拷贝数变异及单核苷酸变异基因型自闭症动物模型 研究进展

孤独症谱系障碍（autism spectrum disorders，ASD）是一种起始于婴幼儿时期的神经发育障 碍性疾病，除社会交往障碍、认知缺失、重复刻板行为等核心症状外，还存在明显的多感官异常，其中 ASD患者疼痛异常会做出重复性的自我伤害行为，这种障碍不仅给患者也对其家庭造成了较为严重的 伤害，引起家庭和社会的广泛关注。对患儿疼痛敏感程度及影响疼痛敏感性的原理及机制进行深入研 究，不仅可以减轻患儿的痛苦体验，也能够为ASD患儿治疗方面提供新的思路。现对近年来在ASD 人 群中流行病学、临床实验、遗传学、影像学及ASD 动物模型的痛觉敏感程度及可能机制的研究进行综述， 在今后的研究中，可以尝试探索优化干预方案，为进一步推广临床提供理论依据。     

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose–response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HR_{Tertile 3 vs. 1} 2.05; 95% confidence interval [CI] 1.23–3.41) and death from this disease (SHR_{Tertile 3 vs. 1} 1.97; 95% CI 1.13–3.41). Similar results were obtained for DII score from food only. A nonlinear dose–response pattern was identified for the aforementioned associations (all p_nonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

黄芪甲苷调节miR-21基因抑制肾癌细胞增殖和诱导细胞凋亡的机制探讨

目的:探讨黄芪甲苷对肾癌细胞增殖、凋亡的影响及其作用机制。方法:用终浓度为20 μmol/L、40 μmol/L、80 μmol/L、160 μmol/L的黄芪甲苷处理肾癌细胞A498作为不同浓度黄芪甲苷处理组，正常培养的细胞作为对照（NC）组；将anti-miR-con、anti-miR-21转染至细胞A498中，记为anti-miR-con组、anti-miR-21组；将miR-con、miR-21转染至细胞A498中再用80 μmol/L黄芪甲苷处理作为HSJG+miR-con组、HSJG+miR-21组。四甲基偶氮唑盐比色法（MTT）检测细胞存活率；蛋白质印迹（Western Blot）检测裂解半胱氨酸天冬氨酸蛋白酶-3（Cleaved-caspase-3）、细胞周期蛋白D1（Cyclin D1）蛋白表达水平；流式细胞术检测细胞凋亡；实时荧光定量PCR（RT-qPCR）检测miR-21表达水平。结果:与对照组相比，不同浓度黄芪甲苷处理组肾癌细胞A498中细胞存活率显著降低，Cyclin D1表达水平显著降低，Cleaved-caspase-3表达水平显著升高，细胞凋亡率显著升高，小鼠肿块重量显著降低，miR-21表达水平显著降低（P＜0.05）。miR-21低表达Cyclin D1表达水平显著降低，Cleaved-caspase-3表达水平显著升高，细胞存活率显著降低，细胞凋亡率显著升高（P＜0.05）。miR-21高表达逆转了黄芪甲苷对肾癌细胞A498增殖抑制和凋亡促进的作用。结论:黄芪甲苷可抑制肾癌细胞A498增殖，促进细胞凋亡，抑制肾癌实体瘤的生长，其机制可能与miR-21表达水平有关。     

Diverting colostomy is an effective and reversible option for severe hemorrhagic radiation proctopathy

A total of 738 continual CRP patients were screened.After exclusion,14 patients in the colostomy group and 25 in the conservative group were included in the final analysis.Preoperative Hb was only 63 g/L±17.8 g/L in the colostomy group compared to 88.2 g/L±19.3 g/L(P<0.001)in the conservative group.All 14 patients in the former group achieved complete remission of bleeding,and the colostomy was successfully reversed in 13 of 14(93%),excepting one very old patient.The median duration of stoma was 16(range:9-53)mo.The Hb level increased gradually from 75 g/L at 3 mo,99 g/L at 6 mo,and 107 g/L at 9 mo to 111 g/L at 1 year and 117 g/L at 2 years after the stoma,but no bleeding cessation or significant increase in Hb levels was observed in the conservative group.Endoscopic telangiectasia and bleeding were greatly improved.Endoultrasound showed decreased vascularity,and magnetic resonance imaging revealed an increasing presarcal space and thickened rectal wall.Anorectal functions and quality of life were significantly improved after stoma reversal,when compared to those before stoma creation.CONCLUSION Diverting colostomy is a very effective method in the remission of refractory hemorrhagic CRP.Stoma can be reversed,and anorectal functions can be recovered after reversal.     

The MHC class I‐LILRB1 signalling axis as a promising target in cancer therapy

Immune checkpoint inhibitors are among the newest, cutting‐edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD‐1/PD‐L1 and CTLA‐4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the “Don't Eat Me” molecule, CD47, antibody‐based drugs that target the macrophage‐related innate immunosuppressive signalling pathway, CD47‐SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti‐CD47 antibodies, a second “Don't Eat Me” molecule on tumour cells, beta 2 microglobulin (β2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express β2m complexed with the MHC class I heavy chain to send a “Don't Eat Me” signal by binding to leucocyte immunoglobulin‐like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I‐LILRB1 signalling axis in tumour‐associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical‐based tumour immunotherapy.     

Quorum-sensing systems trigger catalase expression to reverse the oxyR deletion-mediated VBNC state in Salmonella typhimurium

OxyR is an important regulatory protein that plays a key role in anti-oxygenation, and its deletion causes a special VBNC (Viable But Non-Culturable) state in many bacteria including Salmonella typhimurium. The S. typhimurium in the VBNC state can grow in LB broth but cannot grow on an LB plate unless its concentration is sufficiently high. However, the mechanism that reverses this state is not clear. In this study, conditioned media containing autoinducer collected from the wild type strain can restore the growth of low concentrations of the oxyR mutant strain on LB plates, and S. typhimurium collected from the plate has higher catalase activity than that from the broth, suggesting that a quorum-sensing system can trigger catalase expression to resuscitate the organism from the VBNC state independent of the OxyR regulon. We discovered a novel catalase (STM14_2049, Cat) whose expression is strictly concentration-dependent. The purified Cat protein has obvious catalase activity in vitro and in vivo and can restore the growth of the low concentration oxyR mutant strain. Thus, we believed Cat plays a role in VBNC resuscitation process. By understanding this mechanism, we can further understand the antioxidation and quorum-sensing systems in Salmonella typhimurium.     

环状RNA在慢性阻塞性肺疾病诊断及预后判断中的研究价值

目的探讨血清环状核糖核酸(circRNA)在慢性阻塞性肺病(COPD)诊断及预后判断中的研究价值。 方法选择连云港市第二人民医院2014年1月至2016年12月收治的80例COPD患者以及同期在该院进行健康体检人群30例为研究对象进行回顾性随机对照研究，其中男性58例，女性52例；年龄61~82岁，平均(70±6)岁。通过Arraystar circRNA芯片筛选获得两组受试者血清样本中差异表达的circRNA，再利用qRT-PCR验证了获得的目标circRNA分子，并结合生物信息学软件对其进行注释和功能预测。 结果本研究对circRNA-001988、circRNA-0000344和circRNA-0000284在COPD组和正常组血清中的表达的差异进行了探究：发现与正常组相比，circRNA-001988和circRNA-0000344在COPD组血清样本中的表达分别下调了(6.54±2.75)倍和(5.94±2.89)倍；circRNA-0000284则在COPD组的血清样本中上调表达了(8.54±3.25)倍。差异均有统计学意义(P<0.05)。 结论血清circRNA可作为COPD诊断和预后判断的生物标志物，具有较好的临床预测价值。