Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for Cmax,99.64 to 103.62 percent for AUC0-tand 99.39 to 103.51 percent for AUC0-∞,respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for Cmax,100.37 to 104.51 percent for AUC0-tand 100.71 to 104.63 percent for AUC0-∞,respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of Cmax,AUC0-tand AUC0-∞ for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.

Objective:To investigate the correlation between specific expression of serum micro ribonucleic acid (miRNA) and dilated cardiomyopathy (DCM) in children.Methods:Sixteen children diagnosed with DCM in Pediatric Heart Center of Beijing Anzhen Hospital from November 2013 to March 2016 were enrolled in the DCM group.Meanwhile, 12 age- and gender-matched healthy children who underwent medical examinations at the same time in the same hospital were selected as the healthy control group.Their serum was collected and miRNA sequencing was performed.The sample size was expanded at the later stage (the DCM group included 30 cases, and the healthy control group included 16 cases). The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) verification experiment was conducted on 11 miRNAs with statistically significant sequencing results.Results:Serum miRNA sequencing showed that 172 miRNAs were up-regulated but no miRNAs were down-regulated in the DCM group, compared with the healthy control group (fold change>2, P<0.001). Top 11 significantly up-regulated miRNAs were verified by qRT-PCR, and it was found that 8 of the 11 miRNAs (let-7f, let-7g, miR142-5p, miR143-3p, miR26a, miR27a-3p, miR27b-3p, and miR126-3p) in the DCM group were significantly up-regulated (all P<0.05). In the receiver operating characteristic (ROC) curves of DCM patients, the area under the curves of serum miR142-5p, miR143-3p, miR27b-3p, and miR126-3p were 0.983, 0.992, 0.915 and 0.950, respectively, which were statistically significantly different from those of the healthy control group (all P<0.05). Conclusions:Four serum miRNAs (miR-142-5p, miR-126-3p, miR-143-3p and miR-27b-3p) can distinguish children with DCM from healthy children.Circulating miRNAs are effective in screening DCM children.

Objective The aim of this study is to study the musical ability,auditory ability and speech intelli-gibility and their relationship in children with artificial hearing devices,and to provide clinical evidence for the hear-ing and speech rehabilitation for children with hearing loss.Methods A total of 27 children (14 boys and 13 girls) with prelingual sensorineural hearing loss from Zibo participated in this study.Their hearing levels were from mod-erate to profound.Their chronological ages at evaluation ranged from 9 to 95 months with a mean of 42 months. Their chronological ages at intervention ranged from 1 to 72 months with a mean of 26 months.Their hearing ages at evaluation ranged from 1 to 60 months with a mean of 16 months.They all wore bilateral aids.Musical Ears, CAP and SIR were used to evaluate their musical ability,auditory ability and speech intelligibility,respectively.A linear and regression analysis was done in the statistic procedure.Results The means and standard deviations of the scores of musical ability,auditory ability,and speech intelligibility were 27.1±16.7,4.4±1.9,2.8±1.4,respec-tively.The scores of musical ability and auditory ability were significantly correlated (r= 0.856,P<0.001).The scores of musical ability and speech intelligibility were also significantly related (r= 0.827,P<0.001).Conclusion The musical ability is closely related to auditory ability in children with bilateral aided hearing.The musical ability is also closely related to speech ability for this group of children.

Objective To investigate therapeutic effects of phlorizin on the early stage of diabetic retinopathy(DR)in diabetic db/db mice.Methods The 24 db/db male mice were divided into 3 groups of phlorizin-treated diabetic group(20mg/kg of phlorizin by intragastric gavage)(DMT,n =8),diabetic group(normal saline solution by intragastric gavage)(DM,n=8),with C57BLKS/J db/ m mice as the control group(CC,n=8)for ten weeks.After ten weeks,all mice were sacrificed and the retina was isolated.The specimen was embedded in paraffin wax and sliced.The sections were dyed with Sudan red and observed for retinal morphological change.Meanwhile,the expressions of GSK-3β and phospho-GSK-3β in retinas were determined by western blot.Results During the study,the CC group showed good condition.The DM group featured with polydipsia,polyphagia and a rapid increase of body weight.Phlorizin-treated diabetic mice displayed much better than the DM group.Compared with CC group,DM group showed cells proliferation in capillary endothelia and obvious thickening in basement membrane.After administration of phlorizin,the vascular lesion of central regions was remarkably improved.The expression level of phospho-GSK-3β protein was lower in DM group than in control group(76.2±15.8 vs.255.4 ± 10.7,t =16.30,P＜0.01)and was higher in Phlorizin-treated DM group(188.5±18.4)than in DM group(76.2± 15.8,t=8.05,P＜0.01).Conclusions Phlorizin decreases phospho-GSK-3β3expression in retina in db/db diabetic mice and suppresses the GSK-3βactivity,which leads to the protection of DR.

Objective To investigate the effects of nonlinear frequency compression (NLFC) on sound quality perception by the Mandarin-speaking subjects with high-frequency hearing loss.Methods Twenty-three listeners with sensorineural hearing loss with no previous experiences of using hearing aids participated in this study.They were all fitted binaurally with Phonak Bolero Q hearing aids.The stimuli,including male voice,female voice,bird chirping,music,and self-voice,were presented in a random order with a custom software via a loudspeaker at 65 dB SPL.Regarding NLFC parameters,cut-off frequency (CF) ranged from 4.9 to 6 kHz and compression ratio (CR) was programed as 1.5.Subjects evaluated the sound quality of the stimulus in loudness,clearness,naturalness and overall preference under the conditions of NLFC-on and NLFC-off.A paired-sample t-test was conducted to assess the group differences in sound quality rating between NLFC on and off conditions.Results Paired test showed significant difference of high-frequency hearing threshold under the condition of NLFC-on and NLFC-off at 6 and 8 kHz(P＞0.05).No significant statistical difference was found in subjects' sound quality ratings between NLFC-on and NLFC-off conditions (all P＞0.05).Conclusion NLFC technology resulted in no significant impact on sound quality perception for the non-experienced hearing aid users.

Objective To explore the epidemiologic and clinical features of hand, foot and mouth disease (HFMD) caused by Coxsackie virus A16 (CA16) in Suzhou from 2010 to 2014, and analyze the relationship between the SNPs of oligoadenylate synthetase 1 (OAS1) and HFMD caused by CA16 infection.MethodsThe clinical data of children diagnosed with HFMD caused by CA16 during 2010 and 2014 were collected. The epidemiological characteristics were analyzed. Among them, 167 cases were selected to make comparison of the clinical features with 166 cases of HFMD caused by EV71 infection in the same period. The genotyping ofOAS1 rs10774671 was detected by TaqMan probe technique in 167 cases of CA16 infection children, 166 cases of EV71 infection children with HFMD and 163 healthy children. The relationship between polymorphism of gene and infection of CA 16 was analyzed.ResultsA total of 9 016 children with HFMD were included. CA16 nucleic acid detected to be positive in 762 cases. The detection rate was 8.45%. CA16 infection was most commonly in summer. Children under 5 years old accounted for 94.62% infected. Compared with EV71 infected children, CA16 infected children had shorter fever time, severer oral herpes, ulcer, and rash in hand, foot and hip, lesser nervous system involvement, fewer cases of high lactate dehydrogenase, high C reactive protein, high IgM or IgG, and signiifcant changes in the percentage of CD3+, CD3+CD4+, CD3+CD8+ and CD3-CD19+ (P all?

Objective To explore the nursing program of large dose hormone therapy for the treatment of uveitis patients , and to provide the reference for clinical nursing program .Methods A total of 196 patients with uveitis were randomly divided into observation group and control group with 98 cases 136 eyes each group by the random number table method .All patients were treated with high-dose hormone therapy .The control group received routine nursing care , while the observation group was given comprehensive nursing intervention measures.The clinical efficacy and recurrence rate of two groups were compared .Results After treatment, the total effective rate of observation group was 90.44%, and it was 89.71%in the control group (χ2 =0.041,P>0.05).Over 1 year of follow-up, the recurrence rate in the observation group was 5.15%, while it was 30.88%in the control group, and the recurrence rate of the observation group was significantly lower than that of the control group (χ2 =30.381,P<0.05).Conclusions During the process of high dose hormone therapy of uveitis patients , rigorous observation and comprehensive nursing interventions can help clinical treatment effect, reduce the recurrence rate of uveitis , and is worth of further application .

Objective To retrospectively assess the prognostic impact of diabetes mellitus (DM) on patients with hepatocellular carcinoma (HCC) after curative resection.Methods A total of 417 HCC patients who had undergone curative hepatic resection were included into two groups.108 patients were classified into DM group and 309 patients into the non-DM group.Overall survival,disease-free survival,postoperative morbidity and mortality were compared between the two groups after reducing confounding bias by propensity score matching.Independent prognostic predictors were determined by Cox proportional hazards model.Results Propensity score matching resulted in 89 patients in each group,and variables were balanced between two groups.In the matched cohort,DM and non-DM groups showed similar morbidity and 30-and 90-day mortality after curative hepatectomy (respectively x2 =0.837,x2 =Fisher,x2 =Fisher,all P ＞ 0.05),the 1-,3-,and 5-year overall survival rates were 82.0％,59.9％,and 33.4％ in DM group and 90.7％,79.1％,and 69.3％ in non-DM group,respectively(P =0.001),however,there was no significant difference in disease-free survival between DM and non-DM groups.Cox multivariate analysis revealed that DM is an independent risk factor for overall survival in patients with HCC after curative resection,but not for disease-free survival.Conclusions DM does not increase the postoperative morbidity or mortality for patients with HCC after curative resection,however,DM may increase the risk of mortality of HCC patients in the long-term.

Objective To investigate the effect of hypertension on the large artery elasticity index (C1),the small artery elasticity index (C2) and the medial structure of the ascending aorta as well as the relationship between artery elasticity and the medial structure of the ascending aorta.Methods Sixty patients with CHD receiving coronary artery bypass graft surgery at our hospital were divided into two groups:30 patients in the hypertension group and 30 patients in the non-hypertension group.C1 and C2 were measured using the CVProfilor DO-2020 system.Sections of tissues taken from the anterior wall of the ascending aorta during the surgery were subjected to Masson's trichrome staining for the detection of vascular smooth muscle and collagen fibers and Weigert's resorcin-fuchsin staining for the detection of elastic fibers.The relative areas of vascular smooth muscle fibers,collagen fibers and elastic fibers of the ascending aorta were measured by a computer image analysis system under the light microscope.The linear correlations of C1 and C2 with the medial structure of the ascending aorta were analyzed.Results C1 in the non hypertension group was higher than that in thehypertensiongroup[11.9±1.8 (ml/mmHg×10) w 13.1±2.5 (ml/mmHg×10),t 2.22,P ＜0.05].In the media of the ascending aorta,the relative content of collagen fibers was higher,while the relative content of elastic fibers was lower in the hypertension group than in the non-hypertension group [(46.0±3.8)％ w (42.2±3.0)％,(17.5±3.5)％ vs.(19.3 2.7)％,respectively,t=4.24 and 2.20,P＜0.01 or 0.05].C1 was positively correlated with the relative content of elastic fibers but negatively correlated with the relative content of collagen fibers in both groups (r=0.52 and 0.39,respectively,P＜0.05 or 0.01).Conclusions The main pathogenic basis of hypertension-induced decline in arterial elasticity in CHD patients is increased collagen fibers and reduced elastic fibers with disorganization of the two types of components.C1 may accurately reflect the effect of hypertension on medial collagen fibers and elastic fibers in the ascending aorta.

Designing of natural product-like compounds using natural products as template structures is an important strategy for the discovery of new drugs. Gambogic acid (GA), which is a Garcinia natural product with a unique caged xanthone scaffold, inhibits potent antitumor activity both in vitro and in vivo. This review summarized the researches on the identification of the antitumor pharmacophore of GA, and the design, structural optimization and structure-activity relationship (SAR) of natural product-like caged xanthones based on it.