微小RNA调控骨髓干细胞、成骨破骨细胞在骨代谢中的影响★

背景:最近研究发现微小RNA在间充质干细胞分化过程中发挥着重要的调控作用。目的:总结探讨微小RNA在间充质干细胞中的作用,全面了解间充质干细胞分化的机制,对骨质疏松症的预防和治疗有重要意义。方法:由第一作者检索1990/2008 PubMed数据及万方数据库有关微小RNA调控骨髓间充质干细胞从而影响骨代谢等方面的文献,英文检索词为"microRNA,mesenchymal stem cells,bone metabolism",中文检索词为"微小RNA,骨髓间充质干细胞,骨代谢"。根据纳入标准保留30篇进一步归纳总结。结果与结论:微小RNA通过对多种转录因子、生长因子和信号通路的调节作用,影响着间充质干细胞的自我更新和分化过程。运用高通量技术筛选出与骨髓间充质干细胞分化相关的特异性微小RNA,研究其作用的分子机制,对于骨髓间充质干细胞分化异常所致的骨代谢疾病,如骨质疏松症等发病机制的阐明具有重要作用。微小RNA在骨髓间充质干细胞的分化中作用机制的研究将为骨代谢疾病的预防和治疗提供一个新的方向。     

Altered patterns of resting-state functional connectivity between the caudate and other brain regions in medication-naïve children with attention deficit hyperactivity disorder

BackgroundStructural and functional alterations occur in the caudate of patients with attention-deficit/hyperactivity disorder (ADHD). Here we aimed to investigate the functional connectivity between the dorsal caudate and other brain regions in ADHD children.MethodsResting-state functional connectivity from 30 ADHD and 33 age- and gender-matched “normal” children were measured by functional Magnetic Resonance Imaging.ResultsPositive connectivity with dorsal caudate was observed in the prefrontal areas, cingulate cortex and temporal lobe. Negative functional connectivity was observed in the precuneus, occipital cortices and cerebellum. The connectivity of left dorsal caudate to left inferior frontal gyrus was correlated with severity of ADHD.ConclusionsConnectivity of dorsal caudate with several brain regions was identified in ADHD children.     

Impact of Enzalutamide Administration on Primary Prostate Cancer Volume: A Metabolic Evaluation by Choline Positron Emission Tomography in Castration-Resistant Prostate Cancer Patients

BackgroundEnzalutamide is active in advanced castration-resistant prostate cancer (CRPC) patients, in whom it has shown to be able to increase survival. We report the enzalutamide effect on primary prostate tumors, assessed by changes of metabolic tumor activity detected by ¹⁸F-fluorocholine-positron emission tomography/computerized tomography (¹⁸F-FCH PET/CT).Patients and MethodsWe treated 31 patients with pretreated metastatic CRPC in an enzalutamide named-patient program. All patients were initially evaluated and then followed up by means of repeated ¹⁸F-FCH PET/CT examinations. We identified most radiotracer-avid lesions, which were defined as specific regions of interest (ROIs): for each ROI we defined the maximum radiotracer standardized uptake value (SUV_max) and the threshold-based volume of interest (VOI) with a cutoff SUV value ≥ 2.5. In the 12 patients who did not receive a radical treatment for localized disease, the prostate was also considered an ROI.ResultsThe baseline prostate median SUV_max of 7.25 showed reductions of 25% (P = .012) and 43% (P = .009) after 3 and 7 months of enzalutamide treatment, respectively. The baseline median prostate VOI of 12.73 cm³ showed a reduction of 73% (P = .002) at 3 months and a reduction of 90% (P = .005) at 7 months.ConclusionIn addition to the metabolic changes of metastatic lesions observed with enzalutamide in CRPC patients, our data have shown significant volume reductions of the primary tumors according to ¹⁸F-FCH PET/CT evaluation. These results could suggest the potential of enzalutamide therapy for localized prostate cancer.     

Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation

Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V_max and low K_m values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V_max and V_max/K_m values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation.     

颈动脉加压滴注复方抗栓酶治疗脑梗死的护理方案研究

目的观察颈动脉加压滴注复方抗栓酶治疗脑梗死的有效护理方法。方法选择我院2008年1月至2012年2月期间收治的急性脑梗死患者88例,随机平均分为观察组与对照组:对照组进行常规护理;观察组在常规护理的基础上进行全面有效的护理干预措施,然后比较两组患者的临床效果。结果通过有效的治疗与护理干预后,观察组患者总有效率为95.45%(42/44),明显高于对照组的77.27%(34/44);观察组患者的各种并发症发生率均明显低于对照组,差异均具有统计学意义(P<0.05)。结论颈动脉加压滴注复方抗栓酶是治疗脑血栓有效且简单易行的治疗方法,在有效的护理配合下提高了脑血栓治疗效果,改善了脑血栓患者预后的生活质量,值得临床推广。     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.