调节性T细胞在肝脏免疫及疾病中的作用

免疫抑制是控制免疫系统稳定的一种重要机制．调节性T细胞(regulatory T cells,Tregs)控制着免疫系统对自身抗原的免疫耐受,具有强大的抑制免疫反应能力,广泛参与了各种免疫抑制现象．随着对Tregs研究的不断深入,人们发现Tregs参与调节了肝脏免疫耐受、肝移植、慢性肝炎和肝癌等各种肝脏病理生理现象．Tregs的功能异常也会影响肝脏多种疾病的进程．我们总结了调节性T细胞的相关进展及其在肝脏免疫及疾病中的作用．     

Bone matrix degradation by the plasminogen activation system. Possible mechanism of bone destruction in arthritis

The observed increase in urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR) in synovial tissue of patients with rheumatoid arthritis (RA) suggests pathophysiological involvement of the plasminogen activation (PA) system in inflammatory joint disease. In the present study, we investigated the capacity of the PA system to degrade non-mineralized and mineralized bone-like matrix in vitro as a model for bone destruction. Transfected mouse LB6 cell lines, that expressed either human u-PA or u-PAR, were cultured separately and simultaneously on radiolabelled bone matrix in the presence of plasminogen. Osteoblast-like murine calvarial MC3T3-E1 cells were used to produce a well-characterized, highly organized bone-like matrix, that could be mineralized in the presence of beta-glycerol phosphate. Bone matrix degradation was followed by the release of radioactivity in the culture medium. u-PA-producing cells, in contrast to u-PAR- producing cells, degraded both non-mineralized and mineralized bone matrix. This effect could be inhibited by anti-u-PA antibodies, as well as by tranexamic acid and by aprotinin, indicating that the degrading activity is u-PA mediated and plasmin dependent. Co-cultivation of a small portion of u-PA-producing cells with u-PAR-expressing cells resulted in a marked increase in degradation activity. Reduction of this potentiating effect by suramin or the amino-terminal fragment of u- PA, both competitive inhibitors of u-PA receptor binding, shows that this synergistic effect is due to binding of u-PA to u-PAR. u-PAR must be cell associated, as binding of u-PA to a soluble u-PAR prevented this enhancement. The capability of the PA system to degrade bone matrix in vitro, and the previously demonstrated increased expression of u-PA and u-PAR in synovial tissue of patients with RA, further support a role for the PA system in the development of bone erosions.      

Factors associated with viral rebound among highly treatment-experienced HIV-positive patients who have achieved viral suppression

Objective

More and more highly treatment‐experienced patients are achieving viral suppression. However, the durability of suppression remains unclear.

Methods

Patients from Royal Free Hospital (London, UK) and JW Goethe University Hospital (Frankfurt, Germany) who had failed ≥1 antiretroviral (ARV) regimen in all three main drug classes and ≥3 previous ARV regimens and subsequently achieved viral load <50 HIV‐1 RNA copies/mL were included. They were followed until stopping pre‐combination antiretroviral therapy, end of follow‐up or viral rebound (two viral loads >400 copies/mL).

Results

Two hundred and forty‐seven patients contributed 723 person‐years and 114 viral rebounds [rate=15.8 per 100 person‐years; 95% confidence interval (CI) 12.9–18.7]. More recent calendar years of viral suppression [relative risk (RR)=0.90 per year later; 95% CI 0.81–1.00; P=0.05] and greater number of ARVs in the regimen not previously failed (RR=0.78 per 1 ARV more; 95% CI 0.65–0.95; P=0.01) were associated with lower viral rebound rates. At 0–1, 1–2, 2–3 and >3 years after achieving suppression, the rebound rates were 30.9, 9.2, 4.3 and 3.5 per 100 person‐years, respectively. Compared to 0–1 years, the adjusted RRs (95% CIs) after 1–2, 2–3 and >3 years were 0.33 (0.18–0.58), 0.21 (0.09–0.48) and 0.14 (0.06–0.33), respectively (P<0.0001).

Conclusions

Although rebound rates are high, especially in the first year after viral suppression, this risk reduces substantially if highly treatment‐experienced patients can maintain viral suppression.     

注射用右兰索拉唑治疗急性胃和/或十二指肠溃疡引起的上消化道出血的有效性及安全性

目的：以注射用兰索拉唑为对照,评价注射用右兰索拉唑15 mg q12 h治疗急性胃和/或十二指肠溃疡引起的上消化道出血的有效性及安全性。方法：选取全国31家研究中心的急性胃和/或十二指肠溃疡引起的上消化道出血患者共202例,按照1∶1随机分配至试验组（注射用右兰索拉唑组）和对照组（注射用兰索拉唑组）。主要疗效终点为72 h有效止血率。对主要疗效终点采用非劣效评价,非劣效性界值δ是10%。结果：有效性方面,全分析数据集分析结果显示：用药72 h后,注射用右兰索拉唑组有效止血率为96.08%(98/102);注射用兰索拉唑组有效止血率为98.00%(98/100),两组率差为-1.92%(95%CI-6.58,2.74)。两组72 h有效止血率差异无统计学意义（P=0.682 9）。两组率差的双侧界值均低于δ(10%),注射用右兰索拉唑非劣于注射用兰索拉唑。安全性方面,试验组的不良事件及不良反应发生率与对照组差异无统计学意义,无非预期不良反应和严重不良反应。主要的不良反应为白细胞计数降低、中性粒细胞计数降低等。结论：注射用右兰索拉唑15 mg q12 h在治疗急性胃和/或十二指肠溃疡引起的...