Comorbid illness is an important determinant of health-related quality of life in patients with chronic hepatitis C

OBJECTIVES: Chronic hepatitis C (CHC) patients selected for entry into treatment trials have been reported to have impaired health-related quality of life (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC patients may have been underestimated because of the exclusion of patients with comorbid illness. The aim of this study was to assess HRQOL in an unselected group of CHC patients and to identify factors associated with impairment in HRQOL. METHODS: A total of 220 consecutive eligible CHC patients were enrolled from a hepatology clinic. HRQOL was assessed by the short form 36 (SF-36) and comorbid illnesses were assessed by an interview. RESULTS: CHC patients had significantly lower SF-36 scores in all subscales and in the summary scales when compared to those of the healthy general population in the United States (p < 0.001). Compared to CHC patients entering treatment trials, our patients had lower SF-36 scores on five subscales (p < 0.001). The presence of comorbid illness was the most important predictor of HRQOL in CHC patients. However, CHC alone resulted in significantly lower SF-36 scores in all subscales and summary scales (p < or = 0.003) compared to those of the healthy U.S. population. There was no correlation between SF-36 scores and history of i.v. drug use or dependence. alcohol dependence. and serum aminotransferase levels. CONCLUSIONS: We conclude that unselected CHC patients presenting for medical evaluation have a reduced HRQOL, which is lower than that reported for CHC patients entering treatment trials. CHC alone is associated with significant impairment in HRQOL, but the presence of comorbid illness leads to further diminution in HRQOL.     

Heterogeneous Helicobacter pylori isolates from H. pylori-infected couples in Taiwan

Helicobacter pylori strain diversity was investigated in 55 H. pylori seropositive couples in Taiwan in biopsy samples from the antrum and corpus. Two DNA typing methods were used to characterize 90 isolates from 25 couples. In only 1 of the 25 couples was the same strain colonized from both partners. Comparison of isolates from 2 sites in each of 40 patients showed that 9 pairs were distinct but might be related. Peptic ulcer occurred in 77.8% of these 9 patients compared with 29% of 31 patients with the same predominant strain in 2 biopsies (P=.025). Random amplified polymorphic DNA and sequence analyses of 2 closely related isolates from 1 patient support the hypothesis that development of genetic diversity of H. pylori results from horizontal genetic exchange during long-term colonization of mixed bacterial populations.     

The stochastic piston problem

We obtain analytical solutions for the perturbed shock paths induced by time-varying random motions of a piston moving inside an adiabatic tube of constant area. The variance of the shock location grows quadratically with time for early times and switches to linear growth for longer times. The analytical results are confirmed by stochastic numerical simulations, and deviations for large random piston motions are established.     

慢性乙型肝炎发病机制的超微形态学基础研究

为探讨慢性乙型肝炎（乙肝）肝细胞损伤机制的超微形态学基础，对５０例乙肝患者肝穿刺进行电观察，发现淋巴细胞浸入肝组织后，可以与肝细胞发生接触、质膜融合和胞质沟通。肝细胞和淋巴细胞之间可见电子致密物，这可能是淋巴细胞产生的多种因子。枯否细胞质膜与淋巴细胞质膜融合，浆细胞质膜可与淋巴细胞质膜融合，淋巴细胞之间胞质可互相沟通，提示了免疫细胞间以及免疫细胞与肝细胞间的一些关系，为研究乙肝的细胞免疫反应机制提     

The effect of different treatment strategies on left atrial size in patients with lone paroxysmal atrial fibrillation—a prospective cohort study

INTRODUCTION: The effect of different treatment strategies of atrial fibrillation on left atrial (LA) size has not been compared in lone paroxysmal atrial fibrillation. The objective of the present study was to evaluate the evolution of LA size over time in patients who underwent different treatment interventions. METHODS AND RESULTS: Two hundred forty patients with lone paroxysmal atrial fibrillation were assigned to four groups. The circumferential pulmonary vein ablation (CPVA) group (n = 60) was treated with CPVA, segmental pulmonary vein isolation (SPVI) group (n = 60) with SPVI, AMIO group (n = 60) with amiodarone alone, and AMIO + LO group (n = 60) with amiodarone plus losartan. LA diameter was measured with transthoracic echocardiogram at baseline, 3, 6, 9, and 12 months after the interventions. In the CPVA group, LA size at third, sixth, ninth, and 12th month had a significant decrease than that at baseline and in the other three groups. LA size in patients with atrial fibrillation recurrence in the four groups was significant higher than that in patients with no atrial fibrillation recurrence (P = 0.002-0.001). CONCLUSION: The results suggested that a shortened LA size is not consistent with improved sinus rhythm maintenance. Although maintenance of sinus rhythm is not the only factor in determining shrinking or enlargement of the left atrium, inhibiting or eliminating activity of the pulmonary vein is very important for paroxysmal atrial fibrillation. Atrial fibrillation recurrence is a main factor contributing to enlargement of the LA.     

Association between interleukin-17 gene polymorphisms and risk of coronary artery disease

We conducted a case-control study to estimate the association between IL-17A rs2275913, rs3819025 and rs3748067 polymorphisms and development of coronary artery disease. A total of 415 patients with coronary artery disease and 448 health controls were recruited during the period of March 2013 and October 2014. Genotyping of IL-17A rs2275913, rs3819025 and rs3748067 were analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism. By logistic regression analysis, we found that individuals with the AA genotype (OR, 2.18; 95% CI, 1.35-3.56) and the GA+AA genotype (OR, 1.39, 95% CI, 1.06-1.84) of rs2275913 were associated with an increased risk of coronary artery disease when compared with the GG genotype. Individuals carrying the GA+AA genotype of rs2275913 were more likely to have a higher risk of coronary artery disease in those with hypertension and smoking habit, and the adjusted ORs (95% CI) were 3.92 (2.13-6.82) and 2.74 (1.71-4.40). In conclusion, we suggest that individuals with the AA genotype and the GA+AA genotype of rs2275913 are associated with an increased risk of coronary artery disease, especially in those with hypertension and smoking habit.     

JARID1B deletion induced apoptosis in Jeko-1 and HL-60 cell lines

Aims: To investigate the involvement of JARID1B histone methyltransferase in the epigenetic change of euchromatic promoter in mantle cell lymphoma (MCL) and acute leukemia. Methods: We retrospectively analyzed the protein of JARID1B and tri-methylated histone H3 lysine 4 (H3K4), histone H3 lysine 9 (H3K9), and cyclin D1 and Ki67 in 30 cases of MCL by immunohistochemistry. JARID1B was depleted by small interfering RNA (siRNA), and cell apoptosis and cell proliferation were detected by flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide], histone tri-methylated H3K4 and histone acetylated H3, H4, cyclin D1, Bcl-2, procaspase-3, C-myc were studied by Western blot. Results: We demonstrated that JARID1B was upregulated and histone tri-methylated H3K4 was downregulated in MCL compared to proliferative lymphadenitis, P < 0.05. The expression of histone methylated H3K9 was similar in both. Histone methylation of H3K4 was positively correlated with Ki67 in MCL (Kappa = 0.757, P < 0.05). This study showed that depletion of JARID1B cleavage apoptotic proteins of Bcl-2, procaspase-3, C-myc and resulted in loss cell viability and inducing apoptosis in Jeko-1 and HL-60 cell lines. JARID1B siRNA improved tri-methyl H3K4 and histone acetylated H3 and inhibited cyclin D1, but did not affect histone acetylated H4. Conclusions: This study revealed hyper JARID1B expression and hypo histone H3K4 tri-methylation in MCL. We identify depletion JARID1B as a demethylase which is capable of removing three methyl groups from H3K4 and up-regulating histone acetylation of H3 in both cell lines. Interestingly, depletion of JARID1B inhibits Cyclin D1, which is one of the genes contributes to MCL pathogenesis. JARID1B might be one of therapeutic targets in acute leukemia and MCL.     

Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea

Background/Aims

The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein.

Methods

Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin.

Results

This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naïve patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy.

Conclusions

In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy.     

布托啡诺和曲马多预防丙泊酚注射痛的临床研究

目的观察布托啡诺和曲马多2种静脉给药方式对丙泊酚注射痛的预防效果,获取一种安全有效的处理措施。方法选择2012年10月-2013年3月美国麻醉医师协会分级Ⅰ~Ⅱ级择期手术患者150例,随机分为布托啡诺静脉注射组(BI组)及滴注组(BD组)、曲马多静脉注射组(TI组)及滴注组(TD组)和空白对照组(C组),各30例。麻醉诱导前5 min,BI、TI及C组分别静脉注射布托啡诺2 mg、曲马多100 mg、生理盐水;BD、TD组分别静脉滴注布托啡诺2 mg、曲马多100 mg,丙泊酚静脉注射2.5 mg/(kg·2 min)。采用四分法分别评估布托啡诺和曲马多的预注痛和丙泊酚注射痛及总的疼痛发生率。结果 BI组和TI组预注痛发生率明显高于其他各组,且BI组明显高于TI组(P<0.05);C组的丙泊酚注射痛发生率和疼痛程度明显高于其他各研究组(P<0.05),其中BD组最低(P<0.05),其次为BI组,明显低于TI和TD组(P<0.05);总的疼痛发生率BD组仅为6.7%,明显低于其他各组(P<0.05)。结论静脉注射或滴注布托啡诺和曲马多均可减少丙泊酚注射痛的发生率及疼痛程度,静脉滴注布托啡诺2 mg效果最佳,但应密切观察,避免不良事件发生。