Publications by authors named "Hui-Chun Li"

61 Publications

The role of patient records in research: A bibliometric analysis of publications from an academic medical center in Taiwan.

J Chin Med Assoc 2021 May 21. Epub 2021 May 21.

Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC Medical Library, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan ROC Big Data Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei Taiwan, ROC Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: This study aimed to assess the use of medical record items in clinical research in one large academic medical center in Taiwan.

Methods: A descriptive survey design was adopted to collect the data. Articles published in 2018 by Taipei Veterans General Hospital (TVGH) staff as the first author were obtained. The types of specialties and types of research were analyzed. To understand the conditions for the use of medical records, the retrospective research using hospital's medical records were analyzed. Each article was read in entirety to realize the use and number of patients and the medical record items.

Results: Among the 362 articles first-authored by TVGH staff in 2018, 219 (60.4%) were classified as clinical studies, 60 (16.6%) as basic studies, 53 (14.6%) as database studies, and 30 (8.2%) as other categories. About 50% of the retrospective research using TVGH medical records had a case number less than 100 (67 cases, 49.6%) with an average number of 41 cases and 13 studies (9.6%) had a case number greater than 1000. Analysis of the number of medical record items used in 135 retrospective research studies based on TVGH medical records showed that 118 (87.4%) used basic patient information. In addition to basic information, notes written by professionals were used most frequently (73 cases, 54.0%), whereas medication information was used in 50 cases (37.0%); laboratory test data was used in 49 cases (36.2%) ; and body measurements was used in 27 cases (20%).

Conclusion: More than one-third of publications utilized medical records, but the patient numbers and record items in use were relatively limited. In the era of digitalization and big data analytics, the potential of medical records in research deserves attention. Investment in establishing a more accessible database of medical records to access nonstructural, descriptive medical records could be considered.
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http://dx.doi.org/10.1097/JCMA.0000000000000554DOI Listing
May 2021

Differential age trajectories of white matter changes between sexes correlate with cognitive performances.

Brain Connect 2021 Apr 15. Epub 2021 Apr 15.

National Yang Ming Chiao Tung University, Institute of Neuroscience, Taipei, Taiwan.

Background: Aging is accompanied by a gradual deterioration in multiple cognitive abilities and brain structures. Both cognitive function and white matter (WM) structure are found to be associated with neurodegeneration diseases and correlated with sex during aging. However, it is still unclear whether the brain structural change could be attributable to sex, and how sex would affect cognitive performances during aging.

Method: Diffusion MRI scans were performed on 1127 healthy participants (age range: 21 to 89) at a single site. The age trajectories of the WM tracts microstructure were delineated to estimate the turning age and changing rate between sexes. The canonical correlation analysis and moderated mediation analysis were used to examine the relationship between sex-linked WM tracts and cognitive performances.

Results: The axon intactness and demyelination of sex-linked tracts during aging were multifaceted. Sex-linked tracts in females peak around 5 years later than those in males but change significantly faster after the turning age. Projection and association tracts (e.g., corticospinal tracts and parahippocampal cingulum) contributed to a significant decrease in visuospatial and executive functions. We discovered that there is a stronger indirect effect of sex-linked tracts on cognitive functions in females than in males.

Conclusion: Our findings suggest that the vulnerable projection and association tracts in females may induce negative impacts on integrating multiple functions, which results in a faster decrease in visuospatial and executive functions.
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http://dx.doi.org/10.1089/brain.2020.0961DOI Listing
April 2021

Hepatitis C Viral Replication Complex.

Viruses 2021 03 22;13(3). Epub 2021 Mar 22.

Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan.

The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.
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http://dx.doi.org/10.3390/v13030520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004249PMC
March 2021

His in the pore-lining α4 of the Bacillus thuringiensis Cry4Aa δ-endotoxin is crucial for structural arrangements of the α4-α5 transmembrane hairpin and hence biotoxicity.

Biochim Biophys Acta Proteins Proteom 2021 Jun 23;1869(6):140634. Epub 2021 Feb 23.

Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; Laboratory of Synthetic Biophysics and Chemical Biology, Biophysics Institute for Research and Development (BIRD), Chiang Mai 50230, Thailand; Bacterial Toxin Research Innovation Cluster (BRIC), Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakornpathom 73170, Thailand. Electronic address:

One proposed toxic mechanism of Bacillus thuringiensis Cry δ-endotoxins involves pore formation in target membranes by the α4-α5 transmembrane hairpin constituting their pore-forming domain. Here, nine selected charged and uncharged polar residues in the pore-lining α4 of the Cry4Aa mosquito-active toxin were substituted with Ala. All mutant toxins, i.e., D169A, R171A, Q173A, H178A, Y179A, H180A, Q182A, N183A and E187A, were over-expressed in Escherichia coli as 130-kDa protoxin inclusions at levels comparable to the wild-type toxin. Bioassays against Aedes aegypti larvae revealed that only H178A and H180A mutants displayed a drastic reduction in biotoxicity, albeit almost complete insolubility observed for H178A, but not for H180A inclusions. Further mutagenic analysis showed that replacements of His with charged (Arg, Lys, Asp, Glu), small uncharged polar (Ser, Cys) or small non-polar (Gly, Val) residues severely impaired the biotoxicity, unlike substitutions with relatively large uncharged (Asn, Gln, Leu) or aromatic (Phe, Tyr, Trp) residues. Similar to the trypsin-activated wild-type toxin, both bio-active and -inactive H180 mutants were still capable of releasing entrapped calcein from lipid vesicles and producing cation-selective channels with ~130-pS maximum conductance. Analysis of the Cry4Aa structure revealed the existence of a hydrophobic cavity near the critical His side-chain. Analysis of simulated structures revealed that His-to-smaller residue conversions create a gap disrupting such cavity's hydrophobicity and hence structural arrangements of the α4-α5 hairpin. Altogether, our data disclose a critical involvement in Cry4Aa-biotoxicity of His exclusively present in the lumen-facing α4 for providing proper environment for the α4-α5 hairpin prior to membrane-inserted pore formation.
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http://dx.doi.org/10.1016/j.bbapap.2021.140634DOI Listing
June 2021

N-Terminally Added Tag Selectively Enhances Heterologous Expression of VacA Cytotoxin Variants from Helicobacter pylori.

Protein Pept Lett 2020 Nov 12. Epub 2020 Nov 12.

Bacterial Toxin Research Innovation Cluster (BRIC), Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakornpathom 73170. Thailand.

Background: Gastric pathogen Helicobacter pylori secretes VacA cytotoxin displaying a high degree of polymorphic variations of which the highest VacA pathogenicity correlates with m1-type variant followed by VacA-m2.

Objective: To comparatively evaluate expression in Escherichia coli of the mature VacA variants (m1- and m2-typtes) and their 33- and 55/59-kDa domains fused with His(6) tag at N- or C-terminus.

Methods: All VacA clones expressed in E. coli TOP10 were analyzed by SDS-PAGE and Western blotting. VacA inclusions were solubilized under native conditions (˜150-rpm shaking at 37°C for 2 h in 20 mM HEPES, pH 7.4 and 150 mM NaCl). Membrane-perturbing and cytotoxic activities of solubilized VacA proteins were assessed via liposome-entrapped dye leakage and resazurin-based cell viability assays, respectively. VacA binding to human gastric adenocarcinoma cells was assessed by immunofluorescence microscopy. Side-chain hydrophobicity of VacA was analyzed through modeled structures constructed by homology- and ab initio-based modeling.

Results: Both full-length VacA-m1 and 33-kDa domain were efficiently expressed only in the presence of N-terminal extension while its 55-kDa domain was capably expressed with either N- or C-terminal extension. Selectively enhanced expression was also observed for VacA-m2. Protein expression profiles revealed a critical period in IPTG-induced production of the 55-kDa domain with N-terminal extension unlike its C-terminal extension showing relatively stable expression. Both VacA-m1 isolated domains were able to independently bind to cultured gastric cells similar to the full-length toxin, albeit the 33-kDa domain exhibited significantly higher activity of membrane perturbation than others. Membrane-perturbing and cytotoxic activities observed for VacA-m1 appeared to be higher than those of VacA-m2. Homology-based modeling and sequence analysis suggested a potential structural impact of non-polar residues located at the N-terminus of the mature VacA toxin and its 33-kDa domain.

Conclusion: Our data provides molecular insights into selective influence of the N-terminally added tag on efficient expression of recombinant VacA variants, signifying biochemical and biological implications of the hydrophobic stretch within the N-terminal domain.
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http://dx.doi.org/10.2174/0929866527666201112122831DOI Listing
November 2020

Preferential modification of CyaA-hemolysin by CyaC-acyltransferase through the catalytic Ser-His dyad in esterolysis of palmitoyl-donor substrate devoid of acyl carrier proteins.

Arch Biochem Biophys 2020 11 2;694:108615. Epub 2020 Oct 2.

Bacterial Toxin Research Innovation Cluster (BRIC), Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakornpathom, 73170, Thailand; Department of Biochemistry, School of Medicine, Tzu Chi University, Hualian, 97004, Taiwan; Laboratory of Synthetic Biophysics and Chemical Biology, Biophysics Institute for Research and Development (BIRD), Chiang Mai, 50230, Thailand. Electronic address:

We previously demonstrated that the ~130-kDa CyaA-hemolysin domain (CyaA-Hly) from Bordetella pertussis co-expressed with CyaC-acyltransferase in Escherichia coli was acylated at Lys and thus activated its hemolytic activity. Here, attempts were made to provide greater insights into such toxin activation via fatty-acyl modification by CyaC-acyltransferase. Non-acylated CyaA-Hly (NA/CyaA-Hly) and CyaC were separately expressed in E. coli and subsequently purified by FPLC to near homogeneity. When effects of acyl-chain length were comparatively evaluated through CyaC-esterolysis using various p-nitrophenyl (pNP) derivatives, Michaelis-Menten steady-state kinetic parameters (K and k) of CyaC-acyltransferase revealed a marked preference for myristoyl (C) and palmitoyl (C) substrates of which catalytic efficiencies (k/K) were roughly the same (~1.5 × 10 smM). However, pNP-palmitate (pNPP) gave the highest hemolytic activity of NA/CyaA-Hly after being acylated in vitro with a range of acyl-donor substrates. LC-MS/MS analysis confirmed such CyaC-mediated palmitoylation of CyaA-Hly occurring at Lys, denoting no requirement of an acyl carrier protein (ACP). A homology-based CyaC structure inferred a role of a potential catalytic dyad of conserved Ser and His residues in substrate esterolysis. CyaC-ligand binding analysis via molecular docking corroborated high-affinity binding of palmitate with its carboxyl group oriented toward such a dyad. Ala-substitutions of each residue (S30A or H33A) caused a drastic decrease in k/K of CyaC toward pNPP, and hence its catalytic malfunction through palmitoylation-dependent activation of NA/CyaA-Hly. Altogether, our present data evidently provide such preferential palmitoylation of CyaA-Hly by CyaC-acyltransferase through the enzyme Ser-His nucleophile-activation dyad in esterolysis of palmitoyl-donor substrate, particularly devoid of a natural acyl-ACP donor.
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http://dx.doi.org/10.1016/j.abb.2020.108615DOI Listing
November 2020

MicroRNA-Independent Modulation of DICER1 Expression by hAgo2.

Mol Cell Biol 2020 09 28;40(20). Epub 2020 Sep 28.

Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan

Many proteins, including DICER1 and hAgo2, are involved in the biogenesis of microRNAs (miRNAs). Whether hAgo2 regulates DICER1 expression is unknown. Exogenously overexpressed hAgo2 suppressed DICER1 expression at the levels of both protein and mRNA, and the reduction in hAgo2 expression enhanced DICER1 expression. Precursor miRNA processing mediated by DICER1 was also modulated by hAgo2. However, hAgo2 protein did not suppress DICER1 promoter activity. Therefore, hAgo2 protein probably regulates DICER1 expression at the posttranscriptional level. Indeed, hAgo2 protein inhibited the reporter assay of the DICER1 mRNA 3' untranslated region (3'-UTR). Previous reports have demonstrated that miRNAs (e.g., let-7 and miR-103/107) inhibited DICER1 expression posttranscriptionally. However, hAgo2 still suppressed DICER1 expression in the cells depleted of these miRNAs. Moreover, the reporter activities of the mRNA 3'-UTR without these miRNA binding sites were still suppressed by hAgo2. Therefore, in addition to an miRNA-dependent pathway, hAgo2 can also modulate DICER1 expression through an miRNA-independent mechanism. Downregulation of DICER1 expression was further proven to be dependent on both hAgo2 and AUF1 proteins. Interactions of hAgo2 and AUF1 proteins were demonstrated by the coimmunoprecipitation assay. As expected, hAgo2 could not suppress the mRNA 3'-UTR reporter with a mutation in the potential AUF1-binding site. Thus, downregulation of DICER1 expression through the 3'-UTR requires both hAgo2 and AUF1.
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http://dx.doi.org/10.1128/MCB.00221-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523658PMC
September 2020

Optimized high-purity protein preparation of biologically active recombinant VacA cytotoxin variants from Helicobacter pylori.

Protein Expr Purif 2020 11 16;175:105696. Epub 2020 Jul 16.

Bacterial Toxin Research Innovation Cluster (BRIC), Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakornpathom, 73170, Thailand. Electronic address:

Vacuolating cytotoxin A (VacA) is a highly polymorphic virulence protein produced by the human gastric pathogen Helicobacter pylori which can cause gastritis, peptic ulcer and gastric cancer. Here, we present an optimized protein preparation of the mature full-length VacA variants (m1-and m2-types) and their 33-kDa N-terminal and 55/59-kDa C-terminal domains as biologically active recombinant proteins fused with an N-terminal His tag. All recombinant VacA constructs were over-expressed in Escherichia coli as insoluble inclusions which were soluble when phosphate buffer (pH 7.4) was supplemented with 5-6 M urea. Upon immobilized-Ni affinity purification under 5-M urea denaturing conditions, homogenous products (>95% purity) of 55/59-kDa domains were consistently obtained while only ~80% purity of both mature VacA variants and the 33-kDa truncate was achieved, thus requiring additional purification by size-exclusion chromatography. After successive refolding via optimized stepwise dialysis, all refolded VacA proteins were proven to possess both cytotoxic and vacuolating activity against cultured human gastric epithelial cells albeit the activity observed for VacA-m2 was lower than the m1-type variant. Such an optimized protocol described herein was effective for production of high-purity recombinant VacA proteins in large amounts (~30-40 mg per liter culture) that would pave the way for further studies on sequence-structure and function relationships of different VacA variants.
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http://dx.doi.org/10.1016/j.pep.2020.105696DOI Listing
November 2020

Molecular Insights into Zn Inhibition of the Antibacterial Endopeptidase Lysostaphin from .

Protein Pept Lett 2021 ;28(2):140-148

Laboratory of Synthetic Biophysics and Chemical Biology, Biophysics Institute for Research and Development (BIRD), Chiang Mai, Thailand.

Background: Mature lysostaphin (~28-kDa Lss) from Staphylococcus simulans proves effective in killing methicillin-resistant Staphylococcus aureus (MRSA) which is endemic in hospitals worldwide. Lss is Zn-dependent endopeptidase, but its bacteriolytic activity could be affected by exogenously added Zn.

Objective: To gain greater insights into structural and functional impacts of Znand Nion Lss-induced bioactivity.

Methods: Lss purified via immobilized metal ion-affinity chromatography was assessed for bioactivity using turbidity reduction assays. Conformational change of metal ion-treated Lss was examined by circular dichroism and intrinsic fluorescence spectroscopy. Co-sedimentation assay was performed to study interactions between Zn-treated Lss and S. aureus peptidoglycans. Metal ionbinding prediction and intermolecular docking were used to locate an extraneous Zn-binding site.

Results: A drastic decrease in Lss bioactivity against S. aureus and MRSA was revealed only when treated with Zn, but not Ni, albeit no negative effect of diethyldithiocarbamate-Zn-chelator on Lss-induced bioactivity. No severe conformational change was observed for Lss incubated with exogenous Zn or Ni. Lss pre-treated with Zn efficiently bound to S. aureus cell-wall peptidoglycans, suggesting non-interfering effect of exogenous metal ions on cell-wall targeting (CWT) activity. In silico analysis revealed that exogenous Zn, but not Ni, preferably interacted with a potential extraneous Zn-binding site (His253, Glu318 and His323) placed near the Zn-coordinating Lssactive site within the catalytic (CAT) domain.

Conclusion: Our present data signify the adverse influence of exogenous Zn ions on Lss-induced staphylolytic activity through the exclusive presence within the CAT domain of an extraneous inhibitory Zn-binding site, without affecting the CWT activity.
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http://dx.doi.org/10.2174/0929866527666200613221359DOI Listing
April 2021

[ANAMMOX Reactor with Two Kinds of Inoculated Sludge: Start-up and Kinetics Characteristics].

Huan Jing Ke Xue 2019 Mar;40(3):1405-1411

School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.

Two different mixed sludges (aerobic nitrifying sludge and ANAMMOX-denitrification sludge:R1, and anaerobic digestion flocculent sludge and ANAMMOX-denitrification sludge:R2), were used as inocula in two UBF reactors to enrich Anammox bacteria. Both kinds of mixed sludge set up the Anammox process successfully. It took 36 days for R1, while R2 required 53 days. Nitrogen removal rates of R1 and R2 were high during the whole operation. During the stable operation stage, the removal rates of NH-N, NO-N, and TN were about 99.92%, 96.64%, and 81.87% for R1; and 97.54%, 94.91%, and 80.98% for R2. Illumina High-throughput Sequencing revealed was in the top six taxa in the two reactors with 3.22% relative abundance in R1 and 2.35% in R2 after the successful start-up. Simulation results indicated that the Modified Stover-Kincannon model and the second-order model were appropriate models. It was deduced that the N-removal potential of R1 was a little greater than that of R2 after comparing the projected maximum substrate removal rate of the two reactors.
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http://dx.doi.org/10.13227/j.hjkx.201806120DOI Listing
March 2019

Prevalence and clinical features of atypical depression among patients with major depressive disorder in China.

J Affect Disord 2019 03 17;246:285-289. Epub 2018 Dec 17.

Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital and Peking University Institute of Mental Health, Beijing 100191, China. Electronic address:

Background: Little is known about the demographic and clinical features of the atypical subtype of major depressive disorder (MDD) patients in China. This study set out to investigate the prevalence of atypical depression in MDD patients in China, and identify its demographic and clinical features.

Methods: The study was conducted in 13 major psychiatric hospitals or in the psychiatric units of general hospitals in China, and recruited a sample of 1172 patients diagnosed with MDD. The patients' demographic and clinical features and prescriptions of psychotropic drugs were collected using a standardized questionnaire designed for the study.

Results: The prevalence of atypical depression was 15.3%. In multiple logistic regression analyses, compared to the non-atypical depression patients, the atypical depression patients were more likely to have depressive episodes with suicide ideation and attempts (OR = 1.49, 95% CI = 1.06, 2.10, P = 0.023), depressive episodes with psychotic features (OR = 2.15, 95% CI = 1.43, 3.22, P < 0.001), seasonal depressive episodes (OR = 1.77, 95% CI = 1.12, 2.78, P = 0.014), an earlier age of onset (OR = 0.98, 95% CI = 0.96, 0.99, P = 0.001), and lifetime depressive episodes (OR = 1.07, 95% CI = 1.01, 1.13, P = 0.020).

Limitations: The assessment of atypical features was not based on a validated rating scale.

Conclusion: Our results indicate that atypical depression is common in Chinese patients with MDD. MDD with atypical features may be more severe and debilitating than patients with non-atypical features.
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http://dx.doi.org/10.1016/j.jad.2018.12.020DOI Listing
March 2019

The emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus with additional 120aa deletion in Nsp2 region in Jiangxi, China.

Transbound Emerg Dis 2018 Dec 19;65(6):1740-1748. Epub 2018 Jul 19.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS), which emerged in China in 2006, was characterized by high fever, high morbidity and high mortality. The causative agent of the disease was a highly pathogenic variant of porcine reproductive and respiratory syndrome virus (also called HP-PRRSV), which has a discontinuous deletion of 1 + 29 amino acids (aa) in the Nsp2 coding region, compared to classical PRRSV. In 2014, fattened pigs on a pig farm in Jiangxi Province suffered from clinical symptoms of high fever, dyspnoea and death. A PRRSV, termed JX2014T2, was isolated from samples of the dead pigs. Genomic analysis of the isolated PRRSV indicated that the genome of the virus was 14,960 bp in length and belonged to the North American genotype. In the Nsp2-coding region, there was a discontinuous deletion of 1 + 29 aa, similar to HP-PRRSV; however, an additional continuous deletion of 120 amino acids between aa 628 and 747 was found. Further analysis of the pathogenicity of PRRSV JX2014T2 was performed in piglets, and the results indicated that all infected piglets suffered from typical clinical symptoms of PRRS, such as high fever, cough, mental depression, anorexia, dyspnoea and palpebral swelling and died within 15 days postinfection (dpi). This demonstrated that the newly isolated PRRSV JX2014T2 strain containing an additional deletion of 120 aa is highly pathogenic to piglets, suggesting that a highly pathogenic variant with new genetic features is circulating in China.
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http://dx.doi.org/10.1111/tbed.12947DOI Listing
December 2018

The emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus with additional 120aa deletion in Nsp2 region in Jiangxi, China.

Transbound Emerg Dis 2018 Dec 19;65(6):1740-1748. Epub 2018 Jul 19.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS), which emerged in China in 2006, was characterized by high fever, high morbidity and high mortality. The causative agent of the disease was a highly pathogenic variant of porcine reproductive and respiratory syndrome virus (also called HP-PRRSV), which has a discontinuous deletion of 1 + 29 amino acids (aa) in the Nsp2 coding region, compared to classical PRRSV. In 2014, fattened pigs on a pig farm in Jiangxi Province suffered from clinical symptoms of high fever, dyspnoea and death. A PRRSV, termed JX2014T2, was isolated from samples of the dead pigs. Genomic analysis of the isolated PRRSV indicated that the genome of the virus was 14,960 bp in length and belonged to the North American genotype. In the Nsp2-coding region, there was a discontinuous deletion of 1 + 29 aa, similar to HP-PRRSV; however, an additional continuous deletion of 120 amino acids between aa 628 and 747 was found. Further analysis of the pathogenicity of PRRSV JX2014T2 was performed in piglets, and the results indicated that all infected piglets suffered from typical clinical symptoms of PRRS, such as high fever, cough, mental depression, anorexia, dyspnoea and palpebral swelling and died within 15 days postinfection (dpi). This demonstrated that the newly isolated PRRSV JX2014T2 strain containing an additional deletion of 120 aa is highly pathogenic to piglets, suggesting that a highly pathogenic variant with new genetic features is circulating in China.
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http://dx.doi.org/10.1111/tbed.12947DOI Listing
December 2018

Hepatitis C virus down-regulates SERPINE1/PAI-1 expression to facilitate its replication.

J Gen Virol 2017 Sep 31;98(9):2274-2286. Epub 2017 Aug 31.

Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan, ROC.

Identification of host factors involved in viral replication is critical for understanding the molecular mechanism of viral replication and pathogenesis. Genes differentially expressed in HuH-7 cells with or without a hepatitis C virus (HCV) sub-genomic replicon were screened by microarray analysis. SERPINE1/PAI-1 was found to be down-regulated after HCV infection in this analysis. Down-regulation of SERPINE1/PAI-1 expression at the transcriptional level was verified by the real-time reverse transcriptase (RT)-PCR assay. Reduced SERPINE1/PAI-1 protein secretion was detected in the supernatant of HCV replicon cells and in sera from HCV-infected patients. SERPINE1 gene expression was down-regulated by HCV NS3/4A and NS5A proteins through the transforming growth factor-β (TGF-β) signalling pathway at the transcriptional level. Down-regulated genes in HCV replicon cells could be the factors supressing HCV replication. Indeed, over-expressed PAI-1 inhibited HCV replication but the mechanism is unknown. It has been demonstrated that HCV induces the expression of TGF-β, and TGF-β enhances HCV replication by a not-yet-defined mechanism. SERPINE1/PAI-1 is also known to be potently induced by TGF-β at the transcriptional level through both Smad-dependent and Smad-independent pathways. The exogenously expressed SERPINE1/PAI-1 suppressed the expression of the endogenous SERPINE1 gene at the transcriptional level through the TGF-β signalling but not the Smad pathway. Thus, SERPINE1/PAI-1 could suppress HCV replication possibly by negatively regulating TGF-β signalling. A model is proposed for the interplay betweenthe TGF-β signalling pathway, HCV and SERPINE1/PAI-1 to keep the homeostasis of the cells.
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http://dx.doi.org/10.1099/jgv.0.000901DOI Listing
September 2017

Duration of untreated bipolar disorder: a multicenter study.

Sci Rep 2017 03 22;7:44811. Epub 2017 Mar 22.

Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China.

Little is known about the demographic and clinical differences between short and long duration of untreated bipolar disorder (DUB) in Chinese patients. This study examined the demographic and clinical features of short (≤2 years) and long DUB (>2 years) in China. A consecutively recruited sample of 555 patients with bipolar disorder (BD) was examined in 7 psychiatric hospitals and general hospital psychiatric units across China. Patients' demographic and clinical characteristics were collected using a standardized protocol and data collection procedure. The mean DUB was 3.2 ± 6.0 years; long DUB accounted for 31.0% of the sample. Multivariate analyses revealed that longer duration of illness, diagnosis of BD type II, and earlier misdiagnosis of BD for major depressive disorder or schizophrenia were independently associated with long DUB. The mean DUB in Chinese BD patients was shorter than the reported figures from Western countries. The long-term impact of DUB on the outcome of BD is warranted.
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http://dx.doi.org/10.1038/srep44811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361090PMC
March 2017

Influenza A virus upregulates PRPF8 gene expression to increase virus production.

Arch Virol 2017 May 21;162(5):1223-1235. Epub 2017 Jan 21.

Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.

A ddRT-PCR analysis was performed to detect cellular genes that are differentially expressed after influenza A virus (H1N1) infection of A549 cells. After ddRT-PCR, eight DNA fragments were identified. PRPF8, one of the cellular genes that were upregulated after virus infection, was further analyzed since it has previously been identified as a cellular factor required for influenza virus replication. The upregulation of PRPF8 gene expression after viral infection was confirmed using real-time RT-PCR for mRNA detection and Western blot analysis for protein detection. Influenza A virus also upregulated the PRPF8 promoter in a reporter assay. In addition to H1N1, influenza A virus H3N2 and influenza B virus could also activate PRPF8 expression. Therefore, upregulation of PRPF8 expression might be important for the replication of different influenza viruses. Indeed, overexpression of PRPF8 gene enhanced virus production, while knockdown of expression of this gene reduced viral production significantly. To determine which viral protein could enhance PRPF8 gene expression, individual viral genes were cloned and expressed. Among the different viral proteins, expression of either the viral NS1 or PB1 gene could upregulate the PRPF8 expression. Our results from this study indicate that influenza A virus upregulates cellular PRPF8 gene expression through viral NS1 and PB1 proteins to increase virus production.
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http://dx.doi.org/10.1007/s00705-016-3210-3DOI Listing
May 2017

Demographic and clinical differences between early- and late-onset bipolar disorders in a multicenter study in China.

Psychiatry Res 2016 Dec 30;246:688-691. Epub 2016 Oct 30.

Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China. Electronic address:

Little is known about the demographic and clinical differences between early-onset (EOB) and late-onset bipolar disorders (LOB) in Chinese patients. This multi-center study examined the demographic and clinical characteristics of EOB (≤21 years) and LOB (>21 years) in China. A consecutively recruited sample of 555 patients with bipolar disorder (BD) from 7 psychiatric hospitals and general hospital psychiatric units across China was examined. Patients' demographic and clinical characteristics were collected using a standardized protocol and data collection procedure. There were 181 (34.8%) patients with EOB and 339 (65.2%) with LOB. Univariate analyses revealed that compared to the LOB group, the EOB group were more likely to be older, unemployed, have a longer illness duration, have BD-I and misdiagnosed as schizophrenia but were less likely to be misdiagnosed as major depressive disorder and receiving antidepressants. Multivariate analyses revealed that unemployment and longer duration of illness were independently associated with EOB. The clinical differences between early-onset and late-onset BD patients in China were largely consistent with those found in Western countries. Early-onset BD appear to be associated with poorer outcomes. Prospective studies examining the long-term outcomes in relation to age-at-onset are needed.
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http://dx.doi.org/10.1016/j.psychres.2016.10.063DOI Listing
December 2016

Prescribing patterns of psychotropic medications and clinical features in patients with major depressive disorder with and without comorbid dysthymia in China.

Asia Pac Psychiatry 2017 Mar 19;9(1). Epub 2016 Oct 19.

Faculty of Health Sciences, University of Macau, Macao SAR, China.

Introduction: Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs.

Methods: Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers.

Results: One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups.

Conclusions: There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.
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http://dx.doi.org/10.1111/appy.12261DOI Listing
March 2017

Risk Factors for Anxiety in Major Depressive Disorder Patients.

Clin Psychopharmacol Neurosci 2015 Dec;13(3):263-8

Peking University Sixth Hospital/Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital).

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD).

Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively.

Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p<0.001), were older (t=-4.69, p<0.001), reported more lifetime depressive episodes (z=-3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ(2)=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ(2)=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression.

Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.
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http://dx.doi.org/10.9758/cpn.2015.13.3.263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662170PMC
December 2015

Hepatitis C virus: Virology, diagnosis and treatment.

World J Hepatol 2015 Jun;7(10):1377-89

Hui-Chun Li, Department of Biochemistry, Tzu Chi University, Hualien 97004, Taiwan.

More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000s, pegylated interferon plus ribavirin became the standard anti-HCV treatment. However, this therapy is not ideal. To 2014, boceprevir, telaprevir, simeprevir, sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral, interferon-free, pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these anti-viral treatments. However, not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus, an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.
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http://dx.doi.org/10.4254/wjh.v7.i10.1377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450201PMC
June 2015

Cleavage of Dicer protein by I7 protease during vaccinia virus infection.

PLoS One 2015 27;10(3):e0120390. Epub 2015 Mar 27.

Department of Laboratory Medicine and Medical Biotechnology, Tzu Chi University, Hualien, Taiwan; Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.

Dicer is the key component in the miRNA pathway. Degradation of Dicer protein is facilitated during vaccinia virus (VV) infection. A C-terminal cleaved product of Dicer protein was detected in the presence of MG132 during VV infection. Thus, it is possible that Dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. There is a potential I7 protease cleavage site in the C-terminus of Dicer protein. Indeed, reduction of Dicer protein was detected when Dicer was co-expressed with I7 protease but not with an I7 protease mutant protein lack of the protease activity. Mutation of the potential I7 cleavage site in the C-terminus of Dicer protein resisted its degradation during VV infection. Furthermore, Dicer protein was reduced dramatically by recombinant VV vI7Li after the induction of I7 protease. If VV could facilitate the degradation of Dicer protein, the process of miRNA should be affected by VV infection. Indeed, accumulation of precursor miR122 was detected after VV infection or I7 protease expression. Reduction of miR122 would result in the suppression of HCV sub-genomic RNA replication, and, in turn, the amount of viral proteins. As expected, significant reduction of HCVNS5A protein was detected after VV infection and I7 protease expression. Therefore, our results suggest that VV could cleave Dicer protein through I7 protease to facilitate Dicer degradation, and in turn, suppress the processing of miRNAs. Effect of Dicer protein on VV replication was also studied. Exogenous expression of Dicer protein suppresses VV replication slightly while knockdown of Dicer protein does not affect VV replication significantly.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120390PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376780PMC
March 2016

Studying coronavirus-host protein interactions.

Methods Mol Biol 2015 ;1282:197-212

Institute of Medical Sciences, Tzu Chi University, Hualien, 97004, Taiwan.

To understand the molecular mechanisms of viral replication and pathogenesis, it is necessary to establish the virus-host protein interaction networks. The yeast two-hybrid system is a powerful proteomic approach to study protein-protein interactions. After the identification of specific cellular factors interacting with the target viral protein using the yeast two-hybrid screening system, co-immunoprecipitation and confocal microscopy analyses are often used to verify the virus-host protein interactions in cells. Identification of the cellular factors required for viral survival or eliminating virus infected cells could help scientists develop more effective antiviral drugs. Here we summarize a standard protocol used in our lab to study the coronavirus-host protein interactions, including yeast two-hybrid screening, co-immunoprecipitation, and immunofluorescence microscopy analyses.
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http://dx.doi.org/10.1007/978-1-4939-2438-7_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121234PMC
November 2015

Demographic and clinical differences between early- and late-onset major depressions in thirteen psychiatric institutions in China.

J Affect Disord 2015 Jan 16;170:266-9. Epub 2014 Sep 16.

Faculty of Health Sciences, University of Macau, Macao SAR, China. Electronic address:

Background: Little is known about the demographic and clinical differences between early- and late-onset depressions (EOD and LOD, respectively) in Chinese patients. This study examined the demographic and clinical profile of EOD (<=25 years) compared to LOD (>25 years) in China.

Methods: A consecutively recruited sample of 1178 patients with MDD was assessed in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs including antidepressants, mood stabilizers, antipsychotics and benzodiazepines were recorded using a standardized protocol and data collection procedure.

Results: Two hundred and seventy five (23.3%) of the 1178 patients fulfilled criteria for EOD. In multiple logistic regression analyses, compared to LOD patients their EOD counterparts were more likely to be unmarried and unemployed, had more atypical and psychotic depressive episodes, had bipolar features, while they had more lifetime depressive episodes.

Conclusions: The demographic and more severe clinical features of EOD in Chinese patients were basically consistent with those found in Western populations. The association between socio-cultural factors and development of EOD warrants further studies.
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http://dx.doi.org/10.1016/j.jad.2014.09.008DOI Listing
January 2015

Compositional and proteomic analyses of genetically modified broccoli (Brassica oleracea var. italica) harboring an agrobacterial gene.

Int J Mol Sci 2014 Aug 28;15(9):15188-209. Epub 2014 Aug 28.

Institute of Plant and Microbial Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan.

Previously, we showed improved shelf life for agrobacterial isopentenyltransferase (ipt) transgenic broccoli (Brassica oleracea var. italica), with yield comparable to commercial varieties, because of the protection mechanism offered by molecular chaperones and stress-related proteins. Here, we used proximate analysis to examine macronutrients, chemical and mineral constituents as well as anti-nutrient and protein changes of ipt-transgenic broccoli and corresponding controls. We also preliminarily assessed safety in mice. Most aspects were comparable between ipt-transgenic broccoli and controls, except for a significant increase in carbohydrate level and a decrease in magnesium content in ipt-transgenic lines 101, 102 and 103, as compared with non-transgenic controls. In addition, the anti-nutrient glucosinolate content was increased and crude fat content decreased in inbred control 104 and transgenic lines as compared with the parental control, "Green King". Gel-based proteomics detected more than 50 protein spots specifically found in ipt-transgenic broccoli at harvest and after cooking; one-third of these proteins showed homology to potential allergens that also play an important role in plant defense against stresses and senescence. Mice fed levels of ipt-transgenic broccoli mimicking the 120 g/day of broccoli eaten by a 60-kg human adult showed normal growth and immune function. In conclusion, the compositional and proteomic changes attributed to the transgenic ipt gene did not affect the growth and immune response of mice under the feeding regimes examined.
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http://dx.doi.org/10.3390/ijms150915188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200750PMC
August 2014

Production and pathogenicity of hepatitis C virus core gene products.

World J Gastroenterol 2014 Jun;20(23):7104-22

Hui-Chun Li, Department of Biochemistry, Tzu Chi University, Hualien 97004, Taiwan.

Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including steatosis, cirrhosis and hepatocellular carcinoma, and its infection is also associated with insulin resistance and type 2 diabetes mellitus. HCV, belonging to the Flaviviridae family, is a small enveloped virus whose positive-stranded RNA genome encoding a polyprotein. The HCV core protein is cleaved first at residue 191 by the host signal peptidase and further cleaved by the host signal peptide peptidase at about residue 177 to generate the mature core protein (a.a. 1-177) and the cleaved peptide (a.a. 178-191). Core protein could induce insulin resistance, steatosis and even hepatocellular carcinoma through various mechanisms. The peptide (a.a. 178-191) may play a role in the immune response. The polymorphism of this peptide is associated with the cellular lipid drop accumulation, contributing to steatosis development. In addition to the conventional open reading frame (ORF), in the +1 frame, an ORF overlaps with the core protein-coding sequence and encodes the alternative reading frame proteins (ARFP or core+1). ARFP/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism. In this review, we briefly summarized the current knowledge regarding the production of different core gene products and their roles in viral pathogenesis.
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http://dx.doi.org/10.3748/wjg.v20.i23.7104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064058PMC
June 2014

Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.

BMC Psychiatry 2014 Apr 27;14:123. Epub 2014 Apr 27.

Department of Neurobiology; Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang, P, R, China.

Background: Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder.

Methods: Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects.

Results: The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds.

Conclusion: These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.
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http://dx.doi.org/10.1186/1471-244X-14-123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036745PMC
April 2014

Evaluation of Mood Disorder Questionnaire (MDQ) in patients with mood disorders: a multicenter trial across China.

PLoS One 2014 4;9(4):e91895. Epub 2014 Apr 4.

Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.

Background: The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting.

Methods: 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II.

Results: Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24).

Conclusion: The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976254PMC
June 2015

Evaluation of Mood Disorder Questionnaire (MDQ) in patients with mood disorders: a multicenter trial across China.

PLoS One 2014 4;9(4):e91895. Epub 2014 Apr 4.

Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.

Background: The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting.

Methods: 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II.

Results: Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24).

Conclusion: The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976254PMC
June 2015

Hepatitis C virus non-structural protein 3 interacts with cytosolic 5'(3')-deoxyribonucleotidase and partially inhibits its activity.

PLoS One 2013 9;8(7):e68736. Epub 2013 Jul 9.

Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.

Infection with hepatitis C virus (HCV) is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been demonstrated previously that HCV non-structural protein 3 (NS3) is involved in cell transformation. In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein. Cytosolic 5'(3')-deoxyribonucleotidase (cdN, dNT-1) was found to interact with HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system. Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells. The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems. Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions. Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles. Control of DNA precursor concentration is essential for the maintenance of genetic stability. Reduction of cdN activity would result in the imbalance of DNA precursor concentrations. Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0068736PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706368PMC
February 2014

Gender differences in demographic and clinical features and prescribing patterns of psychotropic medications in patients with major depressive disorder in China.

Compr Psychiatry 2013 Nov 12;54(8):1198-202. Epub 2013 Jul 12.

Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China; Mood Disorders Center, Beijing Anding Hospital, Capital Medical University, Beijing, China. Electronic address:

Purpose: Little is known about gender differences associated with major depressive disorder (MDD) in China. This study examined gender differences associated with other demographic and clinical characteristics and psychotropic drug treatment in Chinese patients with MDD.

Methods: A total of 1178 patients with MDD from 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide were enrolled. Cross-sectional data including patients' demographic and clinical characteristics and prescriptions of psychotropic medications were recorded using a standardized protocol and data collection procedure.

Results: The sample consisted of 793 female and 385 male patients. Univariate analyses revealed that male patients were younger than female patients, had a younger age of onset of depression, had less lifetime depressive episodes and had more bipolar features (i.e. patients who screened positive for hypomanic symptoms on the 32-item Hypomania Checklist, but did not meet the diagnostic criteria for DSM-IV bipolar disorders as measured by the Mini International Neuropsychiatric Interview). Also, men were more likely to be employed than women and less likely to have depressive episodes following stressful life events. In multivariate analyses, being employed, having bipolar features and not having depressive episodes following stressful life events were independently associated with being a male patient with major depressive disorder. There was no difference in use of psychotropic medications by gender.

Conclusions: Most gender differences in MDD patients in this study are not consistent with findings of Western studies suggesting that gender differences in MDD may be determined by both biological and sociocultural differences among ethnically different patient populations.
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http://dx.doi.org/10.1016/j.comppsych.2013.04.018DOI Listing
November 2013