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PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 56 more.
Type: | Journal: Journal of affective disorders | Year: 2014

The relationship between age at onset (AAO) and major depression (MD) has been studied in US, European and Chinese populations. However, larger sample studies are needed to replicate and extend earlier findings.We re-examined the relationship between AAO and the clinical features of recurrent MD in Han Chinese women by analyzing the phase I (N=1848), phase II (N=4169) and total combined data (N=6017) from the CONVERGE project. Linear, logistic, multiple linear and multinomial logistic regression models were used to determine the association of AAO with continuous, binary and categorical variables.The effect size of the association between AAO and clinical features of MD was quite similar in the phase I and phase II samples. These results confirmed that MD patients with earlier AAO tended to suffer more severe, recurrent and chronic illness and cases of MD with earlier AAO showed increased neuroticism, greater family history and psychiatric comorbidity. In addition, we showed that earlier AAO of MD in Han Chinese women was associated with premenstrual symptoms, postnatal depression, a highly authoritarian or cold childhood parental rearing style and a reduced probability for having melancholia.Data were collected retrospectively through interview and recall bias may have affected the results.MD with earlier AAO in Han Chinese women shows a distinct set of clinical features which are similar to those reported in Western populations.

PubMed | Guangzhou Brain Hospital Guangzhou Psychiatric Hospital, Ningbo Kang Ning Hospital, Oxford Genetics, Shantou University and 56 more.
Type: | Journal: Journal of affective disorders | Year: 2014

Phobic fears are common in the general population and among individuals with major depression (MD). We know little about the prevalence, clinical correlates, and structure of phobic fears in Chinese women with MD.We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used exploratory factor analysis to examine the structure of these phobic fears. We examined the relationship between individual phobic fears and the severity of MD, neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia using logistic regression models.The frequency of phobic fears ranged from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly associated with more severe MD, high neuroticism, and co-morbid panic disorder, generalized anxiety disorder and dysthymia. Our factor analysis suggested four underlying subgroups of phobic fears which differed in their clinical correlates, severity and patterns of comorbidity.Data were collected retrospectively through interview and recall bias may have affected the results.Phobic fears are correlated with comorbid MD and more severe MD. These phobic fears clearly subdivide into four subgroups that differ meaningfully from each other.

PubMed | Ningbo Kang Ning Hospital, King Abdulaziz University, Hebei Medical University, Kangning Hospital and 36 more.
Type: Journal Article | Journal: Current biology : CB | Year: 2015

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individuals somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

Chen X.,Shanghai JiaoTong University | Ye G.,First Peoples Hospital of Foshan | Zhang C.,Guangzhou General Hospital of Guangzhou Military Area | Li X.,Shanxi Provincial Cancer Hospital | And 9 more authors.
Breast Cancer Research and Treatment | Year: 2013

The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide (TC) compared with docetaxel, anthracycline, and cyclophosphamide (TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3-36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event-free survival (adjusted hazard ratio [HR] 2.42; 95 % CI 1.11-5.30) and disease-free survival (HR 2.85; 95 % CI 1.21-6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation. © 2013 Springer Science+Business Media New York.

Kassegne K.,Zhejiang University | Hu W.,Zhejiang University | Ojcius D.M.,University of California at Merced | Sun D.,Cornell University | And 5 more authors.
Journal of Infectious Diseases | Year: 2014

Background. Leptospirosis is a global zoonotic disease. Transmission of Leptospira from animals to humans occurs through contact with water contaminated with leptospire-containing urine of infected animals. However, the molecular basis for the invasiveness of Leptospira and transmission of leptospirosis remains unknown.Methods. Activity of Leptospira interrogans strain Lai colA gene product (ColA) to hydrolyze different collagenic substrates was determined by spectrophotometry. Expression and secretion of ColA during infection were detected by reverse-transcription quantitative polymerase chain reaction and Western blot assay. The colA gene-deleted (ΔcolA) and colA gene-complemented (CΔcolA) mutants were generated to determine the roles of ColA in transcytosis in vitro and virulence in hamsters.Results. Recombinant or native ColA hydrolyzed all the tested substrates in which type III collagen was the favorite substrate with 2.16 mg/mL Km and 35.6 h -1 Kcat values. Coincubation of the spirochete with HUVEC or HEK293 cells directly caused the significant elevation of ColA expression and secretion. Compared with wild-type strain, ΔcolA mutant displayed much-attenuated transcytosis through HEK293 and HUVEC monolayers, and less leptospires in blood, lung, liver, kidney and urine and 25-fold-decreased 50% lethal dose and milder histopathological injury in hamsters.Conclusions. The product of colA gene is a collagenase as a crucial virulence factor in the invasiveness and transmission of L. interrogans. © The Author 2013.

PubMed | Zhejiang Traditional Chinese Medical Hospital, ShanXi Cardiovascular Hospital and Zhejiang Chinese Medical University
Type: | Journal: Microvascular research | Year: 2017

Anti-angiogenesis has been proposed as an important strategy for angiogenesis-related diseases. Cryptotanshinone (CPT), an active component of Salvia miltiorrhiza, may be a potential inhibitor of angiogenesis. However, the molecular mechanisms underlying its anti-angiogenic activities remain poorly understood. This study is to investigate the effects of CPT on VEGF-induced angiogenesis and VEGFR2 signaling pathway in human umbilical vein endothelial cells (HUVECs).HUVECs were treated with different concentration of CPT (5-20mol/L) and the viability, endothelial cell migration, invasion, and tubular-like structure formation of HUVECs were detected by MTT, wound-healing migration, Transwell invasion and Matrigel tube formation assays, respectively. To assess the effect of CPT on VEGFR2 signaling pathway, VEGF-induced phosphorylation of VEGFR2 and its downstream molecules, including ERK1/2, p90RSK, Src and FAK were analyzed by Western blot.CPT significantly suppressed VEGF-induced cells proliferation, migration, invasion, and tubular-like structure formation in HUVECs in a dose- and time-dependent manner. Western blot results revealed that CPT significantly suppressed VEGF-induced phosphorylation of VEGFR2 and its key downstream protein kinases, including p-ERK1/2, p-p90RSK, pYOur study suggested that CPT potently inhibits VEGF-induced angiogenesis by suppressing VEGFR2 activation and its downstream Src/FAK and ERK1/2 signaling pathways in HUVECs, highlighting the therapeutic potential for the treatment of angiogenesis-related diseases.

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