Objective To explore the blood drug concentration monitoring of sustained-release valproate(DK)in children with epilepsy,focusing on the selection of sampling time and evaluation of the results.Methods Two hundred and seventy-one children taking DK and 155 children taking sodium valproate syrup(VPA Syr)were involved and their serum were taken when achieved steady state to determine the valproic acid level using fluorescence polarization immunoassay.They were divided into 4 groups,which were DK taken once daily group(DK qd group,126 children),DK taken once daily at night and sampled on morning group(DK qn group,26 children),DK taken every 12 h group(DK q12 h group,119 children),VPA Syr q12 h group(155 children).Determine the proportion of the blood drug concentration of each group below,ithin and above the therapeutic range for valproate(50-100 mg/L)were determined.The data were analyzed by t test.Results The Cmin of DK qd group were(73.09?19.91)mg/L,significantly lower from the serum concentration of DK qn and sampled on morning group [(94.94?25.44)mg/L](P0.05).Conclusions DK qn should sampled at night before the night dose.The Cmin of DK q12 h was higher according to the therapeutic range,it's favorable range still needs clinical practice.

To establish HPLC specific chromatogram and its correlation with the protection effect of Shuanghuanglian on MDCK (Madin-Darby canine kidney) cell injury induced by influenza A virus( H1N1). Nine recipes of Shuanghuanglian based on the official prescription were prepared according to orthogonal test for HPLC analysis and MDCK cells protection experiment separately (cytopathic effect (CPE) method was used for observing the virus infectivity and MTT staining results were used as the determining indexes for drug concentration selection and analyzing cell viability). The results suggested that all the other Shuang-Huang-Lian recipes except recipe1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus (P < 0.01, P < 0.001). Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuanghuanglian on influenza A virus induced MDCK cell injury. Peak 2, 3, 6, 8 and 12 were found to be strongly related with anti-influenza A virus efficacy. Stepwise regression analysis of recipes data and efficacy data showed that Lonicerae Japonicae Flos and Forsythiae Fructus were positively associated with the protecting effect of cells injury. From HPLC fingerprints, we found that peak 2, 3, 12 were from Lonicerae Japonicae Flos and peak 6, 8 were from Forsythiae Fructus. Four peaks were identified through comparing the retention time between the standard and Shuanghuanglian recipes, and they were chlorogenicacid, cryptochlorogenic acid, forsythoside B and 3,4-dicaffeoylquinic acid respectively. Caffeic acid derivatives in Lonicerae Japonicae Flos and Forsythiae Fructus were found to be greatly correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuanghuanglian.
Animals ; Antiviral Agents ; analysis ; pharmacology ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Forsythia ; chemistry ; Influenza A Virus, H1N1 Subtype ; drug effects ; physiology ; Lonicera ; chemistry ; Madin Darby Canine Kidney Cells ; Scutellaria baicalensis ; chemistry

Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

Objective:To investigate whether astaxanthin (AST) down-regulates dynamin-related protein 1 (Drp1) through activating the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway, thereby attenuating contrast-induced acute kidney injury.Methods:Forty adult male Sprague-Dawley rats weighing 160-180 g were randomly divided into five groups: sham surgery group (Sham group), contrast medium injury group (CM group), astaxanthin-intervention group (AST+CM group), SIRT1 inhibitor Ex527 intervention group (Ex527+CM group), and astaxanthin combined with Ex527 intervention group (AST+Ex527+CM group). After 72 hours of modeling, heart blood was removed and kidney tissues were collected for follow-up testing. Serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress-related indexes total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by biochemistry; hematoxylin and eosin staining was performed to observe the pathological changes in the kidney; mitochondrial morphology and number were observed by transmission electron microscopy; reactive oxygen species (ROS) levels were detected by ROS staining in frozen sections; TUNEL staining was performed to detect apoptosis level. The expression levels of SIRT1, p53, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Drp1 and apoptosis-related proteins Bcl-2 and Bax were detected by Western blotting.Results:(1) Compared with the CM group, Scr and BUN level were significantly lower, T-SOD level was higher and MDA level was lower in the AST+CM group, while T-SOD level decreased and MDA level increased after the combination of Ex527 (all P<0.05). (2) ROS expression was lower in the AST+CM group compared to the CM group and higher after the combination of Ex527 (both P<0.05). (3) The number of apoptotic cells was significantly reduced in the AST+CM group compared to the CM group and increased after the combination of Ex527 (both P<0.05). (4) The protein expression levels of SIRT1, PGC-1α and Bcl-2 were increased and the protein expression levels of p53, Drp1 and Bax were decreased (all P<0.05) in the AST+CM group compared with the CM group, and the protein expression levels of SIRT1, PGC-1α and Bcl-2 were decreased and the protein expression levels of p53, Drp1 and Bax were increased when Ex527 was combined (all P<0.05). Conclusion:Astaxanthin can inhibit Drp1-mediated mitochondrial fission by activating the SIRT1 pathway, thereby reducing contrast-induced acute kidney injury in rats.

OBJECTIVETo establish a RP-HPLC method for simultaneous determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of Folium Mori extract (FME).

METHODSAfter a single dose of FME (110 mg/kg) was taken, rat plasma samples were collected. The samples were hydrolyzed with hydrochloric acid (c=3.0 mol/L), the mixed solution was extracted with ether acetone mixture. The total quercetin, kaempferol and isorhamnetin in plasma samples were determined by HPLC, pharmacokinetic parameters were calculated by DAS 3.0 software.

RESULTSThe method was linear over the concentration ranges of 0.0545-8.70, 0.0954-14.7 and 0.0545-8.55 μg/ml for quercetin, kaempferol and isorhamnetin, respectively (r=0.9979, 0.9993, 0.9981). The absolute recoveries were 85.3%-86.1%, 79.4%-86.7% and 62.8%-89.7%, respectively and the assay recoveries were all from 94.7% to 107%. The relative standard deviation (RSD) of intra-and inter-day were less than 9.5% and 9.8%, respectively. The main pharmacokinetic parameters were as follows: T(1/2z) was 92.7, 67.9 and 54.2 h; Tmax was 0.400, 0.400 and 3.87 h; AUC(0-∞) was 68.0, 67.5 and 32.8 mg/h/L; MRT(0-∞) was 128, 85.2 and 72.0 h for quercetin, kaempferol and isorhamnetin, respectively.

CONCLUSIONThe method established in this study is accurate, reliable and reproducible, and can be applied for determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of FME; the pharmacokinetic studies showed that the distribution of drugs is rapid and elimination is very slow.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Flavonols ; blood ; pharmacokinetics ; Kaempferols ; blood ; pharmacokinetics ; Male ; Plant Extracts ; pharmacokinetics ; Quercetin ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Objective To investigate the feasibihty and superiority of transthoracic echocardiography(TTE)guided transcatheter occlusion for patent ductus arteriosus (PDA).Methods Totally 58 patients with simple funnel shape(Type A) PDA were studied retrospectively,and they were divided into angiography group(n =21) and echocardiography group(n =37).The angiography group received traditional transcatheter occlusion technique,and the echocardiography group received TTE guided transcatheter occlusion of PDA.An observation for the effect was taken post operatively,as well as for the comparison between the 2 groups in the aspects of the operation duration,the time of X-ray exposure,the radiation dose,the length of hospital stay and the expense of medication.Results Successful occlusion was performed in all patients.Both of the TTE and angiogram group showed good position of the occlusion devices.Moreover,the velocities of blood flow in left pulmonary artery and the descending aorta were in a normal range.Compared with angiography group,echocardiography group experienced shorter operation duration (P ＜ 0.05),shorter X-ray exposure time (P ＜ 0.05),lower radiation dose,fewer days of hospital stay (P ＜ 0.05) and less expense of the medication (P ＜ 0.05).Conclusions TTE-guided transcatheter occlusion for simple funnel shape PDA (Type A) is a simplified occlusion method,which is effective and preferential treatment to the method of traditional angiography guidance in clinical trials.

Glaucoma, Open-Angle ; etiology ; physiopathology ; Humans ; Intracranial Hypotension ; complications ; physiopathology ; Intraocular Pressure ; Male ; Middle Aged

OBJECTIVE: To investigate the risk factors for poor prognosis of neonatal bacterial meningitis. METHODS: A retrospective analysis was performed for the clinical data of 152 children with neonatal bacterial meningitis. According to their prognosis, they were divided into a good prognosis group with 122 children and a poor prognosis group with 30 children. The two groups were compared in terms of general status, initial symptoms, and laboratory findings, and the risk factors for poor prognosis were analyzed. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of children with a very low birth weight, a peripheral blood white blood cell count (WBC) of <5×10/L or >20×10/L, a C-reactive protein level of >50 mg/L, a cerebrospinal fluid (CSF) WBC of >500×10/L, a CSF glucose level of <1 mmol/L, or a CSF protein level of >2 g/L, as well as significantly higher positive rates of blood culture and/or CSF culture, Gram-positive bacteria, and Streptococcus agalactiae (P<0.05). The multivariate logistic regression analysis showed that a CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L were independent risk factors for poor prognosis of neonatal bacterial meningitis. CONCLUSIONS A CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L are risk factors for poor prognosis of neonatal bacterial meningitis.
Child ; Humans ; Infant, Newborn ; Leukocyte Count ; Meningitis, Bacterial ; Prognosis ; Retrospective Studies ; Risk Factors

Aneurysm, Dissecting ; pathology ; surgery ; Humans ; Male ; Mesenteric Artery, Superior ; pathology ; surgery ; Middle Aged ; Tomography, X-Ray Computed

Objective To investigate the roles and mechanisms of siRNA targeted lipocalin 2 (Lcn 2) gene silencing on hypoxia-induced cell apoptosis in retinal ganglion cells (RGC-5).Methods RGC-5 cells were subjected to hypoxic condition for various time duration (0 h,4 h,8 h,12 h,24 h,48 h),and quantitative real-time PCR and Western blot were used to evaluate the expression of Lcn 2 in mRNA and protein levels.Cells were divided into 4 groups:control group,hypoxia group,siNC + hypoxia group,in which cells were transfected with negative control for siRNA,and then subjected to hypoxic condition for 24 h,and siLcn 2 + hypoxia group,in which cells were transfected with Lcn 2 siRNA,and then subjected to hypoxic condition for 24 h).Next,cell apoptotic rate and Caspase-3 activity were detected using ELISA.The fluorescence intensity of reactive oxygen species (ROS) was assayed using DCFH-DA kit,and mitochondrial membrane potential assay kit was used to evaluate the mitochondrial membrane potential.Finally,the expression levels of cleaved-Caspase-3 (c-Caspase-3),cleaved-PARP (c-PARP),Bax,Bcl-2 and cytochrome C (Cyto C) were detected using Western blot.Results In the hypoxia group,Lcn 2 mRNA level at 4 h,8 h,12 h,24 h and 48 h was higher than that at 0 h (all P ＜0.05).Meanwhile,Lcn 2 protein level at 12 h,24 h and 48 h was also higher than that at 0 h (all P ＜ 0.05).Cell apoptotic rate in the hypoxia group (138.33％ ± 13.76％) was significantly higher than that in the control group (99.66％ ± 2.86％) (P ＜ 0.05),and siLcn 2 + hypoxia group (105.02％ ± 8.60％) was lower than siNC + hypoxia group (142.33％ ± 6.54％) (P ＜ 0.05).In addition,compared with the control group,the relative activity of Caspase-3 and the relative expression of c-Caspase-3 and c-PARP in the hypoxia group were all upregulated (all P ＜ 0.05);whereas the relative activity of Caspase-3 and the relative expression of c-Caspase-3 and c-PARP in the siLcn2 + hypoxia group were downregulated compared with the siNC + hypoxia group (all P ＜ 0.05).Moreover,the fluorescence intensity of ROS in the hypoxia group (4.26 0.63) was more enhanced than that in the control group (1.03 ± 0.11) (P ＜ 0.05),and the siLcn2 + hypoxia group (3.10 ± 0.24) was lower than siNC + hypoxia group (4.73 ± 0.26) (P ＜ 0.05).Furthermore,mitochondrial membrane potential,Cyto C expression and the relative ratio of Bax to Bcl-2 in the siLcn2 + hypoxia group was lower than those in the siNC + hypoxia group.Conclusion Lcn 2 Lcn2 gene silencing can inhibit cell apoptosis and ROS production induced by hypoxia,which may be achieved by suppressing mitochondrial apoptosis signaling pathway.