Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy

3 id="sectitle0010">Purpose3>This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.

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3a2;讨对先天性€33;u32;腔型小€33;畸形؊3;者行全扩张法全€33;再造术后，利用残€33;皮ݎ3;e39;善再造€33;颅€33;沟的效果�3002;方法回顾分析 2012 年 1 月—2017 年 1 月e36;治的 150 例先天性€33;u32;腔型小€33;畸形؊3;者�3002;其中u37; 92 例，֗3; 58 例；年龄 6.5～35.0 岁，ק3;均 11.1 岁�3002;采用一期扩张器埋置�3001;二期全扩张法全€33;再造术后3d1;3b0;上部颅€33;沟浅f3e;；于 6～12 个月后行三期再造€33;修整�3002;将残€33;垂通过“Z”字e39;型转移以再造€33;垂�3002;在残€33;上部作蒂在轮屏切迹的残€33;上部皮ݎ3;，弧形切开松࢞3;并加深上部颅€33;沟，将上部残€33;皮ݎ3;向颅€33;沟创面旋转3a8;进缝合以覆盖创面；将带皮下组织蒂的残€33;软骨组织ݎ3;3d2;入支架底部形成的腔隙内，并缝合固定，以增加支架的高度；€33;u32;腔33a;其余残€33;皮ݎ3;用以覆盖€33;u32;腔创面�3002;߭3;果术后拆线时 1 例؊3;Q3f;皮ݎ3;远端出3b0;直径约 0.5 cm 的表皮l34;疱，经362;36f; 2 周后愈合；其余؊3;者皮ݎ3;成m3b;良好�3002;؊3;者均3b7;随访，随访时间 6～12 个月，ק3;均 9.6 个月�3002;再造€33;上部颅€33;沟均明f3e;加深，再造€33;支架高度不同程度增加，3cc;€33;对称性ӷ3;，€33;u32;腔无明f3e;31b;缩3d8;小，再造€33;外观满意�3002;再造€33;上部表面毛3d1;明f3e;减少，€33;周3d1;际线上移�3002;߭3;论采用€33;u32;腔型小€33;畸形的残€33;皮ݎ3;3ca;残€33;软骨ݎ3;转移，不仅3ef;加深颅€33;沟，而且3ef;增加上部支架的高度，术后颅€33;沟3d8;形ࣸ3;轻，再造€33;与ڶ3;^38;€33;׭3;的对称性更ӷ3;�3002;     

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。     

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.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.