Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.     

两种给药途径致痫大鼠海马神经元超微结构损伤及caspase-3的表达特征

为了观察两种给药途径致痫大鼠海马神经元超微结构的损伤及caspase-3的表达特征,本研究分别采用海人酸腹膜腔注射(A组)和尾静脉注射(B组)诱发大鼠癫痫持续状态(SE)。分别于SE终止后3、6、24、48和72h取海马,电镜观察神经元超微结构的变化,免疫组化方法检测caspase-3的表达。结果显示:两组大鼠均在SE后3h出现线粒体损伤,细胞核的改变出现于SE后24h。A组致痫的潜伏期为97min±11min,神经元以凋亡为主;B组为48min±13min,神经元以坏死为主。SE后6～24h,两组大鼠海马内caspase-3的表达由胞浆向胞核逐渐移位,且均在SE后6h明显增高,24h达顶峰;A组高表达持续至72h,B组在48h显著降低。上述结果提示,线粒体的损伤出现于SE的早期,且可能是神经元损伤的关键环节;致痫方法不同,神经元的死亡形式也不同;而caspase-3的激活是神经元凋亡和坏死的共同通路。     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

藏药独一味药理作用及临床应用新进展

简要综述了独一味及其制剂的药理作用和临床应用研究的最新进展,并对其今后的研究方向提出了建议。认为独一味有良好地利用价值和开发潜力,对其研究开发的前景广阔;对其药效的物质基础及作用机理的研究有待深入,尤其应重点关注其疗效确切的镇痛活性。     

外伤相关黑素瘤87例临床病理特点与预后分析

目的:分析外伤相关黑素瘤的临床病理特点及其与患者预后间的关系。方法:回顾性分析2009—2020年第四军医大学西京皮肤医院87例外伤相关黑素瘤的临床病理特点,通过Mann-Whitney检验分析不同年龄、性别患者间肿瘤Breslow厚度的差异;通过Spearman秩相关分析外伤至发现皮疹的时间与Breslow厚度之间的...     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Comparison of six anthropometric measures in discriminating diabetes: A cross‐sectional study from the National Health and Nutrition Examination Survey

BackgroundTraditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating the risk of diabetes. This study aimed to evaluate the performance of new anthropometric measures and a combination of anthropometric measures for identifying diabetes.MethodsA total of 46 979 participants in the National Health and Nutrition Examination Survey program were included in this study. Anthropometric measures, including weight, BMI, waist circumference (WC), waist‐to‐height ratio (WtHR), conicity index (CI), and A Body Shape Index (ABSI), were calculated. Logistic regression analysis and restricted cubic splines were used to evaluate the association between the anthropometric indices and diabetes. The receiver operating characteristic (ROC) curve analysis was performed to compare the discrimination of different anthropometric measures.ResultsAll anthropometric measures were positively and independently associated with the risk of diabetes. After adjusting for covariates, the per SD increment in WC, WtHR, and CI increased the risk of diabetes by 81%, 83%, and 81%, respectively. In the ROC analysis, CI showed superior discriminative ability for diabetes (area under the curve 0.714), and its optimum cutoff value was 1.31. Results of the combined use of BMI and other anthropometric measures showed that among participants with BMI <30 kg/m², an elevated level of another metric increased the risk of having diabetes (P < .001). Similarly, at low levels of weight, CI, and ABSI, an elevated BMI increased diabetes risk (P < .001).ConclusionsWtHR and CI had the best ability to identify diabetes when applied to the US noninstitutionalized population. Anthropometric measures containing WC information could improve the discrimination ability.     

低辐射剂量CT扫描技术在脑动脉3D打印中的应用研究

目的：探讨低辐射剂量CT扫描数据在脑动脉3D打印的可行性研究。方法：将临床拟行脑动脉3D打印的40例患者随机分为2组,每组20例。A组（常规剂量CT扫描方案）：120 kVp,350 mA和滤波反投影（FBP）算法;B组（低剂量CT扫描方案）：80 kVp,自动管电流调制技术（ATCM）和自适应统计迭代重建（ASiR）算法;2组对比剂浓度均为350 mgI/mL。采用两独立样本t检验（非正态分布采用Mann-Whitney U检验）来比较2组的临床资料、辐射剂量、CT DICOM数据客观评价指标及2组方案完成3D打印产物质量的主观评分。结果：A、B 2组患者的临床资料差异均无统计学意义（P＞0.05）。2组的CT辐射剂量差异具有显著统计学意义（P＜0.05）,B组辐射剂量[（1.30 ± 0.47） mSv]较A组[（4.15 ± 0.62） mSv]减少约68.7%。2组脑动脉3D打印结果主观评分差异无统计学意义（P＞0.05）。2组CT DICOM数据客观评价指标：A组的背景噪声（BN）明显高于B组（P=0.000）,而A组的信噪比（SNR）及对比噪声比（CNR）均低于B组（P=0.000）。结论：采用80 kVp、ATCM技术及ASIR算法的数据行脑动脉3D打印,在保证3D打印质量的同时,可以有效减低辐射剂量。     

角膜曲率计与角膜地形图仪测量角膜屈光度的对比研究

目的：对使用角膜曲率计与角膜地形图仪测量角膜屈光度的结果进行对比研究,提出两种仪器各自在白内障术前测算人工晶状体度数中提供K值的精确性。方法;在无眼表疾病的38例（76只眼）分别使用美国生产的角膜地形图仪和日本生产的角膜曲率计测量角膜屈光度,然后进行统计学处理。结果：角膜曲率计和角膜地形图仪检查结果略有差异,但经统计学处理无显著意义（P＞0．05）。结论：角膜地形图仪系统测量角膜屈光度更为准确、全面,尤其对角膜过陡、过平、有斑翳、云翳者的检测结果更有参考价值。     

Association of Gut Microbiota Enterotypes with Blood Trace Elements in Women with Infertility

Infertility is defined as failure to achieve pregnancy within 12 months of unprotected intercourse in women. Trace elements, a kind of micronutrient that is very important to female reproductive function, are affected by intestinal absorption, which is regulated by gut microbiota. Enterotype is the classification of an intestinal microbiome based on its characteristics. Whether or not Prevotella-enterotype and Bacteroides-enterotype are associated with blood trace elements among infertile women remains unclear. The study aimed to explore the relationship between five main whole blood trace elements and these two enterotypes in women with infertility. This retrospective cross-sectional study recruited 651 Chinese women. Whole blood copper, zinc, calcium, magnesium, and iron levels were measured. Quantitative real-time PCR was performed on all fecal samples. Patients were categorized according to whole blood trace elements (low levels group, <5th percentile; normal levels group, 5th‒95th percentile; high levels group, >95th percentile). There were no significant differences in trace elements between the two enterotypes within the control population, while in infertile participants, copper (P = 0.033), zinc (P < 0.001), magnesium (P < 0.001), and iron (P < 0.001) in Prevotella-enterotype was significantly lower than in Bacteroides-enterotype. The Chi-square test showed that only the iron group had a significant difference in the two enterotypes (P = 0.001). Among infertile patients, Prevotella-enterotype (Log(P/B) > −0.27) predicted the low levels of whole blood iron in the obesity population (AUC = 0.894; P = 0.042). For the high levels of iron, Bacteroides-enterotype (Log(P/B) <−2.76) had a predictive power in the lean/normal group (AUC = 0.648; P = 0.041) and Log(P/B) <−3.99 in the overweight group (AUC = 0.863; P = 0.013). We can infer that these two enterotypes may have an effect on the iron metabolism in patients with infertility, highlighting the importance of further research into the interaction between enterotypes and trace elements in reproductive function.