1.The relationship between the levels of serum oxide and antioxide in patients with Wilson disease and its visceral injury
Journal of Clinical Neurology 1997;0(06):-
Objective To study the relationship between the levels of serum oxide and antioxide in patients with Wilson disease (WD) and its visceral injury.Methods We determined the serum levels of MDA,GSH PX,GSH and VitE in 29 patients with WD and 21 normal controls by the method of reversephase high performance liquid chromatography (RP HPLC) and the chemo colorimetric method.Results The serum levels of MDA in all patients with WD were significantly higher than those of controls( P 0 05 ).Conclusion There was metabolism disorder of free radicals (FRs) in the serum of patients with WD.As compared with normal controls the serum levels of oxides increased and the levels of antioxides decreased in patients with WD,it might be one of important factors for the patients with visce ral injury.
2.Correlation analysis of positive margins after radical prostatectomy with Gleason score of biopsy specimens and percentage of positive biopsy cores in prostate cancer
Zunsheng ZHANG ; Junhao LIANG ; Tielong ZHANG ; Subo QIAN
Chinese Journal of Postgraduates of Medicine 2014;37(11):12-14
Objective To investigate the correlation of positive margins after radical prostatectomy with Gleason score of biopsy specimens and percentage of positive biopsy cores in prostate cancer.Methods One hundred and thirty patients with localized prostate cancer were confirmed by biopsy underwent radical prostatectomy,the relationship between positive margins rate and Gleason scores,percentage of positive biopsy cores were analyzed.Results One hundred and thirty cases of biopsy specimens,Gleason score 6 group 50 cases,positive margins rate was 10.00% (5/50),Gleason score 7 group 65 cases,positive margins rate was 21.54%(14/65),Gleason score 8 group 13 cases,positive margins rate was 0,Gleason score 9 group 2 cases,positive margins rate was 0,the positive margins rate among the different Gleason score group had no significant difference (x2 =5.917 5,P > 0.05).All the statistics of percentage of positive biopsy cores were 89 cases,1%-25% group 30 cases,positive margins rate was 3.33% (1/30),26%-50% group 27 cases,positive margins rate was 11.11% (3/27),51%-75% group 18 cases,positive margins rate was 6/18,76%-100% group 14 cases,positive margins rate was 4/14,the positive margins rate among different percentage of positive biopsy cores group had significant difference (x2 =9.861 8,P < 0.05).Conclusion There is no correlation between Gleason score and positive margins in prostate cancer,but there is correlation between percentage of positive biopsy cores and positive margins.
3.The brain MR features and differential diagnosis of sporadic Creutzfeldt-Jakob Disease
Zunsheng ZHANG ; Zhenzhu HU ; Ke LI ; Yong WANG ; Ju LI ; Guosong XUE
Chinese Journal of Nervous and Mental Diseases 2015;(6):331-335
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.
4.Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection.
Xintong ZHAO ; Jing FENG ; Jie ZHANG ; Zunsheng HAN ; Yuhua HU ; Hui-Hui SHAO ; Tianlei LI ; Jie XIA ; Kangfan LEI ; Weiping WANG ; Fangfang LAI ; Yuan LIN ; Bo LIU ; Kun ZHANG ; Chi ZHANG ; Qingyun YANG ; Xinyu LUO ; Hanyilan ZHANG ; Chuang LI ; Wenxuan ZHANG ; Song WU
Acta Pharmaceutica Sinica B 2023;13(12):4945-4962
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.