利用耳甲腔型小耳畸形残耳皮瓣及软骨改善再造耳颅耳沟效果观察

目的探讨对先天性耳甲腔型小耳畸形患者行全扩张法全耳再造术后，利用残耳皮瓣改善再造耳颅耳沟的效果。方法回顾分析 2012 年 1 月—2017 年 1 月收治的 150 例先天性耳甲腔型小耳畸形患者。其中男 92 例，女 58 例；年龄 6.5～35.0 岁，平均 11.1 岁。采用一期扩张器埋置、二期全扩张法全耳再造术后发现上部颅耳沟浅显；于 6～12 个月后行三期再造耳修整。将残耳垂通过“Z”字改型转移以再造耳垂。在残耳上部作蒂在轮屏切迹的残耳上部皮瓣，弧形切开松解并加深上部颅耳沟，将上部残耳皮瓣向颅耳沟创面旋转推进缝合以覆盖创面；将带皮下组织蒂的残耳软骨组织瓣插入支架底部形成的腔隙内，并缝合固定，以增加支架的高度；耳甲腔区其余残耳皮瓣用以覆盖耳甲腔创面。结果术后拆线时 1 例患儿皮瓣远端出现直径约 0.5 cm 的表皮水疱，经换药 2 周后愈合；其余患者皮瓣成活良好。患者均获随访，随访时间 6～12 个月，平均 9.6 个月。再造耳上部颅耳沟均明显加深，再造耳支架高度不同程度增加，双耳对称性佳，耳甲腔无明显挛缩变小，再造耳外观满意。再造耳上部表面毛发明显减少，耳周发际线上移。结论采用耳甲腔型小耳畸形的残耳皮瓣及残耳软骨瓣转移，不仅可加深颅耳沟，而且可增加上部支架的高度，术后颅耳沟变形较轻，再造耳与正常耳廓的对称性更佳。     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

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.     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

肺癌是世界上发病率最高的癌症之一，且尚无二线进展后的标准治疗方案，而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点，小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路，抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验，且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）获批治疗晚期非小细胞肺癌，本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状，归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分别与化疗、表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs、免疫治疗、放疗等联合）]治疗非小细胞肺癌的疗效与安全性研究，同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等，并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望，同时为肺癌后续的精准治疗及个体化治疗提供新的思路。     

Elevated glycohemoglobin HbA1c is associated with low back pain in nonoverweight diabetics

Background Context

Low back pain (LBP) is a common complaint in clinical practice of multifactorial origin. Although obesity has been thought to contribute to LBP primarily by altering the distribution of mechanical loads on the spine, the additional contribution of obesity-related conditions such as diabetes mellitus (DM) to LBP has not been thoroughly examined.

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

昆明市2013-2017年丙型病毒性肝炎流行特征及趋势分析

目的分析昆明市2013-2017年丙型病毒性肝炎的流行特征和流行趋势,为科学制定防控策略提供依据。方法运用描述性流行病学方法,统计昆明市2013-2017年丙型病毒性肝炎的发病情况,分析其流行特征和趋势。结果昆明市2013-2017年丙型病毒性肝炎呈现先上升后下降的趋势,2015年达到发病高峰,其发病率高达32.80/10万,总体上2013-2017年丙型病毒性肝炎发病率呈现上升趋势,且肝炎和丙肝以官渡区、五华区和西山区为主要的高发地区;无明显的季节性特点,四季均有发病;易发生丙型病毒性肝炎的人群为35~50岁的农民和家务及待业人员。结论昆明市丙型病毒性肝炎发病状况并不乐观,应加强丙肝防控力度,重点关注高发地区和高发人群,通过有效举措控制丙型病毒性肝炎的发病率。