Objective To summarize brain magnetic resonance imaging (MRI) features and differential diagnosis of sporadic Creutzfeldt-Jakob disease. Methods The clinic data of 8 probable Creutzfeldt-Jakob disease cases in our hospital were analyzed retrospectively from January 2009 to June 2014. We mainly analysed the characteristics of brain MR and the causes of misdiagnosis. We had followed up the family members of these patients on the progress and progno?sis of disease. We also analyzed the differential diagnosis of sCJD. Results All the patients presented with rapid progres?sive dementia and mental abnormal behavior as the main clinical manifestations. All the patients had abnormal routine EEG and five of them had a periodical sharp wave complexes. The brain MRI of the 8 patients showed high signal intensi?ties in cerebral cortex (and/or basal ganglia) on diffusion weighted images (DWI) and 5 of them had caudate nucleus and (or) putamen involvement. The lesions were first appeared in DWI imaging as“ribbon-like”high signal, followed by Flair as high signal intensities. lesions were low signal intensities on T1WI and high signal intensities on T2WI. Five pa?tients were misdiagnosed. 2 cases were misdiagnosed as having cerebral infarction,1 case was misdiagnosed as having vi?ral encephalitis, 1 case was misdiagnosed as having Alzheimer's disease, 1 case was misdiagnosed as having vertigo and 1 case was misdiagnosed as having corticobasal degeneration. Conclusions The brain MRI of the sCJD patients showed a certain characteristic. DWI is the most sensitive tool in the detection of lesions which is useful in the early diagnosis of this disease. We should distinguish sCJD form ischemic cerebrovascular disease, encephalitis, and other progressive de?mentia identification.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.