Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants,yet alpha7 nAChR agonists do not improve probabilistic learning

Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment. Improving reward-related learning could synergistically enhance psychosocial treatments and cognition generally. A critical first step is to understand the mechanisms underlying reward learning. The dopamine system has been implicated in such learning, but less known is how indirect activation of this system may affect reward learning. We determined the role of alpha7 nicotinic acetylcholine receptors (nAChR) on a probabilistic reversal learning task (PRLT) in mice that includes reward and punishment. Male alpha7 knockout (KO), heterozygous (HT), and wildtype (WT) littermate mice (n?=?84) were treated with vehicle, 0.03, or 0.3?mg/kg nicotine. Two cohorts of C57BL/6NJ male mice were treated with various alpha7 nAChR ligands, including the full agonists PNU282877 and AR-R-17779, the positive allosteric modulator CCMI, the partial agonist SSR180711, and the antagonist methyllycaconitine. All mice were then tested in the PRLT. Nicotine (0.3?mg/kg) significantly improved initial reward learning in alpha7 WT and HT mice but did not improve learning in KO mice, suggesting an involvement of the alpha7 nAChR in the pro-learning effects of nicotine. Neither alpha7 nAChR treatments (PNU282987, AR-R-17779, CCMI, SSR180711, nor methyllycaconitine) affected mouse PRLT performance however. Nicotine improved reward learning via a mechanism that may include alpha7 nAChRs. This improvement unlikely relied solely on alpha7 nAChRs however, since no alpha7 nAChR ligand improved reward learning in normal mice. Future assessments of the effects of other nAChR subtypes on reward learning are needed.     

四川省三个核设施地区水源水总α、总β放射性水平调查

目的 调查四川省三个核设施地区水源水总α、总β放射性水平,为本省核设施地区水源水放射性水平提供基线数据库。方法 根据国家标准《生活饮用水标准检验方法放射性指标》（GB/T 5750.13-2006）的方法要求,调查四川省三个核设施地区水源水总α、总β放射性水平。结果 三个核设施地区水源水总α比活度范围为（0.016~0.188）Bq/L;总β比活度范围为（0.028~0.229）Bq/L,处于全国平均中下水平,属于正常的本底水平。结论 三个核设施地区水源水总α、总β放射性水平均低于《生活饮用水卫生标准》（GB 5749-2006）中的国家标准限值。     

核磁共振结合血清甲胎蛋白、肌酸激酶水平诊断凶险型前置胎盘合并胎盘植入的价值

目的对核磁共振(MRI)结合血清甲胎蛋白(AFP)、肌酸激酶(CK)表达诊断凶险型前置胎盘合并胎盘植入的价值进行探讨。方法选取2015年1月-2016年10月收治的90例凶险型前置胎盘患者,根据手术和术后病理结果分为凶险型前置胎盘合并胎盘植入组(简称植入组,53例)和凶险型前置胎盘非胎盘植入组(简称非植入组,37例),比较两组患者静脉血中AFP、CK的水平,并将所有患者的MRI结果、血清学检查结果及两者联合检查结果与病理结果进行比较。结果植入组血清AFP和CK表达水平显著高于非植入组(P<0.05)。MRI、血清学检查及二者联用的诊断灵敏度(71.74%vs.67.92%)、漏诊率(28.3%vs.32.13%)、阴性预测值(63.34%vs.63.0%)和符合率(71.12%vs.72.25%)之间比较,差异具有统计学意义(P<0.05),联合诊断的灵敏度(90.56%)、阴性预测值(86.84%)和符合率(90.00%)均显著高于单独的MRI或血清学检查(P<0.05),漏诊率(9.43%)低于单独的MRI或血清学检查(P<0.05)。结论 MRI联合血清AFP、CK表达检测能提高诊断的灵敏度和诊断符合率,优于单项检测,具有一定的诊断价值。     

血清肿瘤标志物联合检测在原发性肝癌诊断中的价值研究

目的:探讨细胞周期素A2(CCNA2)与甲胎蛋白(AFP)、癌胚抗原(CEA)、癌抗原199(CA199)及癌抗原724(CA724)的联合检测在原发性肝癌临床诊断中的价值,以期筛选出理想的肿瘤标志物组合,提高肝癌诊断的准确率。方法:选取2020年10月—2021年3月天津市第三中心医院收治的原发性肝癌患者68例为研究对象,作为原发性肝癌组;另选择同期收治的80例肝病患者作为肝良性疾病组,80例健康体检者作为健康对照组。采集各研究对象清晨空腹静脉血5 mL,采用addicare1100酶免仪利用酶联免疫吸附法(ELISA)检测血清CCNA2,采用罗氏e801全自动电化学发光仪及其配套试剂检测血清AFP、CEA、CA199和CA724。评估上述指标单项及联合检测在早期PLC诊断的应用价值。结果:健康对照组血清肿瘤标志物均显著低于肝良性疾病组与原发性肝癌组,差异有统计学意义(P＜0.05)。68例原发性肝癌患者中,对AFP、CEA、CA199、CA724和CCNA2等血清肿瘤标志物水平予以检测,联合检测的特异性和准确性均显著高于各指标的单项检测结果,差异有统计学意义(P＜0.05)。结论: CCNA2作为一种新型的肿瘤标志物,对肝癌的诊断具有一定的价值。CA199、CEA、AFP、CA724、CCNA2联合检测能显著提升原发性肝癌的诊断阳性率,对尽早诊断原发性肝癌具有重要意义。     

The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle

Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and volunteer’s satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects.     

汕尾市育龄人群中α、β地中海贫血基因型的分布调查

目的 了解汕尾市育龄人群中α、β地中海贫血基因型的分布情况.方法 采用整群抽样方法选择2013年1月1日至2013年12月31日各地区部分住院分娩和引产的孕产妇、配偶共计1200例作为研究对象,分别进行α-地中海贫血和β-地中海贫血调查.结果 在1200份血液标本中共计检测出6种α-地中海贫血基因型,共计62例,63个等位基因,α-地中海贫血基因携带率为5.25％（63/1200）.其基因型构成比：-a3.7/aa 31个,占总数的49.21％;-aSEA/aa 18个,占总数的28.57％;-a4.2/aa 7个,占总数的11.11％;-aTHAI/aa 2个,占总数的3.17％;--SEA/--SEA 3个,占总数的4.76％;--aCSa/aa2个,占总数的3.17％.有13例患者检测出携带β-地中海贫血基因,β-地中海贫血基因携带率为1.08％.基因类型共有5种,其构成比：IVS-2-654（C→T）和-28（A→G）各23.08％,CD41/42（-TCTT）30.77％,CD17（A→T）15.38％,βECD26（C→A）7.69％.结论 汕尾市区α-地中海贫血基因携带率和β-地中海贫血基因携带率从整个省份来讲相对较低,但分析自身数据来看携带率还是较高,主要发生在遗传背景较复杂的地区,并主要以本地人群为主.     

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus

Introduction and objectivesOptimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial.Materials and methodsA total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type.ResultsResection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort.ConclusionsOur results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.