布研究上，可以很好地可视化展示、识别污染分布规律、热点地区和聚集区，为基于问题的监测工作的开展提供技术支持。     

WHO药品预认证微生物实验室质量管理的要求与思考

目的:介绍世界卫生组织(WHO)对药品微生物检测实验室的预认证要求,推动我国药品检测质量管理体系的完善和发展。方法:从预认证实验室应遵循的质量管理原则出发,对照我国实验室ISO/IEC 17025体系要求,分析药品微生物检测实验室在质量管理中的不足。结果:预认证实验室更多地采纳了《药品生产质量管理规范》(GMP)的质量管理理念,而我国药品微生物检测实验室在记录与数据可靠性、基于风险的变更控制和偏差调查等方面的应用与实施还存在较大差距。结论:我国药品微生物检测实验室应学习和借鉴国内外GMP的质量管理经验,不断更新理念,改进质量管理体系,更多地以风险评估方式保障检测数据的可靠性。     

PD-1/PD-L1抑制剂对比常规疗法治疗癌症的有效性和安全性的Meta分析

目的:系统性评价程序性死亡因子1/程序性死亡因子1配体(PD-1/PD-L1)抑制剂对比常规疗法治疗癌症的有效性和安全性。方法:计算机全面检索PubMed、MEDLINE、EMBASE数据库，收集PD-1/PD-L1抑制剂治疗癌症的文献研究，检索时间为2000年1月1日至2019年6月30日。两位研究人员独立收集和整理资料，评价纳入文献研究的偏倚风险，应用Review Manager 5.3软件对纳入研究进行数据整理。结果:最终纳入11项随机对照试验，共6 295例研究对象，其中PD-1/PD-L1抑制剂试验组3 220例，常规疗法药物对照组3 075例。Meta分析结果显示，PD-1/PD-L1抑制剂试验组的客观反应率（ORR）［RR=1.87，95%CI（1.33，2.64），P＜0.001］、完全缓解率（CR）［RR=2.45，95%CI（1.27，4.73），P＜0.001］和部分缓解率（PR）［RR=1.81，95%CI（1.28，2.54），P＜0.001］优于常规疗法对照组，结果均有统计学差异；在疾病控制率（DCR）［RR=1.03，95%CI（0.89，1.20），P=0.65］和疾病进展率（PD）［RR=1.16，95%CI（0.95，1.40），P=0.14］方面，两组比较无统计学差异；而在疾病稳定率（SD）［RR=0.72，95%CI（0.63，0.82），P＜0.001］方面显示常规疗法对照组优于PD-1/PD-L1抑制剂试验组。药物安全性方面，不良反应发生率（AEs）［RR=0.96，95%CI（0.88，1.04），P=0.28］两组无统计学差异，但在3-5级不良反应发生率［RR=0.44，95%CI（0.28，0.68），P＜0.001］方面，PD-1/PD-L1抑制剂试验组明显低于常规疗法对照组。结论:PD-1/PD-L1抑制剂与常规疗法药物相比，可明显提高癌症患者临床治疗的ORR、CR和PR，且出现3-5级不良反应发生率更低，从而证实PD-1/PD-L1抑制剂的有效性和安全性优于常规疗法。     

抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors，ICPI）在国内外临床试验和应用中的逐步推广，越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1，PD-1）及其配体（PD-1 ligand，PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应，皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

自制极简PORT在单孔腹腔镜子宫肌瘤切除术中的应用初步探讨

目的:初步探讨自制极简入路通道（PORT）在单孔腹腔镜子宫肌瘤切除术中应用的可行性及安全性。方法:回顾性分析空军军医大学西京医院妇产科于2017年3月至2018年12月共完成的46例单孔腹腔镜子宫肌瘤切除术患者，其中24例使用商品化PORT，22例使用我科自制极简PORT，所有患者均配合使用常规腹腔镜器械顺利完成手术。比较两组患者年龄、体质量数、手术时间、术中出血量、子宫肌瘤直径、术中及术后相关并发症、手术前后血红蛋白差值、术后排气时间、术后疼痛模拟评分、住院时间、术后随访情况等指标。结果:所有患者均顺利完成手术，无中转开腹或增加穿刺孔，无并发症发生。商品化PORT组和自制极简PORT组患者的一般资料具有可比性。手术相关指标包括手术时间［（75±56.9）min vs （74±55.7）min］、术中出血量［（55±67.9）ml vs （56±65.8）ml］、子宫肌瘤直径［（6±2.8）cm vs （6±3.4）cm］，两组比较无明显统计学差异（P＞0.05）。术后恢复指标包括术后排气时间［（12.6±4.4）h vs （13.5±3.4）h］、术后疼痛模拟评分［（2.1±1.3）分 vs （2.0±1.2）分］、住院时间［（3.4±2.8）d vs （3.5±2.6）d］，同样无统计学差异（P＞0.05）。两组手术效果相同，但术中使用自制极简PORT几乎不增加耗材。结论:自制极简PORT在单孔腹腔镜子宫肌瘤切除术中的应用安全性好，效果确切，节约成本，值得推广。     

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer

Recent studies have reported that tumor‐infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine‐based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine‐based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM‐activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell‐related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine‐based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.     

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

miR-30c Impedes Glioblastoma Cell Proliferation and Migration by Targeting SOX9

miR-30c has been acknowledged as a tumor suppressor in various human cancers, such as ovarian cancer, gastric cancer, and prostate cancer. However, the role of miR-30c in glioblastoma (GBM) needs to be investigated. In our study, we found that the expression of miR-30c was significantly downregulated in GBM tissues and cell lines. We found that overexpression of miR-30c inhibited cellular proliferation of GBM cells in vitro and in vivo. More GBM cells were arrested in the G₀ phase after miR-30c overexpression. Moreover, we showed that miR-30c overexpression suppressed the migration and invasion of GBM cells. Mechanistically, we found that SOX9 was a direct target of miR-30c in GBM cells. Overexpression of miR-30c inhibited the mRNA and protein levels of SOX9 in GBM cells. Moreover, there was a negative correlation between the expression of miR-30c and SOX9 in GBM tissues. Finally, we showed that restoration of SOX9 in GBM cells reversed the proliferation, migration, and invasion of GBM cells transfected with miR-30c mimic. Collectively, our results demonstrated that miR-30c suppressed the proliferation, migration, and invasion of GBM cells via targeting SOX9.     

肺鳞癌治疗新靶点FGFR的研究进展

肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤，其中肺鳞癌经手术、放化疗等综合治疗后，其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果，而肺鳞癌患者中EGFR基因突变及ALK融合基因少见，急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明，FGFR家族（FGFR1-4）是肺鳞癌中突变频率较高的基因，FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关，同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前，许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究，针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。