Publications by authors named "Hong Xiong"

37 Publications

[Clinical characteristics and molecular genetics of seven neonates with congenital nephrogenic diabetes insipidus].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Dec;38(12):1185-1189

Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450066, China.

Objective: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI).

Methods: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results.

Results: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic.

Conclusion: AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200607-00416DOI Listing
December 2021

The Emerging Roles of T Helper Cell Subsets and Cytokines in Severe Neutrophilic Asthma.

Inflammation 2021 Nov 26. Epub 2021 Nov 26.

Public Center of Experimental Technology, The School of Basic Medical Science, Southwest Medical University, Sichuan Province, Luzhou, 646000, China.

Neutrophilic asthma (NA) is a severe type of steroid resistant asthma, and so far the immune mechanisms underlying NA are not clear. In this article, we performed a comprehensive assessment of Th-cell subsets and cytokines in severe NA patients. A total of 13 healthy individuals and 31 severe asthma patients were enrolled in this study. Refractory asthma patients were defined as those with eosinophilic asthma (EA, accounted for 32% of asthmatic patients) or NA (68%) according to sputum neutrophil/eosinophil counts or blood eosinophils. Th-cell subsets in peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry, and cytokines were detected by cytometric bead array (CBA). The results showed significant differences were observed in Th-cell phenotypes, where the number of Th1 cells were reduced and the numbers of Th2 cells were increased in NA and EA groups, respectively, when compared with healthy controls. Th17 cells were not strongly associated with severe neutrophilic asthma. The frequencies of mucosal-associated invariant T (MAIT) cells were strikingly reduced in severe asthma patients, especially in the NA group. This NA group also showed increased levels of IL-17A, IL-17F, TNF-α, and IL-6 in serum and increased levels of IL-17A, IL-17F, IFN-γ, TNF-α, IL-1β, IL-5, IL-6, and IL-8 in sputum. In addition, sputum IL-6 was positively correlated with TNF-α, IFN-γ, IL-17A, and IL-8. Our results uncovered a controversial role for Th17 cells, which were reduced in severe asthma patients. Severe neutrophilic asthma was associated with a striking deficiency of MAIT cells and high pro-inflammatory cytokine levels.
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http://dx.doi.org/10.1007/s10753-021-01598-6DOI Listing
November 2021

Impact of tillage and crop establishment methods on rice yields in a rice-ratoon rice cropping system in Southwest China.

Sci Rep 2021 09 16;11(1):18421. Epub 2021 Sep 16.

Rice and Sorghum Research Institute, Sichuan Academy of Agricultural Sciences/Key Laboratory of Southwest Rice Biology and Genetic Breeding, Ministry of Agriculture, Deyang, 618000, China.

Simplified cultivation methods for rice production offer considerable social, economic, and environmental benefits. However, limited information is available on yield components of rice grown using simplified cultivation methods in a rice-ratoon rice cropping system. A field experiment using two hybrid and two inbred rice cultivars was conducted to compare four cultivation methods (conventional tillage and transplanting, CTTP; conventional tillage and direct seeding, CTDS; no-tillage and transplanting, NTTP; no-tillage and direct seeding, NTDS) in a rice-ratoon rice system from 2017 to 2020. Main season yields for CTDS and NTDS were higher than for CTTP by 6.1% and 2.8%, respectively; whereas ratoon season yields for CTDS and NTDS were equal to or higher than for CTTP. Annual grain yields for CTDS and NTDS were higher than for CTTP by 4.4% and 3.2%, respectively. The higher CTDS and NTDS yields were associated with higher panicle numbers per m and biomass production. Rice hybrids had higher yields than inbred cultivars by 15.8-19.3% for main season and by 15.6-19.4% for ratoon season, which was attributed to long growth duration, high grain weight and biomass production. Our results suggest that CTTP can be replaced by CTDS and NTDS to maintain high grain yields and save labor costs. Developing cultivars with high grain weight could be a feasible approach to achieve high rice yields in the rice-ratoon rice cropping system in southwest China.
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http://dx.doi.org/10.1038/s41598-021-98057-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445942PMC
September 2021

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants.

J Transl Med 2020 10 19;18(1):397. Epub 2020 Oct 19.

Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China.

Background: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants.

Methods: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks.

Results: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96-1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28-29 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000-1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment.

Conclusions: Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073 ; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500 .
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http://dx.doi.org/10.1186/s12967-020-02562-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574422PMC
October 2020

Host-Induced Gene Silencing of Confers Broad-Spectrum Resistance to .

Front Plant Sci 2019 9;10:433. Epub 2019 Apr 9.

Rice Research Institute, Sichuan Agricultural University, Chengdu, China.

Rice blast caused by () is a major threat to global rice production. In recent years, small interference RNAs (siRNAs) and host-induced gene silencing (HIGS) has been shown to be new strategies for the development of transgenic plants to control fungal diseases and proved a useful tool to study gene function in pathogens. We here tested whether feeding artificial siRNAs (asiRNAs) could compromise e virulence and HIGS technique could improve rice blast resistance. Our data revealed that silencing of by feeding asiRNAs targeting (i.e., asiR1245, asiR1362, and asiR1115) resulted in inhibited fungal growth, abnormal spores, and decreased pathogenicity. Among the asiRNAs, asiR1115 was the most inhibitory toward the rice blast fungus. Conversely, the asiRNAs targeting three other genes (i.e., , , and ) had no effect on fungal growth. Transgenic rice plants expressing RNA hairpins targeting exhibited improved resistance to 11 tested strains. Confocal microscopy also revealed profoundly restricted appressoria and mycelia in rice blast-infected transgenic rice plants. Our results demonstrate that asiRNA and HIGS were useful protection approaches that may be valuable to enhance rice blast resistance.
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http://dx.doi.org/10.3389/fpls.2019.00433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465682PMC
April 2019

EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen-activated protein kinase axis.

J Cell Biochem 2018 Oct 18. Epub 2018 Oct 18.

Department of Hematology, Shanghai Xuhui Central Hospital, Shanghai, China.

The transcription factor, early B cell factor 1 (EBF1), plays a vital role in the lineage specification involving early B cell development and the onset of myelodysplastic syndrome (MDS). Therefore, to investigate whether or not EBF1 affects MDS as well as the transcription factor's underlying mechanism, we used CD34+ hematopoietic stem cells in bone marrow from patients with MDS. The extracted cells were then transfected with a series of EBF1, short hairpin RNA against EBF1 (shEBF1), and SB203580 (a specific mitogen-activated protein kinase [MAPK] axis inhibitor). The effects EBF1 gene and MAPK axis had on cell proliferation, apoptosis, and migration were determined by in vitro cell culturing. We made observations that involved EBF1 inhibiting the messenger RNA (mRNA) level of p38 MAPK, increasing the mRNA levels of extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase 5 (ERK5), decreasing the protein expression of Bcl-2-associated X protein (Bax), and finally elevating the protein levels of B cell lymphoma/leukemia-2 (Bcl-2), stem cell factor (SCF), erythropoietin receptor (EpoR), p-ERK, p-JNK, p-ERK5, cyclin D, cyclin E, cyclin-dependent kinase 2 (CDK2), and CDK6, implying that EBF1 may very well have an inhibitory role in the MAPK axis. Another discovery found that EBF1 had a positive effect on the promotion of bone marrow CD34+ cell proliferation as well as its migration, but inhibited the apoptosis of cells. The results we obtained from this study indicated that the EBF1 gene suppresses the activation of the MAPK axis, thereby promoting both the proliferation and migration of bone marrow CD34+ cells as well as inhibiting the associating apoptosis. The effects of the EBF1 gene are likely to present a new therapeutic target in preventing the progression of MDS.
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http://dx.doi.org/10.1002/jcb.27177DOI Listing
October 2018

LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity.

Exp Cell Res 2018 09 23;370(2):254-263. Epub 2018 Jun 23.

Hematology of Shanghai Xuhui Centre Hospital, Shanghai Clinical Centre of Chinese Acadymy of Sciences, CAS, Shanghai 200031, PR China. Electronic address:

Chromosome 17p deletions (del(17p)) are present in about 11% of newly diagnosed multiple myeloma (MM) patients and related to inferior prognosis. Bortezomib (BTZ), the first proteasome inhibitor anticancer drug, has a good therapeutic effect for newly diagnosed, relapsed or refractory MM, but is unable to improve the outcome of MM patients with del(17p). Long noncoding RNA (lncRNA) PRAL is located on chromosome 17p, and is associated with the progression and prognosis of different types of cancers. However, little is known about its role in MM. Here, we found that PRAL was downregulated in primary MM cells and cell lines, especially in MM cells with del(17p), and was associated with ISS (international staging system) stage and Durie-Salmon stage in MM patients. Survival curves showed that MM patients with low PRAL expression had a significantly shorter disease-free survival (DFS) and overall survival (OS) than the patients with high PRAL expression. Multivariate Cox regression analysis showed that PRAL expression was an independent predictor for DFS and OS. Then cell proliferation, viability, Ki67 expression, and caspase-3 activity detection showed that PRAL promoted MM cell growth inhibition and apoptosis, and potentiated the anti-MM effect of BTZ in vitro. We further identified and confirmed that miR-210 was the target of PRAL, and miR-210 overexpression overturned the potentiation effect of PRAL on BTZ efficacy. Subsequently, bone morphogenetic protein 2 (BMP2) was confirmed to be the target of miR-210, and PRAL positively regulated the derepression of BMP2 by sponging miR-210. Overexpression of BMP2 potentiated the anti-MM effect of BTZ in vitro. In addition, animal experiments further confirmed that PRAL potentiated BTZ efficacy in vivo. Collectively, our study first revealed a critical role of PRAL-miR-210-BMP2 axis in MM progression, prognosis and treatment with BTZ, and PRAL could become a novel diagnostic, prognostic and therapeutic candidate for MM patients especially for the MM patients harboring del(17p) in the future.
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http://dx.doi.org/10.1016/j.yexcr.2018.06.026DOI Listing
September 2018

Pharmacometabolomics identifies dodecanamide and leukotriene B4 dimethylamide as a predictor of chemosensitivity for patients with acute myeloid leukemia treated with cytarabine and anthracycline.

Oncotarget 2017 Oct 8;8(51):88697-88707. Epub 2017 Sep 8.

Department of Hematology, The Central Hospital of Xuhui District, Shanghai, 20031, China.

Clinical responses to standard cytarabine plus anthracycline regimen in acute myeloid leukemia (AML) are heterogeneous and there is an unmet need for biological predictors of response to this regimen. Here, we applied a pharmacometabolomics approach to identify potential biomarkers associated with response to this regimen in AML patients. Based on clinical response the enrolled 82 patients were subdivided into two groups: complete remission(CR) responders (n=42) and non-responders (n=40). Metabolic profiles of pre-treatment serum from patients were analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry and the metabolic differences between the two groups were investigated by multivariate statistical analysis. A metabolite panel containing dodecanamide and leukotriene B4 dimethylamide (LTB4-DMA) had the power capacity to differentiate the two groups of patients, yielding an area under the receiver operating characteristic of 0.945 (85.2% sensitivity and 88.9% specificity) in the training set and 0.944(84.6% sensitivity and 80.0% specificity) in the test set. The patients with high levels of LTB4-DMA and low amounts of dodecanamide had good sensitivity to chemotherapeutic agents. The possible reasons were that dodecanamide was produced by leukemic cells as a lipolytic factor to fuel their growth with a potential role in drug resistance and LTB4-DMA was a potent leukotriene B4 antagonist that could be applicable in the treatment of AML. These preliminary results demonstrates the feasibility of relating chemotherapy responses with pre-treatment metabolic profiles of AML patients, and pharmacometabolomics may be a useful tool to select patients that are more likely to benefit from cytarabine plus anthracycline chemotherapy.
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http://dx.doi.org/10.18632/oncotarget.20733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687638PMC
October 2017

Measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease at different gestational weeks using three dimensional ultra sonography and its clinical value.

Pak J Pharm Sci 2016 Nov;29(6 Spec):2141-2146

4th (Xing Yuan) Hospital of Yulin, Shanxi Province, China.

Our study aimed to investigate the measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease (CHD) at different gestational weeks using three dimensional (3-D) ultrasonography and its clinical value. Then, 238 pregnant women who received obstetric ultrasonography in ultrasound department of Internal Medicine of our hospital were enrolled between March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD by prenatal fetal echocardiography, and the other 153 fetuses were normal. Frontal lobe volume, thalamic volume and cerebral blood flow was determined by color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of MCA-PI and CPR in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05), but the level of UA-PI performed significantly higher than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in thalamic volume and frontal lobe volume between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD fetus group performed significantly lower thalamic volume and frontal lobe volume than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in BPD, HC, and GA between the two groups (P<0.05); when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05). If gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe volume and thalamic volume; if gestational age <30 weeks, the level of frontal lobe volume and thalamic volume in fetuses with CHD performed significantly lower than that in normal fetuses.
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November 2016

Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study.

Chin Med J (Engl) 2016 11;129(22):2652-2658

Department of Neonatology, Zhengzhou Children's Hospital, Zhengzhou, Henan 450007, China.

Background: Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.

Methods: All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.

Results: A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.

Conclusions: Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.
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http://dx.doi.org/10.4103/0366-6999.193458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126154PMC
November 2016

[Efficacy of heated humidified high-flow nasal cannula in preterm infants aged less than 32 weeks after ventilator weaning].

Zhongguo Dang Dai Er Ke Za Zhi 2016 Jun;18(6):488-91

Neonatal Intensive Care Unit, Zhengzhou Children's Hospital, Zhengzhou 450018, China.

Objective: To investigate the efficacy of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) in preterm infants aged 26-31(+6) weeks with respiratory distress syndrome after ventilator weaning.

Methods: A total of 161 preterm infants were randomly divided into two groups after ventilator weaning: HHHFNC treatment (n=79) and nCPAP treatment (n=82). The two groups were subdivided into 26-28(+6) weeks and 29-31+6 weeks groups according to the gestational age. The treatment failure rate, reintubation rate within 7 days after extubation, incidence of complications, and mortality during hospitalization were compared between the two groups.

Results: The treatment failure rate and reintubation rate showed no significant differences between the HHHFNC and nCPAP groups. The preterm infants aged 26-28(+6) weeks in the HHHFNC group had a significantly higher treatment failure rate than those in the nCPAP group (P<0.05), while the reintubation rate showed no significant difference. As for the preterm infants aged 29-31(+6) weeks, the treatment failure rate and reintubation rate showed no significant differences between the two groups. The incidence of complications and mortality showed no significant differences between the HHHFNC and nCPAP groups.

Conclusions: In preterm infants aged 29-31(+6) weeks, HHHFNC has a similar efficacy as nCPAP after ventilator weaning, while in those aged less than 29 weeks, HHHFNC should be used with great caution if selected as the first-line noninvasive respiratory support.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389091PMC
June 2016

Potential Yield Increase of Hybrid Rice at Five Locations in Southern China.

Rice (N Y) 2016 Dec 17;9(1):11. Epub 2016 Mar 17.

Southern Regional Collaborative Innovation Center for Grain and Oil Crops (CICGO), Hunan Agricultural University, Changsha, 410128, China.

Background: A number of field studies have demonstrated that the yield potential of hybrid rice cultivars is higher than that of inbred cultivars, although the magnitude of difference between hybrid and inbred cultivars at different yield levels has not been described. The objective of this study is to compare the yield increase potential at different yield levels between hybrid and conventional rice. Ten field experiments were conducted at five locations in southern China in 2012 and 2013. At each location, two hybrid and two inbred cultivars were grown at three N levels: high (225 kg/hm(2)), moderate (161-191 kg/hm(2)) and the control, zero N (0 kg/hm(2)).

Results: Hybrid rice yielded approximately 8 % more grain than did inbred cultivars in Huaiji, Binyang and Haikou; approximately 7 % more in Changsha; and approximately 19 % more in Xingyi. The high grain yields observed for hybrid rice cultivars were attributed to high grain weight and biomass accumulation at maturity. On average, rice yields were approximately 6.0-7.5 t ha(-1) (medium yield) in Huaiji, Binyang and Haikou; approximately 9.0 t ha(-1) in Changsha (high yield); and approximately 12.0 t ha(-1) (super high yield) in Xingyi. The yield gaps among Huaiji, Binyang and Haikou and Changsha were attributed to the differences in spikelets m(-2) and biomass production, whereas the yield gap between Changsha and Xingyi was caused by the differences in grain-filling percentage, grain weight and harvest index. The differences in biomass production among sites were primarily due to variation in crop growth rate induced by varied temperatures and accumulative solar radiation.

Conclusions: The yield superiority of hybrid rice was relatively small in comparison with that of inbred cultivars at medium and high yield levels, but the difference was large at super high yield levels. Improving rice yields from medium to high should focus on spikelets m(-2) and biomass, whereas further improvement to super high level should emphasize on grain-filling percentage, grain weight and harvest index. Favorable environmental conditions are essential for high yields in hybrid rice.
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http://dx.doi.org/10.1186/s12284-016-0085-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794477PMC
December 2016

Thromboxane A2 Receptor Inhibition Suppresses Multiple Myeloma Cell Proliferation by Inducing p38/c-Jun N-terminal Kinase (JNK) Mitogen-activated Protein Kinase (MAPK)-mediated G2/M Progression Delay and Cell Apoptosis.

J Biol Chem 2016 Feb 2;291(9):4779-92. Epub 2016 Jan 2.

the Shanghai Xuhui District Central Hospital, 966 Middle Huaihai Road, Shanghai 200031, China

Multiple myeloma (MM) is a plasma cell malignancy without effective therapeutics. Thromboxane A2 (TxA2)/TxA2 receptor (T prostanoid receptor (TP)) modulates the progression of some carcinomas; however, its effects on MM cell proliferation remain unclear. In this study, we evaluated cyclooxygenase (COX) enzymes and downstream prostaglandin profiles in human myeloma cell lines RPMI-8226 and U-266 and analyzed the effects of COX-1/-2 inhibitors SC-560 and NS-398 on MM cell proliferation. Our observations implicate COX-2 as being involved in modulating cell proliferation. We further incubated MM cells with prostaglandin receptor antagonists or agonists and found that only the TP antagonist, SQ29548, suppressed MM cell proliferation. TP silencing and the TP agonist, U46619, further confirmed this finding. Moreover, SQ29548 and TP silencing promoted MM cell G2/M phase delay accompanied by reducing cyclin B1/cyclin-dependent kinase-1 (CDK1) mRNA and protein expression. Notably, cyclin B1 overexpression rescued MM cells from G2/M arrest. We also found that the TP agonist activated JNK and p38 MAPK phosphorylation, and inhibitors of JNK and p38 MAPK depressed U46619-induced proliferation and cyclin B1/CDK1 protein expression. In addition, SQ29548 and TP silencing led to the MM cell apoptotic rate increasing with improving caspase 3 activity. The knockdown of caspase 3 reversed the apoptotic rate. Taken together, our results suggest that TxA2/TP promotes MM cell proliferation by reducing cell delay at G2/M phase via elevating p38 MAPK/JNK-mediated cyclin B1/CDK1 expression and hindering cell apoptosis. The TP inhibitor has potential as a novel agent to target kinase cascades for MM therapy.
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http://dx.doi.org/10.1074/jbc.M115.683052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813499PMC
February 2016

MicroRNA-212 functions as an epigenetic-silenced tumor suppressor involving in tumor metastasis and invasion of gastric cancer through down-regulating PXN expression.

Am J Cancer Res 2015 15;5(10):2980-97. Epub 2015 Sep 15.

The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University Nanchang 330006, Jiangxi Province, China.

Altered expression of paxillin (PXN) is closely linked to the pathogenesis progression, metastasis and prognosis of different malignancies including gastric cancer (GC). Epigenetic silencing of tumor-suppressive microRNAs (miRNAs) is a crucial component of the mechanism underlying activation of oncogenes in tumor. To screen for epigenetically silenced miRNAs which target PXN in GC, we performed bioinformatics algorithms and real-time PCR analysis, and identified miR-212 as the optimum candidate gene. A luciferase reporter gene assay validated that miR-212 directly targets the 3'UTR region of PXN. Importantly, miR-212 levels were inversely correlated with PXN expression in GC cell lines and clinical tumor tissues. The use of miR-212 minics decrease PXN mRNA and protein level in GC cell lines. Moreover, low expression of miR-212 and its promoter hypermethylation were causally related and were associated with aggressive tumor phenotype and adverse prognosis in GC. Restoring mir-212 expression by exogenous mirprecursor molecules transfection or reexpression of endogenous miR-212 treated by 5-aza-2'-deoxycytidine (5-aza) can exert similar effect that reduce GC cells invasion and metastasis abilities in vitro by interacting PXN gene. In addition, 5-aza-induced PXN reduction could be partically blocked by miR-212 inhibitor, resulting in a reversal of weankening cell migration and invasion ability of 5-aza. A rescue experiment and a loss-of-function experiment in vitro and vivo showed that PXN restoration rescues migration and invasion phenotype in miR-212 overexpressed GC cell lines and PXN knockdown blocks GC cells migration and invasion in the presence miR-212 inhibitors. Taken together, our results clearly show that overexpression of PXN induced by methylationsuppressed miR-212 promotes tumor metastasis and invasion, and regulation of miR-212 expression may be a novel therapeutic strategy for gastric cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656725PMC
December 2015

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

Chin Med J (Engl) 2015 Oct;128(20):2743-50

Department of Neonatal Intensive Care Unit, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310053, China.

Background: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.

Methods: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.

Results: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.

Conclusions: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.
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http://dx.doi.org/10.4103/0366-6999.167312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736874PMC
October 2015

Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

Int J Hematol 2015 Oct 5;102(4):394-400. Epub 2015 Aug 5.

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P < 0.01) than in healthy individuals. Serum BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was <8 g/dL) and higher LDH activity (LDH > 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.
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http://dx.doi.org/10.1007/s12185-015-1851-8DOI Listing
October 2015

Prognosis of very preterm infants with severe respiratory distress syndrome receiving mechanical ventilation.

Lung 2015 Apr 13;193(2):249-54. Epub 2015 Jan 13.

Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China,

Objective: To evaluate the prognosis of very preterm infants with severe respiratory distress syndrome (RDS) receiving mechanical ventilation.

Methods: A total of 288 preterm infants mechanically ventilated for severe RDS and completed follow-up till 18 months of corrected age comprised these study subjects. The associations of prenatal and postnatal factors, mode and duration of conventional mechanical ventilation (CMV), medication and treatment, and complications with cerebral palsy or mental developmental index (MDI) < 70 at 18 months of age were analyzed.

Results: The incidences of CP among study subjects were 17, 5, and 2% in infants less than 28, 28-30, and 30-32 weeks, respectively. The incidences of MDI < 70 were 49, 24, and 13% in infants less than 28 weeks, 28-30 weeks, and 30-32 weeks, respectively. Antenatal corticosteroids, preeclampsia, fetal distress, early and late bacteremia, and decreased weight gain were associated with CP and an MDI < 70. In the CP and MDI < 70 groups, the number of infants on CMV was significantly higher than on high-frequency oscillatory ventilation (HFOV). Longer duration of mechanical ventilation and blood transfusions were associated with an increased risk of having an MDI < 70 or CP. The complications in study subjects associated with an MDI < 70 or CP were BPD, NEC, and IVH grade III-IV.

Conclusion: The prognosis of very preterm infants with severe RDS may be influenced by several prenatal and postnatal factors. HFOV although decreased the duration of mechanical ventilation, whether it will decrease the incidence of neurodevelopmental disability, needs to be explored further.
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http://dx.doi.org/10.1007/s00408-014-9683-5DOI Listing
April 2015

Effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells and leukemia mice.

Int J Clin Exp Med 2014 15;7(11):4031-7. Epub 2014 Nov 15.

Department of Hematology, Shanghai Xuhui Central Hospital & Shanghai Clinical Center, Chinese Academy of Sciences Shanghai 200031, China.

Objective: To investigate the effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells (K562) and the growth of chronic myeloid leukemia mice as well as to explore the potential mechanisms.

Methods: Unbtreated K562 cells (CON), blank lentivirus transfected K562 cells (NC) and K562 cells expressing STAT3 siRNA (STAT3 siRNA) were injected into SCID mice to establish the chronic myeloid leukemia model in mice. The growth, peripheral white blood cell count and spleen index in these mice were determined.

Results: In vitro experiment showed, when compared with control group, the interference efficiency of STAT3 expression was as high as 97.5% in K562 cells. Western blot assay revealed that the expression of c-Myc, Bcl-xL and Cyclin D1 reduced by 17.01%, 7.3% and 6.82%, respectively, showing significant difference when compared with control group (P < 0.01). These findings were consistent with those from fluorescence quantitative PCR. In vivo experiment showed the body weight of mice reduced progressively and the peripheral white blood cell count increased gradually in control group, accompanied by dragging hind limbs and progressive enlargement of the spleen. The body weight remained unchanged, peripheral white blood cell count reduced gradually and the spleen did not enlarge in mice treated with STAT3 siRNA expressing cells.

Conclusion: Lentivirus mediated STAT3 silencing may inhibit the expression of its downstream genes (c-Myc, Bcl-xL and Cyclin D1) related to cell proliferation, apoptosis and cycle to suppress the malignant biological behaviors, and STAT3 silencing also inhibit the leukemogenic potency of K562 cells in mice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276170PMC
December 2014

[Studies of cytokines expressions and karyotype of mesenchymal stem cell from bone marrow microenvironment in MDS patients].

Zhonghua Xue Ye Xue Za Zhi 2014 Jun;35(6):565-7

Shanghai Xuhui Central Hospital/Chinese Academic Sciences, CAS, Shanghai 200031, China.

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2014.06.023DOI Listing
June 2014

The use of the WINROP screening algorithm for the prediction of retinopathy of prematurity in a Chinese population.

Neonatology 2013 24;104(2):127-32. Epub 2013 Jul 24.

Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.

Background: Retinopathy of prematurity (ROP) is a gestational age (GA)-related illness that can lead to blindness in premature infants. Timely screening of premature infants could improve visual prognosis.

Objective: To evaluate the WINROP algorithm as a method of predicting severe ROP in a Chinese population.

Methods: 590 infants with a GA <32 weeks were entered into an online surveillance system (www.winrop.com) that included ROP evaluations and weekly weight measurements from birth to a corrected GA of 40 weeks. If the rate of weight gain decreased to a certain degree, the algorithm signaled an alarm that the infant was at risk for developing sight-threatening ROP. Each infant was categorized as having no, mild, or severe ROP.

Results: Among the 590 infants with a GA <32 weeks, an alarm was triggered in 85 infants (14.4%), 50 of which developed severe ROP and were identified in this alarm group. Twenty-seven infants triggered the alarm signal in the first week after birth and 7 infants triggered the alarm at birth. Seven of the infants developed proliferative ROP and the median GA at birth for these infants was 31 weeks.

Conclusions: The WINROP system had a sensitivity of 87.5% in a Chinese population for the early identification of infants that developed severe ROP. Postnatal weight gain may help predict ROP in lower birth weight infants.
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http://dx.doi.org/10.1159/000351297DOI Listing
March 2014

High-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation plus pressure support in preterm infants with severe respiratory distress syndrome.

Respir Care 2014 Feb 13;59(2):159-69. Epub 2013 Jun 13.

Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Mechanical ventilation and surfactants are the standard treatment of preterm respiratory distress syndrome (RDS). The effects of the primary ventilation model on bronchopulmonary dysplasia (BPD) and long-term neurodevelopment outcomes are controversial. The purpose of this study was to compare the efficacy and safety of high-frequency oscillatory ventilation (HFOV) and synchronized intermittent mandatory ventilation plus pressure support ventilation (SIMV-PSV) in preterm infants with severe RDS.

Methods: A total of 366 eligible preterm infants were randomly assigned to treatment with HFOV (n = 184) or SIMV-PSV (n = 182). Surfactant was applied if PaO2/FIO2 was < 200 mm Hg after 2 hours of ventilation. Primary outcomes were mortality or incidence of BPD. Secondary outcomes were duration of ventilation and hospitalization, surfactant requirements, pneumothorax, retinopathy of prematurity ≥ stage 2, and neurodevelopment at 18 months of corrected age.

Results: Survival and complete outcome data were available for 288 infants at 18 months of corrected age. The incidence of death or BPD was significantly higher in the SIMV-PSV group (P = .001). The duration of mechanical ventilation and hospitalization was shorter and the incidence of surfactant requirement and retinopathy of prematurity was lower in the HFOV group (P < .001, P = .002, P = .04, respectively). Moderate or severe neurological disability was less frequent in the HFOV group than in the SIMV-PSV group at 18 months (P = .03). The combination of HFOV and surfactant dramatically reduced negative outcomes in preterm infants with severe RDS.

Conclusions: Initial ventilation with HFOV in preterm infants with severe RDS reduces the incidence of death and BPD, and improves long-term neurodevelopment outcomes. (ClinicalTrials.gov NCT01496508).
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http://dx.doi.org/10.4187/respcare.02382DOI Listing
February 2014

Characteristics of respiratory distress syndrome in infants of different gestational ages.

Lung 2013 Aug 31;191(4):425-33. Epub 2013 May 31.

Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Background: The purpose of this study was to compare the risk factors, clinical characteristics, and complications of respiratory distress syndrome (RDS) in infants delivered very preterm, late preterm, and term in order to help optimize the management of RDS in neonates.

Methods: A retrospective study was conducted on neonates admitted to the NICU between January 2006 and December 2010. The enrolled infants with RDS were categorized as very preterm (<32(0/7) weeks gestation), moderately preterm (32(0/7)-33(6/7) weeks), late preterm (34(0/7)-36(6/7) weeks), and term (37(0/7)-42(0/7) weeks). The rates, potential risk factors, clinical characteristics, and complications of RDS of these four groups were comparatively analyzed.

Results: There was an increasing trend in incidence of RDS among the NICU admissions annually. Caesarean section without labor was significantly associated with RDS in term and late preterm infants (P < 0.001). Rates of requirements for ventilator and pulmonary surfactant were similar in very preterm and term infants but significantly lower in late preterm infants (P < 0.001). The oxygenation index value was not substantially lower in late preterm and term infants compared to very preterm infants, and the arterial oxygenation efficiency was improved slowly (P < 0.001). Incidence of pneumonia and occurrence of pneumothorax were significantly higher in term infants (P < 0.001).

Conclusions: Term infants with RDS showed an association of RDS with caesarean section without labor and lung infection. These infants also showed slower improvement of oxygenation after surfactant administration and mechanical ventilation, and they experienced a high rate of pneumothorax complication, which was also noticed in late preterm neonates.
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http://dx.doi.org/10.1007/s00408-013-9475-3DOI Listing
August 2013

Genetic inhibition of vascular endothelial growth factor receptor-1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy.

Oncol Rep 2013 May 13;29(5):2030-8. Epub 2013 Mar 13.

Department of Hematology, Tongji Hospital of Tongji University, Putuo, Shanghai 200065, PR China.

Little is known about the role of vascular endothelial growth factor (VEGF) receptor-1 (VEGFR-1) in acute leukemia. In this study, using real-time PCR and ELISA, we found that VEGF and VEGFR-1 are highly expressed in U937 leukemia cells and primary leukemia cells (M4/M5 subtypes), which are associated with an increased migration rate and extramedullary disease. In order to elucidate the role of VEGFR-1 in acute leukemia, we used a lentivirus-mediated shRNA expression system to specifically inhibit VEGFR-1 expression in the U937 cell line. In addition, a series of in vitro experiments were conducted, including cell proliferation and migration assays and drug treatments. Our results showed that shRNA reduced the proliferation and migration of U937 cells. RNA interference targeting VEGFR-1 in combination with bevacizumab did not exert synergistic antitumor effects. However, shRNA enhanced the sensitivity of the U937 cells to cytarabine by decreasing the IC50 of cytarabine, reducing the number of cells in the S phase and suppressing the expression of the survivin gene. Taken together, these results suggest that VEGFR-1 interference may serve as a novel antitumor therapeutic strategy for the treatment of leukemia.
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http://dx.doi.org/10.3892/or.2013.2348DOI Listing
May 2013

N-Propionyl polysialic acid precursor enhances the susceptibility of multiple myeloma to antitumor effect of anti-NprPSA monoclonal antibody.

Acta Pharmacol Sin 2012 Dec 5;33(12):1557-62. Epub 2012 Nov 5.

Department of Hematology, Tongji Hospital, Tongji University, Shanghai 200065, China.

Aim: To study the antitumor effect of anti-NprPSA monoclonal antibody (mAb) in combination with ManNPr, a precursor of N-propionyl PSA, in multiple myeloma (MM), and to explore the mechanisms of the action.

Methods: Human multiple myeloma cell line RPMI-8226 was tested. The cells were pre-treated with ManNPr (1, 2, and 4 mg/mL), and then incubated with anti-NprPSA mAb (1 mg/mL). Cell apoptosis in vitro was detected using MTT assay and flow cytometry. BALB/c nude mice were inoculated sc with RPC5.4 cells. On 5 d after the injection, the mice were administered sc with anti-NprPSA mAb (200 μg/d) and ManNPr (5 mg/d) for 8 d. The tumor size and body weight were monitored twice per week. TUNEL assay was used for detecting apoptosis in vivo. The apoptotic pathway involved was examined using Western blot analysis and caspase inhibitor.

Results: Treatment of RPMI-8226 cells with anti-NprPSA mAb alone failed to inhibit cell growth in vitro. In RPMI-8226 cells pretreated with ManNPr, however, the mAb significantly inhibited the cell proliferation, decreased the viability, and induced apoptosis, which was associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. In the mouse xenograft model, treatment with the mAb in combination with ManNPr significantly inhibited the tumor growth, and induced significant apoptosis as compared to treatment with the mAb alone. Moreover, apoptosis induced by the mAb in vivo resulted from the activation of the caspases and poly(ADP-ribose) polymerase.

Conclusion: The anti-NprPSA mAb in combination with ManNPr is an effective treatment for in vitro and in vivo induction of apoptosis in multiple myeloma.
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http://dx.doi.org/10.1038/aps.2012.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001846PMC
December 2012

Epidemiologic survey on hospitalized neonates in China.

Transl Pediatr 2012 Jul;1(1):15-22

1 Department of Pediatrics, China Medical University Affiliated Shengjing Hospital; 2 Department of Pediatrics, Central South University Affiliated Xiangya Hospital; 3 Department of Pediatrics, Sichuan University Affiliated West China Second Hospital; 4 Zhejiang University School of Medicine Affiliated Children's Hospital; 5 Beihai Maternal and Child Health Care Hospital; 6 Beihai People's Hospital; 7 Beijing Children's Hospital Emergency Center; 8 Capital University of Medical Sciences Affiliated Beijing Obstetrics&Gynecology Hospital; 9 Chengdu Children's Hospital/Chengdu Children's Emergency Center; 10 Chongqing Fifth People's Hospital; 11 Chongqing Fulin District Maternal and Child Health Care Hospital; 12 Chongqing Maternal and Child Health Care Hospital; 13 Chongqing Medical University Affiliated Children's Hospital; 14 Chongqing Three Gorge Central Hospital Children Health Care Center; 15 Dalian Children's Hospital; 16 Fudan University Affiliated Children's Hospital; 17 Fudan University Affiliated Obstetrics & Gynecology Hospital; 18 Gansu Maternal and Child Health Care Hospital; 19 Guangdong People's Hospital; 20 Guangi Minzu Hospital; 21 Guangxi Children's Hospital; 22 Guangxi Maternal and Child Health Care Hospital; 23 Guangzhou Children's Hospital; 24 Guangzhou NO.1 People's Hospital; 25 Guangzhou NO.2 People's Hospital; 26 Guiyang Maternal and Child Health Care Hospital; 27 Haikou Maternal and Child Health Care Hospital; 28 Hainan Maternal and Child Health Care Hospital; 29 Hainan Medical College Affiliated Hospital; 30 Harbin Medical University Affiliated Second Hospital; 31 Hölün Buyer Maternal and Child Health Care Hospital; 32 Hubei Maternal and Child Health Care Hospital; 33 Hunan Children's Hospital; 34 Hunan Maternal and Child Health Care Hospital; 35 Hunan People's Hospital; 36 Inner Mongolia Maternal and Child Health Care Hospital; 37 Jiamusi University Affiliated First Hospital; 38 Jiaozuo Maternal and Child Health Care Hospital; 39 Jiaxi Chi

Objective: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China.

Methods: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed.

Results: The male:female ratio was 1.73:1. Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). The top three diseases during the neonatal period were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. The incidences of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants were higher than those in premature infants, while the incidences of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants were lower than those in premature infants. The incidences of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. The outcomes of these hospitalized neonates included: recovered, 63.9%; improved, 27.3%; discharged due to the family's own decisions, 7.6%, and died, 1.2%. Nearly half (46.4%) of the neonatal death occurred within 24 hrs after admission.

Conclusion: The incidence of premature birth shows an increasing trend among hospitalized neonates. Since the neonatal deaths mainly occur within 24 hrs after admission, monitoring during this period should be enhanced.
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http://dx.doi.org/10.3978/j.issn.2224-4336.2011.10.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728849PMC
July 2012

Epidemiology of respiratory distress and the illness severity in late preterm or term infants: a prospective multi-center study.

Chin Med J (Engl) 2010 Oct;123(20):2776-80

Neonatology Department, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools.

Methods: Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥ 34 weeks' gestational age, admitted at < 72 hours of age, requiring continuous positive airway pressure (CPAP) or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns (ACoRN) Respiratory Score < 5, 5 - 8, and > 8.

Results: During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was (36.8 ± 2.2) weeks, mean birth weight was (2734.5 ± 603.5) g. The majority of the neonates were male (69.4%), late preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals, 76.9%). Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score < 7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed. Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion, bicarbonate infusion or vasopressors therapy (P < 0.05). The incidence of complications was also increased significantly in severe group (P < 0.05). The in-hospital mortality in the severe group was significantly higher than other two groups (P < 0.05). ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version II (SNAP-II) (P < 0.01). High gestational age, high SNAP-II score and oxygenation index (OI), and Apgar score at 5 minutes < 5 were independent risks for death.

Conclusions: Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-II score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.
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October 2010

Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy.

Pediatrics 2009 Aug 27;124(2):e218-26. Epub 2009 Jul 27.

Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy (HIE), by using a randomized, prospective study design.

Methods: A total of 167 term infants with moderate/severe HIE were assigned randomly to receive either erythropoietin (N = 83) or conventional treatment (N = 84). Recombinant human erythropoietin, at either 300 U/kg (N = 52) or 500 U/kg (N = 31), was administered every other day for 2 weeks, starting <48 hours after birth. The primary outcome was death or disability. Neurodevelopmental outcomes were assessed at 18 months of age.

Results: Complete outcome data were available for 153 infants. Nine patients dropped out during treatment, and 5 patients were lost to follow-up monitoring. Death or moderate/severe disability occurred for 35 (43.8%) of 80 infants in the control group and 18 (24.6%) of 73 infants in the erythropoietin group (P = .017) at 18 months. The primary outcomes were not different between the 2 erythropoietin doses. Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE (P = .001) and not those with severe HIE (P = .227). No negative hematopoietic side effects were observed.

Conclusion: Repeated, low-dose, recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE, without apparent side effects.
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http://dx.doi.org/10.1542/peds.2008-3553DOI Listing
August 2009

Transcription factors Xbp-1, Blimp-1, and BSAP are involved in the regulation of plasmacytic differentiation induced by 2-methoxyestradiol in myeloma cell lines.

Int J Hematol 2007 Dec;86(5):429-37

Department of Hematology, Changzheng Hospital, 415 Fengyang Road, Shanghai, China.

Our previous studies demonstrated that a low concentration of 2-methoxyestradiol (2ME2) could induce the differentiation of myeloma cell lines and CD138+ primary myeloma cells from myeloma patients and up-regulate the expression of messenger RNA (mRNA) and protein for the gene encoding X-box binding protein 1 (Xbp-1) in myeloma cell lines. In the present study, we used phosphorothioated antisense oligodeoxynucleotides (ASODN) to investigate the roles and interactions of transcription factors Xbp-1, B-lymphocyte induced maturation protein 1 (Blimp-1), and PAX-5-encoded B-cell-specific activator protein (BSAP), which are thought to be involved in the regulation of B-lymphocytic or plasmacytic differentiation. Blimp-1 ASODN and Xbp-1 ASODN clearly inhibited myeloma cell differentiation and significantly partially inhibited the differentiation effects induced by 2ME2 at low concentration, whereas PAX-5 ASODN clearly induced myeloma cell differentiation and significantly enhanced 2ME2-induced differentiation effects. Moreover, after incubation with Blimp-1 ASODN, the level of Xbp-1 mRNA clearly declined, whereas the level of PAX-5 mRNA significantly increased in myeloma cells. These results demonstrate that transcription factors Xbp-1, Blimp-1, and PAX-5-encoded BSAP play important roles in the regulation of plasmacytic differentiation and exert their effects on differentiation induced by low 2ME2 concentrations. Our primary study provided the rationale for a promising strategy-the future application of transcription-factor ASODN for clinical patients.
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http://dx.doi.org/10.1007/BF02984001DOI Listing
December 2007

Enhanced interferon-gamma secretion and antitumor activity of T-lymphocytes activated by dendritic cells loaded with glycoengineered myeloma antigens.

Chin Med J (Engl) 2007 Oct;120(19):1678-84

Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.

Background: Immunotherapy is emerging as a promising cure for cancer. However, a severe problem in this area is the immune tolerance to tumor cells and tumor-associated antigens, as evidenced by the ability of cancer to escape immune surveillance. To overcome this problem this work examined the potential of improving the antigenicity of myeloma by metabolic engineering of its cell surface carbohydrate antigens (i.e., glycoengineering) and presentation of the modified tumor antigens by dendritic cells (DCs) to generate cytotoxic T-lymphocytes (CTLs).

Methods: CD138+ myeloma cells were isolated from 11 multipe myeloma (MM) patients by the immunomagnetic bead method. The MM cells were treated with N-propionyl-D-mannosamine (ManNPr), a synthetic analog of N-acetyl-D-mannosamine (ManNAc), the natural biosynthetic precursor of N-acetyl sialic acid (NeuNAc), to express unnatural N-propionylated sialoglycans. The glycoengineered cells were then induced to apoptosis, and the apoptotic products were added to cultured functional DCs that could present the unnatural carbohydrate antigens to autologous T-lymphocytes.

Results: It was found that the resultant DCs could activate CD4+ and CD8+ T-lymphocytes, resulting in increased expression of T cell surface markers, including CD8CD28 and CD4CD29. Moreover, upon stimulation by glycoengineered MM cells, these DC-activated T-lymphocytes could release significantly higher levels of IFN-gamma (P < 0.05). Lactate dehydrogenase (LDH) assays further showed that the stimulated T-lymphocytes were cytotoxic to glycoengineered MM cells.

Conclusions: This work demonstrated that glycoengineered myeloma cells were highly antigenic and the CTLs induced by the DCs loaded with the unnatural myeloma antigens were specifically cytotoxic to the glycoengineered myeloma. This may provide a new strategy for overcoming the problem of immune tolerance for the development of effective immunotherapies for MM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178877PMC
October 2007

[Effect of 2-methoxyestradiol on differentiation of primary myeloma cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006 Apr;14(2):262-6

Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.

In order to investigate the differentiation-inducing effect of 2-methoxyestradiol (2ME2), an estrogen derivative, on CD138+ (Syndecan-1) primary myeloma cells from 7 patients with myeloma, primary myeloma cells from 7 patients were enriched by using CD138 immunomagenetic beads. The enriched CD138+ (Syndecan-1) myeloma cells treated with 0.5 micromol/L 2ME2 for 36 h and 72 hours were used to observe the differentiation changes with expression of CD49e and to quantitatively detect the light-chain secretion in the supernatants. The results indicated that 2ME2 caused morphological and immunophenotypic changes with light-chain secretion in the supernatant, and the typical features of differentiation of CD138+ (Syndecan-1) primary myeloma cells. CD138+ (Syndecan-1) myeloma cells became more and more mature in morphology, with decreased ratio of nucleus to plasma, disappearance of nucleoli, and pyknosis of chromatin. The result of detecting the expression of CD49e of CD138+ (Syndecan-1) myeloma cells showed the obvious up-regulation of CD49e expression after exposure to 2ME2 for 72 hours. Quantitative assay for light chain secretion in the supernatant of bone marrow CD138+ cells from patients showed remarkable increment at 72 hours. It is concluded that lower concentrations of 2-methoxyestradiol can induce differentiation of bone marrow CD138+ cells from multiple myeloma patients.
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April 2006
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