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.     

甲状旁腺激素对大鼠牵张成骨过程中O NC、OPN、C-FOS、COL1、VEGF、RUNX2、ALP基因表达的影响

目的：探讨甲状旁腺激素（PTH）对大鼠牵张成骨（DO）过程中ONC、OPN、C-FOS、COL1、VEGF、RUNX2、ALP基因表达的影响。方法30只雄性大鼠制备大鼠下颌骨DO模型。随机分5组，每组6只。第1组（只有牵张无PTH），术后8周取材，应用HE染色及微CT检测，以确定成骨情况。第2组（有牵张无PTH），第3组（有牵张有PTH），第4组（无牵张有PTH），第5组（对照组：无牵张无PTH）。2、3、4组及对照组术后1周取材，RT-PCR测定ONC、OPN、C-FOS、COL1、VEGF、RUNX2、ALP基因的表达。结果第1组，新骨形成，骨质充满牵张区，骨质连续，大鼠建模成功。RT-PCR检测结果显示，2、3、4组与对照组比较，OPN、COL1、RUNX2、ALP基因表达有明显提高（P＜0．05），其中第3组最为明显。ONC、C-FOS、VEGF基因2、3、4组与对照组比较差异无统计学意义（P＞0．05）。结论 PTH在 DO 过程中，间歇性给以 PTH的作用只有在牵张期发挥作用，其对 OPN、COL1、RUNX2、ALP基因表达能够获得理想的协同作用。     

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.     

杜长海名老中医应用药对治疗功能性便秘的临床经验探析

功能性便秘的发生严重困扰着现代人群,进而影响人们的生活质量。杜长海名老中医认为功能性便秘究其内因为大肠传导失常,外因乃现代人的生活方式、紧张的生活氛围等等,因此杜老结合自己数十年的临床经验,根据中医辨证总结出临床常用药对,对有效治疗功能性便秘进行了经验总结。     

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.     

鼻咽癌组织中iNOS的表达与微血管密度计数的研究

目的探讨诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在鼻咽癌中的表达与鼻咽癌生物学行为的关系,探讨肿瘤血管生成与鼻咽癌生物学行为的关系,探讨iNOS的表达与鼻咽癌血管生成的关系。方法采用非生物素二步免疫组化法,检测iNOS在鼻咽癌组织中表达,并根据CD34相关抗原标记血管内皮细胞。结果鼻咽癌组织中MVD显著高于慢性鼻咽炎组织(27.7±8.88 vs 9±3.1,P<0.05)。MVD与年龄、性别无关,临床分期Ⅲ、Ⅳ期组的MVD显著高于Ⅰ、Ⅱ期组(30.7±4.7 vs 22.2±7.5,P<0.05)。淋巴转移组MVD显著高于淋巴结未转移组(29.6±4.8 vs 20.5±4.8,P<0.05)。iNOS在鼻咽癌组织中阳性表达率为56.25%,iNOS的表达与年龄、性别无关。临床分期Ⅲ、Ⅳ期组iNOS的阳性表达率为70.97%,显著高于Ⅰ、Ⅱ期组29.41%(P<0.05)。淋巴转移组iNOS的阳性表达率为65.79%,显著高于淋巴结未转移组20.00%(P<0.05)。iNOS阳性表达组的MVD显著高于iNOS阴性表达组(30.0±5.4 vs 24.0±6.0,P<0.05)。结论血管生成及iNOS的表达与鼻咽癌生物学行为关系密切。iNOS表达促进了鼻咽癌血管生成及颈淋巴结的转移。测定MVD及iNOS的表达有助于判断鼻咽癌的恶性程度及预后。