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Wang S.,Chongqing Medical University | Wang S.,Ministry of Education Key Laboratory of Child Development and Disorders | Yang C.,Chongqing Medical University | Yang C.,Ministry of Education Key Laboratory of Child Development and Disorders | And 7 more authors.
Hepatology | Year: 2014

The purpose of this study was to assess the effectiveness of high-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) in treating pediatric hepatoblastoma. Twelve patients with initially unresectable hepatoblastoma were enrolled in the study. All patients received chemotherapy, TACE, and HIFU ablation. Follow-up materials were obtained in all patients. The tumor response, survival rate, and complications were analyzed. Complete ablation was achieved in 10 patients (83.3%), and the alpha-fetoprotein level was also decreased to normal in these patients. The mean follow-up time was 13.3±1.8 months (range, 2-25 months). At the end of follow-up, two patients died from tumor progression, the other 10 patients were alive. One patient was found to have lung metastasis after HIFU and had an operation to remove the lesion. The median survival time was 14 months, and the 1- and 2-year survival rates were 91.7% and 83.3%, respectively. Complications included fever, transient impairment of hepatic function, and mild malformation of ribs. Conclusion: HIFU combined with TACE is a safe and promising method with a low rate of severe complications. As a noninvasive approach, it may provide a novel local therapy for patients with unresectable hepatoblastoma. © 2013 by the American Association for the Study of Liver Diseases.

PubMed | Ministry of Education Key Laboratory of Child Development and Disorders, Sichuan Cancer Hospital and Chongqing Medical University
Type: Journal Article | Journal: PloS one | Year: 2016

Legumain (LGMN) is highly expressed in breast cancer (BC) and other solid tumors and is a potential anticancer target. Here we investigate the anti-tumor effects of short hairpin RNAs (shRNAs) targeting LGMN embedded in a microRNA-155 (miR-155) architecture, which is driven by a radiation-inducible chimeric RNA polymerase II (Pol II) promoter. Lentiviral vectors were generated with the chimeric promoter which controlled the expression of downstream shRNA-miR-155 cassette. Fluorescence was observed by using confocal microscopy. Real-time quantitative PCR and Western blotting were used to determine the expression level of LGMN, MMP2, and MMP9. Furthermore, the proliferation and invasive ability of BC cells was analyzed via plate colony formation and invasion assays. Here we demonstrated that the chimeric promoter could be effectively induced by radiation treatment. Furthermore, the shRNA-miR-155 cassette targeting LGMN could be effectively activated by the chimeric promoter. Radiation plus knockdown of LGMN impairs colony formation and dampens cell migration and invasion in BC cells. Inhibition of LGMN downregulates MMP2 and MMP9 expression in BC cells. Pol II-driven shRNA-miR-155 could effectively suppress the growth and invasiveness of BC cells, and that the interference effects could be regulated by radiation doses. Moreover, knockdown of LGMN alleviates the aggressive phenotype of BC cells through modulating MMPs expression.

PubMed | University of Maryland University College, Ministry of Education Key Laboratory of Child Development and Disorders and Chongqing Medical University
Type: Journal Article | Journal: Blood | Year: 2016

Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4(+) T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6(+) Tfh cells, but the frequency of ICOS(+) Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS(+) Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS(+) Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4(+) naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6.

PubMed | Capital Institute of Pediatrics, Institute of Environmental Health and Related Products Safety, Chongqing Medical University and Ministry of Education Key Laboratory of Child Development and Disorders
Type: | Journal: BioMed research international | Year: 2016

Background. Prevalence of childhood asthma varies significantly among regions, while its reasons are not clear yet with only a few studies reporting relevant causes for this variation. Objective. To investigate the potential role of city-average levels of air pollutants and climatic factors in order to distinguish differences in asthma prevalence in China and explain their reasons. Methods. Data pertaining to 10,777 asthmatic patients were obtained from the third nationwide survey of childhood asthma in Chinas urban areas. Annual mean concentrations of air pollutants and other climatic factors were obtained for the same period from several government departments. Data analysis was implemented with descriptive statistics, Pearson correlation coefficient, and multiple regression analysis. Results. Pearson correlation analysis showed that the situation of childhood asthma was strongly linked with SO2, relative humidity, and hours of sunshine (p < 0.05). Multiple regression analysis indicated that, among the predictor variables in the final step, SO2 was found to be the most powerful predictor variable amongst all ( = -19.572, p < 0.05). Furthermore, results had shown that hours of sunshine ( = -0.014, p < 0.05) was a significant component summary predictor variable. Conclusion. The findings of this study do not suggest that air pollutants or climate, at least in terms of children, plays a major role in explaining regional differences in asthma prevalence in China.

PubMed | Red Cross, Fudan University, Chongqing Medical University and Ministry of Education Key Laboratory of Child Development and Disorders
Type: | Journal: BMC microbiology | Year: 2015

Pseudomonas aeruginosa is an opportunistic pathogen that is the leading cause of iatrogenic infections in critically ill patients, especially those undergoing mechanical ventilation. In this study, we investigated the effects of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation of P. aeruginosa PAO1.The addition of 0.1 nM, 1 nM, and 10 nM exogenous AI-2 to P. aeruginosa PAO1 increased biofilm formation, bacterial viability, and the production of virulence factors. However, compared to the 10 nM AI-2 group, higher concentrations of AI-2 (100 nM and 1M) reduced biofilm formation, bacterial viability, and the production of virulence factors. Consistent with the changes in morphology, gene expression analysis revealed that AI-2 up-regulated the expression of quorum sensing-associated genes and genes encoding virulence factors at lower concentrations and down-regulated these genes at higher concentrations.Our study demonstrated that exogenous AI-2 acted in a dose-dependent manner to regulate P. aeruginosa biofilm formation and virulence factors secretion via modulating the expression of quorum sensing-associated genes and may be targeted to treat P. aeruginosa biofilm infections.

Liu Z.,Chongqing Medical University | Luo Q.,Chongqing Medical University | Guo C.,Chongqing Medical University | Guo C.,Ministry of Education Key Laboratory of Child Development and Disorders
Cancer Cell International | Year: 2015

Background: ATF2 mediated cytochrome c release is the formation of a channel with some unknown factors larger than that of the individual proteins. BHS-only proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel. According to this facts, we can speculated that there is possible signal relationship with BH3s and ATF2, which is associated with mitochondrial-based death programs. Methods: The growth inhibitory effects of mitochondrial ATF2 were tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins were measured by Western blotting. The interaction of proteins were evaluated by immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial ATF2 were tested in xenograft B16F10 models. Results: Genotoxic stress enabled mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly reduced the conformational activation of Bim, suggesting that Bim acts downstream of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim-depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2 transfection inhibited B16F10 tumor xenografts growth. Conclusions: Altogether, these results show that ATF2 is a component of the apoptosis machinery that involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis. © Liu et al.

PubMed | Chongqing Medical University and Ministry of Education Key Laboratory of Child Development and Disorders
Type: Journal Article | Journal: Oncotarget | Year: 2016

As a promising magnetic resonance imaging (MRI) reporter, ferritin has been used to track cells in vivo; however, its continuous overexpression can be cytotoxic, which restricts its application. In this study, we aimed to develop a switch to turn this genetic reporter on or off while monitoring cell grafts via MRI. To accomplish this, we genetically modified the ferritin heavy chain (FTH1) with a Tet-On switch and assessed the expression of FTH1 in transduced neuroblastoma cells (SK-N-SH) in vitro and in xenografted tumors in vivo. We found that FTH1 expression induced by doxycycline (Dox) in SK-N-SH-FTH1 cells depended on treatment dose and duration. We successfully detected T2-weighted MRI contrast in cell grafts after switching on the reporter gene using Dox, and this contrast disappeared when we switched it off. The genetic reporter FTH1 can thus be switched on or off throughout longitudinal monitoring of cell grafts, limiting expression to when MRI contrast is needed. The controllable imaging system we have developed minimizes risks from constitutive reporter gene overexpression and facilitates tumor cell monitoring in vitro and in vivo.

PubMed | Key Laboratory of Pediatrics in Chongqing, Chongqing Medical University and Ministry of Education Key Laboratory of Child Development and Disorders
Type: Journal Article | Journal: PloS one | Year: 2016

This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants.The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi-RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia.The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies.Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost-effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period.

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