Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway

Invariant natural killer T (iNKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. Agonist alpha-galactosylceramide (alpha-GalCer) of iNKT cells exert a therapeutical effect in type 1 diabetes. We investigated whether iNKT activation with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1 mice, a standard model of rheumatoid arthritis. Here, we have shown that in vivo iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6 mice. alpha-GalCer induced a clear-cut diminution of clinical and histological arthritides. An anti-IL-10 receptor antibody abrogated the protective effect of alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by activated iNKT cells. Confirming these data, disease protection conferred by alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger amounts of IL-10. These findings suggest that in CIA susceptibility to autoimmunity is associated with dysfunctions of iNKT cells. Our demonstration that iNKT cell activation by alpha-GalCer remains efficient in CIA-prone DBA/1 mice to provide protective IL-10 suggests that this could be used therapeutically to treat autoimmune arthritis.     

周围神经端侧缝合与神经移植的实验研究

目的　比较周围神经端侧缝合与神经移植的效果。方法　选用体重 2 0 0～ 30 0gWistar大白鼠 ,左侧后肢腓总神经与胫神经端侧缝合 ,右侧腓总神经采用神经移植修复。结果　 3个月后运动神经传导速度分别为2 9.6 8± 5 .34m/s、 30 .87± 6 .0m/s(P >0 .0 5 ) ,潜伏期 2 .1± 0 .1ms ,2 .0± 0 .1ms(P >0 .0 5 ) ,波幅 12 .5± 0 .6mV、13.9± 0 .5mV(P >0 .0 5 ) ,组织切片中 ,两组均可见大量神经纤维和髓鞘 ,有髓神经纤维计数分别为 75 7.2± 2 2 .31、775± 2 1.87(P >0 .0 5 )。结论　①正常神经发出侧芽能通过端侧缝合口长入远端神经 ,使变性神经再神经化 ;②周围神经端侧缝合能取得与神经移植相近的结果。     

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.     

动态增强磁共振成像在评估女性乳房乳头乳晕血供的应用

目的探究动态增强磁共振成像(DCE-MRI)用于评估女性乳房乳头乳晕血供特点的可行性,为乳房整形手术提供乳头乳晕的血供参考。方法从2012年3月至2019年10月华中科技大学同济医学院附属同济医院影像数据库中收集女性乳腺DCE-MRI图像资料,选择未发现肿物的正常乳房的DCE-MRI图像进行研究。在西门子工作站将患者乳腺DCE-MRI图像通过图像减影获取乳房血管图像,分别对轴位、冠状位和矢状位的最大密度投影(MIP)图像进行评估,结合三维MIP图像识别所有供应乳头乳晕的血管。乳头乳晕的血供被划分为内上、内侧、内下、外上、外侧、外下、中央、上方和下方9个象限,对各个象限血管进行统计和分析,并测量血管至乳房皮肤表面投影的最大距离。采用SPSS 19.0软件进行统计分析,通过卡方检验分别比较左侧与右侧乳房的乳头乳晕复合体(NAC)血供象限分布构成比。计算血管到皮肤距离的平均值、标准差及95%置信区间,通过方差分析比较各象限血管至皮肤距离的差异。P<0.05为差异具有统计学意义。结果共收集到245例患者490只女性乳房DCE-MRI图像,其中97例患者97只乳房发现有乳腺肿物,其余393只为正常乳房(97例单侧乳房、148例双侧乳房),将其作为研究对象。患者年龄23~72岁,平均43.7岁。393只乳房(左侧200只、右侧193只)共发现有637条(左侧311条、右侧326条)乳头乳晕供应血管。在637条血管中,内上象限269条(42.2%),外上180条 (28.3%),内侧57条(8.9%),下方37条(5.8%),中央30条(4.7%),内下25条(3.9%),外下25条(3.9%),上方11条(1.7%),外侧3条(0.5%)。卡方检验表明左侧乳房和右侧乳房在NAC血供象限分布构成比差异无统计学意义(χ2 =6.4,P=0.602)。除中央象限血管以外,所有血管到皮肤表面投影最大距离的平均值为0.91 cm, 95%置信区间为0.86~0.96 cm。方差分析表明各象限供血血管到皮肤投影的最大距离,差异有统计学意义(F=11.4,P<0.001)。结论 DCE-MRI可以清晰地显示乳头乳晕的血供来源。乳头乳晕血供主要来源于内上象限和外上象限的血管,血管在皮下约1 cm深度走行。     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

Das akute Koronarsyndrom in der prähospitalen Phase und in der Notaufnahme

Notfall + Rettungsmedizin - Das akute Koronarsyndrom ist der häufigste Grund für einen Rettungsdiensteinsatz in Deutschland. So resultieren in etwa 20–25 % aller Einsätze...     

五种免疫相关性心血管疾病的免疫学研究

对扩张型心肌病、风湿性心脏病，原发性高血压，冠心病及肥厚型心肌病进行外周血清可溶性白细胞介素２受体，Ｔ淋巴细胞亚群及自然杀伤细胞活性的检测，并与健康对照组比较，结果显示：ＤＣＭ组，ＲＨＤ组及ＥＨＴ组的ｓＩＬ－２Ｒ明显高于ＮＣ组，而ＤＣＭ、ＲＨＤ风湿活动组的ＮＫ活性低于ＮＣ组，ＥＨＴ组ＮＫ活性高于ＮＣ组。     

Elucidating chromatin and nuclear domain architecture with electron spectroscopic imaging

Electron microscopy has been the ‘gold standard’ of spatial resolution for studying the structure of the cell nucleus. Electron spectroscopic imaging (ESI) offers advantages over conventional transmission electron microscopy by eliminating the need for heavy-atom contrast agents. ESI also provides mass-dependent and element-specific information at high resolution, permitting the distinguishing of structures that are primarily composed of protein, DNA, or RNA. The technique can be applied to understand the structural consequences of epigenetic modifications, such as modified histones, on chromatin fiber morphology. ESI can also be applied to elucidate the multifunctional behavior of subnuclear ‘organelles’ such as the nucleolus and promyelocytic leukemia nuclear bodies. The authors dedicate this paper to the memory of Ying Ren (1961–2007). We all benefited from knowing her. Our research advanced through the technical creativity she provided.     

Regional hyperthermia combined with high energy shock wave treatment on Dunning prostate tumors

Male Copenhagen rats implanted with Dunning R3327 prostate carcinoma were treated with regional hyperthermia and high energy shock waves (HESW). Twenty-four rats were divided into four equal groups. All rats in one group were matched with the corresponding rats in the other three groups according to tumor size. Hyperthermia was created by the resistive heating of a 22-gauge 1.5-cm needle; HESW were generated by the Dornier XL-1 experimental lithotripter. In two hyperthermia treatments administered 48 hours apart, the tumor was heated to 46.5 degrees C for 2 hours; HESW treatment involved 1,600 shocks at 18 kV. Twenty-nine days after initiation of this study, animals were sacrificed and tumor growth calculated. Tumor growth in group 1 (combined hyperthermia and HESW) was significantly delayed between the 7th and 29th day (p = 0.05). In group 2 (HESW alone), tumor growth was significantly delayed between the 7th and 22nd day (p = 0.01), while tumor growth in group 3 (hyperthermia alone) was delayed between the 3rd and 22nd day (p = 0.02). On day 22, mean percent change in tumor growth in the control group exceeded that of group 1 by 449% (p = 0.015) as well as that of groups 2 and 3, by 350% (p = 0.034) and by 268% (p = 0.049), respectively. As previous reports demonstrate the efficacy of hyperthermia in combination with irradiation or chemotherapy for the treatment of prostate carcinoma, our results indicate hyperthermia in combination with HESW may also be a useful treatment modality.