Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition

GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2^−/−) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2^−/− mice show cortical PV⁺ interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus. Ccnd2^−/− mice show several neurophysiological and behavioral phenotypes that would be predicted to be produced by hippocampal disinhibition, including increased ventral tegmental area dopamine neuron population activity, behavioral hyperresponsiveness to amphetamine, and impairments in hippocampus-dependent cognition. Remarkably, transplantation of cells from the embryonic medial ganglionic eminence (the major origin of cerebral cortical interneurons) into the adult Ccnd2^−/− caudoventral hippocampus reverses these psychosis-relevant phenotypes. Surviving neurons from these transplants are 97% GABAergic and widely distributed within the hippocampus. Up to 6 mo after the transplants, in vivo hippocampal metabolic activity is lowered, context-dependent learning and memory is improved, and dopamine neuron activity and the behavioral response to amphetamine are normalized. These findings establish functional links between hippocampal GABA interneuron deficits and psychosis-relevant dopaminergic and cognitive phenotypes, and support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.Precursors of most γ-aminobutyric acid (GABA)-releasing interneurons of the cerebral cortex and the hippocampus originate in the embryonic medial ganglionic eminence (MGE) (1–3). A subpopulation of MGE-derived cells differentiates into fast-spiking, parvalbumin-expressing (PV⁺) interneurons that tightly regulate the activity and synchronization of cortical projection neurons (2, 4). Structural and functional deficits in PV⁺ interneurons are hypothesized as a pathophysiological mechanism in schizophrenia and psychotic disorders (4–6).Although psychotic disorders are clearly heterogeneous in etiology, disinhibition within temporolimbic cortical circuits is postulated as a core pathophysiology underlying positive symptoms (e.g., delusions and hallucinations) and a subset of cognitive disturbances that manifest with psychosis (4, 5, 7). Postmortem studies of brains from individuals with psychotic disorders show reduced molecular markers of the number and/or function of PV⁺ interneurons in the hippocampus (6, 8). Consistent with these observations, basal metabolic activity in the hippocampus, as measured with functional magnetic resonance imaging (fMRI), is increased in schizophrenia, a phenotype that predicts psychosis and positive symptom severity (5, 7). This abnormal resting activity is postulated to underlie abnormal recruitment of hippocampal circuits during cognitive performance (5, 9). Striatal dopamine (DA) release capacity is also increased and correlated with positive symptoms in schizophrenia and its risk states (10, 11). Importantly, hippocampal hyperactivity may contribute to DA dysregulation (12), because rodent studies show that caudoventral hippocampal (in the primate, anterior hippocampal) efferents regulate the activity of DA neurons and medial striatal DA release (13, 14).Thus, converging evidence implicates hippocampal disinhibition in the abnormal striatal DA transmission and cognitive impairment in schizophrenia. However, the role of hippocampal inhibitory interneurons in psychosis-relevant circuitry remains to be established. To this end, we used the cyclin D2 (Ccnd2) knockout mouse model (15), which displays a relatively selective deficit in cortical PV⁺ interneurons, and transplantation of interneuron precursors from the MGE to elucidate relationships between reduced hippocampal GABA interneuron function and multiple psychosis-relevant phenotypes, and to explore a novel treatment strategy for psychosis.     

Changes in Early Serum Metal Ion Levels and Impact on Liver,Kidney, and Immune Markers Following Metal-on-Metal Total Hip Arthroplasty

We retrospectively studied 32 consecutive patients (32 hips) who underwent THA with a Durom large-head, MOM articulation between January 2008 and December 2010. Of the patients who underwent THA using a Trilogy metal on polyethylene prosthesis during the same period, 32 were chosen to form the Trilogy group. 32 volunteers were chosen to form the control group. At the last follow-up, serum metal ion levels, liver and kidney function and host immunologic immune responses were evaluated. The mean Co and Cr levels in the Durom group were 4.33- and 1.95-fold higher than those in the Trilogy group. CD3 +, CD4 + and CD8 + cell levels in the Durom group were significantly decreased. The INF-γ level in the Durom group was significantly higher than that in the Trilogy and control groups.     

体脂量是绝经后女性股骨近端骨强度的决定因素

正Lower body weight or body mass index(BMI)has been known to be higher risk of developing osteoporosis and low-energy fractures via mechanical loading and other factors in both men and women[1].Recently,there have been new insights into the relationships between body composition and bone health.However,most of the previous studies regarding the relative effect of body composition on bone mass yielded inconsistent     

皮肤干细胞的定位

应用计算机检索Pubmed数据库1990-2008年、中文期刊全文数据库1998．2008年与皮肤干细胞定位相关的文献，44篇文献资料分析结果显示，毛囊bulge区细胞具有高度增殖潜能，为标记滞留细胞，具有多向分化潜能，不表达分化细胞特异性标志，表达干细胞标志，为目前公认的表皮干细胞的定居处。毛囊真皮鞘包含具有可塑性的干细胞，认为是真皮干细胞的定居处。毛囊真皮乳头内含有具一定增殖分化能力的前体细胞，与真皮鞘相互作用，能够诱导毛囊形成，目前观点认为，真皮乳头内前体细胞移行自真皮鞘干细胞，为其活化的子代细胞。毛囊间皮肤与无毛区皮肤是否存在皮肤干细胞尚存争论，部分实验表明，毛囊间表皮基底层亦有表皮干细胞的存在。     

Evaluation of severe transplant renal artery stenosis with Doppler sonography

PURPOSE: To evaluate and determine Doppler criteria for predicting a severe transplant renal artery stenosis (80%-99% diameter reduction) and to compare the Doppler findings in patients with end-to-end and end-to-side anastomosis. METHODS: We performed Doppler sonography on 16 consecutive patients with transplant renal artery stenosis (TRAS) confirmed by digital subtraction arteriography (DSA). Fourteen patients had end-to-end anastomosis, and 2 had end-to-side anastomosis. Eleven patients were re-evaluated with color Doppler sonography within 4 days after intervention. Seven Doppler parameters, including the peak systolic velocity (PSV) in the renal, iliac and interlobar artery, Pre-PSV ratio (the ratio of the PSV in the renal artery to that in the iliac artery), Post-PSV ratio (the ratio of the PSV in the renal artery to that in the interlobar arteries, acceleration time and resistance index, were measured. In the patients with severe TRAS the measurements of these parameters were compared before and after successful intervention. RESULTS: In the 16 patients with a single transplanted kidney, arteriography demonstrated 14 main renal arteries with severe stenosis, and 3 renal arteries with moderate stenosis. When using the cutoff values of Post-PSV ratio >13, renal artery PSV >4 m/sec, acceleration time >0.06 second, and resistance index <0.5 for the detection of all 14 severe stenoses, the sensitivities were 100%, 71%, 93%, and 50%, respectively. For assessing all 14 severe stenoses and 12 severe stenoses of end-to-end anastomosis, the cutoff value of Pre-PSV ratio >5 had sensitivities of 86% and 100%, respectively. Pre-PSV ratios in severe stenoses of end-to-end anastomosis (range, 5.1-11.5) were significantly greater than those recorded in severe stenoses of end-to-side anastomosis (range, 2.8-3.1). Statistically significant differences before and after successful intervention were found for all 7 Doppler parameters in the 7 patients with severe stenosis. CONCLUSIONS: An 80%-99% diameter reduction of the renal artery can be diagnosed based on a Post-PSV ratio >13 for patients with either end-to-end or end-to-side anastomosis. A Pre-PSV ratio >5 for patients with end-to-end anastomosis and acceleration time >0.06 second are helpful in the diagnosis of severe TRAS.     

Pentoxifylline reduces indirect lung injury of fresh water drowning in canis

BACKGROUND: Previous studies have suggested that pentoxifylline (PTX) exerts multiple beneficial effects on the inflammatory cascade, particularly on the function of neutrophils. We investigated whether continuous infusion of PTX could reduce indirect lung injury (ILI) caused by fresh water drowning and if so, what is the possible molecular mechanism. METHODS: Twenty 4 male canis were divided randomly into control group, fresh water drowning group (right lung), drowning treated with PTX group and PTX alone group. At different time points after drowning, the changes of hemodynamic parameters and wet/dry weight of indirect lung (left lung) tissues were compared among these 4 groups. Other measures included lung histopathology, PMN infiltration assessed by immune staining, CD11b, ICAM-1 mRNA and TNF-alphamRNA in left lung detected by RT-PCR. NF-kappaB activation in blood neutrophils and lungs were measured with electrophoretic mobility shift assay (EMSA). RESULTS: Animals treated with PTX showed a significant reduction in lung injury. PTX suppressed drowning-induced ICAM-1 and TNF-alphamRNA elevation and inhibited NF-kappaB activation in blood neutrophils and lungs. CONCLUSIONS: Continuous infusion of PTX reduces ILI caused by fresh water drowning. PTX decreases expression of ICAM-1 and TNF-alpha, possibly via inhibition of NF-kappaB.     

蛭类转录组中EST-SSR分析及抗凝血相关分子标记的挖掘

目的对蛭类转录组进行SSR分析,是开发功能分子标记、开展对药用蛭类资源的开发利用及进行遗传背景监测的必要手段。方法利用与医学密切相关的医蛭科棒纹牛蛭Poecilobdella javanica和日本医蛭Hirudo nipponia、黄蛭科宽体金线蛭Whitmania pigra和山蛭科洞穴山蛭Heamadipsa cavatuses sp.nov.共14个样本,通过RNA测序及转录组分析,筛选吸血差异unigene,并比较4个种的SSR标记特征和分布,用于挖掘抗凝血相关功能EST-SSR。结果通过SSR密度分析发现,SSR在棒纹牛蛭、日本医蛭、宽体金线蛭和洞穴山蛭转录组中的间隔长度为4 723、6 026、8 059、8 144 bp;SSR组成分析发现三碱基重复的基序占蛭类SSR类型组成中绝大多数;另外,洞穴山蛭的SSR组成与其他3种存在明显区别。比较4种吸血蛭吸血前后转录组中表达丰度显著差异的unigene群,发现4种蛭中包含SSR且抗凝血相关的重叠unigene类群在转录组中呈较高的片段多态性。结论 unigene片段长度、SSR的密度、组成和分布特点能反映物种之间的分类关系;4种蛭重叠的抗凝血相关分子功能对应的EST-SSR,可作为抗凝血相关的功能分子标记侯选EST-SSR。     

清热利湿祛瘀法治疗慢性前列腺炎的临床疗效及对患者局部免疫的影响

目的:探究清热利湿祛瘀法治疗慢性前列腺炎的临床疗效,分析其对患者局部免疫功能的影响。方法:选取2017年1月至2017年6月南京中医药大学附属医院收治的慢性前列腺炎患者228例,按随机数字表法分为对照组和观察组,每组114例,2组患者均进行常规西药治疗,观察组在对照组治疗的基础上联合清热利湿祛瘀汤治疗,2组均以14 d为1个疗程,连续治疗3个疗程。治疗后统计2组临床疗效,评价2组治疗前后临床症状改善情况;分别于治疗前后检测并比较2组患者前列腺液中WBC及免疫指标的变化。结果:治疗后观察组临床总有效率高达93.86%,较对照组的73.68%显著升高(P0.01);与治疗前比较,治疗后2组患者IIEF评分明显升高,且观察组显著高于对照组(P0.01);2组患者NIH-CPSI评分及QOL评分明显降低,且观察组显著低于对照组(P0.01);与治疗前比较,治疗后2组患者前列腺液WBC均明显降低(P0.05或P0.01),且观察组显著低于对照组(P0.05);与治疗前比较,治疗后观察组前列腺液中SIg A及Ig G含量均显著降低,且显著低于对照组(P0.01)。结论:清热利湿祛瘀法可显著改善慢性前列腺患者临床症状,抑制其局部炎性反应,并可有效降低其前列腺液中免疫球蛋白含量,调节局部免疫应答,疗效显著优于常规西药治疗。     

清肺解毒饮治疗肺胃蕴热型痤疮临床研究

目的 评价清肺解毒饮治疗肺胃蕴热型痤疮的疗效.方法 将符合入选标准的93例女性痤疮患者按随机数字表法随机分为3组,每组31例.观察组口服清肺解毒饮,中药对照组口服丹参酮胶囊,西药对照组口服醋酸环丙氯地孕酮,3组均治疗4周.采用ELISA法检测血清双氢睾酮(dihydrotestosterone,DHT)、IL-6、IL-8水平,观察治疗前后的皮损变化,记录治疗期间的不良反应,评价临床疗效.结果 治疗后,观察组血清DHT[(56.94±15.74)pg/ml比(74.48±18.53)pg/ml,t=2.089]、IL-6[(22.84±11.77)pg/ml比(30.37±14.50)pg/ml,t=2.135]、IL-8[(22.64±7.38)pg/ml比(29.54±9.65)pg/ml,t=2.057]水平均低于中药对照组(P<0.05).治疗后,观察组皮损消退率[(65.4±15.0)%比(44.7±12.9)%、(42.7±13.6)%,F=6.862]与综合证候有效率[(57.2±12.6)%比(46.3±12.8)%、(44.8±11.7)%,F=5.322]均高于中药对照组与西药对照组(P<0.05).观察组与中药对照组均未见明显不良反应,西药对照组有1例恶心.结论 清肺解毒饮可降低女性肺胃蕴热型痤疮患者血清DHT、IL-6、IL-8水平,提高皮损消退率与综合证候有效率,疗效优于口服丹参酮胶囊或醋酸环丙氯地孕酮治疗.