隔药灸神阙八阵穴对术后粘连性肠梗阻患者疗效及炎性反应因子的影响

目的：探讨隔药灸神阙八阵穴对术后粘连性肠梗阻（AIO）患者疗效及血清白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平的影响。方法：选取2013年1月至2017年4月唐山市人民医院收治的行腹腔手术患者280例作为研究对象，按照随机数字表法随机分为对照组和观察组，每组140例，对照组采用常规治疗；观察组在对照组基础上给予隔药灸神阙八阵穴，均治疗1周。比较2组患者临床疗效、治疗后肠功能评分、治疗前后胃动素（MOT）水平、IL-6、TNF-α水平。结果：观察组总有效率为91.43%，显著高于对照组77.14%（P<0.05）；治疗后，观察组恢复排气时间、腹部症状缓解时间、肠鸣音恢复时间均短于对照组（P<0.05）、2组患者MOT水平均低于治疗前，且观察组的MOT水平低于对照组（P<0.05）、2组患者的血清IL-6、TNF-α水平均显著低于治疗前，且观察组的血清IL-6、TNF-α水平均低于对照组（P<0.05）。结论：隔药灸神阙八阵穴治疗AIO疗效显著，能改善患者胃肠功能，降低MOT水平，有效调节血清IL-6、TNF-α水平。     

Aberrant expression of Wnt/β-catenin signaling pathway genes in aggressive malignant gastric gastrointestinal stromal tumors

IntroductionRecent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis.Materials and methodsWe investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands.ResultsGEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7.ConclusionWnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST.     

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。     

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.     

结核病患者外周血γ干扰素释放试验假阴性的相关因素分析

目的 分析影响结核病患者外周血γ干扰素释放试验(interferon-gamma release assay,IGRA)检测假阴性的影响因素。方法 回顾性分析2018年1月至2020年3月解放军总医院第八医学中心结核四科收治的资料完整、外周血IGRA检测阴性和阳性的结核病患者,分别作为IGRA假阴性组(38例)和IGRA阳性组(119例),收集其一般情况、病史特点、血清生化指标和外周血淋巴细胞亚群,采用单因素和多因素logistic回归分析导致IGRA检测结果假阴性的影响因素。结果 IGRA假阴性组淋巴细胞计数、T细胞计数、CD4⁺T细胞计数、CD8⁺T细胞计数、NKT细胞计数M(Q₁,Q₃)分别为1.15(0.77,1.58)×10⁹个/L、867.50(508.75,1135.50)个/μl、493.00(256.00,673.75)个/μl、254.50(170.25,429.25)个/μl、38.50(16.50,88.25)个/μl,均明显低于IGRA阳性组[分别为1.46(0.99,1.88)×10⁹个/L、1013.00(667.00,1394.00)个/μl、590.00(386.00,850.00)个/μl、335.00(232.00,561.00)个/μl、57.00(30.00,121.00)个/μl,差异均有统计学意义(Z值分别为-2.512、-2.143、-2.092、-2.303、-2.338,P值分别为0.012、0.032、0.036、0.021、0.019)。logistic回归分析结果显示,NKT细胞计数低于正常值(<40个/μl)的患者,IGRA检测出现假阴性的风险是NKT细胞计数正常者的2.440倍(95%CI:1.159~5.134)。结论 NKT细胞计数的减少可能导致外周血IGRA出现假阴性。     

A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26–104/RFASE in Patients with Advanced Solid Malignancies

Lessons Learned

• The novel therapeutic vaccine hVEGF_26–104/RFASE was found to be safe and well tolerated in patients with cancer.
• hVEGF_26–104/RFASE failed to induce seroconversion against native hVEGF₁₆₅ and, accordingly, neither a decrease in circulating vascular endothelial growth factor (VEGF) levels nor clinical benefit was observed.
• Remarkably, hVEGF_26–104/RFASE induced VEGF₁₆₅-neutralizing antibodies in a nonhuman primate model. The absence of seroconversion in human calls for caution in the interpretation of efficacy of human vaccines in nonhuman primates.

     

MiR-92b-3p ameliorates inflammation and autophagy by targeting TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. Dysregulation of microRNAs (miRNAs) was involved in human diseases, including AP. However, the effects of miR-92b-3p on AP process and its mechanism remain not been fully clarified. The expression levels of miR-92b-3p and tumor necrosis factor receptor-associated factor-3 (TRAF3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of TRAF3, tumor necrosis factor α (TNF-α) TNF-α, interleukin-6 (IL-6), phosphorylated mitogen-activated protein kinase kinase 3 (p-MKK3), MKK3, p38 and phosphorylated p38 (p-p38) were detected by western blot. The concentration of TNF-α and IL-6 in the medium was measured using ELISA kits. The possible binding sites of miR-92b-3p and TRAF3 were predicted by TargetScan and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression level of miR-92b-3p was decreased and TRAF3 expression was increased in AR42J cells stimulated with caerulein. Moreover, the protein levels of pro-inflammatory cytokines (TNF-α and IL-6) were markedly elevated, and the expression levels of autophagy-related markers Beclin1 as well as the ratio of LC3-II/I were obviously increased in AR42J cells treated with caerulein. In addition, overexpression of miR-92b-3p or knockdown of TRAF3 significantly suppressed the release of pro-inflammatory cytokines and autophagy in caerulein-induced AR42J cells. Furthermore, TRAF3 was a direct target of miR-92b-3p and its upregulation reversed the effects of miR-92b-3p overexpression on inflammatory response and autophagy. Besides, overexpression of miR-92b-3p inhibited the activation of the MKK3-p38 pathway by affecting TRAF3 expression. In conclusion, miR-92b-3p attenuated inflammatory response and autophagy by downregulating TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells, providing a novel avenue for treatment of AP.