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Liu L.,Wuhan University | Chen X.,Wuhan University | Xie S.,Gannan Medical University | Zhang C.,Wuhan Medical Care Center for Women and Children | And 2 more authors.
Hepatology | Year: 2012

KIAA0101 overexpression was detected in numerous malignant solid tumors and involved in tumor progression; however, the correlation between KIAA0101 expression level and human hepatocellular carcinoma (HCC) was controversial. Our data revealed abnormal expression of the KIAA0101 transcript variant 1 (KIAA0101 tv1) at both messenger RNA and protein levels in HCC tissues and cell lines assessed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), virtual northern blot, western blot, and immunohistochemical analysis, especially in stage 3-4 HCCs. NIH3T3 cells transfected with KIAA0101 tv1 induced colony formation in vitro and tumor xenorafts in vivo, implying the oncogenic potential of KIAA0101 tv1. Semiquantitative RT-PCR, real-time quantitative RT-PCR, and western blot analysis demonstrated that doxorubicin (Adriamycin, ADR) treatment down-regulated expression of the KIAA0101 tv1, whereas it increased the acetylation of the p53 protein. Additionally, KIAA0101 tv1 prevented cells from apoptosis caused by ADR through suppressing the acetylation of p53 at Lys382. Immunoprecipitation analysis and mammalian two-hybrid assay indicated that KIAA0101 tv1 bound to the transactivation region (1-42 amino acids) of p53 and strongly inhibits its transcriptional activity. Taken together, our data suggest that KIAA0101 tv1 played an important role in the late stage of metastatic HCC and prevented apoptosis after chemotherapeutic drug treatment through inhibiting the transcriptional activity of the p53 gene. Conclusion: KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53. Suppression of the KIAA0101 tv1 function is likely to be a promising strategy to develop novel cancer therapeutic drugs. © 2012 American Association for the Study of Liver Diseases.


Liu L.,Wuhan University | Xie S.,Gannan Medical University | Zhang C.,Wuhan Medical Care Center for Women and Children | Zhu F.,Wuhan University
Critical Reviews in Eukaryotic Gene Expression | Year: 2014

Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to increase the diversity of messenger RNAs expressed by the genome in normal multicellular organisms. Dysregulation of alternative splicing underlies a number of human diseases, including cancers. Increasing evidence supports the important role of this expansive layer of gene regulation in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of its aggressive property and limited therapeutic options. Studies suggest that aberrant alternative splicing promotes generation of oncogenic variants in HCC, whereas tumor suppressors are self-inactivated by aberrant alternative splicing in HCC. Moreover, different spliced variants of the same gene can display distinct and even antagonistic biological functions in HCC. As a result, inhibiting the splicing of oncogenic variants and the self-inactivation of tumor suppressors are likely to be new therapy strategies. This review provides a perspective of the emerging evidence of both alternative splicing as a critical mechanism for the development of HCC and that potential cross-talk through signaling pathways among different variants might aid in the development of novel molecular targets of HCC. © 2014 Begell House, Inc.


PubMed | Wuhan Medical Care Center for Women and Children, Wuhan University and Gannan Medical University
Type: Journal Article | Journal: Critical reviews in eukaryotic gene expression | Year: 2014

Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to increase the diversity of messenger RNAs expressed by the genome in normal multicellular organisms. Dysregulation of alternative splicing underlies a number of human diseases, including cancers. Increasing evidence supports the important role of this expansive layer of gene regulation in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of its aggressive property and limited therapeutic options. Studies suggest that aberrant alternative splicing promotes generation of oncogenic variants in HCC, whereas tumor suppressors are self-inactivated by aberrant alternative splicing in HCC. Moreover, different spliced variants of the same gene can display distinct and even antagonistic biological functions in HCC. As a result, inhibiting the splicing of oncogenic variants and the self-inactivation of tumor suppressors are likely to be new therapy strategies. This review provides a perspective of the emerging evidence of both alternative splicing as a critical mechanism for the development of HCC and that potential cross-talk through signaling pathways among different variants might aid in the development of novel molecular targets of HCC.


Guo Y.,Huazhong University of Science and Technology | Guo Y.,Centers for Disease Control and Prevention | Zhang W.,Wuhan Medical Care Center for Women and Children | Zhang Y.,Huazhong University of Science and Technology | And 4 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2012

OBJECTIVE: Hepatitis B immune globulin (HBIG) injection during pregnancy and/or after birth is an intervention for preventing mother-to-child transmission of the hepatitis B (HB) virus. However, varying cost-effectiveness ratios among various HBIG therapies remain unclear. This study explored these differences in cost-effectiveness ratios. METHODS: Four districts in Wuhan, China, were selected for the current study using stratified random sampling. Pregnant women who were positive for HB surface antigen (HBsAg) and who received prenatal care in district-level maternal and child health hospitals were interviewed. The mothers and their children underwent follow-up visits from the time of pregnancy until the children were six-and-a-half months old. RESULTS: A total of 324 cases completed the follow-up visits on a voluntary basis. Among the 324 HBsAg-positive pregnant women investigated, 60.49% (196/324) were injected with HBIG at different trimesters. A total of 249 neonates (76.85%) received an HBIG injection within 24 h after birth. The HBsAg-positive rate in infants was 5.56% (18/324). The HBIG-injected mother and infant group had the lowest chronic infection rate among children [odds ratio=0.14, 95% confidence interval (CI) 0.02-0.90, P=0.039]. The HBIG-injected infant group exhibited the lowest HBsAb-positive rate (odds ratio=0.07, 95% CI 0.02-0.23). The cost per averted disability-adjusted life years was lowest in the infant group: USD 118.61 (95% CI 105.23-131.99). CONCLUSION: These results indicate that active and passive immunizations (HBIG and HB vaccine) entail the lowest cost in the prevention of chronic HB infection in infants. However, this programme has the lowest HBsAb-positive rate, which possibly prevents children from self-acquiring antibodies. © 2012 Wolters Kluwer Health / Lippincott.


Lin X.,Huazhong University of Science and Technology | Guo Y.,Centers for Disease Control and Prevention | Zhou A.,Wuhan Medical Care Center for Women and Children | Zhang Y.,Huazhong University of Science and Technology | And 5 more authors.
Pediatric Infectious Disease Journal | Year: 2014

Background: Despite effective immunoprophylaxis, vertical transmission of hepatitis B virus (HBV) from infected mothers still occurs. This study aimed to provide an estimate of the prevalence of immunoprophylaxis failure and evaluate associated risk factors. Methods: A hospital-based prospective study was conducted from June 1, 2008, to June 30, 2012. In this prospective study, 294 HBsAg-positive mothers were followed up from their first prenatal care visits until their infants completed the proposed vaccination schedule. Further, studies providing prevalence rates of immunoprophylaxis failure in the Chinese population were identified from electronic databases and were collected for a meta-analysis. Results: In the prospective study, 16 (5.44%) infants developed HBV infection despite passive-active immunoprophylaxis. Twelve of these infants were born to HBeAg-positive mothers with cord blood that was positive for HBV DNA. After adjusting for maternal and infant factors, HBV DNA detectable in cord blood (odds ratio: 22.32, 95% confidence interval: 4.00-124.47) was associated with a significantly greater risk of immunoprophylaxis failure. The prospective study and 23 previous studies were included in the meta-analysis, constituting a total of 7561 Chinese participants. The overall estimated rates of immunoprophylaxis failure for infants with HBsAg-positive and HBeAg-positive mothers were 4.87% and 9.66% respectively. Conclusions: Immunoprophylaxis failure is an extensive problem, and further studies should design and assess novel strategies for the prevention of immunoprophylaxis failure, especially for cases involving HBeAg-positive mothers and infants with cord blood that is positive for HBV DNA. Copyright © 2014 by Lippincott Williams & Wilkins.


Chen J.,Tianjin Medical University | Sun F.,Tianjin Medical University | Fu J.,Wuhan Medical Care Center for Women and Children | Zhang H.,Teda International Cardiovascular Hospital
Pediatric Cardiology | Year: 2015

As a transcription factor mainly expressed in cardiovascular system, T-box 20 (TBX20) plays an important role in embryonic cardiovascular system development and adult heart function. Previous studies have identified associations of two SNPs in the T-box DNA-binding domain of TBX20 with congenital heart disease (CHD) in two Caucasian families, but the associations of TBX20 mutations underlying the more common populations with CHD remain to be uncovered. In this study, 25 unrelated Chinese Han neonates with CHD and 25 healthy children as controls were investigated for TBX20 mutations. SNP genotyping was performed by PCR-DNA sequencing. The selected SNPs were well genotyped and SNP rs3999941 was found to be strongly associated with CHD (p = 0.007). The minor allele of rs3999941 showed a high-risk factor for CHD (OR 4.24; 95 % CI 1.41–12.71). Besides, we found a new SNP site located at the 657th nucleotide of the exon 5 of TBX20 gene which may also be associated with CHD, c.657A>C. The frequency was significantly different between two groups (p = 0.011), the minor allele of SNP c.657A>C also showed a risk factor for CHD (OR 2.56; 95 % CI 1.02–6.46). These findings suggested that the TC genotype of SNP rs3999941 and AC genotype of the new SNP c.657A>C in the TBX20 gene may be risk factors for CHD and thus screening of these SNPs may have some implications in the prevention and treatment of CHD in Han Chinese children. © 2014, Springer Science+Business Media New York.


Ting Y.H.,Chinese University of Hong Kong | Zhou Y.,Wuhan Medical Care Center for Women and Children | Lao T.T.,Chinese University of Hong Kong
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2013

The data in the literature suggests that Methimazole (MMI)/Carbimazole (CMZ) embryopathy is rare. This study examined the incidence of CMZ embryopathy in the Hong Kong Chinese population and the factors associated with its development. METHODS: Of the 145 pregnant women with hyperthyroidism managed from 2008 to 2010, 29 (20%) had taken CMZ during pregnancy. The presence and details of birth defects, the dosage of CMZ, and the period of exposure during pregnancy were examined in these 29 pregnancies. All cases of CMZ embryopathy in the English literature were reviewed in the same way. RESULTS: Of the 27 babies (93.1%) with known outcome, 3 had aplasia cutis and 1 had an omphalocele in addition, and 1 affected baby had a sibling with aplasia cutis and patent vitellointestinal duct. The incidence of CMZ embryopathy in our study group is 11.1%. Amongst the 21 cases of CMZ embryopathy in the literature, 85% were exposed to a CMZ dosage of ≥20 mg/day, and the minimum duration of exposure being 7 weeks from last menstrual period. The most common abnormality is ectodermal anomaly (62%), followed by oro-nasal anomaly (48%), facial dysmorphism (38%), gastrointestinal anomaly (33%) and abdominal wall defect (19%). There was no relationship between the type of abnormality and the dosage or duration of exposure to CMZ. CONCLUSIONS: The incidence of CMZ embryopathy in our study group is 11.1%. Critical factors for its development are exposure to a CMZ dosage of ≥20 mg/day before 7 weeks of gestation. Genetic susceptibility may also play a role. © 2013 Wiley Periodicals, Inc.


Wang K.-P.,Huazhong University of Science and Technology | Wang J.,Wuhan Medical Care Center for Women and Children | Li Q.,Huazhong University of Science and Technology | Zhang Q.-L.,Huazhong University of Science and Technology | And 4 more authors.
Food Research International | Year: 2014

Five polysaccharide fractions (LST1, LST2, LJT1, LJT2 and LJT3) from Lentinus edodes were isolated and purified. Their molecular weights (Mw) were estimated as 65.5~697kDa by using high-performance gel permeation chromatography (HPGPC). The results from monosaccharide analysis indicated that all of them contained glucose as main sugar component. The chemical and spectroscopic analyses implied that these fractions were composed of a main chain consisting of several (2~6) β-(1→3)-d-glucose residues with branching at C6 position. The predicted structural units of the purified polysaccharides were established with different degrees of branching (DB). Congo-red test, X-ray diffraction (XRD) and atomic force microscope (AFM) were used to verify that the natural lentinan contained triple helical spatial conformation. Furthermore, the results from anti-tumor tests in vitro and in vivo revealed that these polysaccharide fractions could have dual anti-tumor effects, including killing tumor cells directly and immunoregulation with low toxicity to the host. Interestingly, the high Mw polysaccharides had smaller DB values and displayed greater anti-tumor effects. © 2014 Elsevier Ltd.


PubMed | Wuhan Medical Care Center for Women and Children and Huazhong University of Science and Technology
Type: Journal Article | Journal: International journal of environmental research and public health | Year: 2015

There have been several epidemiologic studies on the relationship between high birth weight and the risk for bone tumor in the past decades. However, due to the rarity of bone tumors, the sample size of individual studies was generally too small for reliable conclusions. Therefore, we have performed a meta-analysis to pool all published data on electronic databases with the purpose to clarify the potential relationship. According to the inclusion and exclusion criteria, 18 independent studies with more than 2796 cases were included. As a result, high birth weight was found to increase the risk for bone tumor with an Odds Ratio (OR) of 1.13, with the 95% confidence interval (95% CI) ranging from 1.01 to 1.27. The OR of bone tumor for an increase of 500 gram of birth weight was 1.01 (95% CI 1.00-1.02; p = 0.048 for linear trend). Interestingly, individuals with high birth weight had a greater risk for osteosarcoma (OR = 1.22, 95% CI 1.06-1.40, p = 0.006) than those with normal birth weight. In addition, in the subgroup analysis by geographical region, elevated risk was detected among Europeans (OR = 1.14, 95% CI 1.00-1.29, p = 0.049). The present meta-analysis supported a positive association between high birth weight and bone tumor risk.


PubMed | Wuhan Medical Care Center for Women and Children
Type: Journal Article | Journal: Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics | Year: 2013

To investigate changes in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) and their significance in children with left-to-right shunt congenital heart disease (CHD) associated with heart failure (HF).Twenty healthy children (control group), 20 children with HF, without basic heart disease (HF group), 20 children with left-to-right shunt CHD, without HF (CHD group), and 30 children with left-to-right shunt CHD associated with HF (CHD+HF group) were included in the study. These groups were compared in terms of serum IGF-1 and IGFBP-3 levels. According to the New York Heart Association (NYHA) Functional Classification, the CHD+HF group was further divided into NYHA-II, NYHA-III and NYHA-IV subgroups and the subgroups were compared in terms of serum IGF-1, IGFBP-3, and cardiac troponin I (cTnI) levels. The correlation of serum IGF-1 and IGFBP-3 levels with serum cTnI level in the CHD+HF group was analyzed.The CHD group showed decreased serum IGF-1 and IGFBP-3 levels compared with the control group (P<0.01). The CHD+HF group showed a significantly decreased serum IGF-1 level compared with the control group (P<0.01) and CHD group (P<0.05). The HF group had significantly increased serum IGF-1 and IGFBP-3 levels compared with other groups (P<0.01). The NYHA-II subgroup had the highest serum IGF-1 level and the NYHA-IV subgroup had the lowest serum IGF-1 level (P<0.01). In the CHD+HF group, serum IGF-1 and IGFBP-3 levels were negatively correlated with serum cTnI level (r=-0.692, P<0.05; r=-0.530, P<0.05).Serum IGF-1 level can be used as an objective condition evaluation indicator for CHD, and low serum IGF-1 level is a risk factor for HF. This also provides a clinical basis for treatment of HF using exogenous IGF-1.

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