Objective: To standardize the reporting system on hepatitis B in order to improve the quality of monitoring program in Henan province. Methods: A total of 6 sites of Hepatitis B pilot surveillance were selected in Xinzheng of Zhengzhou city, Linzhou of Anyang city, Shanyang district of Jiaozuo city, Shaoling district of Luohe city, Yongcheng of Shangqiu city, Pingqiao district of Xinyang city in Henan province. Subjects under study were those reported hepatitis B cases, from 2012 to 2016. Cases diagnosed in 2011 were chosen as controls. Data on classification of hepatitis B, time that HBsAg became positive and ALT value of the cases were analyzed annually. 5 ml venous blood was collected and anti-HBc IgM confirmed test was made for those suspected acute cases on hepatitis B. Based on the 2016 data from the monitoring system, the incidence of acute hepatitis B in Henan province was estimated. Results: The number of reported hepatitis B cases had declined in 6 sites of Hepatitis B pilot surveillance substantially. A total of 17 436 hepatitis B reported in 2011 but only 2 632 cases were reported in 2016, with a reduction of 84.90%(14 804/17 436) in these six monitoring sites. The number of unclassified hepatitis B cases also dropped sharply. In 2011, 36.87% of the cases were unclassified, but the figure reduced to 0.08% in 2016, from the six sites. The rate on ALT detection also gradually improved. The rate of misdiagnosis on HBV carrier from hepatitis B almost disappeared. From 2013 to 2016, 777 blood samples were collected from six pilot sites. 29.34% (228/777) of the blood samples were tested positive for anti-HBc IgM after confirmed by the hepatitis laboratory of the China Center for Disease Control and Prevention. Conclusions: Since the development of the pilot surveillance program, the quality of reporting system on hepatitis B had been improved, as well as the accuracy of diagnosis. Rate on the accuracy of reporting on hepatitis B and the methods of testing should be improved at the monitoring sites.
China/epidemiology* ; Cities ; Disease Notification/statistics & numerical data* ; Hepatitis A/epidemiology* ; Hepatitis B/epidemiology* ; Hepatitis B Antibodies/blood* ; Hepatitis B Surface Antigens/blood* ; Humans ; Incidence ; Pilot Projects ; Population Surveillance ; Sentinel Surveillance

Objective: To investigate the mechanism of progranulin (PGRN) in the development of tamoxifen resistance of human breast cancer cells. Methods: The breast cancer MCF-7 and T47D cells as well as tamoxifen-resistant MCF-7R and T47DR cells were treated by 4-hydroxytamoxifen (OHT). The 50% inhibitory concentration (IC50) of OHT was detected by CCK-8. The expressions of C-myc, Cyclin D1 and Bcl-2 were determined by Western blotting. The cell proliferation was detected by CCK-8, the apoptosis was detected by FCM. The expression levels of PGRN mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The expression of PGRN in MCF-7R and T47DR cells was interfered by transfection of PGRN-siRNA. Then the changes of PGRN, C-myc, Cyclin D1 and Bcl-2 expressions were detected by Western blotting. Furthermore, the PGRN-interfered MCF-7R and T47DR cells were stimulated by OHT, then the apoptosis was tested by FCM again. Results: The IC50 of OHT in tamoxifen-induced MCF-7R or T47DR cells was higher than that of MCF-7 or T47D cells (both P < 0.001). As compared with MCF-7 or T47D cells, the proliferation of MCF-7R or T47DR cells was enhanced (both P < 0.01), the apoptotic rate was decreased (both P < 0.01), the expressions of proliferation-related proteins C-myc and Cyclin D1 as well as apoptosis-related protein Bcl-2 were significantly increased (all P < 0.01), and the mRNA and protein levels of PGRN were significantly increased in MCF-7R and T47DR cells (both P < 0.05). After the transfection of PGRN-siRNA into MCF-7R and T47DR cells, the protein levels of PGRN, C-myc, Cyclin D1 and Bcl-2 were significantly decreased (all P < 0.01). After stimulation with OHT, the apoptosis rate of PGRN-downregulated MCF-7R and T47DR cells was increased (both P < 0.01). Conclusion: PGRN is overexpressed in human breast cancer MCF-7R and T47DR cells with tamoxifen-resistance. Interference of PGRN gene expression can enhance the sensibility of breast cancer cells to tamoxifen.

Humans ; Diverticulum, Colon ; Fecal Impaction ; Hydrodynamics

Objective: To analyze the disease burden of animal injury in China between 1990 and 2016. Methods: Data obtained from the Global Burden of Disease 2016 were used to analyze the age and gender specific disease burden of animal injury in China, using the incidence and disability adjusted of life years (DALYs) rate. Relative and annual changes were evaluated. Results: In 2016, the age-standardized incidence and DALYs rate of animal injury in China showed as 245.05 per 100 000 people and 12.73 per 100 000. The age-standardized incidence of non-venomous animal injury was significantly higher than that of venomous animal injury, but the differences in age-standardized incidence and DALYs rate between venomous animal injury and non-venomous animal injury were not significant. Between 1990 and 2016, there was a significantly decreasing trend in the age-standardized incidence and DALYs rate of animal injury, and obvious decline could be seen in the incidence of non-venomous animal injury, compared with venomous animal injury. The incidence and DALYs rate of animal injury declined in both males and females and in different age groups. The obvious decline of incidence and DALYs rate could be found in children aged 5-14 years and aged <5 years. Conclusions: Between 1990 and 2016, there was a significant alleviation of the disease burden of animal injury in China. Young children were most prone to animal injury, resulting in serious disability and death, indicating more attention should be paid to this population at high risk and in animal injury prevention and control programs.
Adolescent ; Child ; Child, Preschool ; China/epidemiology* ; Cost of Illness ; Disabled Persons/statistics & numerical data* ; Female ; Global Burden of Disease ; Humans ; Incidence ; Male ; Quality-Adjusted Life Years ; Wounds and Injuries/epidemiology*

OBJECTIVETo characterize recent trends of nosocomial infection (NI) among preterm infants admitted to Canadian Level 3 NICUs during 2008-2012, and its association with neonatal outcomes.

METHODSA retrospective observational cohort study was performed including infants born <33 weeks gestational age and admitted to 24 NICU sites participating in the Canadian Neonatal NetworkTM during 2008-2012. NICU sites were classified into three groups according to their baseline NI rates in 2008 [Low NI group (≤14%), Medium NI group (14.1%-19%) and High NI group (>19%)], and NICU sites were also classified according to their NI trend during 2008-2012 (decreased, null and increased). Trends in NI were further examined for each baseline-NI group. Trends for a composite outcome indicating mortality or severe morbidities (intraventricular hemorrhage grades≥3 or periventricular leukomalacia, retinopathy of prematurity stages≥3, bronchopulmonary dysplasia or necrotizing enterocolitis stages≥2) were examined for each baseline-NI and trend-NI NICU site groups using multivariable logistic regression analyses adjusted for potential confounders.

RESULTSBaseline high NI group showed significantly decreased trends in NI rates, while for with medium or low baseline NI groups showed no significant trends in NI rates. The composite outcome (mortality during NICU stay or any severe neonatal morbidity such as intraventricular hemorrhage grades 3-4, periventricular leukomalacia, retinopathy of prematurity stages 3-5, bronchopulmonary dysplasia and necrotizing enterocolitis stages 2-3) decreased significantly for sites with decreased (OR=0.89, 95% CI=0.85-0.93) or null (OR=0.94, 95% CI=0.90-0.98) NI trends, but no significant trends in the composite outcome were detected for sites with increased NI rates.

CONCLUSIONSThe neonatal outcome is possibly influenced by NI rates and trend. The trend in the mortality and the risk of bronchopulmonary dysplasia, retinopathy of prematurity stage≥3 and intraventricular hemorrhage>2 were significantly decreased for sites with decreased NI trend, suggesting that these improved outcomes may be associated with effort to decrease NI rate.

Cross Infection ; epidemiology ; Gestational Age ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal

OBJECTIVETo study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient.

METHODSLiver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured.

RESULTSIn the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation.

CONCLUSIONSPreconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.

Animals ; Liver Transplantation ; immunology ; Male ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Regulatory ; immunology ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; immunology ; Whole-Body Irradiation

Down syndrome cell adhesion molecule (DSCAM) acts as a netrin-1 receptor and mediates attractive response of axons to netrin-1 in neural development. However, the signaling mechanisms of netrin-DSCAM remain unclear. Here we report that AMP-activated protein kinase (AMPK) interacts with DSCAM through its γ subunit, but does not interact with DCC (deleted in colorectal cancer), another major receptor for netrin-1. Netrin-treatment of cultured cortical neurons leads to increased phosphorylation of AMPK. Both AMPK mutant with dominant-negative effect and AMPK inhibitor can significantly suppress netrin-1 induced neurite outgrowth. Together, these findings demonstrate that AMPK interacts with DSCAM and plays an important role in netrin-1 induced neurite outgrowth. Our study uncovers a previously unknown component, AMPK, in netrin-DSCAM signaling pathway.
AMP-Activated Protein Kinases ; antagonists & inhibitors ; genetics ; metabolism ; Animals ; Cell Adhesion Molecules ; genetics ; metabolism ; Cells, Cultured ; HEK293 Cells ; Humans ; Mice ; Nerve Growth Factors ; pharmacology ; Netrin-1 ; Neurites ; physiology ; Neurons ; cytology ; drug effects ; metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors ; pharmacology ; RNA Interference ; RNA, Small Interfering ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Signal Transduction ; drug effects ; Transfection ; Tumor Suppressor Proteins ; pharmacology

BACKGROUNDThe initiation and expansion of China's national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China.

METHODSWe evaluated all patients ≥ 16 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi. Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis.

RESULTSA total of 83 556 patients were included. Over the study period, 30 635 (37%) of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status, incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective.

CONCLUSIONSSignificant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005 - 2009. However, a sizable proportion of HIV positive patients still lack CD4 testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to link patients with ART services and optimize treatment coverage.

Adult ; CD4 Lymphocyte Count ; Female ; HIV Infections ; diagnosis ; drug therapy ; immunology ; Humans ; Logistic Models ; Male

AIMTo further uncover the possible mechanism of quercetin-mediated inhibitory effect on prostate cancer cells.

METHODSThe cell extracts treated with quercetin or without treatment were used for checking protein expression levels of c-Jun and cAMP response element binding protein (CREB)-binding protein (CBP) by Western blotting assay. Regulatory effects of c-Jun and CBP on the function of androgen receptor (AR) were examined by cotransfection experiment. Finally, a physical interaction of c-Jun and the AR was investigated by coimmunoprecipitation.

RESULTSQuercetin dramatically induced the protein expression of c-Jun which in turn inhibited the AR function. Meanwhile, quercetin had no detectable effect on CBP expression, and the results of transient transfection demonstrated that the ectopic CBP stimulated the transcriptional activity of AR, whereas CBP-mediated stimulation could be attenuated by quercetin. Furthermore, physical interaction of c-Jun and the AR was confirmed by coimmunoprecipitation result.

CONCLUSIONOverexpression of c-Jun induced by quercetin had inhibitory effect on the function of AR protein, and increased CBP expression did not reverse the inhibition by quercetin. Together, quercetin-mediated inhibition on the AR function might be not by competition with limited amount of CBP in the cell, but through a direct association of c-Jun and the AR.

Antineoplastic Agents, Phytogenic ; pharmacology ; CREB-Binding Protein ; genetics ; metabolism ; physiology ; Cell Line, Tumor ; Humans ; Immunoprecipitation ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Protein Binding ; drug effects ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; physiology ; Quercetin ; pharmacology ; Receptors, Androgen ; genetics ; physiology ; Transfection

The nervous system is one of the most complicated organ systems in invertebrates and vertebrates. Down syndrome cell adhesion molecule (DSCAM) of the immunoglobulin (Ig) superfamily is expressed widely in the nervous system during embryonic development. Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching, dendritic tiling and cell spacing. However, the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear. Here, we show that Dscam ( del17 ) mutant mice exhibit severe hydrocephalus, decreased motor function and impaired motor learning ability. Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.
Animals ; Cell Adhesion Molecules ; genetics ; metabolism ; Corpus Callosum ; metabolism ; pathology ; Genotype ; Hydrocephalus ; genetics ; metabolism ; pathology ; Mice ; Mice, Knockout ; Motor Activity ; genetics ; physiology ; Mutation