(Re)organisation of the somatosensory system after early brain lesion: A lateralization index fMRI study

ObjectiveTo evaluate the relationship between neural (re)organization of the somatosensory cortex and impairment of sensory function (2-point discrimination [2PD]) in individuals with unilateral cerebral palsy.MethodsWe included 21 individuals with unilateral cerebral palsy. 2PD thresholds were evaluated on thumb pads, and activation of the somatosensory cortex was recorded by functional MRI (fMRI) during passive movements of the affected hand. A lateralization index (LI) was calculated for the primary sensory (S1) and secondary sensory (S2) cortices and the correlation between the LI and 2PD thresholds was analysed.ResultsWe found a significant negative correlation between the 2PD thresholds and the S2 LI (r = −0.5, one-tailed P-value = 0.01) and a trend towards a negative correlation with the S1 LI (r = −0.4, one-tailed P-value = 0.05).ConclusionHigh levels of activation in the contralesional hemisphere were associated with high levels of sensory impairment in individuals with unilateral cerebral palsy. The interhemispheric (re)organization of the somatosensory system may not effectively compensate for somatosensory impairment.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

早期胃癌内镜治疗后追加外科手术病例特点、适应证和术式选择

内镜治疗技术的发展进一步推动了早期胃癌的微创治疗。然而，随之而来的问题是，部分接受内镜治疗的病人会出现非治愈性切除。早期胃癌内镜治疗后非治愈性病人的后续处理原则值得进一步关注。结合欧洲肿瘤内科学会（ESMO）、美国国家综合癌症网络（NCCN）及日本胃癌学会等国际指南及相关临床研究并回顾分析单中心数据后可得出结论，eCura-C的病人具有相对较高的癌残留风险，在与病人充分沟通后可考虑追加手术，但仍有较高的术后病理学无癌残留的风险。术式选择和切除范围可参考早期胃癌相关规定。如何准确预测非治愈性病人的淋巴结转移仍是未来的重点。前哨淋巴结活检及腹腔镜内镜联合手术是未来的发展方向。     

基于机器学习的脑胶质瘤多模态影像分析

脑部胶质瘤是临床中常见的一种原发性脑肿瘤，具有复发率高、死亡率高以及治愈率低的特点。常规临床诊断主要依靠计算机断层扫描(CT)和磁共振成像(MRI)检查技术进行鉴别。随着成像技术和机器学习方法的不断发展，多模态影像智能分析技术已经逐步成为研究热点，在脑胶质瘤的病灶分割测量、肿瘤分级、预后生存周期预测和基因型辨别等方面具有重要的应用前景。本文重点介绍基于机器学习和多模态影像在脑胶质瘤临床辅助诊断和预后评估中的应用进展。     

程序性死亡蛋白-1抗体治疗晚期胃癌的临床研究新进展

目前化疗仍为晚期胃癌的标准治疗手段,而多数患者诊断时已接近晚期。近年新兴的免疫治疗手段程序性死亡蛋白-1(PD-1,programmed death l)抗体,通过阻断肿瘤细胞逃避自身免疫机制,重新激活自身免疫对肿瘤的杀伤作用,从而达到肿瘤的治疗作用。针对晚期胃癌的PD-1抗体治疗的临床研究已在国内外开展,大部分均有较好效果。本文对近年免疫治疗中的PD-1抗体在晚期胃癌的重要临床研究进展进行介绍。