Li Yang

Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Shi, China

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Publications (318)841.13 Total impact

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    ABSTRACT: Objective: Emotional lability (EL) and oppositional defiant disorder (ODD) frequently co-occur with ADHD. This study evaluates whether EL merely represents the negative "mood/affect" component of ODD or forms a distinct dimension. Method: EL and ODD data from 1,317 ADHD participants were analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for binary data. Results: Within ADHD, 39.4% children had ODD and 42.6% had EL. A sizable proportion expressed only either ODD or EL: 16.6% had ODD-only, 19.7% had EL-only, and 22.9% expressed both. In both EFA and CFA, EL forms a separate dimension from ODD items and the "mood/affect" subdimensions (whether classified by Diagnostic and Statistical Manual of Mental Disorders [5th ed.; DSM-5] or the Burke et al. models or the de novo ODD subdimensions derived from our data). This factorial structure remains invariant across gender. Conclusion: EL is distinct from ODD and its "mood/affect" subdimensions. In line with emerging evidence, our findings provide further evidence of factorial validity for EL as a separate construct from ODD.
    No preview · Article · Feb 2016 · Journal of Attention Disorders
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    Preview · Article · Jan 2016 · Molecules
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    ABSTRACT: Objective: The purpose of this study was to compare the short-term efficacy, tolerability, and 1-year adherence in Chinese children and adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with either osmotic release oral system methylphenidate (OROS MPH) or atomoxetine (ATX). Methods: Children and adolescents meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for ADHD were randomly assigned to receive either OROS MPH (n = 119) or ATX (n = 118). Participants underwent a 1-4 week dose titration period to determine optimal dose, and then were maintained on that dose for 4 weeks (maintenance period). Assessment for efficacy was conducted every week over the titration period and at the end of the maintenance period. The primary efficacy measure was the investigator-rated total ADHD Rating Scale-IV (ADHD-RS-IV) score. Response was further classified as remission (ADHD-RS-IV [18 or 9 items] average score ≤1), robust improvement (ADHD-RS-IV ≥40% decrease in total score), or improvement (≥ 25% decrease in total score) at the end of maintenance period. Medication adherence (taking medication at least 5 days in 1 week) and reasons for nonadherence were evaluated every week over the titration period, at the end of maintenance period, and then at 3, 6, and 12 months. Results: At the end of maintenance period, both OROS MPH and ATX were associated with significant and similar reductions from baseline in ADHD symptoms. Percentages achieving remission, robust improvement, and improvement were comparable for OROS MPH and ATX treatment (35.3% vs. 37.1%, 45.4% vs. 44.8%, 65.5% vs. 66.4%). Medication use decreased over time for both treatments; however, at end of maintenance period, 3 month, 6 month, and 1 year follow-ups, subjects in the OROS MPH group were more likely to be compliant with treatment (74.8%, 50.4%, 38.7%, and 21.8% for OROS MPH vs. 52.5%, 33.9%, 12.7%, and 3.4% for ATX) ( p < 0.05). The most common reasons for nonadherence were adverse events and lack of efficacy. Conclusions: Both OROS MPH and ATX resulted in similar reductions in ADHD symptoms in Chinese children and adolescents with ADHD. Long-term adherence with medication was poor in general, although somewhat better with OROS MPH than with ATX. Clinical trial registration: , Identifier: NCT01065259.
    No preview · Article · Jan 2016 · Journal of child and adolescent psychopharmacology
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    ABSTRACT: Serotonin is an important neurotransmitter that regulates a wide range of physiological, neuropsychological, and behavioral processes. Consequently, serotonin deficiency is involved in a wide variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, and depression. The pathophysiological mechanisms underlying serotonin deficiency, particularly from a lipidomics perspective, remain poorly understood. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2-/-) mice. Using a high-throughput normal-/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF-MS) method, 59 lipid biomarkers encompassing glycerophospholipids (glycerophosphocholines, lysoglycerophosphocholines, glycerophosphoethanolamines, lysoglycerophosphoethanolamines glycerophosphoinositols, and lysoglycerophosphoinositols), sphingolipids (sphingomyelins, ceramides, galactosylceramides, glucosylceramides, and lactosylceramides) and free fatty acids were identified. Systemic oxidative stress in the Tph2-/- mice was significantly elevated, and a corresponding mechanism that relates the lipidomic findings has been proposed. In summary, this work provides preliminary findings that lipid metabolism is implicated in serotonin deficiency.
    No preview · Article · Jan 2016 · Analytical and Bioanalytical Chemistry
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    ABSTRACT: 1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic.2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice.3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0–∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.
    No preview · Article · Jan 2016 · Xenobiotica
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    ABSTRACT: Identifying novel targets to enhance leukemia-cell differentiation is an urgent requirment. We have recently proposed that inhibiting the antioxidant enzyme peroxiredoxin I (Prdx I) may induce leukemia-cell differentiation. However, this concept remains to be confirmed. In this work, we identified H7 as a novel Prdx I inhibitor through virtual screening, in vitro activity assay, and surface plasmon resonance assay. Cellular thermal shift assay showed that H7 directly bound to Prdx I but not to Prdxs II-V in cells. H7 treatment also increased reactive oxygen species (ROS) level and cell differentiation in leukemia cells, as reflected by the upregulation of the cell surface differentiation marker CD11b/CD14 and the morphological maturation of cells. The differentiation-induction effect of H7 was further observed in some non-acute promyelocytic leukemia (APL) and primary leukemia cells apart from APL NB4 cells. Moreover, the ROS scavenger N-acetyl cysteine significantly reversed the H7-induced cell differentiation. We demonstrated as well that H7-induced cell differentiation was associated with the activation of the ROS-Erk1/2-C/EBPβ axis. Finally, we showed H7 treatment induced cell differentiation in an APL mouse model. All of these data confirmed that Prdx I was novel target for inducing leukemia-cell differentiation and that H7 was a novel lead compound for optimizing Prdx I inhibition.
    Preview · Article · Dec 2015 · Oncotarget
  • Ya-Juan Wang · Li Yang · Jian-Ping Zuo
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    ABSTRACT: Chronic Hepatitis B virus (HBV) infection (CHB) is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Although the availability of HBV vaccines effectively reduces the incidence of HBV infection, the healthcare burden from CHB remains high. Several antiviral agents, such as (Pegylated-) interferon-α and nucleos(t)ide analogs are approved by US FDA for chronic HBV infection management. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been recommended as the first-line anti-HBV drugs for excellent viral suppression with a low risk of antiviral resistance, but the cost and need for essentially life-long treatment are considerable challenges. And none of these current treatments can eradicate the intracellular virus. Given these issues, there is still an unmet medical need for an efficient HBV cure. We summarize here the key developments of antivirals against hepatitis B virus, including HBV replication cycle inhibitors and host immune regulators.
    No preview · Article · Dec 2015 · Virus Research
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    ABSTRACT: During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B.
    No preview · Article · Nov 2015 · Antiviral research
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    ABSTRACT: Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P2Y12, and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study, on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production in the presence of high glucose via PI3K/Akt/mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with PBS treatment (15.8 days vs. 20.9 days). Meanwhile, Ft1 increased the rate of re-epithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, TGFβ1, TGFβ3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation and consecutively scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated VEGF, PDGF and FGF at either mRNA or protein levels, and alleviated the inflammation of infiltrated monocytes indicated by reduced TNF-α and IL- 6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU.
    Preview · Article · Nov 2015 · Journal of Pharmacology and Experimental Therapeutics
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    ABSTRACT: Two new alkaloids, plantadeprate A (1) and 1'-(4″-hydroxybutyl)plantagoguanidinic acid (2), along with three known compounds, were isolated from the seeds of Plantago depressa. Their structures were elucidated by physical data analyses including NMR, MS, and electronic circular dichroism (ECD) methods. Plantadeprate A (1), a monoterpene zwitterionic guanidium, possesses a unique 5/5/6-tricyclic ring system. Its absolute configuration was determined by X-ray crystallography and computational methods. Compound 1, plumbagine D (3), and plantagoguanidinic acid (4) exhibited potential antihyperglycemic properties attributed to suppression of hepatic gluconeogenesis with inhibitory rates of 8.2%, 18.5%, and 12.5% at 40 μM, respectively.
    Full-text · Article · Nov 2015 · Journal of Natural Products
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    ABSTRACT: Thermosensitive/magnetic molecularly imprinted polymers (TM-MIPs) were prepared by Pickering emulsion polymerization. With this method, SiO2 nanoparticles were used as the Pickering emulsion stabilizer, N-isopropylacrylamide functioned as the thermosensitive monomer participating in co-polymerization, and bifenthrin (BF) acted as the template molecule. The results of the characterizations demonstrated that the TM-MIPs were porous and magnetic inorganic/polymer composite microparticles with magnetic sensitivity (Ms = 0.7921 emu g−1), thermal stability (below 473 K), and magnetic stability (over the pH range of 2.0–8.0). TM-MIPs were used as sorbents to remove bifenthrin (BF), and then were swiftly split in magnetic field. The Freundlich isotherm model preferably matched with the experimental data. The adsorption kinetic of the TM-MIPs was primely fitted by the pseudo-second-order, indicating that the chemical reaction could be the rate-limiting step in the process of BF absorption. The selective recognition experiments exhibited that the TM-MIPs have obvious effect on selective adsorption of BF with diethyl phthalate and fenvalerate. In aqueous solutions, the adsorption of BF onto the TM-MIPs had response to temperature, and could be used for adsorbing and separating bifenthrin.
    No preview · Article · Nov 2015 · Desalination and water treatment
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    ABSTRACT: Currently, obesity has become a worldwide epidemic associated with Type 2 diabetes, dyslipidemia, cardiovascular disease and chronic metabolic diseases. Emodin is one of the active anthraquinone derivatives from Rheum palmatum and some other Chinese herbs with anti-inflammatory, anticancer and hepatoprotective properties. In the present study, we investigated the anti-obesity effects of emodin in obese mice and explore its potential pharmacological mechanisms. Male C57BL/6 mice were fed with high-fat diet for 12 weeks to induce obesity. Then the obese mice were divided into four groups randomly, HFD or emodin (40mg/kg/day and 80mg/kg/day) or lovastatin (30mg/kg/ day) for another 6 weeks. Body weight and food intake were recorded every week. At the end of the treatment, the fasting blood glucose, glucose and insulin tolerance test, serum and hepatic lipid levels were assayed. The gene expressions of liver and adipose tissues were analyzed with a quantitative PCR assay. Here, we found that emodin inhibited sterol regulatory element-binding proteins (SREBPs) transactivity in huh7 cell line. Furthermore, emodin (80mg/kg/day) treatment blocked body weight gain, decreased blood lipids, hepatic cholesterol and triglyceride content, ameliorated insulin sensitivity, and reduced the size of white and brown adipocytes. Consistently, SREBP-1 and SREBP-2 mRNA levels were significantly reduced in the liver and adipose tissue after emodin treatment. These data demonstrated that emodin could improve high-fat diet-induced obesity and associated metabolic disturbances. The underlying mechanism is probably associated with regulating SREBP pathway.
    No preview · Article · Nov 2015 · European journal of pharmacology
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    ABSTRACT: Drought stress is one of the disadvantageous environmental conditions for plant growth and reproduction. Given the importance of abscisic acid (ABA) to plant growth and abiotic stress responses, identification of novel components involved in ABA signalling transduction is critical. In this study, we screened numerous Arabidopsis thaliana mutants by seed germination assay and identified a mutant mlp43 (major latex protein-like 43) with decreased ABA sensitivity in seed germination. The mlp43 mutant was sensitive to drought stress while the MLP43-overexpressed transgenic plants were drought tolerant. The tissue-specific expression pattern analysis showed that MLP43 was predominantly expressed in cotyledons, primary roots and apical meristems, and a subcellular localization study indicated that MLP43 was localized in the nucleus and cytoplasm. Physiological and biochemical analyses indicated that MLP43 functioned as a positive regulator in ABA- and drought-stress responses in Arabidopsis through regulating water loss efficiency, electrolyte leakage, ROS levels, and as well as ABA-responsive gene expression. Moreover, metabolite profiling analysis indicated that MLP43 could modulate the production of primary metabolites under drought stress conditions. Reconstitution of ABA signalling components in Arabidopsis protoplasts indicated that MLP43 was involved in ABA signalling transduction and acted upstream of SnRK2s by directly interacting with SnRK2.6 and ABF1 in a yeast two-hybrid assay. Moreover, ABA and drought stress down-regulated MLP43 expression as a negative feedback loop regulation to the performance of MLP43 in ABA and drought stress responses. Therefore, this study provided new insights for interpretation of physiological and molecular mechanisms of Arabidopsis MLP43 mediating ABA signalling transduction and drought stress responses.
    Full-text · Article · Oct 2015 · Journal of Experimental Botany
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    ABSTRACT: In-furnace desulfurization has been widely used in circulating fluidized bed boilers. SO2 is removed by reacting with limestone during the process of sulfation after calcination in air combustion. Although CaCO3 is the main component of limestone, there are also other impurities such as CaMg(CO3)2 and SiO2 which can influence the desulfurization. The porous CaO produced by calcination plays an important role in sulfation, and water vapor in the furnace influences the calcination. This work aims to understand the impacts of impurities and water vapor on limestone calcination. Two kinds of China limestone were used to investigate the issues in a rotatable fluidized bed reactor. Mercury injection apparatus (MIP), scanning electron microscope-energy dispersive spectrometer (SEM-EDS), and X-ray diffraction (XRD) techniques were employed to analyze the pore structure, micromorphology, and crystal structure of the CaO calcined, respectively. The results show that the water vapor improves the calcination rate and shortens the reaction time, and those influences are stronger for higher impurity limestone possibly because of more defects in the crystal structure. Water vapor can directly influence the chemical reaction of calcination without affecting the diffusion property of CO2. Higher water vapor content results in slightly lower ultimate degree of conversion of limestone, but for different kinds of limestone the difference is not obvious. The results of SEM and MIP also mean that the existence of water vapor improves sintering and growth of grains. The results of XRD give further evidence to the previous conclusion. These tests and analysis give rise to the mechanisms behind the impacts of water vapor on limestone calcination: the binding ability of H2O to active site O∗ in Ca-O is stronger than that of CO2. H2O tends to replace CO2 on the active site to increase the release of CO2 in calcination. Water vapor also accelerates sintering, most possibly in the initial stage when the sintering neck is formed. There exist two possibilities: H2O molecules are absorbed on the active site of Ca-O∗ to promote the formation of the sintering neck of CaO by interaction between H2O molecules (such as hydrogen bond). Water vapor can also act as a solvent to improve the solid state diffusion from surface to sintering neck which also benefits the fusion and growth of minicrystals.
    No preview · Article · Oct 2015 · Energy & Fuels
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    ABSTRACT: Objective: Atomoxetine is the most widely used nonstimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). It selectively acts on the norepinephrine (NE) system. Dopamine beta hydroxylase (DBH) regulates the synthesis of NE. This study aimed to investigate whether variants in the DBH gene have an effect on the differential response to atomoxetine. Methods: Children and adolescents with ADHD were enrolled in a prospective, open-label study of atomoxetine for 8-12 weeks. The dose was titrated to 1.2-1.4 mg/kg per day and maintained for at least 4 weeks. The primary efficacy measure was the investigator-rated ADHD Rating Scale-IV (ADHD-RS-IV). Three categorical evaluations of treatment effects (defined as response, robust response, and remission) were used. We used a candidate gene approach. Eight single nucleotide polymorphisms (SNPs) in DBH were selected and genotyped based on the functional annotation in literature. Their association with response or remission status was analyzed. Results: Four SNPs were found nominally associated with response status (rs1076150, p = 0.0484; rs2873804, p = 0.0348; rs1548364, p = 0.0383; and rs2519154, p = 0.0097), two were associated with robust response (rs1076150, p = 0.0349; and rs2519154, p = 0.0047), and one was associated with remission (rs2519154, p = 0.0479). The association between rs2519154 and robust response was significant after correction of multiple comparison (p = 0.0384). Two haplotypes of linkage disequilibrium (LD) block1 (constituted by rs1108580, rs2873804, rs1548364, and rs2519154) were nominally associated with response and robust response status (CTAC: p = 0.0301 for response, p = 0.0374 for robust response; TCGT: p = 0.0317 for response, p = 0.021 for robust response), whereas one haplotype (GC) of LD block2 (constituted by rs2073837 and rs129882) was associated with robust response and remission status (p = 0.0377 for robust response; p = 0.0321 for remission), although none achieved significant threshold after multiple comparison. Conclusions: Variants in DBH genes were associated with atomoxetine response in the treatment of ADHD. Further replication in larger samples would be warranted.
    No preview · Article · Oct 2015 · Journal of child and adolescent psychopharmacology
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    ABSTRACT: A new imprinted photocatalyst ICTX@Mfa is prepared by employing a molecular imprinting technique, which is authenticated via a variety of modern analysis methods. It exhibits superior specific oriented recognition capability, stability and retrievability for selectively degrading common antibiotic ciprofloxacin molecules under visible light. Through gaining an insight into the photocatalytic mechanism of ciprofloxacin molecules over ICTX@Mfa, we can confirm that the generation of holes and hydroxyl radicals plays a major role in degrading ciprofloxacin in virtue of the active species detection experiments. This work puts forward a new design idea and provides an illustrative example for selective oriented removal of the specified organic pollutant molecules according to practical requirements.
    No preview · Article · Oct 2015 · Catalysis Science & Technology
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    ABSTRACT: Background Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. Methods We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. Findings Of 2 223 230 patients admitted to the 44 hospitals screened in 2013, 154 950 (7·0%) were suspected of having AKI by electronic screening, of whom 26 086 patients (from 374 286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374 286) by KDIGO criteria and 2·03% (7604 of 374 286) by expanded criteria, from which we estimate that 1·4-2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality Interpretation AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI.
    No preview · Article · Oct 2015 · The Lancet
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    Preview · Article · Oct 2015 · Hong Kong Journal of Nephrology
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    ABSTRACT: Objective: To evaluate the efficacy of a psychoeducation program for parents of children with ADHD in enhancing adherence to pharmacological treatment and improving clinical symptoms. Methods: We developed a psychoeducation program based on the theory of planned behavior (TPB). Eighty-nine children with ADHD were cluster randomly assigned for their families to receive 3 months of well-structured psychoeducation (intervention group, n=44) or only general clinical counseling (control group, n=45). Parents in the intervention group were given an expert lecture (with slides and a parent manual), attended two expert-guided parent group sessions, and were invited to join a professional-guided online community. Measurement of parents' knowledge about ADHD, components of the TPB model, and child ADHD symptoms were taken before and after intervention. Medication adherence was assessed thoroughly at the end of the first and third months. Satisfaction with the psychoeducation program was assessed only in the intervention group. Two-independent-samples t-test, ANOVA, and chi-square test were employed to compare differences between groups. Results: Compared to the control group, medication adherence in the intervention group was significantly higher after 1 and 3 months (97.7% intervention vs 75.6% control, P=0.002, and 86.4% intervention vs 53.3% control, P=0.001, respectively). Accordingly, the ADHD rating scale scores were lower in the intervention group than the control group after intervention (33.7±5.4 vs 45.1±7.9, P=0.008). Greater improvements in parents' knowledge about ADHD and many components of the TPB model were observed in the intervention group, especially increased intention to adhere to medication, compared to the control group (P<0.001). Conclusion: This psychoeducation program had a positive impact on both medication adherence and clinical symptoms of ADHD children. It could be considered as a potential beneficial supplement to clinical practice.
    Full-text · Article · Oct 2015 · Neuropsychiatric Disease and Treatment
  • Han Han · Li Yang · Yue Ding · Guang Ji · Tong Zhang
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    ABSTRACT: A rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for determining protostemonine, a new anti-tussive agent isolated from Radix Stemonae. Separation was performed on a C18 column with mass detection in positive selected reaction monitoring mode at the transitions of m/z 418.2→m/z 320.2 and m/z 416.2→m/z 342.2 for protostemonine and internal standard, respectively. The assay showed good linearity (r>0.998) over the tested concentration range with the lowest limit of quantification of 1.0ng/ml. The intra- and inter-day precisions (RSD, %) were 2.21-9.89% and 3.99-13.19%, respectively; whereas accuracy (RR, %) ranged from 90.35% to 108.32%. The extraction recovery, stability, and matrix effect were demonstrated to be within the acceptable limits. The validated assay was further successfully applied to the pharmacokinetic studies of protostemonine in rat. Protostemonine was rapidly eliminated from plasma following single intravenous administration (2mg/kg) with a t1/2 of 3.06±1.37h. After oral administration (10, 20, and 50mg/kg), protostemonine was rapidly absorbed from the gastrointestinal tract with tmax of approximately 1h, and has shown dose-independent pharmacokinetic behaviors. Oral bioavailability of protostemonine was calculated to be 5.87-7.38%. Moreover, a total of 10 metabolites were structurally identified by using UHPLC-Q/TOF-MS method. The proposed metabolic pathways of protostemonine in rat involve demethylation, hydrolysis, and oxygenation. The current study provides informative data for understanding the in vivo disposition of protostemonine, which, in turn, help in interpreting the mechanism of its effectiveness and toxicity.
    No preview · Article · Sep 2015 · Journal of pharmaceutical and biomedical analysis

Publication Stats

4k Citations
841.13 Total Impact Points


  • 2006-2016
    • Shanghai University of Traditional Chinese Medicine
      • • Institute of Chinese Materia Medica
      • • Key Laboratory of Standardization of Chinese Medicines of Ministry of Education
      Shanghai, Shanghai Shi, China
  • 2015
    • Jiangsu University
      • School of Chemistry and Chemical Engineering
      Chenkiang, Jiangsu, China
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Changsha University of Science and Technology
      Ch’ang-sha-shih, Hunan, China
  • 2014-2015
    • Harbin Institute of Technology
      • School of Energy Science and Engineering
      Charbin, Heilongjiang Sheng, China
    • Qiqihar Medical University
      Zizikar, Heilongjiang Sheng, China
    • The Northwest Normal University
      Kao-lan-hsien, Gansu Sheng, China
  • 2010-2015
    • Beijing Medical University
      • • Department of Medicine
      • • Department of Gastroenterology
      Peping, Beijing, China
    • Northeast Normal University
      • Department of Chemistry
      Hsin-ching, Jilin Sheng, China
  • 2008-2015
    • Chinese Academy of Sciences
      • State Key Laboratory of Drug Research
      Peping, Beijing, China
  • 2004-2015
    • Harvard University
      Cambridge, Massachusetts, United States
    • Shanghai Medical University
      Shanghai, Shanghai Shi, China
  • 2003-2015
    • Peking University
      • • Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education
      • • Institute of Urology
      • • Institute of Mental Health
      • • Institute of Microelectron
      Peping, Beijing, China
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
  • 2011-2014
    • China Academy of Chinese Medical Sciences
      Peping, Beijing, China
    • University of South China
      Heng-nan, Hunan, China
    • Jilin University
      Yung-chi, Jilin Sheng, China
  • 2013
    • Yangtze University
      Hu-pei-ts’un, Shanxi Sheng, China
    • Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region
      Yung-ning, Guangxi Zhuangzu Zizhiqu, China
  • 2010-2013
    • Huazhong University of Science and Technology
      • School of Computer Science and Technology
      Wu-han-shih, Hubei, China
  • 2008-2013
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
    • Tongji University
      Shanghai, Shanghai Shi, China
  • 2006-2013
    • Peking University People's Hospital
      Peping, Beijing, China
  • 2012
    • Peking University Health Science Center
      Peping, Beijing, China
    • China University of Mining Technology
      Peping, Beijing, China
  • 2005-2012
    • China Pharmaceutical University
      • Department of Pharmacognosy
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2010-2011
    • Shanghai Research Institute of Materials
      Shanghai, Shanghai Shi, China
  • 2005-2010
    • Beijing Genomics Institute
      Bao'an, Guangdong, China
  • 2009
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China
  • 2007
    • Tongji Medical University
      • Department of Gastroenterology
      Shanghai, Shanghai Shi, China
  • 2003-2004
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2002-2003
    • Shandong Normal University
      Chi-nan-shih, Shandong Sheng, China