T cell clonal expansions detected in patients with primary biliary cirrhosis express CX3CR1

The intrahepatic biliary destruction of primary biliary cirrhosis (PBC) appears secondary to a multi-lineage response that includes autoantibodies, biliary apotopes, and cellular responses. Although there has been considerable effort in defining the role and specificity of anti-mitochondrial autoantibodies, a major challenge has been the characterization of T effector pathways. This difficulty is due in part to the limitation of current technologies for directly isolating and characterizing autoreactive T cells from patients. Herein, we successfully demonstrate a novel technology for characterizing the surface phenotype of T cell oligoclonal expansions directly ex vivo. Using PBC as a prototypic disease we were able to detect clonal T cell expansions in 15/15 patients examined. Although the T cell expansions from different patients expressed different TCRVβ gene segments, the surface phenotype of the cells was the same. The clonal T cell expansions in PBC patients are CX3CR1⁺ Fas⁺ effector-memory T cells, a finding of particular importance given the known up-regulation of fractalkine on injured biliary epithelial cells (BEC). In contrast to the persistent aberrantly expanded T cells observed in the PBC patients, T cell expansions detected in response to a herpes viral infection were very dynamic and resolved over time. This protocol can be used to characterize T cell expansions in other autoimmune diseases.     

CX3CR1基因多态性与冠心病关联的荟萃分析

目的 探讨CX3CR1-V249I、T280M与冠心病(CAD)的关联性.方法 检索中英文数据库,以得到CX3CR1-V249I、T280M与CAD易感性关系的病例对照研究,采用Meta分析方法 合并V249I、T280M与CAD关联的OR值,同时进行文献发表偏倚检验.结果 共纳入文献6篇.对于V249I,共纳入病例1 551人,对照1 804人,I型相对于V型合并OR=0.85(95%CI=0.67～1.08,P＞0.05);对于T280M,共纳入病例1 555人,对照1 801人,M型相对于T型合并OR=0.82(95%CI=0.70～0.96,P＜0.05).结论 T280M为CAD的保护性因素,V249I与CAD的发生无关联.

Abstract：

Objective To find whether CX3CR1 V249I and T280M are associated with CAD. Methods Database in English and Chinese, including PUBMED, EMbase, were searched to get the case-control studies on the associa-tion between V249I, T280M and CAD. Results Six studies were reviewed. The pooled OR of V249I compared to wild type allele was OR =0. 85(95% CI =0. 67 ～ 1. 08,P >0. 05). The pooled OR of T280M compared to wild type allele was OR =0. 82(95% CI =0. 70 ～ 0. 96, P < 0. 05). Conclusion The T280M is a protective factor of CAD, while the V249I is not associated with CAD.     

甲磺酸多沙唑嗪控释片与酚苄明在嗜铬细胞瘤手术前准备及围术期血压控制效果

目的 将甲磺酸多沙唑嗪控释片与酚苄应用于在嗜铬细胞瘤患者的术前准备,比较两者对围术期血压的控制效果.方法 1978-2006年上交通大学医学院附属瑞金医院40例左侧肾上腺嗜铬细胞瘤患者,根据术前的药物准备情况分为3组:组1,手术前未使用a受体阻滞剂进行术前准备;组2,酚苄明20～40 mg/d,分2～3次口服,平均服用天数为(25.1±2.4)d;组3,甲磺酸多沙唑嗪控释片4～8 mg/d顿服,平均服用天数为(10.6±3.9)d.连续挠动脉内监测血压,记录5个时间点的收缩压.分别为手术麻醉诱导前、麻醉后、探查肿瘤时、肿瘤切除后和手术结束时.结果 麻醉前,3组间收缩压的差异有统计学意义(P＜0.01).组2最低,组3次之,组1最高.麻醉后,3组收缩压都有下降,还是以组2最低,组1次之,组3最高,3组间差异有统计学意义(P＜0.01).探查肿瘤时,三组收缩压均升高,依然是组2最低,组3次之,组1最高,3组间差异有统计学意义(P＜0.001),但是组2与组3间差异无统计学意义(P＞0.05).肿瘤切除后,3三组收缩压均下降,组l与组2的差异无统计学意义(P＞0.05),但是与组3的差异均有统计学意义(P值均＜0.01).手术结束时,3组收缩压的差异无统计学意义(P＞0.05).组2、3的最高与最低血压差小于组1(P值均＜0.01),组3显著小于组2(P＜0.01).结论 在左肾上腺嗜铬细胞瘤手术中,术前服用甲磺酸多沙唑嗪控释片可更好地控制术中收缩压的波动,而酚苄明对术前收缩压的控制更佳.     

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental model is quantifiable and highly reproducible. Five weeks after mechanical compression to the axons of the auditory neurons, the total number of neurons in the CN was evaluated using un-biased stereological methods. A region-specific degeneration of neurons in the dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50% was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN) was not found. An imbalance between excitatory and inhibitory synaptic transmission after de-afferentation may have played a crucial role in the development of neuronal cell demise in the CN. The occurrence of a region-specific loss of adult CN neurons illustrates the importance of evaluating all regions of the CN to investigate the effects of de-afferentation. Thus, this experimental model may be promising to obtain not only the basic knowledge on auditory nerve/CN degeneration but also the information relevant to the application of cochlear or auditory brainstem implants.     

Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy

Background  The complexity of pain from laparoscopic cholecystectomy and the need for treating incident pain provide rationale for multipharmacological analgesia. We investigated the preoperative administration of controlled-release (CR) oxycodone as transition opioid from remifentanil infusion for pain after laparoscopic cholecystectomy. Methods  Fifty consecutive patients undergoing laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment group (n = 25, CR oxycodone: 1 h before surgery and 12 h after the first administration) or to the control group (n = 25, placebo: administered at the same intervals). General anaesthesia was maintained with propofol and remifentanil target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v. Tramadol i.v. was administered for patient-controlled analgesia (PCA) postoperatively. Numerical rating scale for pain at rest and at movement (NRSr and NRSi), tramadol consumption, times to readiness to surgery and awakening, times to modified Aldrete’s and modified Post-Anesthetic Discharge Scoring System (PADSS) >9 and side effects were evaluated. Results  All NRSr and NRSi and tramadol consumption were significantly lower in the treatment group. The oxycodone group showed higher modified Aldrete’s scores at each time and reached a PADSS >9 faster. Side effects and postoperative nausea and vomiting episodes were comparable. Conclusions  We demonstrated the success of a multipharmacological treatment including opioid premedication with CR oxycodone used as transition opioid for TCI remifentanil infusion; the treatment group showed lower pain scores and rescue analgesic consumption, shorter time to discharge from recovery room and from surgical ward, and the same incidence of side effects, comparably to controls. Sources of financial support for the work: University of Parma, viale Gramsci 14, 43100 Parma PR, Italy.     

Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1

Cochlear macrophages have been shown to accumulate in the murine cochlea following acoustic trauma. This investigation was performed to determine whether cochlear macrophages could be replaced by donor transplantation of bone marrow precursors. Lethally irradiated C57BL/6 mice were transplanted with hematopoietic precursors from CX3CR1(GFP/GFP) fetal mice. CX3CR1(GFP/GFP) mice express green fluorescent protein (GFP) in monocytes and macrophages and possess no functional CX3CR1. Donor monocytes and macrophages can be easily traced in the wild-type recipient with fluorescent microscopy. We studied mice at 2-16 weeks after transplantation to assess repopulation of cochlear macrophages. A separate group of chimeras was exposed to octave band noise (8-16 kHz for 2 hours) 2 weeks after transplantation to evaluate the migration properties of donor hematopoietic precursors. We found that macrophages derived from donor hematopoietic precursors appeared in cochlea 3-4 weeks after transplantation and increased week by week. Noise exposure induced a massive accumulation of leukocytes, particularly in the spiral ligament of the basal turn. There was no difference between CX3CR1(GFP/GFP) donor/wild-type recipient chimeras and the wild-type donor/wild-type recipient chimeras in hearing thresholds, accumulation of cochlear macrophages, or tissue injury after noise exposure. These data indicate that cochlear macrophages are derived from bone marrow precursors and that they are an exchanging and migratory population. Furthermore, CX3CR1 in hematopoietic precursors is not necessary for macrophage migration into cochlea and when deleted in this cell population, the absence of CX3CR1 does not substantially effect the outcomes after noise.     

西达本胺联合标准化疗治疗外周T细胞淋巴瘤的Meta分析

目的 采用Meta分析考察西达本胺联合标准化疗治疗外周T细胞淋巴瘤的临床疗效。方法 搜索了中国知网、万方、维普、Web of Science、PubMed、Cochrane Library、Embase等数据库,检索文献发表时间为从数据库建库到2023年6月的西达本胺联合标准化疗治疗外周T细胞淋巴瘤的试验,应用Cochrane中心提供的Revman 5.4软件对数据进行统计学处理分析。结果 筛选符合标准的文献为10篇,共494例患者。西达本胺在外周T细胞淋巴瘤治疗中可显著改善完全缓解率、客观缓解率、1年生存率、1年无进展生存率,与标准化疗间的差异具有统计学意义。结论 对于外周T细胞淋巴瘤患者,西达本胺联合化疗在完全缓解率、客观缓解率、1年生存率、1年无进展生存率均优于单纯化疗。