Inducible nitric oxide synthase expression elicited in the mouse brain by inflammatory mediators circulating in the cerebrospinal fluid

Expression of inducible nitric oxide synthase (iNOS) protein was studied in the brain after intracerebroventricular injections of interferon (IFN)-gamma, and IFN-gamma combined with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha, compared to ovalbumin as control. Wild-type mice and mice with targeted deletion of the IFN-gamma receptor gene were used. Findings based on iNOS immunoreactivity were evaluated at 1, 2, 4 and 7 days post-injection, using also quantitative image analysis and double labeling with glial cell markers. IFN-gamma administration induced iNOS immmunostaining in activated microglia and macrophages in the parenchyma surrounding the ventricular system, several cortical fields and fiber tracts. IFN-gamma-elicited iNOS immunoreactivity was down-regulated after 1 day. The number of iNOS-immunopositive cells was significantly enhanced by co-administration of LPS or TNF-alpha; IFN-gamma+TNF-alpha injections also resulted in longer persistence of iNOS immunoreactivity. No immunopositive cells were seen in the brain of IFN-gamma receptor knockout mice after IFN-gamma administration; very few immunostained macrophages were detected in these cases, mostly around the injection needle track, after co-administration of LPS or TNF-alpha. Western blot analysis confirmed a marked iNOS induction in the brain of wild-type mice 24 h after IFN-gamma+LPS injections. The findings show that inflammatory mediators circulating in the cerebrospinal fluid induce in vivo iNOS in the brain with topographical selectivity and temporal regulation. The data also demonstrate that the signaling cascade activated by IFN-gamma binding to its receptor is critical for iNOS induction, and the synergistic action of LPS and TNF-alpha as iNOS inducers in brain cells is largely mediated by the receptor-regulated action of IFN-gamma.     

人工耳蜗植入术后植入电极的影像学检查

目的 探讨建立螺旋CT扫描及三维重建技术观察人工耳蜗植入电极方法，并比较X线摄片方法与螺旋CT扫描三维重建方法的耳蜗内电极的影像学特征及其临床应用价值。方法 18例人工耳蜗植入患者全部作术后X线摄片检查。其中9例用经眼眶前后位摄片，9例采用侧斜位60。摄片。3例患者施行术后螺旋CT扫描及内耳三维重建方法。结果 2种投射头位的X线摄片均可显示电极形态及单个电极对，可间接判断电极在耳蜗内的植入深度。螺旋CT扫描三维重建图可直观地显示耳蜗形态、电极形态及其在耳蜗内植入的深度，可清晰识别单个电极对。结论 螺旋CT扫描三维重建方法可直观观察植入电极的形态及位置，可准确判断电极在耳蜗内植入的深度，有其独特的临床应用价值。     

Functional localization of epileptic foci in cats using manganeseenhanced MRI

Objective： To determine the encephalic region correlated with epilepsy by manganese-enhanced MRI （MEMRI） and determine the correlation of epilepsy with calcium overloading. Methods： The cats were divided into two groups. The first group underwent EEG examination and ethological observation. The second group underwent MEMRI measurement. Signal enhanced encephalic regions were sectioned. Results： The achievement ratio of convulsive cats intramusclelarly injected with PTZ was 80%. MEMRI showed diffuse signal enhancement in the cerebral cortex of the cats with generalized tonic-clonic convulsive seizures compared with control animals. The enhancement rate of frontal-parietal-occipital lobe was 34.6% and 22.9% in temporl lobe compared with the control groups. Signal enhancement on frontal-parietal lobe persisted for 24 h after epileptic seizures were induced. The neurons of enhanced encephalic regions showed obvious degeneration and necrosis. Conclusion： Seizures can be induced in cats by intramuscular injection of PTZ （55 mg/kg）. Frontal-parietal lobe is the correlated encephalic regions of epilepsy. MEMRI plays an important role in localizing and revealing pathogenesis of epileptic seizures.     

大鼠NSCs向多巴胺能神经元分化研究

目的：探讨IL-1β对神经干细胞（NSCs）分化为多巴胺能神经元作用：方法：体外培养和鉴定中脑来源NSCs，用免疫学方法检测分化细胞酪氨酸羟化酶（TH）表达.结果：血清组、IL-1β10pg／ml组、IL-1β120pg／ml组、IL-1β150pg／ml组、IL-1β200pg／ml组诱导7d后TH细胞分别平均为0,45％、0．6％、7.2％、12．5％、8．75％：结果显示IL-1β诱导NSCs明显提高TH细胞表达率，与血清组比较有显著性差异（P〈0，05），在IL-1β150pg／ml剂量范同内TH细胞表达率与剂量呈正相关。结论：IL-1β有诱导NSC向多巴胺能神经元分化的显著作用：     

舌下含服米索前列醇配伍米非司酮在终止早孕中的应用

目的 :探讨舌下含服米索前列醇配伍米非司酮用于早孕流产的可行性、安全性及有效性。方法 :将孕周在 7wk内的孕妇随机分为舌下组、口服组各 12 0例。 2组均经米非司酮预治疗后 ,舌下组含服米索前列醇 2 0 0 μg ,1h后重复 ,总量不超过6 0 0 μg ;口服组单次口服米索前列醇 6 0 0 μg。 结果 :舌下组完全流产率比口服组高 ,清宫率比口服组低 (P均 <0 0 1) ,引 -流时间缩短 (P <0 0 1) ,阴道流血及药物不良反应两者无明显差异。结论 :舌下组终止早孕具有简便、有效 ,引 -流时间短等优点     

Selenium substituted axitinib reduces axitinib side effects and maintains its anti-renal tumor activity

Axitinib is a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, which has a strong inhibitory effect on the three isoforms of VEGFR 1–3. Having strong therapeutic efficacy, its broad use is limited by its side effects such as hypertension, proteinuria, cardiovascular damage, and liver and kidney dysfunction. Selenium compounds are broadly reported to have a good protective effect on cardiovascular disease, inflammation, infection, and immune function. In this study, a selenium substitute of axitinib was synthesized, and its anti-renal cell carcinoma activity and side effects were investigated. The results of the study indicated that Se-axitinib had potent antitumor activity on renal cell carcinoma (RCC), alleviated vascular hyperpermeability, and also alleviated axitinib-related side effects including hypertension, liver dysfunction and kidney dysfunction significantly. Therefore, we suggest that Se-axitinib could be a solution to the severe side effects of VEGFR inhibitors and provide evidence to improve the outcome of RCC treatment.

Se-axitinib is a selenium substitution of sulfur in axitinib, which reduced the side effect of VEGFR inhibitors and maintained the potent anticancer activity of the original drug.     

女性尿道括约肌控尿和压力性尿失禁发病的机制

女性尿道括约肌控尿机制和压力性尿失禁发病机理的研究经历了长期和曲折的过程,目前认为,女性尿道括约肌是由尿道横纹肌括约肌、尿道平滑肌括约肌和尿道固有膜等结构,共同参与组成的一个构造精细而有序的尿道括约肌复合体或称尿道括约肌系统.压力性尿失禁的发生主要与尿道括约肌本身解剖结构和功能缺陷,以及尿道周围附属结构和支撑结构缺陷有关.     

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α–GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.Key words: Pregnane X receptor, Hepatocyte nuclear factor 4-alpha, Glucose transporter 2, Hepatic glucose uptake, Diabetes, Drug-induced hyperglycemia     

Gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor in adults: a case report and literature review

Intussusception mostly occurs in childhood and is rare in adults. Although intussusception can occur in any part of the gastrointestinal tract, gastroduodenal intussusception caused by a gastric tumor is relatively uncommon in clinical practice. A PubMed search identified 24 published cases of gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor (GIST); however, it is possible that we missed other cases not included in PubMed. Here we report a case of gastroduodenal intussusception caused by gastric GIST in an 85-year-old man. He came to the hospital because of recurrent black stools. Plain computed tomography (CT) scan indicated a mass in the gastric antrum, with slight enhancement in the arterial phase on enhanced CT scan. He was diagnosed with GIST. In addition, images indicated that the mass overlapped into the duodenum, and gastroduodenal intussusception was thus considered. Gastroscopy showed a huge mass in the gastric body. According to the gastroscopy and CT results, gastroduodenal intussusception caused by a gastric tumor was considered. The patient underwent complete surgical removal, which revealed a mass originating from the gastric antrum and overlapping into the duodenum. The postoperative pathological diagnosis was intermediate-risk gastric GIST. The patient was followed up for 4 months without tumor recurrence.