The effect of short‐term intensive insulin therapy on inflammatory cytokines in patients with newly diagnosed type 2 diabetes

BackgroundDiabetes mellitus was a chronic low‐grade inflammatory disease and had increased circulating inflammatory cytokines and acute phase proteins. We aimed to identify the changes of inflammatory cytokines in newly diagnosed type 2 diabetic patients after short‐term intensive insulin therapy using continuous subcutaneous insulin infusion (CSII).MethodsThirty‐three newly diagnosed type 2 diabetic patients were enrolled between September 2020 to December 2020. Expression of 40 inflammatory cytokines of the patients were tested with RayBiotech antibody array before and after 1 week of intensive insulin therapy of CSII. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out to explore the signaling pathway involved in the therapy.ResultsFive inflammatory cytokines were downregulated significantly after 1 week of CSII therapy. They were interleukin‐6 receptor (IL‐6R), regulated upon activation normal T‐cell expressed and secreted (RANTES), intercellular adhesion molecule‐1 (ICAM‐1), tissue inhibitor of metalloproteinase‐1 (TIMP‐1), and platelet‐derived growth factor type BB (PDGF‐BB) (p < 0.05 and foldchange <0.83). Among patients with baseline glycated hemoglobin (HbA1c) < 10%, three proinflammatory cytokines were decreased significantly after therapy: IL‐6R, RANTES, and ICAM‐1. As for the patients with baseline HbA1c ≥ 10%, eight inflammatory cytokines were inhibited significantly after the treatment, including ICAM‐1, IL‐6R, RANTES, TIMP‐1, TIMP‐2, macrophage inflammatory protein‐1 beta (MIP‐1β), PDGF‐BB, and tumor necrosis factor receptor type II (TNF RII). No matter which subgroup of baseline HbA1c level was considered, the decreased cytokines after CSII therapy were significantly involved in TNF signaling pathway. Nuclear factor‐kappa B (NF‐κB) signaling pathway was mainly enriched in patients with baseline HbA1c ≥ 10%.ConclusionsA panel of 40 inflammatory cytokines, measured by protein microarray, were evaluated for 1 week of CSII treatment in newly diagnosed type 2 diabetic patients. After treatment, many proinflammatory cytokines decreased. In the higher baseline HbA1c subgroup, more proinflammatory cytokines improved. No matter which subgroup of HbA1c level was considered, IL‐6R, RANTES, and ICAM‐1, which were involved in TNF signaling pathway, decreased significantly after CSII therapy. This was the first report showing that the cytokines of IL‐6R, TIMP‐2, PDGF‐BB, and TNF RII decreased after the CSII therapy.     

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse‐1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2‐photon microscopy, we analyzed the effects of DNAse‐1 on NETs in mouse orthotopic lung allografts damaged by ischemia‐reperfusion injury. Although DNAse‐1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4⁺ T cells and donor‐derived antigen presenting cells. DNAse‐1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen‐specific CD4⁺ T cell proliferation through activating toll‐like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil‐specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse‐1 administration to wild‐type recipients promotes the recognition of allo‐ and self‐antigens and prevents immunosuppression‐mediated lung allograft acceptance through a MyD88‐dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.     

Protective effect of glutamine-enriched early enteral nutrition on intestinal mucosal barrier injury after liver transplantation in rats

Background

The effect of glutamine-enriched early enteral nutrition (Gln-EEN) on intestinal mucosal barrier injury after liver transplantation (LT) remains uncertain.

Methods

The Wistar-to-Wistar rat LT model was used to explore the protective effect of Gln-EEN. Morphologic changes of intestinal mucosa, levels of intestinal malondialdehyde and secretory immunoglobulin (sIgA), plasma endotoxin, D-lactic acid, serum tumor necrosis factor-α (TNF-α), rates of bacterial translocation, and expression of intestinal nuclear factor-κB, TNF-α, and intercellular adhesion molecule-1 were determined.

Results

After LT, intestinal mucosa was damaged seriously. At 12, 24, and 48 hours posttransplantation, levels of intestinal sIgA were decreased; levels of malondialdehyde, endotoxin, D-lactic acid, and TNF-α, the ratio of bacterial translocation, and the expression of intestinal nuclear factor-κB, TNF-α, and intercellular adhesion molecule-1 all were increased. However, changes in earlier-mentioned parameters in recipients treated with Gln-EEN were attenuated remarkably at 24 to 48 hours.

Conclusions

Our data show that Gln-EEN is a potent protectant against intestinal mucosal barrier injury after LT.     

散发性乳腺癌中BRCA1和BRCA2基因突变的研究

目的检测BRCA1和BRCA2基因在散发性乳腺癌中的突变情况,探讨BRCA1和BRCA2基因突变与乳腺癌的关系。方法选取2000年12月至2005年9月收治的144例乳腺癌患者标本作实验组,另取非癌乳腺组织标本30例作对照组。用酚-氯仿抽提法提取DNA。针对各个外显子的碱基序列特征,设计有助于筛查基因碱基突变的聚合酶链反应（PCR）引物。每例DNA标本均用PCR扩增BRCA1基因的全部22个外显子和BRCA2基因的exon10和exon14两个外显子。分别将每例外显子的PCR扩增产物进行单链构象多态性分析,对泳动变位或出现异常区带的PCR扩增产物进行DNA测序。结果对照组未检测出BRCA1和BRCA2基因突变,实验组中检测出20例BRCA1基因碱基改变,总突变率为13．9％,其中错义突变率为11．1％。BRCA2基因exon10和exon14未检测出突变。结论BBCA1突变与乳腺癌密切相关,筛查BRCA1基因突变对于中国人群乳腺癌患病风险评估、早期诊断及基因治疗具有重要意义。     

IL-1β对ATDC5成软骨分化细胞miR-455-3p的影响

目的：检测IL-1β对ATDC5成软骨分化细胞miR-455-3p表达的影响,探索miR-455-3p在骨关节炎中的作用。方法诱导ATDC5细胞成软骨分化后,予10 ng/ml的IL-1β刺激,在刺激4、12、24、48 h时应用实时荧光定量PCR检测miR-455-3p、C/EBPβ和软骨特征性标记物的表达情况;并利用抑制剂IKK-NBD阻断NF-κB通路后,应用实时荧光定量PCR检测IL-1β作用下miR-455-3p的表达水平。结果在IL-1β作用下的ATDC5成软骨分化细胞中miR-455-3p、C/EBPβ和软骨退变标记物（ MMP13、ADAMTS5）均上调,而软骨基质合成标记物（ ACAN、COL2A1、SOX9）则下调,且后期更为明显;而IKK-NBD可抑制IL-1β诱导的miR-455-3p表达。结论 IL-1β可上调ATDC5成软骨分化细胞miR-455-3p的表达水平,且受NF-κB通路的调节。     

公正世界信念在大学生攻击行为与心理弹性之间的中介作用

为了解大学生攻击行为、心理弹性和公正世界信念之间的关系,为大学生心理健康和职业素养研究提供科学依据.于2019年12月,采用Buss-Perry攻击行为问卷、Connor-Davidson心理弹性问卷中文版和公正世界量表对576名大学生进行问卷调查.结果显示:在攻击行为方面,不同性别医学生在攻击行为问卷总分差异无统计学...     

一例典型的同心圆性硬化报告并文献复习

同心圆性硬化(Balo病)是一种罕见的中枢神经系统脱髓鞘疾病,我们最近收治一典型病例,现报告如下。患者,女,49岁,当地农民。因“头晕头痛半年,左侧肢体乏力1月余”于2005年11月10日入院。患者于半年前无明显诱因下开始出现头晕头痛,以劳累后为主,休息后可缓解,当     

正念减压疗法联合化疗对骨髓瘤骨病患者生存质量的影响

目的探究正念减压疗法联合化疗对提高骨髓瘤骨病患者的生存质量及疾病缓解率的效果,为改善骨髓瘤骨病患者的生活质量和治疗依从性提供参考。方法选取2018年1月-2020年1月在绵阳市第三人民医院血液科住院治疗的84例骨髓瘤骨病患者为研究对象,采用随机数字表法分为研究组和对照组各42例,两组患者均按BDT(硼替佐米+地塞米松+沙利度胺)化疗方案治疗3~5个周期,研究组在此基础上接受为期8周的正念减压疗法干预。在干预前、干预后第3月、第6月采用卡氏评分表(KPS)评定生存质量,采用疼痛强度数字评分(NRS)评定骨痛程度,按照国际骨髓瘤工作组疗效标准(IMWG标准)进行疗效评估。结果干预后第6个月,研究组和对照组生活质量改善率差异有统计学意义(61.90%vs.33.33%,χ2=6.65,P<0.05)。干预后第3个月及第6个月,研究组NRS评分均低于对照组,差异均有统计学意义(P均<0.05),但两组疾病缓解程度比较差异均无统计学意义(P均>0.05)。结论正念减压疗法联合化疗对改善骨髓瘤骨病患者生存质量、缓解骨痛的效果可能优于单纯传统化疗。