Objective To explore the application value of cellular automata(CA)in simulating the epidemic spread of out-break of influenza A(H1N1).Methods The publications regarding influenza A(H1N1)from January 2009 to March 2015 were collected from the China National Knowledge Infrastructure(CNKI),epidemiological data of H1N1 were retrieved ac-cording to inclusion criteria,the Matlab 7.0 software was adopted to construct CA model for simulating and analyzing the epidemic of H1N1 occurred in a university in Chongqing between October 12 and November 20,2009.Results There were a total of 17 820 students in this university,the epidemic of influenza lasted 40 days in 2009;When the parameter,the ef-fective infection rate was 0.04,the model of CA fit well,and gave estimate for basic reproduction number (R0 )1.202. Conclusion CA has certain reliability in simulating epidemics of airborne infectious diseases,it can provide reference for the prevention and control of disease.

Humans ; Sinus of Valsalva ; Death, Sudden, Cardiac/etiology* ; Coronary Stenosis/complications*

Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

Dimethyl sulfide (DMS) has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients. In our recent study, DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging. We found that at near- physiological concentrations, DMS reduced reactive oxygen species (ROS) in cultured PC12 cells and alleviated oxidative stress. The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense. Methionine sulfoxidereductase A (MsrA), the key antioxidant enzyme in Met-centered defense, bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72, Tyr103, Glu115, followed by the release of dimethyl sulfoxide (DMSO). MTT assay and trypan blue test indicated that supplement of DMS exhibited cytopro?tection against 6-hydroxydopamine and MPP + induced cell apoptosis. Furthermore, MsrA knockdown abolished the cytoprotective effect of DMS at near- physiological concentrations. The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC). Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib, sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate (ORR) than IFN (47% versus 12%, P<0.000001). Bevacizumab plus IFN produced a superior PFS [risk ratio (RR): 0.86, 95% confidence interval (CI): 0.76-0.97; P=0.01] and ORR (RR: 2.19; 95% CI: 1.72-2.78; P<0.00001) in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects (RR: 1.31; 95% CI: 1.20-1.43; P<0.00001) as compared with IFN. The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months). It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.

Objective:To identify anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibody in patients with encephalitis of unknown etiology and describe the clinical features of anti-DPPX antibody-associated encephalitis in Chinese patients.Methods:For patients registered in the Peking Union Medical College Hospital Encephalitis and Paraneoplastic Syndrome Registration Project from 2016 to 2019 with negative findings in autoimmune encephalitis routine antibody profile and paraneoplastic antibody profile, but with positive tissue-based assay (TBA) results, further tests for rare antibodies, including cell-based assay (CBA) of anti-DPPX antibody, were performed. Patients positive for anti-DPPX antibody were enrolled and the clinical data were collected.Results:Two patients with anti-DPPX antibody-associated encephalitis were found from 2016 to 2019 among about 15 000 patients. Both were females, aged 46 and 75 years. One patient had diarrhea, cachexia, cognitive dysfunction, agitation, myoclonus, tremor, and seizures. The other had cognitive impairment, restlessness, memory loss, disorientation, and sleep disturbance. The second patient had medical history of systemic lupus erythematosus and secondary Sj?gren′s syndrome.Conclusions:TBA should be combined with CBA in identification of anti-DPPX antibody to confirm the diagnosis. Anti-DPPX antibody-associated encephalitis has clinical manifestations of encephalopathy with diarrhea and cachexia, and can coexist with systemic lupus erythematosus.

Objective To investigate the predictive value of metabolic syndrome in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).Methods A total of 660 patients with ACS admited to cardiovascular department,first affiliated hospital of zhengzhou university were enrolled in this study from January 2009 to June 2010.The enrollment criteria were:the stenosis degree were above 75％ in at least one coronary artery by coronary angiography and successful PCI procedure.Exculsion criteria were:liver and renal insufficiency,malignancies and valvular heart diseases.The relevant clinical data and labtory examination were recorded after admission. The patients were followed up by outpatients interview or telephone from March to June 2011 and adverse cardiovascular events were recorded.The patients were divided into MS and non-MS groups,and basic clinical data were compared between two groups.The proportion difference between two groups were tested by chi square. Multivariate logistic regression was established to analyze the factors related to progonosis.The survival ratio was estimated using the Kaplan-Meier method.Statistical significance was established at a P value of less than 0.05.Results ①A total of 606 (91.7％) patients successfully accepted follow-up.Mean follow-up time were ( 14.3 ±1.7 ) months.95 patients experienced adverse cardiovascular events ( 15.7％ ).②There were 393 patients (64.96％ ) satisfied the definition of metabolic syndrome.The patients in MS group were with higher BMI,SBP,DBP,blood glucose and disordered lipid (all P ＜ 0.05 ),with less fale patients (P =0.016),less current somking (P =0.008 ) and with higher platelet (P =0.037 ). The incidence of adverse cardiovascular events in two groups were 17.81％ and 11.79％ ( P ＞ 0.05 ). ③ Multivarite logistic regression revealed that the predictors of adverse cardiovascular events were age [ OR =2.628,95％ confidence interval (CI) 1.395 ～ 4.954,P =0.003 ],New York Heart Association (NYHA) ≥ 3 grade ( OR =2.310,95％ CI 1.095 ～4.870,P =0.028) and left ventricular ejection fraction (LVEF) ( OR =4.328,95％ CI 1.955 ～9.580,P ＜ 0.001 ).However,MS was not related with prognosis ( OR =1.170,95％ CI 0.583 ～ 2.345,P =0.659 ).④The cumulative survival rates of no adverse cardiovascular events in the two groups were no significant difference ( P ＞ 0.05 ).Conclusions MS is a risk factor with coronary heart disease.Howerer,it has no relationship with adverse cardiovascular events in patients with ACS after PCI.

OBJECTIVETo investigate the value of Diffusion-Weighted Imaging (DWI) in the diagnosis of early stage liver diffuse lesions.

METHODSDiethylnitrosamine (DEN) was used to induce liver lesions in rats. Sequential DWI studies were performed on the livers from 1 to 14 weeks after DEN was administered through drinking water. Comparing studies with a blank control group was set and pathohistological examinations of the livers were performed.

RESULTSNo obvious routine MRI morphological change was found in either group during this period, but DWI demonstrated heterogeneous changes in the test group at the cirrhosis stage. There was no significant alteration of the apparent diffusion coefficient (ADC) value in the control group during this period (P > 0.05). The ADC values of the test group began to decline from the fifth week. Until the tenth week, the ADC value of the test group decreased drastically and when b = 300 s/mm2 statistic, the results showed an obvious difference between the two groups. There were also differences between the ADC values at the 10th, the 9th and the 1st weeks of the test group (P < 0.05). When b = 600 s/mm2 and 1000 s/mm2, significant differences were found after the sixth week between the two groups (P < 0.01). The main pathohistological liver change in the test group during the 1 to 4 week period after DEN was administered was swelling of hepatocytes; during the 5 to 8 week period it was fibrous tissues hyperplasia, and in the 9 to 14 week period it was cirrhotic nodule formation.

CONCLUSIONMR functional DWI could detect liver diffuse lesions earlier than conventional MR imaging. Measurement of ADC value may be of use in early diagnosis of liver diffuse diseases and for monitoring the changes of the lesions.

Animals ; Chemical and Drug Induced Liver Injury ; Diethylnitrosamine ; Diffusion Magnetic Resonance Imaging ; methods ; Liver Diseases ; diagnosis ; pathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the new hydrolysate of aconitine using HPLC-MS(n) and quantum chemistry calculation.

METHODThe HPLC method was applied in gradient elution program and the mass spectrometry was in positive ion mode. Geometries of the possible hydrolysates were optimized at DFT/6-31G(d) level.

RESULTThe new hydrolysate was found and its protonated molecularions was at m/z 482. The quantum chemistry calculation results show that the product of elimination reations at C8 and C15 got the lowest energy conformation. The compound at m/z 482 was decluced to be the hydrolysate of carbony at C15.

CONCLUSIONDelydration aconine was detected for the first time and the new hydrolysis pathways of aconitine in water were deduced.

Aconitine ; chemistry ; Chromatography, High Pressure Liquid ; Hydrolysis ; Mass Spectrometry ; Models, Molecular ; Molecular Conformation

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC).Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC.This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy.The electronic databases were searched.Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib,sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included.Data were pooled to meta-analyze.A total of 7 RCTs with 3451 patients were involved.The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC.Among them,sunitinib had a higher overall response rate (ORR) than IFN (47％ versus 12％,P＜0.000001).Bevacizumab plus IFN produced a superior PFS [risk ratio (RR):0.86,95％ confidence interval (CI):0.76-0.97; P=0.01] and ORR (RR:2.19; 95％ CI:1.72-2.78; P＜0.00001) in patients with mRCC over IFN,but it yielded an increase by 31％ in the risk of serious toxic effects (RR:1.31; 95％ CI:1.20-1.43; P＜0.00001) as compared with IFN.The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months).It was concluded that compared with IFN therapy,VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC.However,the risk to benefit ratio of these agents needs to be further evaluated.