甲状腺结节恶性分层系统在社区医院的应用价值研究

背景　甲状腺结节恶性分层系统可以规范甲状腺结节超声诊断,对甲状腺结节诊疗具有重要指导意义,但目前仍缺乏统一的版本。目的　比较Kwak版甲状腺影像报告与数据系统（Kwak TI-RADS）、2015年美国甲状腺学会（ATA）《成年人分化型甲状腺癌诊治指南》（以下简称ATA指南）超声风险分层评估及2017年美国放射学会甲状腺影像与数据系统（ACR TI-RADS）在社区医院甲状腺结节诊断中的应用价值。方法　回顾性分析2012年1月-2018年8月上海市闵行区浦江社区卫生服务中心经上海市浦东新区公利医院手术病理及甲状腺细针抽吸细胞学检查（FNA）证实的825例患者（986个甲状腺结节）的二维超声声像图特征,分别用Kwak TI-RADS、ATA指南超声风险分层评估及ACR TI-RADS进行分类,绘制受试者工作特征（ROC）曲线,评价并比较各风险分层系统对甲状腺结节良恶性鉴别的价值。结果　986个甲状腺结节中,病理及FNA确诊恶性结节479个,良性结节507个。Kwak TI-RADS、ATA指南超声风险分层评估及ACR TI-RADS的ROC曲线下面积（AUC）分别是0.887〔95%CI（0.864,0.909）〕、0.857〔95%CI（0.832,0.882）〕、0.870〔95%CI（0.846,0.895）〕,诊断界值分别为≥4c类、≥高危、≥5类。Kwak TI-RADS、ATA指南超声风险分层评估及ACR TI-RADS在甲状腺结节良恶性鉴别中均有诊断价值（P<0.05）,且Kwak TI-RADS诊断效能优于ATA指南超声风险分层评估及ACR TI-RADS（Z=4.811、2.513,P<0.05）。结论　Kwak TI-RADS、ATA指南超声风险分层评估及ACR TI-RADS在甲状腺良恶性结节的诊断中均有良好价值,前者诊断效能稍优于后两者,且该版本简单明确、易于掌握,适合在基层医院推广。     

Structure of the rhesus monkey TRIM5α PRYSPRY domain, the HIV capsid recognition module

Tripartite motif protein TRIM5α blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/PRYSPRY domain. Here we report a high-resolution structure of a TRIM5α PRYSPRY domain, the PRYSPRY of the rhesus monkey TRIM5α that potently restricts HIV infection, and identify features involved in its interaction with the HIV capsid. The extensive capsid-binding interface maps on the structurally divergent face of the protein formed by hypervariable loop segments, confirming that TRIM5α evolution is largely determined by its binding specificity. Interactions with the capsid are mediated by flexible variable loops via a mechanism that parallels antigen recognition by IgM antibodies, a similarity that may help explain some of the unusual functional properties of TRIM5α. Distinctive features of this pathogen-recognition interface, such as structural plasticity conferred by the mobile v1 segment and interaction with multiple epitopes, may allow restriction of divergent retroviruses and increase resistance to capsid mutations.     

静态张应力作用下人牙周膜干细胞核心结合因子Cbfa1表达的变化

目的检测静态张应力作用对人牙周膜干细胞核心结合因子Cbfa1表达变化的影响。方法有限稀释法克隆化培养纯化人牙周膜干细胞(hPDLSCs),应用内外双层套筒式硅胶膜细胞加力装置对人牙周膜干细胞加力,加力时间点为0、3、6、12、24小时。采用原位杂交和实时定量PCR检测各加力时间点Cbfa1 mRNA的表达;蛋白免疫印迹法(Western blot)检测人牙周膜干细胞受力后Cbfa1蛋白的表达。结果人牙周膜干细胞受到静态张应力作用后3小时、6小时、12小时Cbfa1 mRNA表达均升高(P0.05),且以加力3小时最为明显,6小时后开始下降,24小时后基本恢复到不加力时的表达水平。加力3小时Cbfa1蛋白表达未见明显升高,加力6小时后Cbfa1蛋白逐渐升高,一直持续到加力24小时(P0.05)。结论静态张应力作用下,人牙周膜干细胞核心结合因子Cbfa1在RNA水平和蛋白水平的表达均发生变化,说明Cbfa1在机械力促使人牙周膜干细胞向成骨细胞方向分化的过程中起到了重要作用。     

OSAHS患者戴用自行调节式口腔矫治器下颌骨位置变化的研究

目的 为下颌前伸式口腔矫治器治疗阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea and hypopnea syndrome,OSAHS)的下颌定位提供参考.方法 采用X线头影测量分别对32例患者戴用自行调节式口腔矫治器于治疗前、医师经验位及患者调节位时下颌水平及垂直测量项目的具体数据进行统计学处理.结果 医师经验位和患者调节位与治疗前比较时测量项目均有差异,两者比较,S-Ar-Go P值为0.095,H-MP P值为0.84,均大于0.05,其他测量项目均有显著差异(P.<0.05).结论 自行调节式口腔矫治器的医师经验位和患者调节位的下颌位置存在差异,该差异可以为下颌前伸类口腔矫治器个性化治疗的下颌前伸定位研究提供参考.     

纳米载银无机抗菌剂对白色念珠菌生物膜形成的影响

目的:研究纳米载银无机抗菌剂对白色念珠菌生物膜形成的影响。方法:XTT减低法检测纳米载银无机抗菌剂对白色念珠菌生物膜活性的影响,结晶紫含量测定法检测纳米载银无机抗菌剂对白色念珠菌生物膜生物量的影响,并以结晶紫染色观察生物膜形态。结果:在0.62mg/ml抗菌剂应用液中,白色念珠菌生物膜活性及生物量分别减少(96.1±3.0)%和(95.4±2.7)%,倒置显微镜下观察发现,生物膜没有形成。结论:纳米载银无机抗菌剂可抑制白色念珠菌生物膜的形成。     

Podoplanin在口腔鳞状细胞癌中的表达及与淋巴结转移的关系

目的:采用淋巴管特异性标志物podoplanin标记口腔鳞癌组织和正常口腔组织中的淋巴管,并计数淋巴管密度(lymphatic vessel density,LVD)值,探讨口腔鳞癌及癌周淋巴管密度与淋巴结转移的相关性及可能机制。方法:采用免疫组织化学方法检测21例正常口腔黏膜组织和88例口腔鳞癌患者组织的podoplanin表达;用podoplanin标记淋巴管,并计数口腔鳞癌和癌周组织的淋巴管密度。采用SPSS13.0软件包对数据进行t检验,分析正常组织和癌组织、淋巴结转移组和未转移组的淋巴管密度(癌周、癌内)。结果:口腔鳞癌及癌周组织的淋巴管密度均高于正常口腔黏膜组织,有显著差异(P<0.05)。癌组织内淋巴管小而闭锁,癌组织周围的淋巴管大而扩张;淋巴结转移组的癌周淋巴管密度(14.270±4.610)显著高于无转移组(9.450±2.411),差异具有显著性(P<0.05),癌组织淋巴管密度在2组间无显著差异。结论:口腔鳞癌患者癌周淋巴管的生成可能是影响区域淋巴结转移的重要因素。     

Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML

Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.     

CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease

The chemokine CCL3/MIP-1α is a risk factor in the outcome of multiple myeloma (MM), particularly in the development of osteolytic bone disease. This chemokine, highly overexpressed by MM cells, can signal mainly through 2 receptors, CCR1 and CCR5, only 1 of which (CCR1) is responsive to CCL3 in human and mouse osteoclast precursors. CCR1 activation leads to the formation of osteolytic lesions and facilitates tumor growth. Here we show that formation of mature osteoclasts is blocked by the highly potent and selective CCR1 antagonist CCX721, an analog of the clinical compound CCX354. We also show that doses of CCX721 selected to completely inhibit CCR1 produce a profound decrease in tumor burden and osteolytic damage in the murine 5TGM1 model of MM bone disease. Similar effects were observed when the antagonist was used prophylactically or therapeutically, with comparable efficacy to that of zoledronic acid. 5TGM1 cells were shown to express minimal levels of CCR1 while secreting high levels of CCL3, suggesting that the therapeutic effects of CCX721 result from CCR1 inhibition on non-MM cells, most likely osteoclasts and osteoclast precursors. These results provide a strong rationale for further development of CCR1 antagonists for the treatment of MM and associated osteolytic bone disease.