多参数磁共振成像影像组学鉴别高级别胶质瘤及单发脑转移瘤的价值

目的:利用多参数磁共振成像(magnetic resonance imaging,MRI)影像组学鉴别高级别胶质瘤及单发脑转移瘤。方法:回顾性收集经病理活检证实为高级别胶质瘤或单发脑转移瘤患者的MRI结构序列及功能序列表观扩散系数(apparent diffusion coefficient,ADC)影像,共103例。手动勾画感兴趣区域容积(volumes of interest,VOI),包括肿瘤核心区域、周围水肿区域以及肿瘤全域。使用Python中的开源Pyradiomics包进行影像组学特征提取。然后选择t检验和最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)方法进行特征筛选及降维。最后使用逻辑回归(Logistic regression,LR)、随机森林(random forest,RF)、支持向量机(support vector machines,SVM)及K-邻近(K-nearest neighbors,KNN)四种分类器建模,对比鉴别高级别胶质瘤及单发脑转移瘤的效能。结果:高级别胶质瘤及单发脑转移瘤患者的性别及年龄之间不存在统计学差异,肿瘤位置之间存在统计学差异。基于肿瘤核心区域鉴别两者取得最高的诊断效能,曲线下面积(area under curve,AUC)最高为0.924。在多序列组合模型中,ALL_TCR_LR模型的AUC值最高,为0.924,被选为最优分类器模型。结论:基于肿瘤核心区域的多序列影像组学使用LR机器学习分类器可实现高级别胶质瘤及单发脑转移瘤的鉴别,为临床决策和实践提供了较大的帮助。

Opisthorchis viverrini:The carcinogenic human liver fluke

Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.

Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Tiny 2D silicon quantum sheets:a brain photonic nanoagent for orthotopic glioma theranostics

We report that atomically thin two-dimensional silicon quantum sheets(2D Si QSs),prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation,can serve as a highperformance brain photonic nanoagent for orthotopic glioma theranostics.With the lateral size of approximately 14.0 nm and thickness of about 1.6 nm,tiny Si QSs possess high mass extinction coefficient of 27.5 Lg^(-1)cm^(-1)and photothermal conversion efficiency of 47.2%at 808 nm,respectively,concurrently contributing to the best photothermal performance among the reported 2 D mono-elemental materials(Xenes).More importantly,Si QSs with low toxicity maintain the trade-off between stability and degradability,paving the way for practical clinical translation in consideration of both storage and action of nanoagents.In vitro Transwell filter experiment reveals that Si QSs could effectively go across the b End.3 cells monolayer.Upon the intravenous injection of Si QSs,orthotopic brain tumors are effectively inhibited under the precise guidance of photoacoustic imaging,and the survival lifetime of brain tumor-bearing mice is increased by two fold.Atomically thin Si QSs with strong light-harvesting capability are expected to provide an effective and robust 2D photonic nanoplatform for the management of brain diseases.

Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

Nano-therapeutic approach for clinical implementation of tumors remains a longstanding challenge in the medical field. The main challenges are rapid clearance, offtarget effect and the limited role in the treatment of metastatic tumors. Toward this objective, a cell-mediated strategy by transporting photothermal reagents and CpG adjuvant within macrophage vehicles is performed. The photothermal reagents are constructed by conjugating of hyperbranched polyethyleimine（PEI） to golden nanorode（GNR） via S-Au bonds.GNR-PEI/CpG nanocomposites, formed via electrostatic interaction and displayed excellent near-infrared（NIR） photothermal performance, exhibit immense macrophage uptake and negligible cytotoxic effect, which is essential for the fabrication of GNR-PEI/CpG loaded macrophages. GNR-PEI/CpG loaded macrophages demonstrated admirable photothermal response in vitro. Benefited from the functionalization of the binding adhesion between macrophages and 4 T1 cells, GNR-PEI/CpG loaded macrophages significantly promoted tumor accumulation in vivo and dramatically enhanced the efficiency of photothermal cancer therapy. Moreover, the immune system is activated after photothermal therapy, which is mainly attributed to the generation of tumor specific antigens and CpG adjuvant in situ. Our findings provide a potential cell-mediated nanoplatform for tumor therapy by combination of near infrared photothermal therapy and immunotherapy.

Cellular adaptation to hypoxia and p53 transcription regulation

Tumor suppressor p53 is the most frequently mutated gene in human tumors. Meanwhile, under stress conditions, p53 also acts as a transcription factor, regulating the expression of a series of target genes to maintain the integrity of genome. The target genes of p53 can be classified into genes regulating cell cycle arrest, genes involved in apoptosis, and genes inhibiting angiogenesis, p53 protein contains a transactivation domain, a sequence-specific DNA binding domain, a tetramerization domain, a non-specific DNA binding domain that recognizes damaged DNA, and a later identified proline-rich domain. Under stress, p53 proteins accumulate and are activated through two mechanisms. One, involving ataxia telangiectasia-mutated protein （ATM）, is that the interaction between p53 and its down-regulation factor murine double minute 2 （MDM2） decreases, leading to p53 phosphorylation on Serl 5, as determined by the post-translational mechanism; the other holds that p53 increases and is activated through the binding of ribosomal protein L26 （RPL26） or nucleolin to p53 mRNA 5＇ untranslated region （UTR）, regulating p53 translation. Under hypoxia, p53 decreases transactivation and increases transrepression. The mutations outside the DNA binding domain of p53 also contribute to tumor progress, so further studies on p53 should also be focused on this direction. The subter- ranean blind mole rat Spalax in Israel is a good model for hypoxia-adaptation. The p53 of Spalax mutated in residue 172 and residue 207 from arginine to lysine, conferring it the ability to survive hypoxic conditions. This model indicates that p53 acts as a master gene of diversity formation during evolution.