IL-33与人类疾病关系的研究进展

IL-33是近年来发现的一种具有多种生物学功能活性的细胞因子,属于IL-1家族新成员,可作为核内定位分子发挥转录因子的作用,亦可作为一种前炎性细胞因子参与组织特异性免疫病理损伤.IL-33还被认为是细胞坏死后释放的一种“警报素”,在激发免疫系统引起组织损伤或反应中发挥重要作用.近年来证实,IL-33通过与其受体ST2结合,活化胞内核转录因子(NF)-κB等信号通路,参与调节炎症反应、感染性疾病、心血管疾病及肿瘤等多种疾病的发生发展过程.     

MicroRNA-33/33* inhibit the activation of MAVS through AMPK in antiviral innate immunity

Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated. As vital orchestrators in cholesterol homeostasis, microRNA-33/33* have been widely investigated in cellular metabolism. However, their role in antiviral innate immunity is largely unknown. Here, we report that VSV stimulation decreased the expression of miR-33/33* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. In addition, miR-33/33* specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein (MAVS) from forming activated aggregates by targeting adenosine monophosphate activated protein kinase (AMPK), subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation. Our findings establish miR-33/33* as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.     

Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the human TGF-β III receptor gene

We found 11 single nucleotide polymorphisms and one triple nucleotide insertion in the cDNA of the human transforming growth factor β (TGF-β) III receptor gene (TGFBR3) located on 1p33–p32, encoding betaglycan, a component of the TGF-β receptor system. Inside the 5′ untranslated region (UTR), a G→A polymorphism was identified at position 311. In the open reading frame (ORF), a non-conservative T→C polymorphism was identified at position 392, and three conservative polymorphisms were found at positions 563 (G→A), 1548 (G→A), and 2370 (C→T). A triple nucleotide insertion (GCA) was identified at position 1419. Inside the 3′ UTR, six polymorphisms were identified: four G→A, at positions 2918, 3055, 3098, and 3355; one T→A, at position 3183; and one G→C, at position 3966. In addition to these changes, some divergences from the published sequence were observed in all 12 chromosomes tested. These included, in the ORF, an additional C after position 555, two additional G after position 563, and an additional T after position 1388. No T was found at position 1394. The alterations translate to a changed amino acid sequence. Inside the 3′ UTR, additional discrepancies were identified. The discovered changes and polymorphisms may be useful for further genetic studies of TGFBR3 receptor deficiencies. Received: December 22, 1999 / Accepted: February 25, 2000     

ATP/IL‐33‐triggered hyperactivation of mast cells results in an amplified production of pro‐inflammatory cytokines and eicosanoids

IL‐33 and ATP are alarmins, which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high‐density expression of the IL‐33 receptor T1/ST2 (IL‐33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL‐33 or ATP in damaged peripheral tissues. Whereas IL‐33 induces the MyD88‐dependent activation of the TAK1‐IKK2‐NF‐κB signalling, ATP induces the Ca²⁺‐dependent activation of NFAT. Thereby, each signal alone only induces a moderate production of pro‐inflammatory cytokines and lipid mediators (LMs). However, MCs, which simultaneously sense (co‐sensing) IL‐33 and ATP, display an enhanced and prolonged activation of the TAK1‐IKK2‐NF‐κB signalling pathway. This resulted in a massive production of pro‐inflammatory cytokines such as IL‐2, IL‐4, IL‐6 and GM‐CSF as well as of arachidonic acid‐derived cyclooxygenase (COX)‐mediated pro‐inflammatory prostaglandins (PGs) and thromboxanes (TXs), hallmarks of strong MC activation. Collectively, these data show that co‐sensing of ATP and IL‐33 results in hyperactivation of MCs, which resembles to MC activation induced by IgE‐mediated crosslinking of the FcεRI. Therefore, the IL‐33/IL‐33R and/or the ATP/P2X7 signalling axis are attractive targets for therapeutical intervention of diseases associated with the loss of integrity of cellular barriers such as allergic and infectious respiratory reactions.     

肘关节后内侧旋转不稳的研究进展

目的综述肘关节后内侧旋转不稳（posteromedial rotatory instability，PMRI）的研究进展。方法查阅国内外有关肘关节 PMRI 病理解剖、生物力学、诊断及治疗的研究文献，并进行总结分析。结果外侧韧带复合体（lateral collateral ligament complex，LCLC）损伤、内侧韧带复合体（medial collateral ligament complex，MCLC）后束损伤以及冠突前内侧面骨折是导致肘关节 PMRI 的重要因素。临床检查包括肘关节内翻及外翻应力试验等；X 线片可显示骨折情况，CT 尤其是三维重建诊断价值更大，另外 MRI、关节镜及动态超声等可辅助判断软组织损伤情况。LCLC 及 MCLC 的修复重建及冠突骨折的固定对恢复肘关节稳定性至关重要。韧带损伤的治疗有原位修复及功能重建，具体包括直接缝合、钻孔修复、带线锚钉修复、移植修补等；冠突骨折的治疗包括螺钉固定、钢板固定、不可吸收线缝合固定及关节镜技术等。结论恢复关节稳定性及早期功能锻炼是治疗肘关节 PMRI 的重要原则。根据受伤机制采用个体化治疗方案，可保护软组织、降低术后并发症及提高功能预后，最终改善患者生活质量。     

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Abstract

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.

Methods: This cross-sectional study included women with preeclampsia (n?=?106) and women with an uncomplicated pregnancy (n?=?131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.

Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p?<?0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p?=?0.7 and p?=?1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman’s Rho?=?0.72 and 0.63; each p?<?0.0001), and negatively with PlGF (Spearman’s Rho?=??0.56, p?<?0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (<37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.

Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.     

股骨转子间骨折的稳定性重建概念演化与研究进展

目的总结近年来股骨转子间骨折在稳定性重建方面的概念演化与研究进展。方法查阅国内外相关文献并结合自身经验，从股骨转子间骨折的解剖特点、稳定型骨折与不稳定型骨折分类、稳定性复位与不稳定性复位、术中加压初始稳定与术后滑动二次稳定、内固定术后稳定性评估、早期下地站立负重等方面进行总结分析。结果股骨转子间骨折发生于股骨颈干骺端转换区，具有天然的内翻不稳定倾向。骨折复位质量是影响后续内固定物安放的最重要前提因素。判断骨折复位质量有对线和对位两方面，对线采用 Garden 指数；在对位方面，随着皮质对位理念（正性、中性、负性）的提出，特别强调前内侧皮质的相互砥住支撑（解剖、正性），是获得骨折稳定性复位的关键，而不再强调后内侧小转子骨块的作用。术后影像学的稳定性评分为早期下地站立负重提供了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动获得二次稳定的过程中，仍有皮质对位丢失现象，需研究其危险因素和防范措施。结论股骨转子间骨折在取得良好对线的基础上，只要获得了前内侧皮质的相互砥住和支撑，并用内固定器械维持住，就获得了术后稳定性。术后稳定性评分优良者，可以安全地早期下地负重、站立行走活动。