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1.
《Cancer cell》2022,40(3):318-334.e9
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2.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
3.
目的探讨慢性泪囊炎患者应用鼻内镜下鼻腔泪囊造口术的临床效果及安全性。方法选取2018年1月至2019年12月因慢性泪囊炎于本院接受治疗的46例患者为研究对象,随机分为研究组与对照组,各23例。对照组接受泪囊鼻腔造口治疗,研究组取鼻内镜下鼻腔泪囊造口术治疗,比较两组临床效果、手术指标以及并发症发生情况。结果研究组治疗总有效率高于对照组(P<0.05);研究组术中出血量少于对照组,手术及住院时间均短于对照组(P<0.05);研究组并发症总发生率低于对照组(P<0.05)。结论慢性泪囊炎患者采用鼻内镜下鼻腔泪囊造口术治疗效果显著,并发症较少,安全性较高,值得临床推广应用。 相似文献
4.
目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例,随机均分为3组:对照组(C组)、体温保护组(T组)和体温保护联合右美托咪定组(T-D组),每组30例。C组常规体温保护,T组和T-D组综合体温保护;T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时(T0)、手术开始30 min(T1)、60 min(T2)、90 min(T3)、120 min(T4)以及手术结束时(T5)的鼻咽温度;于T0、术后2 h(T6)、24 h(T7)和48 h(T8)时抽取静脉血标本,测定T淋巴细胞亚群(CD3+、CD4+和CD8+)和自然杀伤细胞(NK cell)水平;记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T0比较,C组T2~T5时点鼻咽温度均明显降低(P < 0.05);与C组比较,T组和T-D组T2~T5时点鼻咽温度明显升高(P < 0.05)。与T0时点比较,C组、T组和T-D组T6、T7和T8时点CD3+和NK cell活性均明显降低(P < 0.05);C组在T6、T7和T8时点,T组和T-D组在T6和T7时点,CD4+活性均明显降低(P < 0.05)。与C组比较,T组和T-D组T6和T7时点CD3+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6和T7时点,CD4+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6、T7和T8时点,NK cell活性均明显升高(P < 0.05)。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定,减少围手术期意外低体温(IPH)的发生,并有效提高患者苏醒期质量,减轻免疫抑制程度,加速患者早期恢复。 相似文献
5.
《Vaccine》2022,40(42):6048-6054
BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies. 相似文献
6.
7.
Her-Shyong Shiah Nai-Jung Chiang Chia-Chi Lin Chia-Jui Yen Hui-Jen Tsai Shang-Yin Wu Wu-Chou Su Kwang-Yu Chang Ching-Chiung Wang Jang-Yang Chang Li-Tzong Chen 《The oncologist》2021,26(4):e567-e579
Lessons Learned
- SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
- This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
- SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.
8.
9.
《中国现代医生》2020,58(8):65-67
目的 研究大剂量干扰素辅助治疗口腔黏膜恶性黑色素瘤的临床效果,探讨治疗应用的安全性。方法 选取我院于2017年11月~2018年11月收治的80例口腔黏膜恶性黑色素瘤患者作为研究对象,按照治疗方法不同分为两组,每组40例。对照组患者仅采用单纯手术治疗,治疗组在此基础上采用大剂量干扰素辅助治疗。观察两组患者生存情况、疾病复发情况以及毒副反应。结果 治疗组患者生存期限及无复发生存期明显长于对照组,治疗组复发率为5.00%,明显低于对照组的22.50%,差异有统计学意义(P0.05)。两组患者毒副反应比较差异无统计学意义(P0.05)。结论 口腔黏膜恶性黑色素瘤患者予以大剂量干扰素辅助疗法安全有效,值得临床推广。 相似文献
10.
发作性睡病是致残性白天睡眠增多的最常见原因之一,其治疗旨在减少白天睡眠增多和猝倒,改善夜间睡眠紊乱、睡眠瘫痪及与睡眠有关的幻觉。2019年,组胺H3受体拮抗剂替洛利生(Pitolisant)和多巴胺及去甲肾上腺素再摄取抑制剂索利氨酯(Solriamfetol)分别在欧盟和美国上市,前者具有促醒和抗猝倒作用,后者也有促醒作用,且戒断症状和滥用的发生率更低。目前,控释型羟丁酸钠(FT218)、低钠型羟丁酸盐(JZP-258)、选择性去甲肾上腺素再摄取抑制剂(瑞波西汀,又称AXS-12)以及莫达非尼联合氟卡尼制剂(THN102)等药物仍在开发和测试中,均可作为治疗发作性睡病相关白天睡眠增多和猝倒的潜在药物。本文重点介绍这些最近研发的发作性睡病治疗药物。 相似文献