The relationship between physical activity and depression among community-dwelling adults in Wuhan, China.

Background: While the association between physical activity (PA) and depression has been established, there is limited research on the effect of PA on the risk of depression among Chinese individuals. Thus, this study aimed to investigate the relationship between PA and depression among Chinese individuals. Methods: We used a stratified random sampling approach to recruit participants from five urban districts in Wuhan, China. A total of 5,583 permanent residents aged 18 years or older completed questionnaires, which included the International Physical Activity Questionnaire Short Form (IPAQ-SF) to measure PA, and the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. To control for potential confounders, multiple logistic regression was employed to assess the association of PA with depression. Results: The depression group had significantly lower weekly PA levels, measured in metabolic equivalent of task-minutes per week (MET-min/w), compared to the non-depression group [1,770 (693-4,200) MET-min/w vs. 2,772 (1,324-4,893) MET-min/w, p < 0.001]. In the fully adjusted model, the moderate and high PA level groups had lower odds ratios (ORs) for depressive symptoms compared to the low PA level group [OR (95% confidence interval (CI)) = 0.670 (0.523-0.858), 0.618 (0.484-0.790), respectively]. Among males, moderate and high levels of PA were associated with lower risk of depression compared to low PA levels [OR (95% CI) = 0.417 (0.268-0.649), 0.381 (0.244-0.593), respectively]. However, this association was not observed in females [OR (95% CI) = 0.827 (0.610-1.121), 0.782 (0.579-1.056), respectively]. The study found a significant interaction between PA levels and gender in relation to depression (P for interaction = 0.019). Conclusion: The findings suggest a negative association between PA and risk of depressive symptoms, indicating that moderate to high levels of PA may serve as a protective factor against depressive symptoms.

Evaluation of the Relationship Between BDNF Val66Met Gene Polymorphism and Attention Deficit Hyperactivity Disorder: A Meta-Analysis.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in childhood. Brain-derived neurotrophic factor (BDNF) is widely distributed in the central nervous system and plays an important role in neural development. Despite several previous studies have examined the association between the Val66Met polymorphism BDNF and ADHD, the results are conflicting. Objective: This study aimed to evaluate the association between Val66Met polymorphism and ADHD in case-control and transmission disequilibrium test (TDT) studies using a meta-analysis. Methods: Keywords "rs6265" or "Val66Met" and "Attention deficit hyperactivity disorder" were used to search in the PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases before April 2021. Genotype data were extracted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Fifteen studies, comprising of 8,692 samples (containing 4,364 cases, 4,328 controls) and 1,578 families were included and results demonstrated that rs6265 was not associated with susceptibility to ADHD (OR = 0.95, 95% CI: 0.87-1.04, P = 0.291). Stratified analyses by study design, ethnicity, and sample size further supported that rs6265 was not associated with ADHD. Conclusion: The present study shows that the polymorphism of the BDNF Val66Met gene is not associated with susceptibility to ADHD.

Cost-effectiveness of perampanel as an adjunctive treatment for uncontrolled focal seizures in pediatric patients: a Chinese perspective.

Background: The incidence of epilepsy is 41-187 per 100,000 person-year in children. The health care costs for children with uncontrolled epilepsy is a huge burden. Perampanel (PER) was effective, safety and well-tolerated as add-on therapy in pediatric patients aged 4 to <12 years with uncontrolled focal seizures. However, there is still limited evidence on cost-effectiveness of PER in pediatric patients. We aimed to evaluate the cost-effectiveness of PER as an add-on therapy for pediatric patients with uncontrolled focal seizures. Methods: A Markov model was established to conduct an analysis from the perspective of the Chinese health system and society. The incremental cost-effectiveness ratio (ICER) of patients using PER and conventional therapy versus patients using conventional therapy alone were estimated and compared. The transition probability of the response level, health state utility values, and costs were derived from clinical trials and the literature. Costs, including medical, drug, transportation and indirect costs, were calculated. We performed 1-way sensitivity analyses and probabilistic sensitivity analyses. A subgroup analysis of different ages was also conducted. Results: The base-case analysis indicated that compared to maintaining conventional therapy, adding PER as an adjuvant drug therapy had an increased cost of $3,449.85 over 5 years, with an incremental quality-adjusted life years (QALY) value of 0.40, resulting in an ICER of $8,582.58 per additional QALY. The health state utility value had the greatest effect on the ICER. The probabilistic sensitivity analyses showed that the probability of PER being cost-effective was 76.72% at a willingness-to-pay of $11,293/QALY. The ICER of the subgroup ranged from $7,167.95/QALY to $19,710.96/QALY. Conclusions: Our study demonstrated that PER is a cost-effective add-on therapy for pediatric patients.

Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study.

Objective: This study aimed to determine the efficacy and clinical factors related to the pharmacodynamics of single or combination therapies of valproic acid (VPA), carbamazepine (CBZ), and oxcarbazepine (OXC), three commonly used anti-epileptic drugs (AEDs) in China. Methods: The study evaluated the records of 2027 outpatients in a Changsha hospital, located in China, from December 23, 2015 to October 28, 2019. The baseline seizure frequency was assessed during the first visit. AED efficacy was determined based on the reduction in seizures from baseline at the subsequent visits. Multivariable ordinal regression analysis was used to determine the association between the clinical factors (demographic characteristics, clinical features, and medication situation) and AED efficacy. For validation, the clinical efficacies of AEDs were compared as both single agents and in combinations. Differences in adverse effect (AEs) categories were analyzed by Chi-square between AED groups. Results: Records of patients receiving VPA, CBZ, and OXC were evaluated. Serum concentrations of VPA and CBZ is significantly correlated with efficacy (OR 1.030 [1.024-1.037], p < 0 0.0001; OR 1.250 [1.146-1.63], p < 0.0001, respectively) and OXC efficacy correlated to the serum concentration of the metabolite 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) serum concentrations (OR 1.060 [1.031-1.089], p < 0.0001). Significant differences existed between females and males in VPA efficacy (OR 1.318 [1.033-1.682], p = 0.027). After validation, VPA, in combination with OXC (OR 1.93 [1.38-2.70], p<0.001), or with VGB (Vigabatrin) (OR 2.36 [1.38-2.70], p = 0.002), showed significantly better efficacy than as a single agent. OXC efficacy was also affected by the duration of epilepsy (OR 0.965 [0.946-0.984], p < 0.001). Additionally, the efficacies of OXC and VPA were also affected by the seizure type. Seizure reduction improved significantly with an increasing number of pharmacists' educations in the first three visits period. There were no differences in AEs incidence among these 3 AEDs except for Psychiatric (0.02) and nervous system disorders (0.0001). Conclusion: Serum concentrations of VPA and CBZ may positively affect their efficacies, while OXC efficacies are correlated to MHD serum concentrations. The efficacy of VPA was higher in females compared to males. VPA-OXC and VPA-VGB combinations had higher efficacies compared to monotherapy. Besides, OXC efficacy is probably reducing by the duration of epilepsy. Additionally, VPA efficacy for focal or generalized seizures is superior to mixed-type seizures. OXC was more effective for focal seizures compared to mixed-type ones. Education provided by pharmacists improved the seizures to some extent, and there were no significant differences between most categories of adverse effects for the investigated AEDs.

Effect of rifampicin on anticoagulation of warfarin: A case report.

BACKGROUND: The drug interaction between warfarin and rifampicin is widely known, but there are still some difficulties in managing the combination of the two drugs. CASE SUMMARY: A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin. The dose of warfarin was increased to 350% in 3 mo before reaching the lower international normalized ratio treatment window. No obvious adverse reaction occurred during the drug-adjustment period. This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range. CONCLUSION: Anticoagulation for valve replacement in Chinese patients differs from that in other races. Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.

Population pharmacokinetics of unbound valproic acid in pediatric epilepsy patients in China: a protein binding model.

PURPOSE: The purpose of this study was to establish a protein binding model of unbound valproic acid (VPA) based on Chinese pediatric patients with epilepsy and provide a reference for clinical medication. METHODS: A total of 313 patients were included and both their total and unbound VPA concentrations (375 pairs of concentrations) were measured. NONMEM software was used for population pharmacokinetic modeling. The stepwise method was used to screen the potential covariates. Goodness-of-fit plot, bootstrap, and visual predictive check were used for model evaluation. In addition, dose recommendations for typical patients aged 0 to 16 years were proposed by Monte Carlo simulations. RESULTS: A one-compartment model of first-order absorption and first-order elimination was used to describe the pharmacokinetic characteristics of unbound VPA, and the linear non-saturable binding equation was introduced to describe the protein binding. Body weight, age-based maturation, and co-medicated with lamotrigine could affect the CL/F of unbound and bound VPA. Model evaluation showed satisfactory robustness of the final model. The dosing regimens for children aged 0 to 16 years were proposed based on the final established model. CONCLUSION: We developed a population pharmacokinetic model of unbound and bound VPA that took account of protein binding. The VPA dosing regimen in pediatric patients with epilepsy needs to be optimized by the body weight, age, and co-medications.

Determination of unbound valproic acid in plasma using centrifugal ultrafiltration and gas chromatography:Application in TDM.

AIM: In order to monitor the free concentration of VPA in plasma, a simple and rapid method needs to be developed. METHODS: The free fraction of VPA in plasma was obtained by centrifugal ultrafiltration (CF-UF) devices. Cyclohexanecarboxylic acid was used as internal standard. Valproate in plasma was converted to VPA by sulphuric acid acidification, and dichloromethane was used as solvent for extraction. Nitrogen was the carrier gas, the samples were separated by capillary column, and the flame ionization detector was used to detect VPA fragment ions for quantitative analysis. RESULTS: The assay had good specificity and stability. The linear range of the assay was 0.56-28.11 mg/L. The intra-day and inter-day precision (RSDs) of the assay were all within 15%, and the accuracy (RE) was 2.58%. The recoveries of VPA with three different concentrations were 102.03 ±â€¯1.05, 101.45 ±â€¯2.08 and 102.58 ±â€¯3.38. The results of therapeutic drug monitoring (TDM) in pediatric inpatient group and outpatient group showed significant differences between the two groups (P < 0.001). CONCLUSION: This assay has low cost and good analytical performance, so it can be developed into a routine TDM method of unbound VPA. We recommend the monitoring of unbound VPA concentration in pediatric inpatients during clinical use of VPA.

Pharmacist impact on adherence of valproic acid therapy in pediatric patients with epilepsy using active education techniques.

There is limited information on the impact of active education by a pharmacist in the population of pediatric patients with epilepsy (PWE) in China. The objective of this study was to assess the effect of education by pharmacists on medication adherence and percentage of valproic acid (VPA) samples reaching therapeutic reference range in these patients. This study was conducted at two teaching hospitals in Changsha, China. Patients were retrospectively identified from January 2016 to December 2017. Active education by a pharmacist in both oral and written formats was provided at the intervention hospital whereas standard passive pharmacist service (dispensing and answering questions) was provided at the control hospital. Medication adherence was assessed by the simplified medication adherence questionnaire (SMAQ), and serum concentrations of VPA were collected. The correlation between pharmacist education and medication adherence and percentage of VPA samples reaching therapeutic reference range were analyzed. A total of 2165 patients and 4343 serum VPA concentrations were included in the analysis. For the first therapeutic drug monitoring (TDM) measurement, there was no statistical difference between the two hospitals: 41.3% of VPA samples reached therapeutic range at the intervention hospital compared with 45.4% at the control hospital (χ2 = 3.686, P > 0.05). After pharmacist intervention at the intervention hospital, however, there were significant differences in the percentage of therapeutic VPA samples reaching therapeutic range between the first and the second, third, fourth, and fifth TDM measurements (χ2 = 9.756, P < 0.01; χ2 = 22.840, P < 0.01; χ2 = 15.816, P < 0.01; χ2 = 27.613, P < 0.01). Based on the SMAQ adherence assessment, adherence increased from a minimum of 56.0% to a maximum of 73.9% with stabilization during the last six months of follow-up at the intervention hospital. Both the medication adherence rate and the percentage of VPA samples reaching therapeutic range increased as the result of active education by a pharmacist, suggesting that continuous pharmacist intervention had a positive impact in outpatient pediatric PWE.

Comparative Transcriptional Profiling and Physiological Responses of Two Contrasting Oat Genotypes under Salt Stress.

Salinity is one of the major abiotic factors that affect productivity in oat. Here, we report a comparison of the transcriptomes of two hexaploid oat cultivars, 'Hanyou-5' and 'Huazao-2', which differ with respect to salt tolerance, in seedlings exposed to salt stress. Analysis of the assembled unigenes from the osmotically stressed and control libraries of 'Hanyou-5' and 'Huazao-2' showed that the expression of 21.92% (36,462/166,326) of the assembled unigenes was differentially regulated in the two cultivars after different durations of salt stress. Bioinformatics analysis showed that the main functional categories enriched in these DEGs were "metabolic process", "response to stresses", "plant hormone signal transduction", "MAPK signalling", "oxidative phosphorylation", and the plant-pathogen interaction pathway. Some regulatory genes, such as those encoding MYB, WRKY, bHLH, and zinc finger proteins, were also found to be differentially expressed under salt stress. Physiological measurements also detected significant differences in the activities of POD (76.24 ± 1.07 Vs 81.53 ± 1.47 U/g FW) in the two genotypes in response to osmotic stress. Furthermore, differential expression of 18 of these genes was successfully validated using RNA-seq and qRT-PCR analyses. A number of stress-responsive genes were identified in both cultivars, and candidate genes with potential roles in the adaptation to salinity were proposed.

Transcriptome analysis of hexaploid hulless oat in response to salinity stress.

BACKGROUND: Oat is a cereal crop of global importance used for food, feed, and forage. Understanding salinity stress tolerance mechanisms in plants is an important step towards generating crop varieties that can cope with environmental stresses. To date, little is known about the salt tolerance of oat at the molecular level. To better understand the molecular mechanisms underlying salt tolerance in oat, we investigated the transcriptomes of control and salt-treated oat using RNA-Seq. RESULTS: Using Illumina HiSeq 4000 platform, we generated 72,291,032 and 356,891,432 reads from non-stressed control and salt-stressed oat, respectively. Assembly of 64 Gb raw sequence data yielded 128,414 putative unique transcripts with an average length of 1,189 bp. Analysis of the assembled unigenes from the salt stressed and control libraries indicated that about 65,000 unigenes were differentially expressed at different stages. Functional annotation showed that ABC transporters, plant hormone signal transduction, plant-pathogen interactions, starch and sucrose metabolism, arginine and proline metabolism, and other secondary metabolite pathways were enriched under salt stress. Based on the RPKM values of assembled unigenes, 24 differentially expressed genes under salt stress were selected for quantitative RT-PCR validation, which successfully confirmed the results of RNA-Seq. Furthermore, we identified 18,039 simple sequence repeats, which may help further elucidate salt tolerance mechanisms in oat. CONCLUSIONS: Our global survey of transcriptome profiles of oat plants in response to salt stress provides useful insights into the molecular mechanisms underlying salt tolerance in this crop. These findings also represent a rich resource for further analysis of salt tolerance and for breeding oat with improved salt tolerance through the use of salt-related genes.

Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα.

UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation. Multiple regions of UBXN1, including its UBA domain, were critical for its activity. Elimination of UBXN1 resulted in early murine embryonic lethality. shRNA-mediated knockdown of UBXN1 enhanced human immunodeficiency virus type 1 (HIV) production up to 10-fold in single cycle assays. In primary human fibroblasts, knockdown of UBXN1 caused prolonged degradation of IκBα and enhanced NFκB signaling, which was also observed after CRISPR-mediated knockout of UBXN1 in mouse embryo fibroblasts. Knockout of UBXN1 significantly up- and down-regulated hundreds of genes, notably those of several cell adhesion and immune signaling pathways. Reduction in UBXN1 gene expression in Jurkat T cells latently infected with HIV resulted in enhanced HIV gene expression, consistent with the role of UBXN1 in modulating the NFκB pathway. Based upon co-immunoprecipitation studies with host factors known to bind Cul1, models are presented as to how UBXN1 could be inhibiting Cul1 activity. The ability of UBXN1 and other family members to negatively regulate the NFκB pathway may be important for dampening the host immune response in disease processes and also re-activating quiescent HIV from latent viral reservoirs in chronically infected individuals.

High-level production of replication-defective human immunodeficiency type 1 virus vector particles using helper-dependent adenovirus vectors.

Gene transfer vectors based upon human immunodeficiency virus type 1 (HIV) are widely used in bench research applications and increasingly in clinical investigations, both to introduce novel genes but also to reduce expression of unwanted genes of the host and pathogen. At present, the vast majority of HIV-based vector supernatants are produced in 293T cells by cotransfection of up to five DNA plasmids, which is subject to variability and difficult to scale. Here we report the development of a HIV-based vector production system that utilizes helper-dependent adenovirus (HDAd). All necessary HIV vector components were inserted into one or more HDAds, which were then amplified to very high titers of ~10(13) vp/ml. These were then used to transduce 293-based cells to produce HIV-based vector supernatants, and resultant VSV G-pseudotyped lentiviral vector (LV) titers and total IU were 10- to 30-fold higher, compared to plasmid transfection. Optimization of HIV-based vector production depended upon maximizing expression of all HIV vector components from HDAd. Supernatants contained trace amounts of HDAd but were free of replication-competent lentivirus. This production method should be applicable to other retroviral vector systems. Scalable production of HIV-based vectors using this two-step procedure should facilitate their clinical advancement.

Validation of the Chinese version of the Quality of Nursing Work Life scale.

Quality of Nursing Work Life (QNWL) serves as a predictor of a nurse's intent to leave and hospital nurse turnover. However, QNWL measurement tools that have been validated for use in China are lacking. The present study evaluated the construct validity of the QNWL scale in China. A cross-sectional study was conducted conveniently from June 2012 to January 2013 at five hospitals in Guangzhou, which employ 1938 nurses. The participants were asked to complete the QNWL scale and the World Health Organization Quality of Life abbreviated version (WHOQOL-BREF). A total of 1922 nurses provided the final data used for analyses. Sixty-five nurses from the first investigated division were re-measured two weeks later to assess the test-retest reliability of the scale. The internal consistency reliability of the QNWL scale was assessed using Cronbach's α. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC). Criterion-relation validity was assessed using the correlation of the total scores of the QNWL and the WHOQOL-BREF. Construct validity was assessed with the following indices: χ2 statistics and degrees of freedom; relative mean square error of approximation (RMSEA); the Akaike information criterion (AIC); the consistent Akaike information criterion (CAIC); the goodness-of-fit index (GFI); the adjusted goodness of fit index; and the comparative fit index (CFI). The findings demonstrated high internal consistency (Cronbach's α = 0.912) and test-retest reliability (interclass correlation coefficient = 0.74) for the QNWL scale. The chi-square test (χ2 = 13879.60, df [degree of freedom] = 813 P = 0.0001) was significant. The RMSEA value was 0.091, and AIC = 1806.00, CAIC = 7730.69, CFI = 0.93, and GFI = 0.74. The correlation coefficient between the QNWL total scores and the WHOQOL-BREF total scores was 0.605 (p<0.01). The QNWL scale was reliable and valid in Chinese-speaking nurses and could be used as a clinical and research instrument for measuring work-related factors among nurses in China.

Vertical profiles of soil water content as influenced by environmental factors in a small catchment on the hilly-gully Loess Plateau.

Characterization of soil water content (SWC) profiles at catchment scale has profound implications for understanding hydrological processes of the terrestrial water cycle, thereby contributing to sustainable water management and ecological restoration in arid and semi-arid regions. This study described the vertical profiles of SWC at the small catchment scale on the hilly and gully Loess Plateau in Northeast China, and evaluated the influences of selected environmental factors (land-use type, topography and landform) on average SWC within 300 cm depth. Soils were sampled from 101 points across a small catchment before and after the rainy season. Cluster analysis showed that soil profiles with high-level SWC in a stable trend (from top to bottom) were most commonly present in the catchment, especially in the gully related to terrace. Woodland soil profiles had low-level SWC with vertical variations in a descending or stable trend. Most abandoned farmland and grassland soil profiles had medium-level SWC with vertical variations in varying trends. No soil profiles had low-level SWC with vertical variations in an ascending trend. Multi-regression analysis showed that average SWC was significantly affected by land-use type in different soil layers (0-20, 20-160, and 160-300 cm), generally in descending order of terrace, abandoned farmland, grassland, and woodland. There was a significant negative correlation between average SWC and gradient along the whole profile (P<0.05). Landform significantly affected SWC in the surface soil layer (0-20 cm) before the rainy season but throughout the whole profile after the rainy season, with lower levels on the ridge than in the gully. Altitude only strongly affected SWC after the rainy season. The results indicated that land-use type, gradient, landform, and altitude should be considered in spatial SWC estimation and sustainable water management in these small catchments on the Loess Plateau as well as in other complex terrains with similar settings.

Human CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells.

Productive replication of human immunodeficiency virus type 1 (HIV-1) occurs efficiently only in humans. The posttranscriptional stages of the HIV-1 life cycle proceed poorly in mouse cells, with a resulting defect in viral assembly and release. Previous work has shown that the presence of human chromosome 2 increases HIV-1 production in mouse cells. Recent studies have shown that human chromosome region maintenance 1 (hCRM1) stimulates Gag release from rodent cells. Here we report that expressions of hCRM1 in murine cells resulted in marked increases in the production of infectious HIV-1 and feline immunodeficiency virus (FIV). HIV-1 production was also increased by hSRp40, and a combination of hCRM1 and hSRp40 resulted in a more-than-additive effect on HIV-1 release. In contrast, the overexpression of mouse CRM1 (mCRM1) minimally affected HIV-1 and FIV production and did not antagonize hCRM1. In the presence of hCRM1 there were large increases in the amounts of released capsid, which paralleled the increases in the infectious titers. Consistent with this finding, the ratios of unspliced to spliced HIV-1 mRNAs in mouse cells expressing hCRM1 and SRp40 became similar to those of human cells. Furthermore, imaging of intron-containing FIV RNA showed that hCRM1 increased RNA export to the cytoplasm.By testing chimeras between mCRM1 and hCRM1 and comparing those sequences to feline CRM1, we mapped the functional domain to HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats 4A to 9A and a triple point mutant in repeat 9A, which showed a loss of function. Structural analysis suggested that this region of hCRM1 may serve as a binding site for viral or cellular factors to facilitate lentiviral RNA nuclear export.

Transmembrane protein aptamers that inhibit CCR5 expression and HIV coreceptor function.

We have exploited the ability of transmembrane domains to engage in highly specific protein-protein interactions to construct a new class of small proteins that inhibit HIV infection. By screening a library encoding hundreds of thousands of artificial transmembrane proteins with randomized transmembrane domains (termed "traptamers," for transmembrane aptamers), we isolated six 44- or 45-amino-acid proteins with completely different transmembrane sequences that inhibited cell surface and total expression of the HIV coreceptor CCR5. The traptamers inhibited transduction of human T cells by HIV reporter viruses pseudotyped with R5-tropic gp120 envelope proteins but had minimal effects on reporter viruses with X4-tropic gp120. Optimization of two traptamers significantly increased their activity and resulted in greater than 95% inhibition of R5-tropic reporter virus transduction without inhibiting expression of CD4, the primary HIV receptor, or CXCR4, another HIV coreceptor. In addition, traptamers inhibited transduction mediated by a mutant R5-tropic gp120 protein resistant to maraviroc, a small-molecule CCR5 inhibitor, and they dramatically inhibited replication of an R5-tropic laboratory strain of HIV in a multicycle infection assay. Genetic experiments suggested that the active traptamers specifically interacted with the transmembrane domains of CCR5 and that some of the traptamers interacted with different portions of CCR5. Thus, we have constructed multiple proteins not found in nature that interfere with CCR5 expression and inhibit HIV infection. These proteins may be valuable tools to probe the organization of the transmembrane domains of CCR5 and their relationship to its biological activities, and they may serve as starting points to develop new strategies to inhibit HIV infection.

Authentication is fundamental for standardization of Chinese medicines.

Chinese medicines (CMs) are being used more and more widely throughout the world. Since there are many poisoning incidents caused by misuse or confusion of CMs, their safe use has become a critical issue internationally. In this paper, based on the investigation of the current market of CMs, reasons for various confusions of Chinese Materia Medica (CMM) are analyzed and clarified, such as herbs with multiple sources, regional custom-herbs, confusion in nomenclature, similarity in appearance, and complexity of processed products. Authentication of plant material is critical to the safe and effective use of CMM. In this paper, several authentication methods, such as taxonomy, morphology, microscopy, physical and chemical authentication, DNA molecular biology and their advanced applications in this area, are introduced. Furthermore, it is proposed that an authority on the authentication of CMM be established, as a physical institution and/or as an electronic database.

Simultaneous determination of naphthoquinone derivatives in Boraginaceous herbs by high-performance liquid chromatography.

A high-performance liquid chromatographic method using diode-array detection (HPLC-DAD) has been developed for the simultaneous quantification of eight naphthoquinone derivatives namely shikonin, acetylshikonin, deoxyshikonin, beta-acetoxyisovalerylshikonin, isobutylshikonin, beta,beta-dimethylacrylshikonin, 2-methyl-n-butyrylshikonin and isovalerylshikonin in nine species of the Boraginaceae family. These species, coming from different areas of China, are all used as interchangeable sourcing plants for the Chinese Materia Medica known as "Zicao", and are Arnebia euchroma (Royle) Johnston., A. guttata Bunge, Lithospermum erythrorhizon Sieb. et Zucc., Onosma paniculatum Bur. et Franch., O. exsertum Hemsl., O. confertum W.W. Smith, O. hookerii Clarke var. longiflorum Duthie, O. hookerii Clarke and O. waltonii Duthic. Quantification of the eight naphthoquinones in all the Zicao samples are reported and compared with each other. Furthermore, two positional isomers, 2-methyl-n-butyrylshikonin and isovalerylshikonin, were successfully separated and quantified for the first time in the present study. The results showed that, besides the three officially used species (namely, A. euchroma, A. guttata and L. erythrorhizon) that were listed in Chinese pharmacopoeia as interchangeable sourcing plants for Zicao, other six species of Onosma used by native peoples in Tibet and Yunnan Province also contain various types and considerable amounts of naphthoquinones and that O. waltonii contains the most. Therefore, these species of Onosma could be developed as new sources of naphthoquinones. The entire analytical procedure is reproducible and suitable for the quantification of naphthoquinones in all related Boraginaceous plants for quality assessment purposes.

Application of microscopy in authentication of Chinese patent medicine--Bo Ying compound.

To establish a quality control method for the Chinese Patent Medicine (CPM)-Bo Ying Compound (BYC), a comparison study was carried out on it with microscopy. The micro-morphological characteristics of its 22 components in the CPM and in the crude constituents have been documented and compared with each other. Their corresponding features were described and documented with color digital micrographs, so as to authenticate the presence of genuine crude constituents in BYC. The results showed that almost all constituents of BYC are found within their representative fragments in the CPM except one (Borax) that could dissolve or merge with the other components. Also the study indicated that light microscopy, an easy and economical method, could be used for the identification of this kind of CPM that contains plant and animal materials without the specific characteristic chemical marker compounds.