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1.
Gui-Qi Zhu Ke-Qing Shi Sha Huang Gui-Qian Huang Yi-Qian Lin Zhi-Rui Zhou Martin Braddock Yong-Ping Chen Ming-Hua Zheng 《Medicine》2015,94(11)
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. 相似文献
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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. 相似文献
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Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation 下载免费PDF全文
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. 相似文献
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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. 相似文献
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子宫内膜异位症其异位内膜组织虽然在形态学上呈良性表现,却具有类似恶性肿瘤的生物学特性。中医学一般认为,“正虚伏邪”为恶性肿瘤的病机特点;那么,肾虚血瘀既属于“正虚伏邪”的范畴,又体现了EMs发病学和疾病发生、发展过程中的主要特点。在“病证相应”的中医治则之下,补肾化瘀法的临床疗效主要表现为:缓解痛经症状、提高受孕率,以及调整月经周期。本文基于EMs与恶性肿瘤的相关性,通过分析补肾化瘀法治疗EMs的理论依据及其抑制异位内膜侵袭的调控机制,主要包括解除免疫抑制、阻断局部微血管新生等,旨在阐明其疗效显著的原因,为临床推广提供可靠的基础研究证据。 相似文献