Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.     

Aortitis no infecciosa: experiencia con tocilizumab en un hospital comarcal

ObjectivesDescribe patients with noninfectious aortitis and their response to treatment in a regional hospital.MethodsReview of patients with noninfectious aortitis, diagnostic technique used and immunosuppressive therapy received.ResultsWe report 8 patients (7 women and one man) diagnosed with aortitis by positron emission tomography (PET). The mean age was 69 years (interquartile range [IQR] 62-72.2). Three months of treatment with tocilizumab improved symptoms, erythrocyte sedimentation rate and C-reactive protein level (P < .001 and P < .012, respectively) in the 6 patients in whom it was used.ConclusionsTocilizumab was an effective and safe treatment in those patients diagnosed with aortitis refractory to steroids and conventional immunosuppressive therapy.     

Assessing the CT findings and clinical course of ED patients with first-time versus recurrent acute pancreatitis

Study objectives

The primary objective of this study was to compare Emergency Department patients with first-time versus recurrent acute pancreatitis.

心血管内科临床实习教学中引入微课的应用研究

目的 为了满足学生的个性化学习需求、推动教育信息化，探究“微课”教学模式在心血管内科临床实习教学中的应用情况。方法 纳入2016 年1-9月西安交通大学第二附属医院在心血管内科实习的学生98例，随机地将其分为对照组和观察组，对照组实习生进行传统实习教学，观察组实习生在传统实习教学中引入“微课”教学模式，对比两组在心血管内科实习的理论和技能考核成绩，并且进行对心内科实习教学满意度情况的调查。结果 观察组实习生的临床技能考核成绩显著高于对照组，差异有显著性(P<0.05)。并且，观察组对心血管内科教学方法满意度明显高于对照组，差异有显著性(P<0.05)。结论 将“微课”模式引入心血管内科临床实习教学中可显著增强实习生对临床操作技能的掌握，并且可增强实习生对心血管内科实习教学的满意度     

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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原发性卵巢非霍奇金淋巴瘤1例及相关文献复习

目的:探讨原发性卵巢弥漫性大B细胞淋巴瘤的病因、临床表现、诊断、治疗及预后。方法:报道1例原发性卵巢弥漫性大B细胞淋巴瘤的临床病理资料及术后免疫组化结果，并阅读及复习国内外相关文献。结果:该例患者为（右）卵巢弥漫性大B细胞淋巴瘤，积极治疗后现考虑肿瘤复发。结论:原发性卵巢弥漫性大B细胞淋巴瘤罕见，确诊依赖于术后病理及免疫组化，预后不佳，常采用以手术为主，辅以化疗和放疗的综合治疗。     

Chiauranib selectively inhibits colorectal cancer with KRAS wild-type by modulation of ROS through activating the p53 signaling pathway

Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiauranib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiauranib in the treatment of CRC remain to be elucidated. Our study shows that Chiauranib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiauranib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiauranib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiauranib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiauranib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiauranib. Our findings provide the rationale for further clinical evaluation of Chiauranib as a therapeutic agent in treating KRAS wild-type CRC.     

Activated hepatic stellate cells promote progression of post-heat residual hepatocellular carcinoma from autophagic survival to proliferation

Background: Microscopic residual tumor often occurs after thermal ablation for medium-large hepatocellular carcinoma (HCC), leading to early aggressive recurrence or late relapse during follow-up. The mechanism how microscopic residual HCC cells survive sublethal heat stress and develop rapid outgrowth remains poorly understood.

Methods: HCC cells were exposed to sublethal heat treatment and co-cultured with conditioned media from activated HSCs (HSC-CM). Changes of cell proliferation, parameters of cell autophagy and activation of signaling pathways in heat-treated residual HCC cells were analyzed. An HCC orthotopic model was subjected to partial thermal ablation and antitumor effects of a combined treatment regimen were studied.

Results: HCC cells survived sublethal heat stress via activation of autophagy. HSC-CM enhanced autophagic survival within 24?h and then promoted proliferation of heat-treated residual HCC cells through HGF/c-Met signaling. Inhibition of autophagy or c-Met increased apoptosis of heat-treated residual HCC cells and reversed the protective effect of HSC-CM. HGF modulated biological status in autophagic survival or proliferation of heat-treated residual HCC through HGF/c-Met/ERK signaling and downstream components of ATG5/Beclin1 or cyclinD1. In an animal model, inhibiting autophagy in combination with c-Met inhibitor significantly thwarted tumor progression of residual HCC after incomplete thermal ablation via the suppressed autophagy, the decreased proliferation and the increased apoptosis.

Conclusions: Activated HSCs promote progression of residual HCC cells after sublethal heat treatment from autophagic survival to proliferation via HGF/c-Met signaling. A combined treatment regimen of inhibiting autophagy and c-Met signaling could be used to suppress tumor progression of residual HCC after incomplete thermal ablation.