Identification of peptides presented through the MHC-II of dendritic cells stimulated with Mycobacterium avium

Mycobacterium avium (M. avium) represents a species of concern, because of its ability to modulate the host’s innate immune response, and therefore influence trajectory of adaptative immunity. Since eradicative response against mycobacteria, and M. tuberculosis/M. avium, relies on peptides actively presented on a Major Histocompatibility complex-II (MHC-II) context, we assessed paradoxical stimulation of Dendritic Cell resulting on immature immunophenotype characterized by membrane minor increase of MHC-II and CD40 despite of high expression of the pro-inflammatory tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in supernatants. Identification of M. avium leucine rich peptides forming short α-helices shutting down Type 1T helper (Th1), contribute to the understanding of immune evasion of an increasingly prevalent pathogen, and may provide a basis for future immunotherapy to infectious and non-infectious disease.     

Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while β-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of β-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of β-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of β-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.     

新型冠状病毒疫苗接种后发生急性荨麻疹19例临床分析

回顾分析2021年1月至2021年6月我院新型冠状病毒疫苗(北京生物生产)接种后发生的19例急性荨麻疹的临床资料。19例患者中,男8例,女11例,最小年龄18岁,最大年龄60岁。1例患者于疫苗注射后1小时,周身出现红色风团,喉头水肿,轻微憋喘症状,其余18例均于注射疫苗24小时内周身出现风团,瘙痒明显,无发热、关节痛等伴随症状,19例患者给予相应治疗后,均痊愈。     

腹腔注射刀豆蛋白A诱导昆明小鼠肝纤维化模型的建立

目的 建立昆明小鼠肝纤维化模型.方法 48只昆明小鼠随机分组.实验组40只,腹腔注射20 mg/kg剂量的刀豆蛋白A(ConA),每周一次,共9次.对照组8只,每周一次腹腔注射PBS.所有小鼠在每次注射后24 h采血测ALT、AST.实验组分别于第6、7、8、9次注射后1周各处死8只小鼠,余8只第9周起停止注射,第13周处死.对照组第9次注射后1周处死.所有小鼠处死后取肝脏计算肝脏指数,并作病理检查.结果 实验组第8次注射后出现典型肝纤维化,停止刺激4周仍然有纤维化表现.结论 反复腹腔注射ConA可以建立昆明小鼠肝纤维化模型.     

Experimental and Numerical Study on Uniaxial Compression Failure of Concrete Confined by Nylon Ties

The developments in the cisvil engineering fields have led to an increased demand for structural reinforcements. Therefore, designing an effective, green, convenient, and low-cost reinforcement method is considerably important. Nylon ties have high strength and good heat resistance, and they can retain good tensile properties after high-temperature cooling. Further, they are inexpensive and can be recycled. Thus, they are considered suitable for structural reinforcement engineering. In this study, the core concrete was reinforced by the active confinement of prestressed nylon ties. A uniaxial compression test was performed to evaluate the reinforcement effect of the preload generated by the high-temperature cooling of the tie rod on the core concrete. The results show that nylon ties can effectively improve the mechanical properties of the core concrete. Combined with numerical simulation technology, a damage model of a confined concrete column (CC) was established, and the damage evolution law of CC under uniaxial axial compression was analyzed. Combined with numerical simulation and experimental research, the effectiveness of nylon tie reinforced concrete and the reliability of the damage model were verified, providing a reference for research on engineering reinforcement.     

新型颈椎前路经椎弓根固定钉板系统的研制及生物力学分析

背景:临床中为了解决颈椎翻修/骨质疏松/长节段固定等问题,一般选择进行前、后路联合内固定来获得满意的术后稳定性,难免加重患者的手术创伤,增加术后并发症概率及住院费用.而颈前路反向椎弓根内固定可通过一次前路手术获得前后路联合内固定的稳定性,但临床缺少适用的颈前路椎弓根内固定系统.目的:依据颈椎相关解剖结构研制出新型颈椎前...     

真核起始因子4E对小鼠动脉粥样硬化发生、发展的炎症调节作用*

目的 探讨真核起始因子4E（eIF4E）在小鼠动脉粥样硬化发生、发展过程中的炎症调节作用。方法 分别用200?ng/μl脂多糖（LPS）和20?ng/μl白细胞介素-4（IL-4）诱导RAW264.7细胞12?h后提取mRNA,24?h后提取蛋白,采用实时荧光定量聚合酶链反应（qRT-PCR）和Western blotting检测eIF4E mRNA和蛋白在M1型和M2型巨噬细胞中的表达变化。复制ApoE-/-动脉粥样硬化小鼠模型,检测小鼠腹主动脉eIF4E mRNA和蛋白表达变化;组织免疫荧光检测eIF4E在主动脉根部中分别与M1型和M2型巨噬细胞中的共表达。结果 M1型巨噬细胞eIF4E mRNA和蛋白表达高于M2型巨噬细胞（P?<0.05）。在ApoE-/- 小鼠动脉粥样硬化模型中,ApoE-/-小鼠腹主动脉eIF4E mRNA和蛋白表达高于C57BL/6J小鼠（P?<0.05）;eIF4E与CD86的共定位表达高于eIF4E与CD206的共定位表达。结论 eIF4E在动脉粥样硬化的发展过程中主要在M1型巨噬细胞中起作用,进而对动脉粥样硬化产生影响。     

重型颅脑损伤并发低钠血症的临床诊治

目的 探讨重型颅脑损伤后并发低钠血症的病因、临床特点及诊治措施.方法 回顾分析51例重型颅脑损伤(其中38例需要手术治疗)后并发低钠血症的临床资料,分析其原因,总结其临床特点及治疗方法和效果.结果 重型颅脑损伤并发低钠的51例患者,低钠血症治愈47例,因脑损伤严重死亡2例,需长期高钠饮食以维持血钠正常1例,家属放弃治疗...     

shRNA-CTGF重组质粒对瘢痕疙瘩Ⅰ型胶原蛋白表达的影响

目的 构建pGPU6/GFP/Neo-shRNA-CTGF重组质粒（简称shRNA-CTGF）,通过RNA干扰（RNAi）技术对结缔组织生长因子（connective tissue growth factor,CTGF）进行体内、体外干预,分析其对瘢痕疙瘩Ⅰ型胶原蛋白（collagen-Ⅰ,COL-Ⅰ）表达的影响.方法 设计并构建特异性shRNA-CTGF重组质粒,RNAi转染体外培养瘢痕疙瘩成纤维细胞（keloid fibroblast,KFB）,检测CTGF基因沉默情况及KFB分泌的COL Ⅰ量;将shRNA-CTGF重组质粒对构建的裸鼠瘢痕疙瘩动物模型进行体内转染,检测CTGF基因沉默情况及COL-Ⅰ基因、蛋白表达水平.结果 成功构建了CTGF重组质粒,其在体内、体外环境下均可成功沉默CTGF表达,其抑制率为86.8％和54.1％;RNA体外干扰KFB定向沉默CTGF的同时可显著抑制COL-Ⅰ表达,其mRNA、蛋白水平抑制率分别为76.8％和65.6％;RNA体内干预实验也可显著降低COL-Ⅰ表达,其mRNA、蛋白水抑制率分别为52.7％和48.0％.结论 shRNA-CTGF重组质粒在体外及体内环境下均可成功沉默CTGF基因表达,沉默CTGF能显著降低瘢痕疙瘩中COL-Ⅰ蛋白含量,提示CTGF基因是病理性瘢痕治疗的潜在靶点.