经胸体外直流电复律治疗心房颤动的进展

虽然心房颤动的治疗已取得很大的进展,经胸体外直流电复律仍然是临床上常用的治疗心房颤动的方法,它高效、安全,近年来,为使其效率进一步提高,现就采取的一些改进措施进行综述。包括:(1)电极板的位置、数量:多数研究证实前-后位置复律优于前-前(侧)位置,表现在复律的成功率高、用电量低上;还可应用X线透视以优化电极板的位置,使其尽可能包绕心房肌,以此来提高复律成功率;另外,同时应用2台体外除颤器的更高能量的电复律对那些标准能量复律无作用的心房颤动患者有效,并且同样安全。(2)输出波形为双相波形时对心房颤动的转复具有比单相波形更高的效率,要求的电量更低,且同样对心肌无损害。(3)首次放电量较高,如≥150 J时复律的成功率高。(4)除了抗心律失常药物,近几年新出现的一些药物如血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂以及他汀类药物也可影响心房颤动体外电复律的效果。     

血清肝纤维化指标与肝脏病理学对照研究

评价血清肝纤维化指标诊断肝纤维化病理分期的临床价值。 6 9例肝穿确诊的慢性乙型病毒性肝炎患者 ,同时进行血清HA、Ⅳ -C、PⅢP、LN的检测。以肝活检组织纤维化病理分期为金标准对以上血清学指标的诊断价值进行分析。HA、Ⅳ -C、PⅢP、LN与纤维化分期的相关系数分别为 0 30 2 (P <0 0 1)、0 6 6 3(P <0 0 1)、0 346 (P<0 0 5 )、0 0 5 6 (P >0 0 5 )。除LN外 ,其余指标血清水平均随着肝纤维化程度的加重而逐渐上升 ,其中HA、Ⅳ -C、PⅢPS3 、S4期血清水平与S1期比较有统计学差异 (P <0 0 1)。S4作为早期肝硬化诊断标准时 ,通过ROC曲线分析HA、Ⅳ -C、PⅢP、LN的曲线下面积分别为 0 74 5、0 90 9、0 732、0 4 2 5。敏感度Ⅳ -C >PⅢP >HA >LN ;特异度HA >Ⅳ -C >PⅢP >LN。血清肝纤维化指标对肝脏纤维化程度的判断有一定的指导意义。     

Targeting NF-kappaB in Waldenstrom macroglobulinemia

The nuclear factor-B (NF-B) path-way has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized that combination of agents that target differentially NF-B pathway will induce significant cytotoxicity. Therapeutic agents that target proteasome and Akt pathways should induce significant activity in B-cell malignancies as both pathways impact NF-B activity. We demonstrated that perifosine and bortezomib both targeted NF-B through its recruitment to the promoter of its target gene IB using chromatin immunoprecipitation assay. This combination led to synergistic cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to be critical for survival of WM cells. Moreover, a combination of these drugs with the CD20 monoclonal antibody rituximab further increased their cytotoxic activity. Thus, effective WM therapy may require combination regimens targeting the NF-B pathway.      

Effect of interferon-gamma on hepatic fibrosis in chronic hepatitis B virus infection: a randomized controlled study.

BACKGROUND & AIMS: Hepatic fibrosis due to chronic HBV infection has enormous socioeconomic impact. Besides strategies targeting virus elimination, prevention or reversal of liver fibrosis is amenable. Given the antifibrotic activity of interferon-gamma (IFN-gamma), a randomized open-labeled multicenter trial was initiated to test IFN-gamma in HBV infection. METHODS: HBsAg-positive patients with biopsy proven hepatic fibrosis (n = 99, stages 2-4, Scheuer criterion) were treated with diammone-glycyrrhizinate and potassium-magnesium aspartate. Sixty-six randomly assigned patients were treated with 50 mug IFN-gamma intramuscularly on a daily basis for 3 months and on alternate days the subsequent 6 months. Efficacy was evaluated by liver biopsy and serologic markers. RESULTS: Fifty-four patients in the IFN-gamma group and 29 patients in the control group completed the study. The hepatic fibrosis score was significantly reduced in 63% of IFN-gamma treated patients compared with 24.1% in the control group by using a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for the total fibrosis score decreased from 13.8 +/- 5.8 to 10.1 +/- 5.1 in the IFN-gamma group (P = .0001), whereas they were unchanged in control subjects (13.2 +/- 6.8 vs 12.6 +/- 4.8, P = .937). The Scheuer system showed 12 out of 54 patients improved >or=1 stage(s) in the IFN-gamma group compared with 1 of 29 in the control group. Antifibrotic activity might be attributed to decreased transforming growth factor-beta signaling via phosphorylated Smad2 and reduced number of activated, alpha-smooth muscle actin positive hepatic stellate cells. CONCLUSIONS: IFN-gamma treatment for 9 months improves fibrosis scores in patients with chronic HBV infection most likely by antagonizing profibrogenic transforming growth factor-beta effects.     

beta2-adrenoceptor gene polymorphisms and blood pressure variations in East Anglian Caucasians

OBJECTIVE: The amino-terminal polymorphisms, Arg16Gly and Gln27Glu, of the beta2-adrenergic receptor (beta2AR) have been shown to affect regulation of the receptor expression by an agonist in cell culture studies. The Arg16Gly polymorphism has also been recently shown to be associated with essential hypertension. We therefore evaluated whether the amino-terminal polymorphisms of beta2AR are associated with hypertension in a Caucasian population. SUBJECTS AND METHODS: We performed an association study in 298 hypertensive patients and an equal number of age-matched normotensive controls from the East Anglian region, with blood pressure assessed categorically and quantitatively. We also examined the influence of the amino-terminal polymorphisms on blood pressure response to beta-blockade in 144 of the patients randomly assigned to this class of drug. Genotyping of the Arg16Gly polymorphism was undertaken by a newly designed mismatched polymerase chain reaction (PCR) and digestion with Nde I, whereas the Gln27Glu polymorphism was genotyped by PCR followed by Fnu4H I cleavage. RESULTS: We found no differences in the genotype or allele frequencies of the beta2AR polymorphisms between hypertensive and normotensive participants. There was also no association between the beta2AR genotypes and variations in either basal blood pressure or the blood pressure response to a beta-blocker. CONCLUSION: These findings suggest that the amino-terminal polymorphisms of the beta2AR gene are unlikely to constitute major susceptibility for essential hypertension in the East Anglian population.     

ERCP插管操作模式改变的回顾性分析

目的 探讨逆行胰胆管造影(ERCP)插管操作模式的转变,对于ERCP的插管成功率、术后并发症发生率及操作时间的影响.方法 回顾分析2000年6月至2008年6月间因胆管疾病行诊治性ERCP的患者120例,其中选择常规插管法插管60例,使用导丝插管法插管60例.分别统计分析2组在ERCP操作过程中的目标管腔插管成功率、操作时间和术后7 d内的胰腺炎及感染发生情况.结果导丝插管组患者较常规插管组的插管成功率高(P<0.05).除外其他因素,与常规插管相比,采用导丝插管患者的操作时间缩短.常规插管组术后胰腺炎的发病率为10.0%(6/60),感染发生率为23.3%(14/60);导丝插管组术后胰腺炎的发病率为3.3%(2/60),感染发生率为10.0%(6/60).2组均未见出血并发症的发生.结论 ERCP中应用导丝进行目标管腔插管的操作模式,减少了操作的时间,显著提高了操作成功率,并降低了术后并发症发生率,但还需进一步具体研究.     

慢性乙型肝炎肝组织中碱性成纤维细胞生长因子及其mRNA的表达

目的研究肝组织中碱性成纤维细胞生长因子(bFGF)及bFGFmRNA的表达与慢性乙型肝炎(CHB)肝血管增生、改建及肝血管纤维化的关系。方法对120例CHB肝标本进行bFGF免疫组织化学(免疫组化)染色及bFGFmRNA原位杂交。结果随着CHB肝细胞变性坏死及肝血管病变的加重,bFGF在肝血管及肝窦壁表达强阳性逐渐上升(P<0.01),部分固缩性肝细胞也示强阳性显色。原位杂交显示,bFGFmRNA主要分布于血管纤维化区域肝窦壁及部分肝细胞。结论bFGF通过激活血管及肝窦内皮细胞,引发其增生和凋亡,最终导致肝血管纤维化、肝窦毛细血管化及假小叶纤维间隔形成。     

Survival rate,causes of death,and risk factors in systemic sclerosis: a large cohort study

To investigate the clinical pattern, survival rate, causes of death and risk factors in a large cohort of Chinese Han patients with systemic sclerosis (SSc). Inpatients treated from 2002 to 2014 were included in this study. Patients were classified into diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc-overlap syndrome groups. Data were analyzed using Chi-squared tests, Kaplan–Meier curves, log-rank tests, and Cox proportional hazards modeling. Among a total of 201 patients, dcSSc (50.2%) was the major subtype, followed by lcSSc (30.3%) and SSc-overlap (19.4%). Interstitial lung disease (ILD, 148/201, 74%) was the most frequent organ involvement. The overall survival rates were 98% and 95% at 5 and 10 years, respectively. The overall standard mortality ratio (SMR) was 2.22. The most common cause of death was ILD combined with infection (8/16, 50%), followed by kidney failure (2/16, 12.5%). On crude analysis, pulmonary hypertension, ILD, cardiac involvements, renal involvements, and digital ischemia were associated with poor prognosis. On multivariate analysis, pericardial effusion (p?=?0.000) and digital ischemia (p?=?0.016) were independent prognostic factors of death. The mortality rate of patients with SSc is mildly increased in comparison with the general population. ILD is the most common systemic involvement and the principal cause of death in SSc. Pericardial effusion and digital ischemia are independent factors associated with death.     

糖尿病大鼠坐骨神经病变与细胞黏附分子-1和P-选择素变化的相关性及西洛他唑的治疗作用

目的　研究糖尿病 (DM )大鼠黏附分子CD5 4、CD6 2p变化及其与坐骨神经病变的关系 ,探讨西洛他唑对糖尿病神经病变 (DPN)和黏附分子的影响。　方法　将实验大鼠分为正常组 (8只 )、糖尿病组 (8只 )、胰岛素组 (7只 )和西洛他唑组 (7只 )。测定各组坐骨神经传导速度和血浆单个核细胞CD5 4、血小板CD6 2p含量 ,观察坐骨神经超微结构变化。　结果　西洛他唑治疗组与DM组相比 :(1)坐骨神经传导速度明显加快 ;DM组 =(2 0 .3± 2 .2 )m/s ,西洛他唑组 =(2 8.9± 7.9)m /s ,q =3 .50 ,P <0 .0 5。 (2 )血浆单个核细胞表面CD5 4水平明显降低 ;DM组 =(65± 15) % ,西洛他唑组 =(2 5± 9) % ,q =7.50 ,P <0 .0 5。 (3 )西洛他唑有降低血小板表面CD6 2p的趋势 ,与DM组相比无显著差异。 (4)坐骨神经超微结构的病理变化明显改善。　结论　DM大鼠CD5 4、CD6 2p表达增加与DPN有明显的相关性 ,西洛他唑可降低其表达并改善糖尿病神经病变