Search

Dorzagliatin is a novel allosteric glucokinase activator targeting both pancreatic and hepatic glucokinase currently under clinical investigation for treatment of type 2 diabetes (T2D). This study aimed to investigate the effect of renal impairment (RI) on dorzagliatin’s pharmacokinetics (PKs) and safety, and to guide appropriate clinical dosing in patients with diabetic kidney disease, including end‐stage renal disease (ESRD). Based on the results from physiologically‐based pharmacokinetic modeling, the predicted outcome of RI on dorzagliatin PK property would be minimum that the plasma exposure area under concentration (AUC) of dorzagliatin in patients with ESRD would increase at about 30% with minimal change in peak concentration (Cmax) comparing to those in healthy volunteers (HVs). To definitively confirm the prediction, a two‐part RI study was designed and conducted based on regulatory guidance starting with the patients with ESRD matched with HVs. Results of the RI study showed minimum difference between patients with ESRD and HVs with respect to dorzagliatin exposure with geometric mean ratio of ESRD to HV at 0.81 for Cmax and 1.11 for AUC. The elimination half‐life, volume of distribution, and systemic clearance for dorzagliatin were similar between the two groups. Dorzagliatin was well‐tolerated in patients with ESRD during the study. Therefore, RI showed no significant impact on dorzagliatin PK, suggesting that dorzagliatin can be readily used in patients with T2D at all stages of RI without need for dose adjustment.

Introduction The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated. Methods In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject participated in both parts with a washout time of at least 40 h. Results The safety and tolerability parameters of ciprofol were similar to those of propofol, and all treatment-emergent adverse events were mild. The incidences of injection pain and respiratory depression in subjects given ciprofol were lower than those receiving propofol. The pharmacokinetic parameters Cmax, tmax, t1/2, λz and MRT for ciprofol and propofol were similar, while CL, Vd and Vss were statistically significantly different. Pharmacodynamic parameters including the Richmond Agitation Sedation Scale and bispectral index profiles of ciprofol were similar to those of propofol. Conclusion Ciprofol has potential for clinical application for continuous intravenous infusion to maintain sedation for 12 h with the same safety, tolerability and efficacy as propofol. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01914-4.

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Neighborhoods have begun to play an increasingly prominent role in shaping mental health during the coronavirus disease 2019 (COVID-19) pandemic because residents are spending more time at home and...

Objective To assess the current efficacy, safety, and risk factors of the Woven EndoBridge (WEB) in treating wide-neck intracranial aneurysms. Data Source We searched the PubMed, Ovid MEDLINE, and EMBASE databases between December 1, 2012 and June 30, 2018. Study Selection Studies that included five or more patients undergoing WEB for wide-neck intracranial aneurysms, reported an angiographic or clinical outcome and risk factors, and were published after December 1, 2012 were eligible. Data Extraction And Synthesis Major outcomes included initial or short-term complete and adequate occlusion. Secondary outcomes included treatment failure, recanalization, mortality, morbidity, and complication (e.g., thromboembolism or intraoperative rupture) rates. A random effect model was used to pool the data. To assess risk factors for short-term angiographic outcomes and the most common complications, we conducted subgroup analyses and obtained odds ratios with 95% confidence intervals. Results We included 36 studies (1759 patients with 1749 aneurysms). The initial complete and adequate occlusion rates were 35% and 77%, respectively. After a mean follow-up of 9.34 months, the short-term complete and adequate occlusion rates were 53% and 80%, respectively. Thromboembolism and recanalization were the most common complications (both 9%), followed by mortality (7%), morbidity (6%), failure (5%) and intraoperative rupture (3%). The following factors were related to higher short-term obliteration rates: unruptured status, in the anterior circulation, a medium neck (4-9.9 mm), newer-generation WEB and treatment without additional devices. Ruptured status, anterior circulation, preoperative antiplatelet therapy and newer-generation WEB were not significantly related withto thromboembolism. Conclusion WEB has a satisfactory safety profile and shows promising efficacy in treating wide-neck intracranial aneurysms. We preliminarily identified several risk factors for short-term angiographic outcomes.

Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and the original extended release (ER) formulation tablets administered with an opioid antagonist in patients with chronic pain. In this open-label, randomized, cross-over study, the enrolled patients were randomised to receive a single dose of 40 mg OTR or 40 mg OXYCONTIN® (OXY) tablet administered with naltrexone blockade under fasting conditions. Serial blood samples for pharmacokinetic analysis were collected. Plasma oxycodone was quantified by a high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. A total of 38 patients were enrolled and 33 subjects completed the study. After a single dose of 40 mg tablets, pharmacokinetic results of the new OTR tablet were found to be similar to those of original extended-release oxycodone tablet. OTR 40 mg was bioequivalent to OXY 40 mg and was well tolerated in patients with chronic pain. The new OTR formulation could provide a new choice in the treatment of chronic pain and reduce the potential for oxycodone abuse. Chictr.org identifier: ChiCTR1800017253.

Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973–2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan–Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.

Introduction Major depressive disorder (MDD) is associated with a significant burden of disease in China. Awareness and better access to treatments could help alleviate the burden associated with MDD. Because variations have been observed in the pharmacokinetics (PK) of antidepressants across different races and ethnicities, evaluation of the clinical pharmacology of vortioxetine in diverse populations remains important to assess the potential need for dose adjustments. Methods Data were pooled from two phase I open-label PK studies in healthy Chinese subjects, and one phase III double-blind noninferiority study in Chinese patients with MDD to describe the PK and safety data for vortioxetine. Doses in these studies ranged from 10 mg (single dose) to 10 and 20 mg (multiple daily doses). A population PK analysis of vortioxetine in the Chinese population was conducted using nonlinear mixed-effect modeling. Results In total, 186 individuals were included in the PK analysis: 79 healthy Chinese subjects and 107 Chinese patients with MDD. No clinically significant differences in the PK of vortioxetine were observed between the Chinese population and the previous data in non-Chinese populations. Because of a generally lower weight in the Chinese population compared with the non-Chinese population, exposures were 19% and 18% higher in the Chinese population than in the non-Chinese population (for maximum observed plasma concentration and area under the plasma concentration–time curve, respectively), which is not considered clinically relevant. A high prevalence of pruritus was observed in one phase I PK study (56% overall); however, this was not reflected in the phase III study in Chinese patients with MDD (0.8%). Conclusions The PK parameters of vortioxetine in Chinese subjects were comparable to previous data in non-Chinese subjects. Overall, no new safety concerns were raised among the Chinese population. On the basis of this analysis, the tolerability profile of vortioxetine in Chinese healthy subjects and in patients with MDD is expected to be comparable to that in the non-Chinese population. Funding H. Lundbeck A/S, Valby, Denmark. Trial Registration NCT01676571. Electronic supplementary material The online version of this article (10.1007/s12325-019-01092-4) contains supplementary material, which is available to authorized users.

Background: bladder cancer (BCa) is a common malignancy in the urinary system. But the hematogenous metastatic pattern of it was poorly explored. The aim of this study was to provide a better understanding of the prognosis of the different distant metastatic pattern from stage IV BCa patients and support for making a suitable clinical decision.Methods: The Surveillance, Epidemiology and End Result database (SEER) provided data for this study include BCa from 2010 to 2015. Kaplan–Meier method was used to evaluate the survival prognosis of patients of metastatic BCa. Cox proportional hazards regression model was utilized to analyzed risk factors. All statistical tests were two-sided.Results: At the time of diagnosis, a total of 6808 eligible patients at stage IV were extracted from SEER database. Patients who suffered metastasis to either one of the four sites occupied 25.31% (1723/6808) of BCa. Bone was the most common distant metastatic site of BCa (1225 cases), and brain metastases had the worst prognosis whose mean survival was 6.282 months. The results of univariate survival analysis presented that diagnostic age, race, gender, primary site surgery, tumor size, T stage, N stage, primary tumor site, histology, marital status and metastatic number were independent prognostic factors affecting overall survival (OS) (PConclusion: In analysis of single metastatic sites, patients with brain metastasis had the worst overall survival and lung metastasis had the best outcomes than other three distant metastases. Knowledge of these differences in metastatic patterns is helpful for clinicians to make better pre-treatment evaluation and clinical decisions.

Background : Ammoxetine is a novel selective serotonin and norepinephrine reuptake inhibitor. Preclinical studies have indicated the potential utility of ammoxetine for therapy in major depressive disorder. Purpose : To investigate the first-in-human safety, tolerability, and pharmacokinetics (PK) of ammoxetine in healthy subjects and evaluate the effect of CYP2C19 polymorphisms on metabolism of ammoxetine. Methods : In this randomized, double-blind, placebo-controlled phase I study, healthy Chinese subjects were allocated to receive 2.5, 7.5, 15, 30, 45, 65, 100 mg ammoxetine or placebo in single-dose part and 15, 30, 45 mg ammoxetine or placebo twice daily for 8 days in multiple-dose part. Pharmacokinetic, safety and tolerability assessments were performed. Results : A total of 134 subjects were screened and 94 were enrolled. All the ammoxetine-related adverse events (AEs) were mild and resolved spontaneously. No hepatic AEs were reported during the study. Ammoxetine was well absorbed after oral administration with Tmax reached in 5.0-6.0 h. After single-dosing, Cmax and AUC increased proportionally with dose, except at 65 mg. After multiple-dosing, the exposures of ammoxetine at steady state increased slightly in a more-than-dose-proportional manner over the dose range studied, probably due to the saturated elimination. Steady state was achieved 6 days after multiple-dosing was initiated. The low extent of urinary excretion of ammoxetine ( Conclusions : Ammoxetine has a favorable pharmacokinetic profile after oral administration and good safety properties. The PK and safety profiles of ammoxetine could enable further clinical development in patients with major depressive disorder.

This work aims to investigate how the bile acid metabolism of newborns differs from that of adults along the axis of primary, secondary, and tertiary bile acids (BAs). The total unconjugated BA profiles were quantitatively determined by enzyme digestion techniques in urine of 21 newborns born by cesarean section, 29 healthy parturient women, 30 healthy males, and 28 healthy nonpregnant females. As expected, because of a lack of developed gut microbiota, newborns exhibited poor metabolism of secondary BAs. Accordingly, the tertiary BAs contributed limitedly to the urinary excretion of BAs in newborns despite their tertiary-to-secondary ratios significantly increasing. As a result, the primary BAs of newborns underwent extensive oxidative metabolism, resulting in elevated urinary levels of some fetal-specific BAs, including 3-dehydroCA, 3β,7α,12α-trihydroxy-5β-cholan-24-oic acid, 3α,12-oxo-hydroxy-5β-cholan-24-oic acid, and nine tetrahydroxy-cholan-24-oic acids (Tetra-BAs). Parturient women had significantly elevated urinary levels of tertiary BAs and fetal-specific BAs compared with female control, indicating that they may be excreted into amniotic fluid for maternal disposition. An in vitro metabolism assay in infant liver microsomes showed that four Tetra-BAs and 3-dehydroCA were hydroxylated metabolites of cholate, glycocholate, and particularly taurocholate. However, the recombinant cytochrome P450 enzyme assay found that the fetal-specific CYP3A7 did not contribute to these oxidation metabolisms as much as expected compared with CYP3A4. In conclusion, newborns show a BA metabolism pattern predominated by primary BA oxidations due to immaturity of secondary BA metabolism. Translational studies following this finding may bring new ideas and strategies for both pediatric pharmacology and diagnosis and treatment of perinatal cholestasis-associated diseases. SIGNIFICANCE STATEMENT: The prenatal BA disposition is different from adults because of a lack of gut microbiota. However, how the BA metabolism of newborns differs from that of adults along the axis of primary, secondary, and tertiary BAs remains poorly defined. This work demonstrated that the urinary BA profiles of newborns born by cesarean section are characterized by oxidative metabolism of primary BAs, in which the fetal-specific CYP3A7 plays a limited role in the downstream oxidation metabolism of cholate.

In order to obtain the organic photodetector with high photomultiplier efficiency by using the method of electron trap assisted hole injection, it is proposed that a ternary organic photomultiplier detector with C70:C60 double electron traps doped in the P3HT:PTB7:PC61BM photoactive layer in this paper. Under the conditions of −2 V, λ = 460 nm and Pin = 0.21 mW·cm−2, the R, D* and EQE of the device are 7.28 A·W−1, 9.55 × 1012Jones and 1691.65% when the doping concentration of C70:C60 is 2.5 wt%:1.5 wt%, which these are 4.67, 4.85 and 4.66 times by compared with C70 single-doped (2.5 wt%). In addition, the electron trap concentration Nq of the C70:C60 double-doped device reaches 1.10 × 1018 cm−3, which is an order of magnitude higher than the C70 single-doped device(Nq = 4.38 × 1017 cm−3). As a consequence, the C70:C60 double-doped can effectively increase the trap doping concentration in the photoactive layer, thus improving the external quantum efficiency and photomultiplier of the device. This paper provides a new idea for high concentration trap doping of organic active layer.

Background BDP/FF/GB pMDI is a novel triple fixed-dose combination of extra-fine inhalation aerosol beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB). Limited data on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of BDP/FF/GB fixed-dose combination in healthy subjects was available. Purposes This study aimed to evaluate the pharmacokinetics, pharmacodynamics and safety of BDP/FF/GB pMDI in healthy Chinese subjects. Methods This is an open-label, parallel-group, randomized, single and multiple dose study. In the single dose group, subjects received single supra-therapeutic inhaled dose of BDP/FF/GB pMDI (BDP/FF/GB 400/24/50 µg). In the multiple dose group, subjects received therapeutic inhaled dose of BDP/FF/GB pMDI (BDP/FF/GB 200/12/25 µg), twice daily, for 7 consecutive days. Plasma BDP, B17MP, formoterol and GB were determined by a validated ultra performance liquid chromatography method with tandem mass spectrometric detection (UPLC/MS-MS). Heart rate (HR), QTcF, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated as the surrogate indicators of pharmacodynamic effects. Results A total of 24 subjects were randomized and 22 (11 in each group) completed the study. The dose adjusted pharmacokinetic profiles of BDP, beclomethasone-17-monopropionate (B17MP, the most active metabolite of BDP), formoterol and GB were overall similar in therapeutic and supra- therapeutic dose group, showing dose proportional increase of the systemic exposure to BDP, B17MP, formoterol and GB. The pharmacodynamic variables were within the normal range and showed no significant difference between the two groups. All the treatment-emergent adverse events (TEAEs) were mild and no severe TEAE was reported. Conclusions Dose adjusted PK profiles were similar between therapeutic and supra-therapeutic dose for all compounds, nearly dose proportional systemic exposure to B17MP, formoterol and GB after BDP/FF/GB pMDI administration in healthy Chinese subjects. BDP/FF/GB pMDI was safe and well tolerated in healthy Chinese subjects. The PK profiles were comparable to previously published data from Western European healthy Caucasian subjects.

Current solutions for improving the light extraction efficiency of flip-chip light-emitting diodes (LEDs) mainly focus on relieving the total internal reflection at sapphire/air interface, but such methods hardly affect the epilayer mode photons. We demonstrated that the prism-structured sidewall based on tetramethylammonium hydroxide (TMAH) etching is a cost-effective solution for promoting light extraction efficiency of flip-chip mini-LEDs. The anisotropic TMAH etching created hierarchical prism structure on sidewall of mini-LEDs for coupling out photons into air without deteriorating the electrical property. Prism-structured sidewall effectively improved light output power of mini-LEDs by 10.3%, owing to the scattering out of waveguided light trapped in the gallium nitride (GaN) epilayer.

Background Bencycloquidium bromide (BCQB) is a novel inhaled anticholinergic bronchodilator with high selectivity for muscarinic M3 receptor. BCQB's potential utility of for therapy in Chronic obstructive pulmonary disease (COPD) has been indicated in pre-clinical studies. Purpose To investigate the initial safety, tolerability and pharmacokinetics of BCQB delivered via pressurised Metered Dose Inhaler (pMDI) in healthy subjects. Methods This study consisted of single-ascending-dose (SAD), multiple-ascending-dose (MAD) tolerability study periods, and single- plus multiple-dose pharmacokinetic study periods. Randomized, double-blind, placebo-controlled, dose-escalating tolerability and pharmacokinetic studies were conducted. Seventy-two healthy subjects were assigned 3:1 (BCQB: placebo) to 7 single-dose cohorts (125, 250, 500, 750, 1125, 1500 and 2000 μg) and 2 multiple-dose cohorts (1500 μg/d and 2000 μg/d). In the pharmacokinetic periods, 12 subjects were allocated three-way crossover to receive single dose of 250, 750 or 2000 μg BCQB, respectively. Subsequently, the same 12 subjects received multiple dose of 750 μg/d and 1000 μg/d for 7 days. Pharmacokinetic, safety and tolerability assessments were performed. Results BCQB administered by inhalation was well tolerated, especially with favorable cardiovascular safety profile. BCQB was rapidly absorbed into plasma after inhalation through pMDI, with peak concentrations achieved within 5 to 10 minutes. Repeated inhalation caused certain degree of accumulation with the accumulation ratio RCmax 2.50, RAUC 3.49 for 3 times-a-day and RCmax 2.23, RAUC 3.44 for 4 times-a-day, respectively. Twice-a-day or even once-a-day dosage could be suggested in phase II study. Sex didn't affect the pharmacokinetics of BCQB and dose adjustments based on sex is not anticipated in clinical use. Approximately 4% of the BCQB dose excreted unchanged in urine and liver metabolism is the main biotransformation route of BCQB in human. Conclusions The results of our study provided the initial safety, tolerability and pharmacokinetic profiles of BCQB inhalation, and could enable further clinical development in COPD patients.

The paper aims to provide a reference for policy-making on reproductive health services for university students by investigating the recognition degree of reproductive health knowledge and current status of reproductive health service needs of students of three universities in Huangjiahu University Town. The author carries out the questionnaire surveys in the three universities using “wjx”, a platform for questionnaire-making, then adopts descriptive analysis and spss analysis to process the data obtained from the questionnaire survey. Sexual behavior among university students is a common phenomenon. However, due to the low cognition degree of reproductive health, they have a strong demand for reproductive health services.

Background Few pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China. Purpose 1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions. Methods This open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1 week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests. Results Totally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, T max 9.94 ± 6.59 and 9.47 ± 5.47 h, C max 435.74 ± 348.10 and 346.54 ± 155.66 ng · mL − 1 , AUC 0 -t 8600.52 ± 5264.77 and 9315.10 ± 6820.03 ng · mL − 1 · h, AUC 0–∞ 8845.38 ± 5838.18 and 9669.24 ± 7326.53 ng · mL − 1 · h, t 1/2 10.06 ± 8.83 and 9.87 ± 10.35 h; single dosing under fasting conditions, T max 7.29 ± 4.87 and 6.57 ± 1.85 h, C max 247.85 ± 110.05 and 244.64 ± 132.43 ng · mL − 1 , AUC 0 -t 3385.41 ± 1418.92 and 3496.24 ± 1767.29 ng · mL − 1 · h, AUC 0–∞ 3781.53 ± 1556.96 and 3829.56 ± 1981.25 ng · mL − 1 · h, t 1/2 13.07 ± 17.24 and 10.26 ± 7.78 h; single dosing under fed conditions, T max 17.72 ± 9.42 and 19.50 ± 9.84 h, C max 183.90 ± 74.52 and 168.14 ± 60.67 ng · mL − 1 , AUC 0 -t 3181.71 ± 1368.24 and 3575.11 ± 1416.39 ng · mL − 1 · h, AUC 0–∞ 3442.39 ± 2002.53 and 3624.44 ± 1418.12 ng · mL − 1 · h, t 1/2 8.76 ± 12.28 and 6.67 ± 4.84 h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC 0–t and AUC 0–∞ were located within 80%–125%, 90% CI for C max was within 70%–143%. Conclusions Similar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence. Chictr.org identifier: ChiCTR-TTRCC-14004853.

Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal prescription. It is effective in treating traumatic brain injury (TBI). However, the underlying molecular mechanisms remain unclear.This study aimed to reveal the possible mechanisms of XFZYD in treating acute TBI through proteomics clues.Controlled Cortical Impact (CCI) rats were given gavage administration of XFZYD (9 g/kg/d) or distilled water (equal volume) for three days. The Modified Neurological Severity Score (mNSS), brain water content, HE staining, Nissl staining and immunohistochemistry were performed to assess the effects of XFZYD for TBI treatment. Additionally, tandem mass tag-based (TMT) quantitative proteomics technology was applied to detect proteins of brain cortex. Bioinformatics analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Protein-protein interaction (PPI) networks were used to analyze differentially expressed proteins (DEPs). Bioinformatics Analysis Tool for Molecular mechanism of TCM (BATMAN-TCM) was conducted to anchor diseases and pathways. Besides, western blotting and immunofluorescence were exerted to verify related proteins.XFZYD improved neurologic functions, reduced encephaledema and ameliorated cell morphology around the injured area in CCI rats. A total of 6099 proteins were identified with false discovery rate (FDR) 1%. Overlapping DEPs (105 DEPs) were identified (295 DEPs and 804 DEPs in CCI/Sham or XFZYD/CCI group, respectively). Of these DEPs, 17 were regulated by XFZYD. Bioinformatics analysis showed that the 17 DEPs were predominantly related to platelet activation and PI3K-Akt signaling pathway. Next, PLG and CD34 were verified with molecular biotechnology.XFZYD exerts therapeutic effects through multi-pathways regulation in the treatment of TBI. This work may provide proteomics clues for the continuation of research on TBI treatment with XFZYD.

Leading-zero counter (LZC) is a basic component in floating point operation. This paper aims at speeding up the operation of LZC. Based on new derived Boolean functions and complex logic gates, 8-bit LZC circuit is accomplished. Moreover, 16-bit LZC architecture is implemented in Xilinx field-programmable gate array (FPGA) and 32-bit LZC structure is realized on the platform of Application Specific Integrated Circuit (ASIC) in 65nm technology. Synthesis results are obtained on their special platforms. By comparison, our proposed design is faster than the reported designs.

Carry look-ahead adder (CLA) is a fast adder. This paper is delicated to accelerate the 4-bit CLA circuit. In proposed circuit structure, XOR gate is replaced by NOR gate. Moreover, logic gates have less fan-in and fan-out and signal throughs one less MOS transistor in critical path. All designs are built in dynamic CMOS logic gates. Simulation results show that the proposed architecture has advantages over conventional circuits in speed, area and power consumption.

Hierarchical hybrid filing system is a research hotspot in the field of data storage, and also is widely accepted in the industrial circle, which is widely used from personal storage to data center. This paper introduces an energy-efficient optical storage at a lower cost to solve the energy consumption problem of large data center, with an attempt to build a hybrid filing system comprised of array, online optical disk library and off-line optical disk library, discusses the guarantee mechanism of data consistency and the elastic design of system, and focuses on the research of the file caching and prefetching mechanism of hybrid magneto-optical filing system based on the read-write features of optical medium. Through experiments, the system is proved to be capable of effectively saving energy and maintaining the timeliness of data retrieval and query.

With the ceaseless propulsion of informatization process, a great deal of data accumulated in the production system resulted in archiving demand; meanwhile, with the increasingly enriching types of data information, big data technology enhanced the function of unstructured data. This paper designs and realizes the KingCloud intelligent object archiving system, which achieves classification of text files through document classification technology and provides logic views of documents and achieves the acquisition of content elements through image identification, video keyframe and other technologies. As for the overall storage structure, document prefetching, memory buffer, data layout and strategy perception etc. can be optimized by combining the semantic studies of file system, and data can be intelligently classified, summarized, discovered, predicted and analyzed to remarkably improve the service ability, service quality and service performance of memory system.

Based on the grey theory, a novel model is built to predict the input signal of fast control power supply used in Experimental Advanced Superconducting Tokamak (EAST). The model can be used as online metabolic grey filtering and one-step prediction of different input signals. Results of simulation and experiment show that the predicting algorithm based on the grey system model can predict the input signal primarily.

Combined an air bearing platform and a laser interferometer,a set of non-contact and high precision system for curvature radius measurements of lenses is developed based on the axial focusing of confocal technique.The developed system is characterized by that the peak point of the confocal axial intensive curve corresponds to the focus of an objective.On the characteristic,it identifies precisely the cat-eye and confocal positions of the test lens.Then it takes the laser interferometer to obtain the position coordinates of the cat-eye and confocal positions and calculates the curvature radius of the lens.Furthermore,the main control software drives an air bearing slider with a test lens to achieve the scanning measurement near the cat eye and confocal positions,and then acquires signals and processes data.Experimental results show that the measurement system has the reproducibility less than 2 μm,which meets the requirements of curvature radius measurement for high precision.The developed measurement system has the advantages of high test speed,easy operation,simple structure and easy to be miniaturized.

Cloud computing has been a hot researching area of computer network technology, since it was proposed in 2007. Cloud computing also has been envisioned as the next-generation architecture of IT Enterprise [1]. Cloud computing infrastructures enable companies to cut costs by outsourcing computations on-demand. It moves the application software and database to the large data centers, where the management of the data and services may not be fully trustworthy [2]. This poses many new security challenges. In this paper, we just focus on data storage security in the cloud, which has been the most important aspect of quality of service. To ensure the confidentiality and integrity of user’s data in the cloud, and support of data dynamic operations, such as modification, insertion and deletion, we propose a framework for storage security, which includes cryptographic storage scheme and data structure. With our framework, the untrusted server cannot learn anything about the plaintext, and the dynamic operation can be finished in short time. The encryption algorithm and data storage structure is simple, and it’s easy to maintain. Hence, our framework is practical to use today.

The increasing number of applications for large data, such as Web search engines, we need to have high availability 7*24 tracking, storage and analysis of a large number of real-time user access logs. Traditional common trading application high availability solution, always not efficient enough to store this high-rate only inserted into the archive stream. This paper presents an integrated approach to save of this archive of data streams in a database cluster and rapid recovery. This method is based on a simple replication protocol and high performance data loading and query strategy. Experimental results show that our approach can reach efficient data loading and query and get shorter recovery time than the traditional database cluster recovery methods.

Due to the huge scale and the number of components, big data is difficult to work with the use of relational databases and desktop statistics and visualization package. Much database replication technology is used to increase the MTTF, but few have a large database system, the traditional method of backup is not feasible, expensive manpower costs reduce MTTR. On the basis of analyzing the characteristics of data in large databases, we propose a new method called Detaching Read-Only (DRO) mechanism and its changes DRO+. It reduces MTTR by reducing the physical change of the data in each database, by separating data node size granularity. Analysis and experimental results show that our method can not only reduce the MTTR an order of magnitude, but there is no additional hardware costs, but also reduce the high human costs.

PurposeThe purpose of this paper is to identify the key characteristics of the post‐investment relationship between the venture capital firm and its investee companies.Design/methodology/approachThe research is a case study of a major UK venture capital firm using qualitative research to determine the key characteristics of the post‐investment relationship. The study is based on interviews with parties on both sides of the relationship.FindingsWhile the results reflect the findings of the entrepreneurship and venture capital literature they also point to the importance of network growth and development for organizational learning in the venture capital industry, professionalization of investee firms and as a context in which the selection of the entrepreneur and the post investment relationship are set.Research limitations/implicationsThe research has the limitation of most case studies that the results cannot readily be generalized, in this case to the wider population of venture capital firms. Confidentiality issues also limited the extent to which a longitudinal study could be conducted.Practical implicationsA better understanding of the post‐investment relationship can inform entrepreneurs in their pitch for funds and in their anticipation of the post investment relationship. This understanding can also assist venture capital firms in the management of this relationship.Originality/valueThe case study uses data from rare access to a venture capital firm. It also differs by interviewing both parties to the post‐investment relationship, that is venture capitalist and investee firm.

The computer aid simulation of optical properties of thin films has been used to optimize SiO2/TiO2/SiO2 multilayer films to obtain high transparent films in this paper. The maximum transmittance at the visible light wavelength range is proper criteria for optical films optimizing design. The effect of design parameters (film thickness and refractive index) on optical properties of SiO2/TiO2/SiO2 multilayer films were also discussed in detail. According to the result of optimization, high quality SiO2/TiO2/SiO2 multilayer film with a maximum of > 99% at visible light wavelength range can be achieved on the glass.

Many approaches have been used to model the performance and efficiency of ozone contactors based on some assumptions to characterize the backmixing in fluids. Recently, computational fluid dynamics (CFD) technique has been proposed to simulate and optimize ozone contactors by calculating residence time distribution of fluid. To improve the ozone contactor performance of Bijianshan Water Treatment Plant in Shenzhen in South China, CFD was used for simulation and development of new optimization measures. Results showed that the low depth/length ratio of the contactor chambers in the original design resulted in short circuiting and backmixing, with the T10/HRT being only 0.40. Installation of guide plates substantially reduced short circuiting and backmixing with a much higher T10/HRT (0.66), increased by 73% compared with the original design.

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56–63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles ( p p = 0.0019). Conclusion: Iodine ( 131 I) metuximab injection is safe and active for HCC patients.

The first motivation of this paper is to study the existence of cyclical properties among FX markets with the use of spectral analysis. Secondly, the economic value of a trading model is studied based on spectral analysis compared with technical trending models replicating the performance of typical currency managers as in Lequeux and Acar (European Journal of Finance, 4, 311–330, 1998). It is found that both spectral models and moving average convergence divergence (henceforth MACD) technical trending models fail to perform satisfactorily when markets display cyclical properties. Spectral filters are then proposed to take alternative trading strategies during such times: the results show that in the three periods considered, trading performances are significantly enhanced by the addition of the two spectral filters proposed, either to close all market positions when markets are in cyclical mode (a ‘no-trade’ filter) or to reverse the original MACD trading signals during such times (a ‘reverse’ filter).

This study conducts an event-related potential (ERP) study to investigate the temporal neural dynamics of semantic processing in bilinguals. The experiment was done with Korean speakers of English as an L2, divided into two groups depending on their L2 proficiency level. The typical semantic anomaly paradigm was adopted for the material; semantically anomalous sentences end with a word which is not congruent in the sentence context. It was investigated if semantically anomalous stimuli elicit N400. Overall, similar pattern of the N400 effect was observed in the high proficiency group, while no significant effect was found in the low proficiency group. Though the results do not show a complete match in every detail, the study suggests that the bilinguals' semantic processing resembles monolinguals' semantic processing to a significant extent. This study also suggests that proficiency has a close correlation with brain responses in semantic processing in L2.

The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0−∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0−∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in healthy Chinese male volunteers as those found in Caucasic population. The test and reference febuxostat tablets formulations met the regulatory criteria for bioequivalence at 40-mg and 80-mg strengths in fasting healthy Chinese male volunteers. Trial Registration: Chictr.org ChiCTR-TTRCC-14004288

Diffusion of innovation (DOI) is widely cited in the HIV behavior change literature; however there is a dearth of research on the application of DOI in interventions for sex workers. Following a randomized-controlled trial of HIV risk reduction among female entertainment workers (FEWs) in Shanghai, China, we used qualitative approaches to delineate potential interpersonal communication networks and contributing factors that promote diffusion of information in entertainment venues. Results showed that top-down communication networks from the venue owners to the FEWs were efficient for diffusion of information. Mammies/madams, who act as intermediaries between FEWs and clients form an essential part of FEWs’ social networks but do not function as information disseminators due to a conflict of interest between safer sex and maximizing profits. Diffusion of information in large venues tended to rely more on aspects of the physical environment to create intimacy and on pressure from managers to stimulate communication. In small venues, communication and conversations occurred more spontaneously among FEWs. Information about safer sex appeared to be more easily disseminated when the message and the approach used to convey information could be tailored to people working at different levels in the venues. Results suggest that safer sex messages should be provided consistently following an intervention to further promote intervention diffusion, and health-related employer liability systems in entertainment venues should be established, in which employers are responsible for the health of their employees. Our study suggests that existing personal networks can be used to disseminate information in entertainment venues and one should be mindful about the context-specific interactions between FEWs and others in their social networks to better achieve diffusion of interventions.