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The hepatitis C virus (HCV), an obligatory intracellular pathogen, highly depends on its host cells to propagate successfully. The HCV life cycle can be simply divided into several stages including viral entry, protein translation, RNA replication, viral assembly and release. Hundreds of cellular factors involved in the HCV life cycle have been identified over more than thirty years of research. Characterization of these cellular factors has provided extensive insight into HCV replication strategies. Some of these cellular factors are targets for anti-HCV therapies. In this review, we summarize the well-characterized and recently identified cellular factors functioning at each stage of the HCV life cycle.

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.

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-types) 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 (pH7.4) 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 Cterminal 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 provide 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.

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 Zn2+-dependent endopeptidase, but its bacteriolytic activity could be affected by exogenously added Zn2+. Objective: To gain greater insights into structural and functional impacts of Zn2+and Ni2+on 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 Zn2+-treated Lss and S. aureus peptidoglycans. Metal ionbinding prediction and intermolecular docking were used to locate an extraneous Zn2+-binding site. Results: A drastic decrease in Lss bioactivity against S. aureus and MRSA was revealed only when treated with Zn2+, but not Ni2+, albeit no negative effect of diethyldithiocarbamate—Zn2+-chelator on Lss-induced bioactivity. No severe conformational change was observed for Lss incubated with exogenous Zn2+ or Ni2+. Lss pre-treated with Zn2+ 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 Zn2+, but not Ni2+, preferably interacted with a potential extraneous Zn2+-binding site (His253, Glu318 and His323) placed near the Zn2+-coordinating Lssactive site within the catalytic (CAT) domain. Conclusion: Our present data signify the adverse influence of exogenous Zn2+ ions on Lss-induced staphylolytic activity through the exclusive presence within the CAT domain of an extraneous inhibitory Zn2+-binding site, without affecting the CWT activity.

In addition to the receptor-binding domain (DII), the C-terminal domain (DIII) of three-domain Cry insecticidal δ-endotoxins from Bacillus thuringiensis has been implicated in target insect specificity, yet its precise mechanistic role remains unclear. Here, the 21 kDa high-purity isolated DIII fragment derived from the Cry4Ba mosquito-specific toxin was achieved via optimized preparative FPLC, allowing direct rendering analyses for binding characteristics toward its target receptor—Aedes aegypti membrane-bound alkaline phosphatase (Aa-mALP). Binding analysis via dotblotting revealed that the Cry4Ba-DIII truncate was capable of specific binding to nitrocellulose-bound Aa-mALP, with a binding signal comparable to its 65 kDa Cry4Ba-R203Q full-length toxin. Further determination of binding affinity via sandwich ELISA revealed that Cry4Ba-DIII exhibited a rather weak binding to Aa-mALP with a dissociation constant (Kd) of ≈1.1 × 10−7 M as compared with the full-length toxin. Intermolecular docking between the Cry4Ba-R203Q active toxin and Aa-mALP suggested that four Cry4Ba-DIII residues, i.e., Glu522, Asn552, Asn576, and Leu615, are potentially involved in such toxin–receptor interactions. Ala substitutions of each residue (E522A, N552A, N576A and L615A) revealed that only the L615A mutant displayed a drastic decrease in biotoxicity against A. aegypti larvae. Additional binding analysis revealed that the L615A-impaired toxin also exhibited a reduction in binding capability to the surface-immobilized Aa-mALP receptor, while two bio-inactive DII-mutant toxins, Y332A and F364A, which almost entirely lost their biotoxicity, apparently retained a higher degree of binding activity. Altogether, our data disclose a functional importance of the C-terminal domain of Cry4Ba for serving as a potential receptor-binding moiety in which DIII-Leu615 could conceivably be exploited for the binding to Aa-mALP, highlighting its contribution to toxin interactions with such a target receptor in mediating larval toxicity.

Family physicians play an essential role as gatekeepers in primary health care. However, most studies in the past focused on the geographic maldistribution of family physicians, and few studies focused on the distribution of family physicians between private practices and hospitals. This study aims to analyze the trends in practice locations of family physicians in Taiwan between 1999 and 2018, using the databases of the Taiwan Association of Family Medicine and Taiwan Medical Association. Although the annual number of physicians registered as family physicians had steadily increased from 1876 in 1999 to 3655 in 2018, the ratio of family physicians practicing in hospitals to total family physicians remained stable around 40% in the study period. Even after eliminating the trainees who were entirely registered at hospitals, the proportion of hospital-based family physicians still accounted for about one-third of the total in each year. In conclusion, family physicians had been continuously demanded by hospitals in Taiwan. If the supply of primary care-oriented family physicians is insufficient outside hospitals, health manpower planning would require urgent adjustments.

The COVID-19 pandemic was caused by SARS-CoV-2 infection. To prevent the spread of SARS-CoV-2, an effective vaccine is required. Two linear peptides from potential B-cell epitopes in the spike protein of SARS-CoV-2 (a.a. 440–460; a.a. 494–506) were synthesized and used to immunize rabbits. High-titer antibodies of IgG were produced, purified, and verified by Western blot analysis. Antibodies against these two epitopes could effectively neutralize SARS-CoV-2 pseudoviral particles with the spike proteins from not only the original strain (basal; wild-type), but also a strain with a single point mutation (D614G), and two other emerging variants (the Alpha and Beta variants) prevalent around the world, but not from SARS-CoV. In conclusion, antibodies against these two epitopes are protective. This information is important for the development of vaccines against SARS-CoV-2.

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. Materials and Methods: Diffusion magnetic resonance imaging (MRI) scans were performed on 1127 healthy participants (age range: 21-89) at a single site. The age trajectories of the WM tract 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 functions (VS) and executive functions (E). 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 VS and E. Impact statement By recruiting a healthy population for diffusion magnetic resonance imaging (MRI) scan, we demonstrated that the age-related changes of white matter (WM) integrity were manipulated by sex. Sex-linked tracts in females reached the turning age 5 years later, but change faster than those in males after the turning age. The most significant sex effect was found in projection and association tracts. Our results indicated that sex affected both WM microstructure and cognitive functions and was further involved in the mediation of the age-WM-cognition relationship. The vulnerability of projection and association tracts in females may induce negative impacts on visuospatial and executive functions.

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.

Background: Bipolar disorder (BD) is a kind of mental disorder with the greatest risk of suicide, but it is often misdiagnosed as major depressive disorder (MDD) clinically. This study aimed to analyze the sociodemographic factors and clinical characteristics associated with suicide attempts (SA) in patients with BD misdiagnosed with MDD in China. Methods: A total of 1487 MDD patients were consecutively enrolled in 13 mental health centers in China. Data on patients’ sociodemographic and clinical characteristics were collected using a standardized protocol. Of these, 306 BD patients were misdiagnosed with MDD according to the Mini International Neuropsychiatric Interview (MINI). Suicide attempters and non-attempters were classified by the suicidality module of the MINI. Multiple logistic regression analyses were performed to assess the association between the independent variables of interest and SA in BD patients misdiagnosed with MDD. Results: Of the 306 BD patients misdiagnosed with MDD, 225 (73.5%) were non-attempters and 81 (26.5%) were attempters. Compared to non-attempters, attempters were older (Z =2.2, p = 0.03) and had more admissions(χ2 =6.1, p = 0.013), more frequent depressive episodes, more atypical characteristics (e.g. increased appetite, weight gain, and more sleep time)(χ2 = 5.8, p = 0.016), more suicidal ideation (χ2 = 27.3, p < 0.001), more psychotic symptoms (χ2 = 7.4, p = 0.006) and more seasonal depressive episodes (χ2 = 5.6, p = 0.018). Multiple logistic regression analyses revealed that attempters were characterized by more suicidal ideation (OR = 5.7, 95% CI: 2.6–12.5) and frequent depressive episodes (OR = 2.4, 95% CI: 1.3–4.6). The limitations of this study include its cross-sectional design and data collection by suicide attempters’ retrospective recall. Conclusions: The findings of this study suggest that BD patients misdiagnosed with MDD are at a higher risk of suicide, and more frequent depressive episodes and suicidal ideation are risk factors for attempted suicide. Early identification of and interventions for these risk factors might reduce the risk of suicide in BD patients misdiagnosed with MDD.

Introduction A family history of psychiatric disorders is one of the strongest risk factors for schizophrenia. The characteristics of patients with a family history of psychiatric disorders have not been systematically evaluated. Methods This multicenter study (26 centers, 2425 cases) was performed in a Chinese population to examine the sociodemographic and clinical characteristics of schizophrenia patients with a family history of psychotic disorders in comparison with those of patients with sporadic schizophrenia. Results Nineteen percent of patients had a family history of mental disease. Multiple logistic regression analysis revealed that ≥4 hospitalizations (OR = 1.78, P = .004), tobacco dependence (OR = 1.48, P = .006), alcohol dependence (OR = 1.74, P = .013), and physical illness (OR = 1.89, P = .001) were independently and significantly associated with a family history of mental disease. Conclusion Patients with a family history of mental disorders present different demographics and clinical features than patients without a family history of psychiatric disorders.

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 His180 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 His180 side-chain. Analysis of simulated structures revealed that His180-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 His180 exclusively present in the lumen-facing α4 for providing proper environment for the α4-α5 hairpin prior to membrane-inserted pore formation.

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(6) 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-Ni2+ 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.

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

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

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China.Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis.Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12–38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09–9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients.Limitations: Cross-sectional design, retrospective recall of suicide attempt data.Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.

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.

Background This study investigated suicide risk and its correlates among major affective disorder patients in China and examined possible risk factors for future suicide among individuals with major affective disorder to inform appropriate interventions and management approaches to minimize and prevent suicide. Methods A total of 1478 major affective disorder patients were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI), and suicide risk was assessed by the suicide risk module of the MINI. Results Of the patients, 963 (65.2%) were in the nonsuicidal risk group and 515 (34.8%) were in the suicidal risk group. Compared to major depressive disorder patients, bipolar disorder patients had higher suicide risk levels ( χ 2=10.0, df=1, P =0.002); however, there were no statistically significant differences ( χ 2=2.6, df=1, P =0.1) between bipolar disorder-I and bipolar disorder-II patients. Suicide risk factors were associated with 6 variables in major affective disorder patients, as follows: male gender, unemployed, more frequent depressive episodes (>4 in the past year), depressive episodes with suicidal ideation and attempts, depressive episodes with psychotic symptoms, and no current antidepressant use. Limitations Most of the data were retrospectively collected and, therefore, subject to recall bias. Conclusions This study suggested that bipolar disorder patients have a higher suicide risk than major depressive disorder patients. The factors that were significantly associated with suicide risk may aid in identifying major affective disorder patients who are at risk for future suicidal behavior.

Objectives Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to compare demographic and clinical features between patients with MDD and those with BD, but being misdiagnosed as MDD, in China. Methods A total of 1487 patients diagnosed with MDD were consecutively evaluated in 13 psychiatric hospitals or psychiatric units of general hospitals nationwide in China. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini-International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses, and identify patients with MDD and those with BD, but being misdiagnosed with MDD. Results The proportions of BD (all types), bipolar I disorder (BD-I), and bipolar II disorder (BD-II) misdiagnosed as MDD in clinical practice were 20.8%, 7.9%, and 12.8%, respectively. Multiple logistic regression analyses revealed that compared to MDD patients, BD-I was characterized by more atypical depressive features (increased appetite, increased sleep, and weight gain) [odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.2–3.2], more psychotic symptoms (OR = 2.1, 95% CI: 1.3–3.5), more lifetime depressive episodes (OR = 1.1, 95% CI: 1.1–1.2), and earlier age of onset (OR = 0.97, 95% CI: 0.9–0.99); BD-II was characterized by more psychotic symptoms (OR = 2.1, 95% CI: 1.4–3.1) and earlier age of onset (OR = 0.96, 95% CI: 0.9–0.97). In addition, compared to BD-II patients, BD-I patients were characterized by more frequent depressive episodes per year (OR = 3.1, 95% CI: 1.5–6.6). Conclusions Depressive episodes in the context of BD-I and BD-II, among those who were misclassified as MDD, present some different clinical features compared to MDD. This finding should be taken into account in guiding diagnostic practices in China.

Background Bipolar disorder (BD) is often misdiagnosed as a major depressive disorder (MDD). This study aimed to test the usefulness of the screening tool, the Mood Disorders Questionnaire (MDQ), to identify BD patients misdiagnosed as MDD in Chinese clinical settings. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients’ socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The MDQ was completed by patients to identify symptoms characteristic of BD. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI). Results Three hundred-nine of the 1487 patients (20.8%) satisfied DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. The optimal cut-off point on the MDQ to differentiate BD from MDD was 3, while cut-off points of 5 and 3 differentiated BD-I and BD-II from MDD, respectively. The maximum sensitivity was 0.31, 0.45 and 0.22 for differentiating BD, BD-I and BD-II from MDD, respectively. Conclusions The optimal cutoff points of the MDQ for screening BD in Chinese patients originally diagnosed as MDD were considerably lower than those in earlier studies. The routine clinical use of the MDQ as a screening scale for BD in Chinese patients treated for MDD does not seem to be justified.

Aim To investigate the results of the Hypomania Checklist-32 (HCL-32) administered as a screening instrument in clinical settings to mood disorders patients in the depressive phase. Methods A total of 1487 patients diagnosed and being treated for major depressive disorder (MDD) in 13 mental health centers across China were self-rated by the HCL-32 and independently examined by the Mini International Neuropsychiatric Interview (MINI). Results After examination by the MINI, 309 (20.8%) of the 1487 patients clinically diagnosed as having MDD satisfied DSM-IV criteria for bipolar disorder (BD): 118 (7.9%) for bipolar I disorder (BD-I) and 191 (12.8%) for bipolar II disorder (BD-II). The mean HCL-32 score of the BD patients was statistically higher than that of patients with unipolar depression (UD, major depressive disorder), BD-II higher than UD, while no significant difference between BD-I and BD-II. The HCL-32 distinguished between BD and UD (best cutoff score 14), between BD-II and UD (best cutoff 12). At the optimum cutoff of 12 between BD and UD, the sensitivity was 0.86, specificity 0.69. Limitations No standardized instruments were used to measure the severity of depressive symptoms. Depressed patients with a previous history of BD were excluded from this study. Conclusions The HCL-32 results in this multicenter study of patients in the depressive phase were similar to those of earlier, generally smaller-scale studies which subjects could be in any mood phases. A score of 12 could be used as the optimum cutoff between BD and UD to improve screening for BD-II if the HCL-32 was applied in clinical settings in China.

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.

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.

Objective Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. Methods A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. Results Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1–2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04–2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1–7.2, p

Background Bipolar disorder (BD) is a recurrent, complex illness and often misdiagnosed and treated as a major depressive disorder (MDD). This study set out (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV diagnostic criteria; (2) to test the usefulness of the screening tool — the 32-item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether MDD patients with subthreshold manic features (patients who screened positive for BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as measured by Mini International Neuropsychiatric Interview (MINI)) differ from those with BD, and from those suffering from MDD without manic features in terms of basic demographic and clinical variables. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The HCL-32 was self-completed by patients to identify hypomanic symptoms, and the MINI was used by clinicians to establish DSM-IV diagnoses. Results The proportions of undiagnosed BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL-32 had low positive predictive value (0.43). Compared to MDD patients without subthreshold manic features, MDD patients with subthreshold manic features were younger at onset, less likely to be married and had more depressive episodes on a seasonal basis, and more frequent depressive episodes overall. Compared to BD patients, MDD patients with subthreshold manic features had an older age at onset and less frequent depressive episodes and less family history of psychiatric disorders, appetite, weight gain and time spent sleeping, suicide ideation and attempts and psychotic symptoms. Conclusions At least one fifth of Chinese patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to identify broader subthreshold bipolar features. The findings need to be confirmed by longitudinal studies using more comprehensive, standardized instruments.

Summary Background: This study was designed to assess clinical and functional outcomes associated with switching to duloxetine treatment in patients with major depressive disorder (MDD) experiencing emotional and painful physical symptoms in their current episode. Methods: In this 8-week, multinational, multicentre, single-arm, open-label clinical trial, 242 MDD patients were switched to duloxetine 60 mg/day after selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) treatment. The primary analysis compared mean change from baseline in Brief Pain Inventory – Modified Short Form (BPI-SF) interference score between initial responders [≥ 50% reduction from baseline on the 17-item Hamilton Depression Rating Scale (HAMD17) Maier subscale] and initial non-responders after 4 weeks. Initial responders continued with duloxetine 60 mg/day. Initial non-responders received duloxetine 120 mg/day for the remaining 4 weeks. Depression, pain, anxiety and functional outcomes were also compared after 8 weeks. Results: BPI-SF interference decreased from baseline in initial responders (n = 108) and initial non-responders (n = 85) after 4 weeks of duloxetine treatment, with greater reductions in initial responders [BPI-SF mean difference in reduction: 1.01 (95% CI 0.42–1.61); p

Objective To explore the association of brain-derived neurotrophic-factor (BDNF) Val66Met polymorphism with both baseline health related quality of life (HRQOL) scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine. Methods Patientswithmajordepressivedisorder(MDD)tookfluoxetine(20mg/day)for6 weeks.TheHRQOL was measuredwith theMedical Outcomes Study Short Form-36 (SF-36) at baseline and at 6th week. Patients were genotyped for Val66Met polymorphism of BDNF gene. Results There was a significant association between social function (SF) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had better SF (compared with Val/Val P ¼0.004; compared with Val/Met P ¼0.005). A significant association was found between improvement in SF and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in SF (compared with Val/Val P ¼0.010; compared with Val/Met P ¼0.001). Similar association was found between improvement in mental component summary (MCS) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in MCS (compared with Val/ Val P ¼0.066; compared with Val/Met P ¼0.006). Conclusions These results indicate that there may be association between BDNF Val66Met polymorphism and both baseline HRQOL (SF) scores and improvement in HRQOL (SF, MCS) scores in Chinese major depressive patients treated with fluoxetine. Copyright # 2010 John Wiley & Sons, Ltd. key words—health related quality of life; major depressive disorder; brain-derived neurotrophic factor; polymorphism; SSRIs

Background: Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in antidepressant action, and the BDNF gene has been suggested to be involved in the pharmacological treatment of major depressive disorder (MDD). In this study, the relationship between BDNF Val66Met polymorphism (Single Nucleotide Polymorphism Database ID: rs6265) and severity of depression, efficacy of fluoxetine and its side effects was tested in Chinese patients with MDD. Methods: Patients with MDD took the oral selective serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg/day) for 6 weeks. Its clinical efficacy and side effects were measured by the 17-item Hamilton Rating Scale for Depression and the Treatment-Emergent Symptoms Scale (TESS), respectively. The patients were genotyped for Val66Met polymorphism of the BDNF gene. Results: In the multivariate regression analysis, there was no significant association between severity of depression and BDNF Val66Met polymorphism. There was no association between efficacy of fluoxetine and BDNF Val66Met polymorphism, but there was a marginal positive suggestion that heterozygous patients tended to have a better remission with fluoxetine in comparison with homozygous analogs. Insomnia and decreased sexual desire, side effects of fluoxetine, may have an association with the BDNF Val66Met polymorphism, and Met allele carriers showed a lower incidence of these side effects. Conclusions: These results indicate that there was a lack of association between severity of depression and BDNF Val66Met polymorphism in Chinese patients with MDD. The BDNF Val66Met polymorphism may play a major role in the efficacy and side effects of SSRI (fluoxetine) in Chinese patients with MDD.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) structural proteins (S, E, M, and NC) localize in different subcellular positions when expressed individually. However, SARS-CoV M protein is co-localized almost entirely with S, E, or NC protein when co-expressed in the cells. On the other hand, only partial co-localization was observed when S and E, S and NC, or E and NC were co-expressed in the cells. Interactions between SARS-CoV M and other structural proteins but not interactions between S and E, S and NC, or E and NC were further demonstrated by co-immunoprecipitation assay. These results indicate that SARS-CoV M protein, similar to the M proteins of other coronaviruses, plays a pivotal role in virus assembly. The cytoplasmic C-terminus domain of SARS-CoV M protein was responsible for binding to NC protein. Multiple regions of M protein interacted with E and S proteins. A model for the interactions between SARS-CoV M protein and other structural proteins is proposed. This study helps us better understand protein-protein interactions during viral assembly of SARS-CoV. Electronic supplementary material The online version of this article (doi:10.1007/s11373-008-9278-3) contains supplementary material, which is available to authorized users.

The ARFP/F protein is synthesized from the +1 reading frame of the hepatitis C virus (HCV) core protein gene. The function of this protein remains unknown. To study the function of the HCV ARFP/F protein, we have conducted the yeast two-hybrid screening experiment to identify cellular proteins that may interact with the ARFP/F protein. MM-1, a c-Myc interacting protein, was found to interact with HCV ARFP/F protein in this experiment. The physical interaction between ARFP/F and MM-1 proteins was further confirmed by the GST pull-down assay, the co-immunoprecipitation assay and confocal microscopy. As MM-1 can inhibit the gene transactivation activity of c-Myc, we have conducted further analysis to examine the possible effect of the ARFP/F protein on c-Myc. Our results indicate that the HCV ARFP/F protein can enhance the gene trans-activation activity of c-Myc, apparently by antagonizing the inhibitory effect of MM-1. The ability of the ARFP/F protein to enhance the activity of c-Myc raises the possibility that ARFP/F protein might play a role in hepatocellular transformation in HCV patients.

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.

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.

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.

Objective: To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms. Methods: Forty-six Chinese patients met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously. Results: Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation. Conclusion: This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.

Objective: This study is aimed at exploring the relationship between hemodynamic changes and depressive and anxious symptom in depression patients. Methods: The cardiac function indices including the left stroke index (LSI), ejection fraction (EF), heart rate (HR), diastolic pressure mean (DPM), systolic pressure mean (SPM), left ventricle end-diastolic volume (LVDV), effective circulating volume (ECV), resistance total mean (RTM) and blood flow smooth degree (BFSD) were determined in 65 patients with major depressive disorders and 31 healthy normal controls. The clinical symptoms were assessed with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA). Results: In patients with depression without anxiety, LSI, EF, LVDV, DPM, SPM, ECV, BFSD were significantly lower than those in controls, while RTM was higher than that in controls. Patients with comorbidity of depression and anxiety showed decreased LVDV, ECV, BFSD, and increased HR in comparison with the controls. The anxiety/somatization factor score positively correlated with LSI, EF, LVDV, but negatively correlated with RTM. There was negative correlation between retardation factor score and DPM, SPM, LVDV. Conclusion: The study indicated that there are noticeable changes in left ventricle preload and afterload, blood pressure, peripheral resistance, and microcirculation in depressive patients, and that the accompanying anxiety makes the changes more complicated.

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.

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.

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.

EPR of spin labeled TnC at Cys98 was used to explore the possible structural coupling between TnC in the thin filament and myosin trapped in the intermediate states of ATPase cycle. Weakly attached myosin heads (trapped by low ionic strength, low temperature and ATP) did not induce structural changes in TnC as compared to relaxed muscle, as spin labeled TnC displayed the same narrow orientational distribution (Li, H.-C., and Fajer, P. G. (1994) Biochemistry 33, 14324). Ca 2+ -binding alone resulted in disordering of the labeled domain of TnC. Additional conformational changes of TnC occurred upon the attachment of strongly bound, prepower stroke myosin heads (trapped by AlF4 - ). These changes were not present in ghost fibers which myosin had been removed, excluding direct effects of AlF4 - on the orientation of TnC in muscle fibers. The postpower stroke heads (rigor‚ADP/Ca 2+ and rigor/Ca 2+ ) induced further changes in the orientational distribution of labeled domain of TnC irrespective of the degree of cooperativity in thin filaments. We thus conclude that troponin C in thin filaments detects structural changes in myosin during force generation, implying that there is a structural coupling between actomyosin and TnC. Muscle contracts when the thick and thin filaments slide past each other to relieve the strain generated by the interaction of the globular head of myosin with actin. In vertebrate skeletal muscle, the thin filament proteins sactin, tropomyosin (Tm), 1 and troponin (Tn)sregulate contraction.

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.