10种抗精神病药物对多巴胺D2受体占有率的模拟分析

目的 模拟分析10种抗精神病药物氟哌啶醇（haloperidol）、舒必利（sulpiride）、美哌隆（melperone）、氯氮平（clozapine）、喹硫平（quetiapine）、利培酮（risperidone）、齐拉西酮（ziprasidone）、瑞莫必利（remoxipride）、氨磺必利（amisulpride）、雷氯必利（raclopride）口服给药后在人体内对多巴胺D₂受体（DRD₂）占有的时间过程。方法 通过对10种抗精神病药物的口服给药和静脉给药的药动学数据模拟计算获取建模的药动学（PK）参数;通过已发表的文献数据计算获取10种抗精神病药物的结合动力学（BK）参数和细胞内DRD₂受体合成动力学（TK）参数;基于获取的PK、BK、TK参数建立10种抗精神病药物的DRD₂受体占有率数学计算模型（PK-BK-TK模型）。结果 已上市的9种（不包含雷氯必利）抗精神病药物在临床推荐剂量下对DRD₂的最大受体占有率均在65%以上,预测的DRD₂受体占有率曲线与其临床药效持续时间有良好的一致性;雷氯必利的合理给药剂量为2mg。结论 利用PK-BK-TK数学模型能准确预测抗精神病药物口服后在人体内对DRD₂受体的占有过程。该模型可为评估化合物在体内拮抗DRD₂受体的活性与潜在毒性提供一种新的研究思路和方法。     

Artificial intelligence in screening,diagnosis, and classification of diabetic macular edema: A systematic review

We review the application of artificial intelligence (AI) techniques in the screening, diagnosis, and classification of diabetic macular edema (DME) by searching six databases– PubMed, Scopus, Web of Science, Science Direct, IEEE, and ACM– from January 1, 2005 to July 4, 2021. A total of 879 articles were extracted, and by applying inclusion and exclusion criteria, 38 articles were selected for more evaluation. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). We provide an overview of the current state of various AI techniques for DME screening, diagnosis, and classification using retinal imaging modalities such as optical coherence tomography (OCT) and color fundus photography (CFP). Based on our findings, deep learning models have an extraordinary capacity to provide an accurate and efficient system for DME screening and diagnosis. Using these in the processing of modalities leads to a significant increase in sensitivity and specificity values. The use of decision support systems and applications based on AI in processing retinal images provided by OCT and CFP increases the sensitivity and specificity in DME screening and detection.     

Sudden-onset unilateral painless vision loss

A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.     

静息状态脑功能连接磁共振成像的分析方法及应用

多数功能磁共振成像(fMRI)研究是在特定的实验任务条件下对大脑的活动进行分析.然而,大脑在静息状态下仍存在自发神经元活动,这些自发活动具有较强的低频同步性,对于静息状态下的大脑活动的研究有利于全面认识大脑的内在活动机制.本文主要综述目前静息状态脑功能连接fMRI常用分析方法及其在临床疾病中的初步应用.     

Effects of systemic antibiotic therapy on bacterial persistence in the respiratory tract of mechanically ventilated patients

Objective Bacterial respiratory tract colonization predisposes critically ill patients to intensive care unit (ICU)-acquired infections. It is unclear to what extent systemic antibiotics affect colonization persistence. Persistence of respiratory tract colonization, and the effects of systemic antibiotics hereon, were determined in a cohort of ICU patients. Design Clinical and microbiological data were collected from 715 admitted mechanically ventilated ICU patients with bacterial growth documented in respiratory tract samples. First day of colonization, persistence of colonization and antibiotic effects hereon were analyzed for six groups of pathogens: Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae, Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae. Systemic antibiotics were grouped into ‘effective’ and ‘ineffective’ antibiotics, based on in-vitro susceptibility data for the relevant bacteria. The effects of antibiotics were quantified as relative risk (RR) of bacterial persistence in the absence of effective antibiotics. Measurements and results Persistence of colonization differed significantly between pathogens, ranging from 4 days (median) for H. influenzae and Strep. pneumoniae to 8 days for P. aeruginosa. Systemic antibiotics were administered on 7,102 (61%) of patient days. Antibiotic use was associated with non-persistence for all pathogens, except Acinetobacter species and P. aeruginosa. RR for non-persistence (as compared to ineffective or no antibiotics) ranged from 3.1 (95% CI 1.4–6.6) for H. influenzae to 0.5 (0.3–1.0) for Acinetobacter species. Conclusions In mechanically ventilated patients, persistence dynamics of bacterial respiratory tract colonization, and the effects of (in-vitro) effective antibiotics hereon, are pathogen-specific.     

Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress in a preclinical model of Alzheimer disease: A novel mechanism of action

Alzheimer disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss, inability to perform the activities of daily living and personality changes. Unfortunately, drugs effective for this disease are limited to acetylcholinesterase inhibitors that do not impact disease pathogenesis. Statins, which belong to the class of cholesterol-reducing drugs, were proposed as novel agents useful in AD therapy, but the mechanism underlying their neuroprotective effect is still unknown. In this study, we show that atorvastatin may have antioxidant effects, in aged beagles, that represent a natural higher mammalian model of AD. Atorvastatin (80 mg/day for 14.5 months) significantly reduced lipoperoxidation, protein oxidation and nitration, and increased GSH levels in parietal cortex of aged beagles. This effect was specific for brain because it was not paralleled by a concomitant reduction in all these parameters in serum. In addition, atorvastatin slightly reduced the formation of cholesterol oxidation products in cortex but increased the 7-ketocholesterol/total cholesterol ratio in serum. We also found that increased oxidative damage in the parietal cortex was associated with poorer learning (visual discrimination task). Thus, a novel pharmacological effect of atorvastatin mediated by reducing oxidative damage may be one mechanism underlying benefits of this drug in AD.     

Combining support vector machine with genetic algorithm to classify ultrasound breast tumor images

To promote the classification accuracy and decrease the time of extracting features and finding (near) optimal classification model of an ultrasound breast tumor image computer-aided diagnosis system, we propose an approach which simultaneously combines feature selection and parameter setting in this study.In our approach ultrasound breast tumors were segmented automatically by a level set method. The auto-covariance texture features and morphologic features were first extracted following the use of a genetic algorithm to detect significant features and determine the near-optimal parameters for the support vector machine (SVM) to identify the tumor as benign or malignant.The proposed CAD system can differentiate benign from malignant breast tumors with high accuracy and short feature extraction time. According to the experimental results, the accuracy of the proposed CAD system for classifying breast tumors is 95.24% and the computing time of the proposed system for calculating features of all breast tumor images is only 8% of that of a system without feature selection. Furthermore, the time of finding (near) optimal classification model is significantly than that of grid search. It is therefore clinically useful in reducing the number of biopsies of benign lesions and offers a second reading to assist inexperienced physicians in avoiding misdiagnosis.