Association between R1 resection and oncological outcome in resectable gastrointestinal stromal tumors without tumor rupture: A systematic review and meta-analysis

BackgroundThe influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly associated with the occurrence of R1 resection and may be a confounder of R1 resection in GISTs. The present meta-analysis evaluated the real influence of R1 resection on the prognosis of GISTs by excluding the confounding effect of tumor rupture.MethodsThe PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were searched. Studies that compared R1 with negative microscopic margin (R0) resection in GIST patients and reported the time-to-event data of recurrence-free survival (RFS) or disease-free survival (DFS) were eligible for inclusion. The quality of the observational studies was assessed using the Newcastle–Ottawa scale.ResultsOf the 4896 records screened, 23 retrospective studies with 6248 participants were selected. In the overall analysis, R1 resection resulted in a significantly shorter RFS/DFS than R0 resection for GISTs (HR = 1.80, 95% CI = 1.54–2.10, P < 0.001, I² = 14%). However, the inferior RFS/DFS vanished when tumor rupture cases were excluded (HR = 1.34, 95% CI = 0.98–1.83, P = 0.07, I² = 33%). Sensitivity analysis by high-quality studies brought about a more robust HR of 1.15 (95% CI = 0.88–1.50, P = 0.29), with low heterogeneity (I² = 0%). The qualities of evidence for the outcomes were high.ConclusionsThis meta-analysis shows that R1 resection did not influence the survival outcome of GISTs. Reresection may not be necessary when positive microscopic margins exist. This analysis could provide high-quality evidence for the development of guidelines.     

GLP-1类似物在糖尿病肾病患者中的疗效分析

目的观察胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)类似物对2型糖尿病早期肾病患者的肾脏保护作用。方法2017年11月—2019年12月间选取使用GLP-1类似物并参与随访的2型糖尿病早期肾病患者30例,收集患者治疗6个月前后的体重,体质指数(body mass index,BMI),腰围,臀围,血糖,生化指标等,计算胰岛β细胞功能相关指标,进行对比分析。结果治疗后腰围、2 hPG、HbA1c、HOMA-IR、TC、TG、ALB、MA/Cr、UA较治疗前降低,HOMA-β较治疗前升高,差异有统计学意义(P<0.05)。Pearson相关性分析示:HbA1c与MA/Cr呈负相关性(r=-0.421,P<0.05);HOMA-β、TG、TC、UA与MA/Cr呈正相关性(r=0.777,P<0.05;r=0.757,P<0.05;r=0.470,P<0.05;r=0.443,P<0.05)。HbA1c与ALB呈负相关性(r=-0.433,P<0.05);HOMA-β、TG、TC、UA与ALB呈正相关性(r=0.723,P<0.05;r=0.756,P<0.05;r=0.493,P<0.05;r=0.374,P<0.05)。结论GLP-1类似物对2型糖尿病早期肾病患者有较好的降糖、调脂、改善胰岛功能、保护肾脏的作用,而且降血糖、降血脂、改善胰岛功能可能有益于肾脏保护。     

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

BackgroundMajor depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.MethodsMDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.ResultsMDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.ConclusionWithin MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.Registration of clinical trialsThe ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”     

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

整合素α5β1在苯妥英钠促进大鼠PDLSCs和BMMSCs黏附于牙骨质中的作用

目的 探讨在苯妥英钠(Phenytoin,PHT)促进大鼠牙周膜干细胞(Rat periodontal ligament stem cells,rPDLSCs)、大鼠骨髓间充质干细胞(Rat Bone Marrow Mesenchymal Stem Cells,rBMMSCs)黏附于牙骨质过程中,整合素α5β1(Integrin α5β1)起到的作用。方法 提取大鼠BMMSCs和PDLSCs,培养并纯化。通过细胞鉴定后,将获得的两种细胞各分为4组:40 mg/L PHT处理组、40 mg/L PHT+整合素α5抗体处理组、40 mg/L PHT+整合素β1抗体处理组、PBS处理组,每组细胞放入置有牙骨质片的96孔板处理4 h后,检测黏附于牙骨质片上的细胞量并做以比较。最后,利用qRT-PCR和Western blot检测40 mg/L PHT组与对照组细胞的整合素α5、β1亚基的mRNA与蛋白表达量。结果 40 mg/L PHT可促进rBMMSCs及rPDLSCs黏附于牙骨质片,加入整合素α5、β1抗体后,均明显抑制了40 mg/L PHT对rBMMSCs、rPDLSCs黏附于牙骨质的促进作用(P＜0.01)。qRT-PCR、Western-blot结果显示PHT处理组的整合素α5、β1亚基表达量高于空白对照组(P＜0.05)。结论 40 mg/L PHT能促进rBMMSCs、rPDLSCs黏附于牙骨质,该作用与整合素α5β1的表达上调密切相关。     

磁敏感加权成像黑质“燕尾征”在帕金森病中的诊断价值

目的:探讨3.0 T磁敏感加权成像(susceptibility weighted imaging,SWI)中"燕尾征"缺失在帕金森病(Parkinson's dis-ease,PD)的诊断价值并分析黑质小体-1 (nigrosome-1)可视化与PD患者临床资料的相关性.方法:收集2017年9月至2019年11月于重庆医科大学附属第一医院神经内科住院的50例PD患者及年龄、性别与之匹配的57例非PD患者.所有受试者均接受3.0 T头颅SWI检查.在获得的SWI图像上,由2名临床医师采用盲法独立对双侧"燕尾征"进行评估.一侧"燕尾征"缺失即判定为PD.计算"燕尾征"缺失诊断PD的灵敏度、特异度、预测值和准确度,并分析nigrosome-1可视化与PD患者临床资料的相关性.结果:以临床诊断作为金标准,45例PD患者判断正确,评估者之间的一致性很高(k=0.963,P=0.000)."燕尾征"缺失诊断PD的灵敏度为90.0％,特异度为91.2％,阳性预测值为90.0％,阴性预测值为91.2％,准确度为90.7％.44例PD患者临床症状不对称,其中32例患者nigrosome-1可视化不对称.PD患者nigrosome-1可视化偏侧和临床症状偏侧比较差异无统计学意义(x2=5.756,P=0.056).11例PD患者双侧nigrosome-1全部缺失,纳入全部缺失组,其余PD患者为非全部缺失组.全部缺失组和非全部缺失组患者的汉密尔顿抑郁量表评分差异有统计学意义(U=126.500,P=-0.038),而病程、帕金森病统一评定量表第Ⅲ部分、改良Hoehn-Yahr(H-Y)分级、简易智能状态量表和蒙特利尔认知评估量表评分差异均无统计学意义(P=0.768、0.140、0.839、0.054、0.067).结论:"燕尾征"缺失诊断PD的准确率较高,缺失程度可能与PD患者的抑郁程度有关,对PD的诊断有一定参考价值.     

Single and combined effect of bisphenol A with high sucrose diet on the diabetic and renal tubular dysfunction phenotypes in Drosophila melanogaster

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction.