Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.     

全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用

目的:研究全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用效果。方法:选择60岁以上择期行腹腔镜直肠癌根治术患者60例,随机分为G组和GA组,每组各30例。G组患者为单纯全麻组,GA组患者为硬膜外复合全麻组。GA组患者在诱导前取L1~2硬膜外穿刺置管,予0.5%罗哌卡因5 ml,术中每小时追加5~7 ml。两组患者诱导方法相同:即,咪哒唑仑0.04 mg/kg、舒芬太尼0.3~0.4μg/kg、顺阿曲库铵0.15~0.20 mg/kg、依托咪酯0.2~0.3 mg/kg。监测并记录患者血压(BP),心率(HR),心电图(ECG),术中全麻药用量及术后患者苏醒情况。结果:GA组患者气腹后、拔管前BP、HR明显低于G组(P<0.05),且全麻药用量明显低于G组(P<0.05)。结论:全麻复合硬膜外应用于老年腹腔镜直肠癌手术较单纯全麻用药量减少,术中循环更加稳定,是腹腔镜直肠癌根治术比较安全可行的麻醉方法。     

Challenges facing HIV-positive persons who use drugs and their families in Vietnam

It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden.     

Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

Subscapularis Transthoracic Versus Posterolateral Approaches in the Surgical Management of Upper Thoracic Tuberculosis: A Prospective,Randomized Controlled Study

The objective of the present study was to evaluate the clinical, radiological, and functional outcomes of a subscapularis transthoracic surgical approach and a posterolateral surgical approach with debridement, bone graft fusion, and internal fixation for the treatment of upper thoracic tuberculosis.There is currently debate over the best surgical approach for the treatment of upper thoracic tuberculosis. Traditionally, the subscapularis transthoracic approach has been preferred; however, the posterolateral approach has gained popularity in the past few years.A prospective, consecutive cohort of 43 upper thoracic tuberculosis patients with a mean age of 39 years (range: 20–52 years) was followed up for a minimum of 12 months (range: 12–60 months). Patients were randomly divided into 2 groups. Group A (n = 21) was treated by the subscapularis transthoracic approach and group B (n = 22) was treated by the posterolateral approach. All cases were evaluated for clinical, radiological, and functional outcomes. Intraoperative blood loss, operative duration, intraoperative and postoperative complications, hospital stay, the cure rate, fusion time, and the Frankel scale were used for clinical and functional evaluation, whereas the kyphosis angle was used for radiological evaluation.Grafted bones were fused by 10 months in all cases. There was no statistically significant difference between groups before surgery in terms of gender, age, segmental tuberculosis, erythrocyte sedimentation rate (ESR), Frankel scale, or Cobb''s angle (P > 0.05). The average operative duration for Group B was lower than that of Group A. There were no significant differences in intraoperative blood loss, intraoperative and postoperative complications, hospital stay, grafted bone fusion time, or cure rate between groups (P > 0.05). The Cobb''s angle correction rate for group B (68.5%) was significantly better than that of group A (30.9%). The neurological score showed significant postoperative improvement in both groups, with no significant difference between the groups.The subscapularis transthoracic approach and the posterolateral approach with debridement, bone graft fusion, and internal fixation are both sufficient and satisfactory for the surgical treatment of upper thoracic tuberculosis. However, the posterolateral approach is superior to the subscapularis transthoracic approach in terms of surgical trauma, operative time, and kyphosis correction.     

改良睑黄色瘤切除手术的观察

目的 观察改良睑黄色瘤切除术的应用效果。方法 选择病灶〈10mm以下的瘤体为手术观察对象，共22例（38眼）。按超皮损病灶边界1mm设计切口缘，梭形切除病灶，深达真皮层，在显微镜下清除皮下组织及切缘脂肪组织，松解切口边缘皮肤，连续皮内缝合切口。另外，酌情行上睑松弛矫治术。结果 失访2例（2眼），随访20例（36眼）6—12个月，未见黄色瘤复发，切口平整，痕迹隐约。结论 采用改良睑黄色瘤切除术更会增强眼睑形态美感。