Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression

Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2–M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-X_L. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression. This revised version was published online in July 2006 with corrections to the Cover Date.     

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.     

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

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。     

Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes

This study was to explore the effect and mechanism of Probucol on STZ-induced erectile dysfunction in diabetic rats. Thirty SD male rats aged 12 weeks were given intraperitoneal injection of STZ after fasting for 12 hr. Diabetic rats were haphazardly partitioned under two assemblies and administered 0 or 500 mg/kg probucol by oral gavage to 12 weeks. Control group was intraperitoneally injected with physiological saline, and saline was administered by oral gavage daily. Intracorporeal pressure was used to evaluate erectile function. Levels of proteins were detected using immunohistochemistry and Western blotting. α-SMA and vWF were detected using immunofluorescence staining. After treatment, erectile function in probucol group was significantly improved. Endoplasmic reticulum stress-related proteins were expressed higher in DM group than in sham group, while expression of these proteins decreased significantly in probucol group. However, α-SMA and vWF were expressed at lower levels in DM group than in sham group, and probucol treatment reversed this phenomenon. Finally, Bax and Caspase3 were expressed at higher levels and Bcl-2 was expressed at lower levels in DM group, while the opposite result was obtained in probucol group. In conclusions, probucol improves erectile function by reducing endothelial dysfunction and inhibiting PERK/ATF4/CHOP pathway in STZ-induced diabetic rats.     

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。