3-磷酸甘油酸脱氢酶促进丝氨酸合成在肿瘤进展中的机制

丝氨酸生物合成途径活性的上调是许多癌症明显的共同特征。该途径的第一种限速酶3-磷酸甘油酸脱氢酶(PHGDH)在黑色素瘤、乳腺癌和肾癌等癌组织中高表达，对肿瘤细胞增殖、转移、侵袭有着重要作用。糖酵解中间产物3-磷酸甘油酸在PHGDH作用下，氧化为磷酸羟基丙酮酸并最终合成丝氨酸。丝氨酸转化为甘氨酸，然后在核苷酸、s-腺苷甲硫氨酸(SAM)和还原型谷胱甘肽(GSH)的合成中起着重要的作用。PHGDH 有望成为肿瘤治疗的新靶点。     

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。     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。     

Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.     

Retinal disease in the C3 glomerulopathies and the risk of impaired vision

Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.     

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.