B细胞介导的体液免疫应答在肝移植急性排斥反应中的作用

目前，国内外肝移植学界对肝移植术后急性排斥反应(AR)的机制阐释为T细胞介导的细胞免疫应答，但为获得长期生存仍需长期乃至终身服用免疫抑制剂。即使如此，临床上AR仍时有发生，并导致相当一部分受者移植肝功能丧失，更重要的是受者术后还受到感染、肿瘤和其他一系列不良反应及沉重经济负担的影响。因此，为肝移植AR机制提出新的理论解释，更全面深入阐明肝移植免疫排斥反应的内在机制，进而依据新的机制研制出新型免疫抑制剂已势在必行。本文就B细胞介导的体液免疫应答在肝移植AR中的作用作一综述。     

Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells

1. Download : Download high-res image (179KB)
2. Download : Download full-size image

     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Utility of the 3‐Vessel and 3‐Vessel and Trachea Views in Prenatal Diagnosis of a Pulmonary Artery Sling

A pulmonary artery (PA) sling is a very rare congenital cardiovascular anomaly, and only a few studies have reported PA slings in fetuses. The relationship of the PA, aorta, ductus arteriosus, and trachea can be evaluated in the 3‐vessel and 3‐vessel and trachea views during fetal echocardiography. A PA sling can be detected by abnormal positioning of the left PA in relation to the trachea when sweeping from the 3‐vessel view cranially to the 3‐vessel and trachea view. Here we report 3 cases of fetal PA slings and their follow‐ups. Two cases were confirmed by postnatal echocardiography, and the other case was confirmed by a cardiovascular cast after pregnancy termination. We emphasize that the 3‐vessel and 3‐vessel and trachea views are of crucial importance in the prenatal diagnosis of a PA sling.     

玻璃体切割联合内界膜剥除治疗糖尿病性黄斑水肿

评估玻璃体切割联合内界膜剥除对糖尿病性黄斑水肿（DME）的疗效。方法：回顾性病例对照研究。2014年6月至2017年1月间因糖尿病视网膜病变合并玻璃体积血或增殖病变于温州医科大学附属眼视光医院杭州院区行玻璃体切割手术治疗，且术前或术中经光学相干断层扫描（OCT）检查确诊合并DME的患者31例（33眼）纳入研究。16例（18眼）术中联合内界膜剥除作为剥膜组，15例（15眼）仅接受玻璃体切割手术治疗者作为对照组。所有手术均由同一医师主刀完成。术后1、3个月随访时复查OCT，对比观察黄斑中心厚度（CMT）和视力的术后变化情况。随访中CMT和最佳矫正视力（BCVA）比较采用重复测量方差分析，组间CMT和BCVA比较采用独立样本t检验。结果：手术前，手术后1、3个月2组间比较LogMAR视力总体差异有统计学意义（F=15.93，P<0.001）。术后 1个月时剥膜组BCVA高于对照组（t=2.55，P=0.02），但术后3个月时2组间差异无统计学意义（t=0.82， P=0.42）。手术前，手术后1、3个月CMT总体差异无统计学意义（F=2.85，P=0.065）。术后1、3个月时，剥膜组的CMT均低于对照组，2组间差异均有统计学意义（t=2.24，P=0.03；t=3.79，P=0.001）。术后1个月时，剥膜组有效（与术前比CMT减少20%以上）、无效（变化不超过20%）及恶化（增厚超过 20%）的例数分别为8、6、4例，术后3个月时则分别为11、5、2例，与对照组相比，术后1个月时组间差异无统计学意义（Z=-1.687，P=0.092），术后3个月时剥膜组DME改善有效比例明显高于对照组，组间差异有统计学意义（Z=-2.177，P=0.029）。结论：对于非牵拉性DME，内界膜剥除有助于术后早期DME消退。     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

二补助育汤对胚胎着床障碍小鼠子宫血管生成相关因子表达的影响

目的：探讨二补助育汤对胚胎着床障碍模型小鼠子宫内膜形态及血管生成素-1（Ang-1）mRNA、血管内皮生长因子（VEGF）mRNA的表达和定位的影响。方法：24只ICR雌性小鼠随机分为空白组、模型组、戊酸雌二醇组、二补助育汤组，每组6只，用米非司酮建立胚胎着床障碍动物模型，各组给予相应药物灌胃，妊娠第5天处死小鼠后，检测各组妊娠率、平均着床位点数、子宫内膜Ang-1和VEGF mRNA表达量及其蛋白定位。结果：模型组小鼠平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量明显低于空白组（均P<0.05）；与模型组比较，二补助育汤组平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量显著提高（均P<0.05）。结论：二补助育汤可提高子宫内膜Ang-1和VEGF蛋白表达量，促进子宫内膜血管生成，从而提高子宫内膜容受性。     

Hiperplasia endotelial papilar intravascular (tumor Masson) de localización ginecológica

Intravascular papillary endothelial hyperplasia or Masson's tumour is a non-neoplastic vascular lesion of reactive character. It is a rare diagnosis, clinically non-specific and with diverse locations. It is essential to take it into consideration and make a differential diagnosis with malignant vascular tumours such as angiosarcoma. Pathological study is fundamental for diagnosis. Treatment consists of complete resection of the tumour, including sufficiently wide margins to avoid recurrence.The case reported is an exceptional event, because of the pelvic location of the Masson's tumour that was diagnosed as part of the surgical staging of an ovarian cancer.     

Aloe-Emodin Protects RIN-5F (Pancreatic β-cell) Cell from Glucotoxicity via Regulation of Pro-Inflammatory Cytokine and Downregulation of Bax and Caspase 3

To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic β-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-γ, IL-1β,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE (20 μM) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.