GOLPH3蛋白在新疆哈萨克族食管鳞癌中的表达及其临床意义

目的:研究GOLPH3蛋白在新疆哈萨克族（哈族）食管鳞癌中的表达及其临床意义。方法:本次研究选取50例术前未经放化疗干预且手术切除的新疆哈族食管鳞癌组织及50例哈族癌旁相对正常食管组织作为研究对象，截止日期为2018年6月，应用免疫组织化学技术，检测GOLPH3蛋白在哈族食管鳞癌组织及癌旁组织的表达特点及情况。结果:GOLPH3蛋白在哈族食管鳞癌组织的表达率为70.0%，高于癌旁正常组织28.0%，差异具有统计学意义(P=0.001)；低分化组阳性表达率82.9%高于高分化组40.0%，差异具有统计学意义(P=0.02)；淋巴结转移组阳性表达率85.3%高无淋巴结转移组37.5%，差异具有统计学意义(P=0.01)；临床分期在Ⅲ-Ⅳ组阳性表达率83.3%，高于Ⅰ-Ⅱ组的50.0%，差异具有统计学意义(P=0.012)；男性组中GOLPH3蛋白的表达阳性率为64.7%，女性组为81.3%，差异无统计学意义(P=0.234)；高龄组（≥60岁）GOLPH3蛋白的表达阳性率79.2%，低龄组（＜60岁）为61.5%，差异无统计学意义(P=0.174)。结论:GOLPH3蛋白的表达可能与哈族食管鳞癌的分化、增殖和转移等过程有关。     

Evaluation of Mast Cell Density using CD117 antibody and Microvessel Density Using CD34 Antibody in Different Grades of Oral Squamous Cell Carcinoma

Objective: To compare mast cell and microvessel densities among histologic grades of oral squamous cell carcinoma. Setting: Armed Forces Institute of Pathology. Materials and Methods: A total of 60 specimens of OSCC comprising 20 each of well, moderately and poorly differentiated were evaluated. Immunohistochemical analysis was performed to measure MCD and MVD by applying monoclonal CD117 antibody and monoclonal CD34 antibody, on formalin fixed and paraffin embedded sections. ANOVA and Post Hoc Tukey test was employed to assess the densities and to compare the differences between different grades of OSCC. A p-value     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single‐arm study

Cryoprobe is a novel transbronchial biopsy (TBB) tool that yields larger tissue samples than forceps. Pathological diagnosis and biomarker analysis, such as genetic alterations and programmed death‐ligand 1 (PD‐L1) expression, are paramount for precision medicine against lung cancer. We evaluated the safety and usefulness of cryoprobe TBB for lung cancer diagnosis and biomarker analysis. In this single‐center, prospective single‐arm study, patients suspected of having or diagnosed with primary lung cancer underwent cryoprobe TBB using flexible bronchoscopy after conventional forceps TBB from the same lesion. Cryoprobe TBB was performed in 121 patients. The incidence rate of severe bleeding and serious adverse events (4% [90% confidence interval: 2%‐9%]) was significantly lower than the expected rate (20% with 30% threshold, P < 0.01). Combining both central and peripheral lesions, the diagnostic yield rate of cryoprobe samples was 76% and that of forceps samples was 84%. Compared with forceps TBB samples, cryoprobe TBB samples were larger (cryoprobe 15 mm² vs forceps 2 mm²) and resulted in a larger proportion of definite histomorphological diagnosis (cryoprobe 86% vs forceps 74%, P < 0.01), larger amounts of DNA extracted from samples (median: cryoprobe, 1.60 µg vs forceps, 0.58 µg, P = 0.02) and RNA (median: cryoprobe, 0.62 µg vs forceps, 0.17 µg, P < 0.01) extracted from samples, and tended to yield greater rates of PD‐L1 expression >1% (51% vs 42%). In conclusion, cryoprobe is a safe and useful tool for obtaining lung cancer tissue samples of adequate size and quality, which allow morphological diagnosis and biomarker analysis for precision medicine against lung cancer.     

Occludin在非小细胞肺癌组织中的表达及其临床意义

目的:检测非小细胞肺癌（NSCLC）组织中闭合蛋白（Occludin）的表达水平及其临床意义。方法:应用免疫组织化学方法检测73例NSCLC组织及其配对正常肺组织中Occludin蛋白表达水平，分析Occludin蛋白的表达差异及其与临床病理参数的相关性。结果:Occludin蛋白在肿瘤组织中的阳性表达率显著低于配对正常肺组织（P＜0.05）。Occludin蛋白的表达水平与患者性别、肿瘤大小、淋巴结转移、组织学类型、Ki-67表达水平显著相关。结论:Occludin蛋白表达下调与NSCLC细胞的增殖、转移能力相关，在肿瘤进展中发挥重要作用。     

杜仲醇提取物可促进根尖周炎模型大鼠骨组织的愈合

文题释义：杜仲：杜仲是中国传统的中药药材，其具有增加机体免疫性、强身健骨的疗效，研究表明杜仲可以促进成骨细胞的增殖并且可以促进骨组织的愈合。近年来对于杜仲的研究主要集中于其有效成分的提取及分析。 杜仲醇：是杜仲的主要有效成分之一，可以增强关节炎大鼠骨组织的强度，并且具有降血压以及促进伤口愈合的能力。 背景：目前关于杜仲的研究主要集中于其治疗骨关节炎能增强骨组织的愈合能力，但是关于杜仲对根尖周炎骨破坏的修复作用尚未见报道。 目的：探讨杜仲醇提取物对根尖周炎大鼠组织蛋白酶K的影响。 方法：选取24只SD大鼠随机分为根尖周炎组20只及对照组4只，根尖周炎组于右侧下颌第一磨牙开髓后建立根尖周炎模型，对照组不做任何处理。饲养4周后，取根尖周炎组及对照组各4只拍摄MICRO-CT，计算根尖周炎骨破坏量，确认大鼠根尖周炎动物模型构建成功。饲养第5周，将剩余16只根尖周炎大鼠随机分为杜仲醇提取物组及生理盐水组，每组8只，每天灌胃杜仲醇提取物5 mL/kg或等量生理盐水。灌胃4周后，每组取4只大鼠拍摄MICRO-CT，分析杜仲醇提取物对根尖周骨组织的修复能力，另外取4只大鼠采用免疫组化染色观察右下颌第一磨牙牙槽骨组织蛋白酶K的表达。 结果与结论：①MICRO-CT结果显示，对照组骨吸收体积为(0.223±0.009) mm³，根尖周炎组骨吸收体积为(0.945±0.037) mm³，两组骨吸收量比较差异有显著性意义(P=0.00)，说明大鼠根尖周炎模型构建成功；②灌胃4周后，MICRO-CT结果显示杜仲醇提取物组骨吸收体积较灌胃前减小，差异有显著性意义(P < 0.05)；③灌胃4周后，免疫组化结果显示杜仲醇提取物根尖周炎骨破坏标志因子组织蛋白酶K的表达较灌胃前降低，差异有显著性意义(P < 0.05)；④结果表明，杜仲醇提取物可以抑制骨破坏标志因子组织蛋白酶K的表达，并且可以促进大鼠根尖周炎骨组织的愈合。 ORCID: 0000-0001-5450-7016(吴大雷) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

Viral infection in placenta relevant cells – a morphological and immunohistochemical cell culture study

Viral infections in pregnancy are known to cause fetal malformation, growth restriction, and even fetal death. Macroscopic placental examination usually shows slight and unspecific changes. Histology may show secondary, non‐specific tissue reaction, i.e. villitis with lymphocytic invasion. Primary specific morphology characteristics are known for some virus, like cytomegalovirus, parvovirus, and herpes simplex, however many viral infections show non‐specific changes. Placenta relevant cells as human first trimester trophoblasts HTR8/SVneo, primary human umbilical vein endothelial cells (HUVEC), and primary human embryonic fibroblasts were examined following infection with commonly occurring virus like adenovirus and enterovirus. Morphology in routine stained sections and virus‐specific immunostains were studied 4, 8, 24, 48, 72 h after infection. Nuclear enlargement was seen in the infected cells. A specific diagnosis of adenovirus or enterovirus infection, however, was not possible without specific immunostains.