Publications by authors named "Haitao Bai"

33 Publications

Effects of a structured team nursing model on the efficacy and quality of cardiopulmonary resuscitation in myocardial infarction patients undergoing PCI.

Am J Transl Res 2021 15;13(4):3129-3137. Epub 2021 Apr 15.

Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430014, Hubei Province, China.

Objective: This study aimed to evaluate the effects of a structured team nursing model on the efficacy and quality of cardiopulmonary resuscitation (CPR) in acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI).

Methods: With the random number table, 130 myocardial infarction patients undergoing PCI were divided into two groups, including the control group (n=65) receiving routine emergency resuscitation and nursing care, and the study group (n=65) receiving a structured team care model. The efficacy of CPR, cardiac function, exercise tolerance, ability of daily living activities, quality of life, complication rate and nursing satisfaction were compared between the two groups.

Results: The door-to-balloon time, length of stay at the emergency department, duration of balloon dilation, bedtime and hospital stay in the study group were shorter than those in the control group (<0.05). The study group showed lower LVEDD and LVESD and higher LVEF than the control group after nursing (<0.05). The extend of physical limitation, angina stability, level of disease awareness, number of angina attacks, and treatment satisfaction scores in the 6-MWT, MBI, and SAQ scales in the study group after nursing were higher than those in the control group (<0.05). The complication rate in the study group (7.69%) was lower than that in the control group (20.00%) (<0.05). The study group had higher satisfaction with operational skills, teamwork, clinical practice, rescue awareness, orderliness, and timeliness than the control group (<0.05).

Conclusion: Structured team nursing model is helpful to improve the timeliness and quality of CRP, shorten the treatment time, improve patients' cardiac function and exercise tolerance, improve self-care ability and quality of life, reduce the occurrence of complications, and enhance the patient-nurse relationship.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129222PMC
April 2021

Gene knockout in highly purified mouse hematopoietic stem cells by CRISPR/Cas9 technology.

J Immunol Methods 2021 Aug 4;495:113070. Epub 2021 May 4.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. Electronic address:

The CRISPR/Cas9 system has been used for genome editing of human and mouse cells. In this study, we established a protocol for gene knockout (KO) in mouse hematopoietic stem cells (HSCs). HSCs were highly purified from the bone marrow of tamoxifen-treated Cas9-EGFP/Cre-ER transgenic mice, maintained in serum-free polyvinyl alcohol culture with cytokines, lentivirally transduced with sgRNA-Crimson, and transplanted into lethally irradiated mice with competitor cells. Previous studies of Pax5 KO mice have shown B cell differentiation block. To verify our KO HSC strategy, we deleted Pax5 gene in 600 CD201CD150CD48c-KitSca-1Lin cells (HSC1 cells), highly enriched in myeloid-biased HSCs, and CD201CD150CD48 c-KitSca-1Lin cells (HSC2 cells), highly enriched in lymphoid-biased HSCs. As predicted, both Pax5 KO HSC1 and HSC2 cells showed few B cells in the peripheral blood and the accumulation of pro-B cells in the bone marrow of recipient mice. Our data suggesetd that myeloid-biased and lymphoid-biased HSCs share a common B cell differentiation pathway. This population-specific KO strategy will find its applications for gene editing in a varity of somatic cells, particuarly rare stem and progenitor cells from different tissues.
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http://dx.doi.org/10.1016/j.jim.2021.113070DOI Listing
August 2021

Multi-centre study of the clinical features and gene variant spectrum of Gitelman syndrome in Chinese children.

Clin Genet 2021 Apr 2;99(4):558-564. Epub 2021 Feb 2.

Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.

Based on the Chinese Children Genetic Kidney Disease Database (CCGKDD), we established a pediatric Gitelman syndrome (GS) cohort to explore the phenotype and genotype characteristics. Thirty-two patients with SLC12A3 gene variants were collected. Five cases (16%) were homozygous, 16 (50%) were compound heterozygous, 10 (31%) carried only a single variant, and the other one harbored two de novo variants beyond classification. p.(T60M) was found in eight patients. The average diagnosis age was 7.79 ± 3.54 years. A total of 31% of the patients were asymptomatic. Muscle weakness was the most common symptom, accounting for 50%. Earlier age of onset (4.06 ± 1.17 yr vs. 8.10 ± 3.46 yr vs. 8.61 ± 3.56 yr, p< 0.05) and lower urinary calcium-creatinine ratio (p = 0.024) were found in the homozygous group than those in the heterozygous and compound heterozygous group. Patients with p.(T60M) variant had an earlier age of onset (4.01 ± 2.83 yr vs. 6.92 ± 3.07 yr, p = 0.025) and lower urinary calcium-creatinine ratio (p = 0.056). Thus, more than 30% of GS children have no clinical symptoms. Homozygous variant and the p.(T60M) variant may be associated with earlier onset and lower urinary calcium excretion in Chinese pediatric GS.
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http://dx.doi.org/10.1111/cge.13913DOI Listing
April 2021

Analysis and Isolation of Mouse Leukemic Stem Cells.

Methods Mol Biol 2021 ;2185:51-63

Department of Regenerative Medicine, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Flow cytometry has been widely used in basic and clinical research for analysis of a variety of normal and malignant cells. Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) can be highly purified by flow cytometry. Isolated HSCs and LSCs can be functionally identified by transplantation assays and can also be studied at the molecular level. Here we describe the flow cytometry methods for analysis and isolation of mouse HSCs and LSCs.
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http://dx.doi.org/10.1007/978-1-0716-0810-4_4DOI Listing
March 2021

Clinical Features and Prognostic Impact of Coexpression Modules Constructed by WGCNA for Diffuse Large B-Cell Lymphoma.

Biomed Res Int 2020 7;2020:7947208. Epub 2020 Jun 7.

Department of Haematology, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Hongkou District, Shanghai 200080, China.

Objective: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive malignant tumor, accounting for 30-40% of non-Hodgkin's lymphoma. Our aim was to construct novel prognostic models of candidate genes based on clinical features.

Methods: RNA-seq and clinical data of DLBCL were retrieved from TCGA database. Coexpression modules were constructed by WGCNA. Then, we investigated the interactions between modules and clinical features. By overall survival analysis, prognostic candidate genes from modules of interest were identified. A coexpression network of prognostic candidate genes was then constructed through WGCNA. GEPIA was used to analyze the expression of a candidate gene between DLBCL and normal samples.

Results: 19 coexpression modules were constructed by 12813 genes from 52 DLBCL samples. The number of genes in modules ranged from 34 to 5457. We found that the purple module was significantly related with histological type ( value = 1-04). Overall survival analysis revealed that MAFA-AS1, hsa-mir-338, and hsa-mir-891a were related with prognosis of DLBCL ( value = 0.027, 0.039, and 0.022, respectively). A coexpression network was constructed for the three prognostic genes. MAFA-AS1 was interacted with 36 genes, hsa-mir-891a was interacted with 11 genes, while no gene showed interaction with hsa-mir-338. Using GEPIA, we found that MAFA-AS1 showed low expression in DLBCL samples ( < 0.01).

Conclusion: We constructed a coexpression module related with histological type and identified three candidate genes (MAFA-AS1, hsa-mir-338, and hsa-mir-891a) that possessed potential value as prognostic biomarkers and therapeutic targets of DLBCL.
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http://dx.doi.org/10.1155/2020/7947208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298280PMC
March 2021

IPDN-China promotes the development of pediatric dialysis in China.

Pediatr Nephrol 2020 11 11;35(11):2163-2171. Epub 2020 Jun 11.

Division of Nephrology, Henan Children's Hospital, Henan, China.

Background: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012.

Methods: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed.

Results: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT).

Conclusions: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.
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http://dx.doi.org/10.1007/s00467-020-04630-3DOI Listing
November 2020

Heme oxygenase-1 alleviates eosinophilic inflammation by inhibiting STAT3-SOCS3 signaling.

Pediatr Pulmonol 2020 06 16;55(6):1440-1447. Epub 2020 Apr 16.

Department of Pediatrics, the First Affiliated Hospital of Xiamen University, Xiamen, China.

Airway inflammation of eosinophilic asthma (EA) attributes to Th2 response, leaving the role of Th17 response unknown. Signal transducer and activator of transcription 3 (STAT3) induce both suppressors of cytokine signaling 3 (SOCS3) and retinoic acid receptor-related orphan nuclear receptor γ (RORγt) to initiate Th17 cell differentiation which is inhibited by SOCS3, a negative feedback regulator of STAT3. Heme oxygenase-1 (HO-1) is a stress-responsive, cytoprotective, and immunoregulatory molecular. Two other isoforms of the enzyme includes HO-2 and HO-3. Because HO-2 does not exhibit stress-related upregulation and distributes mainly in nervous system and HO-3 shows a low enzymatic activity, we tested a hypothesized anti-inflammatory role for HO-1 in EA by inhibiting STAT3-SOCS3 signaling. Animal model was established with Ovalbumin in wild type Balb/C mice. Hemin or SNPP was intraperitoneally (IP) injected ahead of the animal model to induce or inhibit HO-1 expression. Airway inflammation was evaluated by bronchoalveolar lavage, hematoxyline and eosin staining, enzyme-linked immunosorbent assay, and Western blot analysis. In vivo results showed that HO-1 induction inhibited phosphorylation of STAT3 and expression of SOCS3 and RORγt, decreased Th2 and Th17 immune responses, and alleviated airway inflammation. In vitro results revealed that HO-1 inhibited phosphorylation of STAT3 and expression of SOCS3 in naive CD4 T cells. These findings identify HO-1 induction as a potential therapeutic strategy for EA treatment by reducing STAT3 phosphorylation, STAT3-SOCS3-mediated Th2/Th17 immune responses, and ultimate allergic airway inflammation.
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http://dx.doi.org/10.1002/ppul.24759DOI Listing
June 2020

Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system.

Clin Genet 2019 11 25;96(5):402-410. Epub 2019 Jul 25.

Department of Nephrology, The Children's Hospital of Guiyang City, Guiyang, China.

To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe the genotype and phenotype of the national cohort of children with renal disease from 13 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). Genetic diagnosis was confirmed in 42.1% of our cohort of 1001 pediatric patients with clinical suspicion of a genetic renal disease. Of the 106 distinct monogenetic disorders detected, 15 accounted for 60.7% of genetic diagnoses. The diagnostic yield was 29.1% in steroid resistant nephritic syndrome (SRNS), 61.4% in cystic renal disease, 17.0% in congenital anomalies of the kidney and urinary tract (CAKUT), 62.3% in renal tubular disease/renal calcinosis, and 23.9% for chronic kidney disease (CKD) 3 to 5 stage with unknown origin. Genetic approaches of target gene sequence (TGS), singleton whole-exome sequencing (WES) and trio-WES were performed with diagnostic rates of 44.8%, 36.2%, and 42.6%, respectively. The early use of trio-WES could improve the diagnostic rate especially in renal tubular disease and calcinosis. We report the genetic spectrum of Chinese children with renal disease. Establishment of the CCGKDD will improve the genetic work on renal disease.
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http://dx.doi.org/10.1111/cge.13606DOI Listing
November 2019

Lineage marker expression on mouse hematopoietic stem cells.

Exp Hematol 2019 08 9;76:13-23.e2. Epub 2019 Jul 9.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; National Clinical Research Center for Hematological disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; Department of Regenerative Medicine, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Electronic address:

Whether hematopoietic stem cells (HSCs) express lineage markers is controversial. In this study, we highly purified HSCs from the adult bone marrow of C57BL/6 mice and examined their gene expression and reconstitution potential. We first focused on the integrin family. Single-cell reverse transcription polymerase chain reaction revealed that the expression of ItgaM/Itgb2 (Mac-1) and Itga2b/Itgb3 (CD41/CD61) gradually increased along HSC differentiation, whereas Itga4, Itga5, Itga6, and ItgaV (CD51) together with Itgb1 were highly expressed in both HSCs and hematopoietic progenitor cells (HPCs). We next fractionated HSCs based on their expression of Mac-1, CD41, and CD51 by flow cytometry. We detected Mac-negative and Mac-low, but not Mac-high cells, in the HSC population. We also detected CD41-negative, -low, and -high cells in the HSC population. Competitive repopulation revealed that Mac-1-negative and -low HSCs were functionally similar, and CD41-negative and -low HSCs were functionally similar, at the single-cell level, but CD41-high HSCs were not detectable. We then found that the selection of Mac-1-negative HSCs or CD41-negative HSCs had no advantage in HSC purification. We moreover found that HSCs expressed more CD51 than CD41, and HPCs expressed more CD41 than CD51, suggesting that CD51 expression was gradually replaced by CD41 expression during megakaryocyte differentiation. We concluded that low levels of Mac-1 and CD41 expression are irrelevant to the self-renewal and differentiation potentials in HSCs.
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http://dx.doi.org/10.1016/j.exphem.2019.07.001DOI Listing
August 2019

Mouse acute leukemia develops independent of self-renewal and differentiation potentials in hematopoietic stem and progenitor cells.

Blood Adv 2019 02;3(3):419-431

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

The cell of origin, defined as the normal cell in which the transformation event first occurs, is poorly identified in leukemia, despite its importance in understanding of leukemogenesis and improving leukemia therapy. Although hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were used for leukemia models, whether their self-renewal and differentiation potentials influence the initiation and development of leukemia is largely unknown. In this study, the self-renewal and differentiation potentials in 2 distinct types of HSCs (HSC1 [CD150CD41CD34LineageSca-1c-Kit cells] and HSC2 [CD150CD41CD34LineageSca-1c-Kit cells]) and 3 distinct types of HPCs (HPC1 [CD150CD41CD34LineageSca-1c-Kit cells], HPC2 [CD150CD41CD34LineageSca-1c-Kit cells], and HPC3 [CD150CD41CD34LineageSca-1c-Kit cells]) were isolated from adult mouse bone marrow, and examined by competitive repopulation assay. Then, cells from each population were retrovirally transduced to initiate MLL-AF9 acute myelogenous leukemia (AML) and the intracellular domain of NOTCH-1 T-cell acute lymphoblastic leukemia (T-ALL). AML and T-ALL similarly developed from all HSC and HPC populations, suggesting multiple cellular origins of leukemia. New leukemic stem cells (LSCs) were also identified in these AML and T-ALL models. Notably, switching between immunophenotypical immature and mature LSCs was observed, suggesting that heterogeneous LSCs play a role in the expansion and maintenance of leukemia. Based on this mouse model study, we propose that acute leukemia arises from multiple cells of origin independent of the self-renewal and differentiation potentials in hematopoietic stem and progenitor cells and is amplified by LSC switchover.
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http://dx.doi.org/10.1182/bloodadvances.2018022400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373745PMC
February 2019

Pitting Corrosion and Microstructure of J55 Carbon Steel Exposed to CO₂/Crude Oil/Brine Solution under 2⁻15 MPa at 30⁻80 °C.

Materials (Basel) 2018 Nov 26;11(12). Epub 2018 Nov 26.

College of Petroleum Engineering, Key Laboratory of Environment Pollution Control Technology of Oil Gas and Reservoir Protection in Shaanxi Protection, Xi'an Shiyou University, Xi'an 710065, China.

This study aimed to evaluate the corrosion properties of J55 carbon steel immersed in CO₂/crude oil/brine mixtures present in the wellbores of CO₂-flooded production wells. The main corroded position of wellbore was determined and wellbore corrosion law was provided. Corrosion tests were performed in 30% crude oil/brine solution under the simulated temperature (30⁻80 °C) and pressure (2⁻15 MPa) conditions of different well depths (0⁻1500 m). The corrosion behavior of J55 carbon steel was evaluated through weight-loss measurements and surface analytical techniques, including scanning electron microscopy, energy dispersive spectrometer, X-ray diffraction analysis, and optical digital microscopy. Corrosion rate initially increased and then decreased with increasing well depth, which reached the maximum value of 1050 m. At this well depth, pressure and temperature reached 11 MPa and 65 °C, respectively. Under these conditions, FeCO₃ and CaCO₃ localized on sample surfaces. Microscopy was performed to investigate corrosion depth distribution on the surfaces of the samples.
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http://dx.doi.org/10.3390/ma11122374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317236PMC
November 2018

Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood for patients with hematologic malignancies: a prospective, phase II study.

Bone Marrow Transplant 2019 07 16;54(7):1049-1057. Epub 2018 Nov 16.

Department of Hematology, Shanghai General Hospital (affiliated to Shanghai Jiao Tong University), No. 100 Haining Road, 200080, Shanghai, China.

Nowadays, the most wildly used regimens for graft-versus-host disease (GvHD) prophylaxis in haplo-hematopoietic stem cell transplantation (Haplo-HSCT) are based on in vivo T-cell depletion (TCD) with anti-thymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCy). To improve the efficiency of GvHD prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood (Haplo-PBSCT-Cord), a novel regimen, which is composed of low dose of ATG (5 mg/kg) and low-dose PTCy (50 mg/kg) for GvHD prophylaxis, was evaluated in a prospective phase II clinical trial (Clinicaltrials.org NCT03395860). Thirty-two patients diagnosed with hematological malignancies were enrolled in this trial. All patients received myeloablative conditioning regimens except for three patients. The cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD were 19.4% (95% CI, 5.5-33.3%) and 6.9% (95% CI, 0-16.3%) by day 100, respectively. The 1-year probability of relapse, disease free survival (DFS) and overall survival (OS) was 25.1% (95% CI, 7.3-42.9%), 59% (95% CI, 33.3-84.7%) and 78.4% (95% CI, 63-93.8%), respectively. The CIs of CMV and EBV reactivation by day 180 were 37.5% (95% CI, 19.8-55.2%) and 40.6% (95% CI, 22.6-58.6%), respectively. The results suggested that low-dose ATG with low-dose PTCy as GvHD prophylaxis in Haplo-PBSCT-Cord had promising activity.
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http://dx.doi.org/10.1038/s41409-018-0382-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760546PMC
July 2019

Bacterial Pathogens Differed Between Neutropenic and Non-neutropenic Patients in the Same Hematological Ward: An 8-Year Survey.

Clin Infect Dis 2018 11;67(suppl_2):S174-S178

Department of Hematology, Shanghai Jiao Tong University-affiliated Shanghai General Hospital, China.

Background: Bacterial infections are very common among patients with hematological diseases. Scant data are available regarding differences in the epidemiology and biological features of bacterial infections in neutropenic and non-neutropenic patients.

Methods: The aim of this survey was to compare the bacterial pathogens in neutropenic and non-neutropenic patients in the same ward during an 8-year period.

Results: A total of 1139 bacterial strains were isolated from 1071 patients with hematological diseases. The percentage of Gram-negative bacteria was significantly higher in neutropenic patients than in non-neutropenic patients (70.4% vs. 55.0%, respectively, P < .01). In neutropenic patients, the most commonly-isolated bacterium was Pseudomonas aeruginosa, followed by Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Stenotrophomonas maltophilia. In respiratory exudates, Gram-negative bacteria were also more frequently isolated from neutropenic patients than from non-neutropenic patients (79.1% vs. 56.1%, respectively, P < .01). The proportion of non-fermentative Gram-negative bacilli was significantly higher in neutropenic patients than in non-neutropenic patients (52.9% vs. 30.5%, respectively, P < .01). In blood culture samples from neutropenic patients, the most frequently identified pathogens, apart from coagulase negative staphylococcus, were Gram-negative bacilli (58.2%). In addition, the proportion of Escherichia coli in neutropenic patients was significantly higher than that in non-neutropenic patients (P < .01). Escherichia coli and Klebsiella pneumoniae strains from neutropenic patients also produced extended-spectrum β-lactamases at a higher rate of than those strains from non-neutropenic patients (Escherichia coli, 57.6% vs. 30.3%, respectively, P < .01; Klebsiella pneumonia, 31.9% vs. 13.0%, respectively, P < .01).

Conclusions: This study showed that there are significant differences in the epidemiology and biological features of bacteria isolated from neutropenic and non-neutropenic patients.
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http://dx.doi.org/10.1093/cid/ciy643DOI Listing
November 2018

Effect of CO₂ Partial Pressure on the Corrosion Behavior of J55 Carbon Steel in 30% Crude Oil/Brine Mixture.

Materials (Basel) 2018 Sep 18;11(9). Epub 2018 Sep 18.

College of Petroleum Engineering, Key Laboratory of Environment Pollution Control Technology of Oil Gas and Reservoir Protection in Shaanxi Protection, Xi'an Shiyou University, Xi'an 710065, China.

The influence of CO₂ partial pressure on the corrosion properties, including corrosion rate, morphology, chemical composition, and corrosion depth, of J55 carbon steel in 30% crude oil/brine at 65 °C was investigated. A corrosion mechanism was then proposed based on the understanding of the formation of localized corrosion. Results showed that localized corrosion occurred in 30% crude oil/brine with CO₂. The corrosion rate sharply increased as the CO₂ partial pressure (P co 2 ) was increased from 0 to 1.5 MPa, decreased from P co 2 = 1.5 MPa to P co 2 = 5.0 MPa, increased again at P co 2 = 5.0 MPa, and then reached a constant value after P co 2 = 9.0 MPa. The system pH initially decreased, rapidly increased, and then stabilized as CO₂ partial pressure was increased. In the initial period, the surface of J55 carbon steel in the CO₂/30% crude oil/brine mixtures showed intense corrosion. In conclusion, CO₂ partial pressure affects the protection performance of FeCO₃ by changing the formation of corrosion scale and further affecting the corrosion rate.
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http://dx.doi.org/10.3390/ma11091765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164131PMC
September 2018

JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling.

J Clin Invest 2018 05 26;128(5):1737-1751. Epub 2018 Mar 26.

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Leukemia-initiating cells (LICs) are responsible for the initiation, development, and relapse of leukemia. The identification of novel therapeutic LIC targets is critical to curing leukemia. In this report, we reveal that junctional adhesion molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplantations in an MLL-AF9-induced murine acute myeloid leukemia model. In contrast, Jam3 deletion does not affect the functions of mouse hematopoietic stem cells. Moreover, knockdown of JAM3 leads to a dramatic decrease in the proliferation of both human leukemia cell lines and primary LICs. JAM3 directly associates with LRP5 to activate the downstream PDK1/AKT pathway, followed by the downregulation of GSK3β and activation of β-catenin/CCND1 signaling, to maintain the self-renewal ability and cell cycle entry of LICs. Thus, JAM3 may serve as a functional LIC marker and play an important role in the maintenance of LIC stemness through unexpected LRP5/PDK1/AKT/GSK3β/β-catenin/CCND1 signaling pathways but not via its canonical role in cell junctions and migration. JAM3 may be an ideal therapeutic target for the eradication of LICs without influencing normal hematopoiesis.
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http://dx.doi.org/10.1172/JCI93198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919829PMC
May 2018

Early tapering of immunosuppressive agents after HLA-matched donor transplantation can improve the survival of patients with advanced acute myeloid leukemia.

Ann Hematol 2018 Mar 18;97(3):497-507. Epub 2017 Dec 18.

Department of Hematology, Shanghai General Hospital affiliated to Shanghai Jiao Tong University, Haining road 100, Shanghai, 200080, China.

Disease recurrence is the most important obstacle to achieve long-term survival for patients with advanced acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to reduce the relapse risk and improve the survival, the strategy of early tapering of immunosuppressive agents was prospectively evaluated. Thirty-one patients with advanced AML received early tapering of immunosuppressive drugs, while 32 patients with AML in complete remission (CR) were given the routine tapering of immunosuppressive agents after HLA-matched donor transplantation. All advanced AML patients achieved CR after allo-HSCT. At 24 months after transplantation, relapse incidences were 22% in advanced group and 16% in CR group (P = 0.553); disease-free survival (DFS) and overall survival (OS) were 57.7 and 57.8% in advanced group, while in CR group were 66.6% (P = 0.388) and 66.2% (P = 0.423); immunosuppressive agent-free DFS (IDFS) were similar between two groups (P = 0.407). Acute graft-versus-host disease (aGvHD) incidences were similar between two groups (P = 0.311). Chronic GvHD (cGvHD) incidence was much higher in advanced group than in CR group (70.4 vs 38.7%, P = 0.02), but severe cGvHD had no difference. In multivariate analysis, cGvHD was an independent prognostic factor for lower risk of relapse and better DFS and OS; early tapering of immunosuppressive agents was an independent prognostic factor for cGvHD. The study suggested that advanced AML patients could be directly treated with allo-HSCT and its survival could be improved through the strategy of early tapering of immunosuppressive agents without significant adverse effects ( Clinicaltrials.org NCT03150134).
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http://dx.doi.org/10.1007/s00277-017-3204-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797220PMC
March 2018

Involvement of miR-125a in resistance to daunorubicin by inhibiting apoptosis in leukemia cell lines.

Tumour Biol 2017 Apr;39(4):1010428317695964

1 Department of Hematology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.

In this study, we investigated whether miR-125a participated in the resistance of the leukemia cell lines to the chemotherapeutic agent daunorubicin. Higher expression of miR-125a is correlated with lower treatment response and shorter overall survival in acute leukemia patients. Overexpression of miR-125a induced drug resistance in HL-60, K562, and THP-1cell lines through reducing apoptosis. We also showed that miR-125a mediated daunorubicin resistance in leukemia cell lines through the decrease of GRK2 and Puma which were proved to be direct targets of miR-125a. This study may provide novel therapeutic targets for therapy and improve predictions of therapeutic responses in leukemia to daunorubicin.
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http://dx.doi.org/10.1177/1010428317695964DOI Listing
April 2017

CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27 signaling.

Haematologica 2017 04 25;102(4):707-718. Epub 2017 Jan 25.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, China

Targeting leukemia initiating cells is considered to be an effective way to cure leukemia, for which it is critical to identify novel therapeutic targets. Herein, we demonstrate that CD244, which was initially reported as a key regulator for natural killer cells, is highly expressed on both mouse and human leukemia initiating cells. Upon CD244 knockdown, human leukemia cell lines and primary leukemia cells have markedly impaired proliferation abilities both and Interestingly, the repopulation ability of both mouse and human hematopoietic stem cells is not impaired upon CD244 knockdown. Using an MLL-AF9-induced murine acute myeloid leukemia model, we show that leukemogenesis is dramatically delayed upon CD244 deletion, together with remarkably reduced Mac1/c-Kit leukemia cells (enriched for leukemia initiating cells). Mechanistically, we reveal that CD244 is associated with c-Kit and p27 except for SHP-2 as previously reported. CD244 co-operates with c-Kit to activate SHP-2 signaling to dephosphorylate p27 and maintain its stability to promote leukemia development. Collectively, we provide intriguing evidence that the surface immune molecule CD244 plays an important role in the maintenance of stemness of leukemia initiating cells, but not in hematopoietic stem cells. CD244 may represent a novel therapeutic target for the treatment of acute myeloid leukemia.
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http://dx.doi.org/10.3324/haematol.2016.151555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395111PMC
April 2017

A dose increased once-weekly bortezomib-based combination therapy for multiple myeloma.

Oncotarget 2016 Oct;7(43):70168-70174

Department of Hematology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.

Background: The purpose of the current study was to evaluate the efficacy and safety of a dose increased weekly Bortezomib (Bor) based combination therapy in multiple myeloma (MM) patients.

Results: The overall response rate (ORR) in the modified Bor group was 76.6%, composed of 40% complete response (CR), 3.3% very good partial response (VGPR) and 33.3% partial response (PR). The ORR was 82.3%, with 26.5% CR, 5.9% VGPR and 50% PR in control. A subgroup analysis showed both groups had equal efficacy in newly diagnosed MM patients ( P = 1.000). The median progression free survival was 16 (11.7-20.3) months for the modified Bor group and 12 (10.5-13.5) months for the control (P = 0.503), and the median overall survival was 36 (9.4-62.6) vs 28 (21.6-34.4) months (P = 0.759). The incidences of AEs were similar except grade 1-4 peripheral neuropathy (PN) rate was 10% in modified regime group and 32.4% in control (P = 0.038).

Materials And Methods: This was a monocentric, prospective, non-randomized, phase IV, non-inferiority trial. Thirty MM patients were treated with modified Bor-based combination therapy (Bor 1.6 mg/m2 on day 1, 8), with 34 MM patients on conventional Bor-based combination therapy (1.3 mg/m2 on day 1, 4, 8, 11) as control. The responses and adverse events (AEs) were compared.

Conclusions: The increased-dose weekly Bor-based combination therapies were not inferior to conventional ones in terms of response and survival benefit, but showed lower rate of peripheral neuropathy (PN).
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http://dx.doi.org/10.18632/oncotarget.12162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342543PMC
October 2016

[A patient with eosinophilic gastroenteritis presenting with acute pancreatitis].

Zhonghua Er Ke Za Zhi 2015 Jul;53(7):542-3

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July 2015

MicroRNA-21 is involved in X-ray irradiation resistance in K562 leukaemia cells.

Hematology 2015 Jul 20;20(6):343-8. Epub 2014 Sep 20.

Background: Many studies have demonstrated that microRNA-21 (miR-21) acts as an oncogene in the tumourigenesis of a variety of tumours and may be involved in the chemotherapeutic drug resistance of tumour cells. In this study, we utilized the leukaemia cell line K562 as an in vitro cell model to investigate whether miR-21 is involved in X-ray irradiation resistance.

Methods: Retroviral transduction and antisense oligonucleotide transfection were used to overexpress or knock down miR-21 expression, respectively. An MTT assay was used to measure cell viability, and western blotting was performed to detect the expression of the miR-21 target gene, PTEN (phosphatase and tensin homologue), and its downstream signalling components, phosphatidylinositol 3-kinase (PI3K), and AKT.

Results: The overexpression of miR-21 decreased the protein expression levels of PTEN, increased the phosphorylation level of AKT, and enhanced the X-ray irradiation resistance in K562 cells. In contrast, the knockdown of miR-21 increased the PTEN protein expression, reduced the phosphorylation levels of the AKT, and increased the sensitivity of K562 cells to X-ray irradiation. The overexpression of PTEN or the knockdown of AKT also increased the sensitivity of K562 cells to X-ray irradiation.

Conclusion: By regulating the expression of its target gene PTEN, which subsequently affects the PI3K/AKT signalling pathway, miR-21 exerts its regulatory role on the radiation sensitivity of K562 cells. These results may help to provide the basis for microRNA-based targeted therapies to overcome radiation resistance in tumour cells.
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http://dx.doi.org/10.1179/1607845414Y.0000000201DOI Listing
July 2015

microRNA‑125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis.

Mol Med Rep 2014 May 6;9(5):1909-16. Epub 2014 Mar 6.

Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.

microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP‑1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.
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http://dx.doi.org/10.3892/mmr.2014.2011DOI Listing
May 2014

Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia.

Int J Oncol 2014 May 27;44(5):1661-8. Epub 2014 Feb 27.

Department of Hematology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, P.R. China.

Imatinib mesylate (IM), a targeted competitive inhibitor of the BCR-ABL tyrosine kinase, has revolutionized the clinical treatment of chronic myeloid leukemia (CML). However, resistance and intolerance are still a challenge in the treatment of CML. Autophagy has been proposed to play a role in IM resistance. To investigate the anti-leukemic activity of specific and potent autophagy inhibitor-1 (spautin-1) in CML, we detected its synergistic effect with IM in K562 and CML cells. Our results showed that spautin-1 markedly inhibited IM-induced autophagy in CML cells by downregulating Beclin-1. Spautin-1 enhanced IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2. We further demonstrated that the pro-apoptotic activity of spautin-1 was associated with activation of GSK3β, an important downstream effector of PI3K/AKT. The findings indicate that the autophagy inhibitor spautin-1 enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, leading to downregulation of Mcl-1 and Bcl-2, which represents a promising approach to improve the efficacy of IM in the treatment of patients with CML.
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http://dx.doi.org/10.3892/ijo.2014.2313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904104PMC
May 2014

Rituximab and fludarabine or cyclophosphamide combination treatment for older waldenström macroglobulinemia patients.

Turk J Haematol 2013 Dec 5;30(4):422-3. Epub 2013 Dec 5.

Department of Hematology, Shanghai First People's Hospital, Shanghai, Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.4274/TJH.2013.0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874973PMC
December 2013

Citrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1α signaling.

Mol Med Rep 2013 Nov 24;8(5):1379-84. Epub 2013 Sep 24.

Department of Hematology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, P.R. Chian.

The present study aimed to investigate the anti-tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl-2, caspases-3 and -9, hypoxia-inducible factor 1α (HIF‑1α) and its target gene GLUT-1, were assayed by western blotting and the role of HIF‑1α was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl-2, while it induces the activation of caspases-3 and -9. In addition, citrate induces U937 apoptosis in a dose- and time-dependent manner by regulating the expression of HIF‑1α and its downstream target GLUT-1. The results suggest that citrate performs an anti-acute monocytic leukemia action by targeting HIF‑1α signaling and may be a promising clinical approach.
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http://dx.doi.org/10.3892/mmr.2013.1702DOI Listing
November 2013

MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen.

Int J Hematol 2013 Feb 30;97(2):223-31. Epub 2012 Dec 30.

Department of Haematology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, Shanghai, China.

Numerous studies have demonstrated that microRNA-21 (miR-21), as an oncogene, is involved in the occurrence of many types of tumor and the sensitivity of tumor cells to chemotherapeutic drugs. In the present study, we investigated whether miR-21 is involved in regulating the sensitivity of the diffuse large B-cell lymphoma (DLBCL) cell line CRL2631 to the cyclophosphamide, vincristine, Adriamycin, and prednisone (CHOP) chemotherapeutic regimen. Knockdown of miR-21 with antisense oligonucleotides significantly increased the cytotoxic effects of the CHOP regimen in CRL2631 cells. A luciferase reporter assay showed that PTEN is a target gene of miR-21 in CRL2631 cells, and subsequent experiments demonstrated that miR-21 impacts the PI3K/AKT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen. Furthermore, knockdown of NF-κB decreased miR-21 expression and sensitized CRL2631 cells to CHOP treatment. These results provide evidence that it may be possible to overcome microRNA-based DLBCL drug resistance.
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http://dx.doi.org/10.1007/s12185-012-1256-xDOI Listing
February 2013

An in vivo functional screen uncovers miR-150-mediated regulation of hematopoietic injury response.

Cell Rep 2012 Oct 19;2(4):1048-60. Epub 2012 Oct 19.

Department of Genetics, Yale Stem Cell Center, Yale Cancer Center and Yale Center for RNA Science and Medicine, Yale University, New Haven, CT 06520, USA.

Hematopoietic stem and progenitor cells are often undesired targets of chemotherapies, leading to hematopoietic suppression requiring careful clinical management. Whether microRNAs control hematopoietic injury response is largely unknown. We report an in vivo gain-of-function screen and the identification of miR-150 as an inhibitor of hematopoietic recovery upon 5-fluorouracil-induced injury. Utilizing a bone marrow transplant model with a barcoded microRNA library, we screened for barcode abundance in peripheral blood of recipient mice before and after 5-fluorouracil treatment. Overexpression of screen-candidate miR-150 resulted in significantly slowed recovery rates across major blood lineages, with associated impairment of bone marrow clonogenic potential. Conversely, platelets and myeloid cells from miR-150 null marrow recovered faster after 5-fluorouracil treatment. Heterozygous knockout of c-myb, a conserved target of miR-150, partially phenocopied miR-150-forced expression. Our data highlight the role of microRNAs in controlling hematopoietic injury response and demonstrate the power of in vivo functional screens for studying microRNAs in normal tissue physiology.
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http://dx.doi.org/10.1016/j.celrep.2012.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487471PMC
October 2012

Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms.

Proc Natl Acad Sci U S A 2012 Oct 24;109(41):16636-41. Epub 2012 Sep 24.

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

Deregulation of microRNA (miRNA) expression can lead to cancer initiation and progression. However, limited information exists on the function of miRNAs in cancer maintenance. We examined these issues in the case of myeloproliferative diseases and neoplasms (MPN), a collection of hematopoietic neoplasms regarded as preleukemic, thereby representing early neoplastic states. We report here that microRNA-125a (miR-125a)-induced MPN display a complex manner of oncogene dependence. Following a gain-of-function genomics screen, we overexpressed candidate miR-125a in vivo, which led to phenotypes consistent with an atypical MPN characterized by leukocytosis, monocytosis, splenomegaly, and progressive anemia. The diseased MPN state could be recapitulated in a doxycycline-inducible mouse model. Upon doxycycline withdrawal, the primary MPN phenotypes rapidly resolved after the discontinuation of miR-125a overexpression. However, reinduction of miR-125a led to complex phenotypes, with some animals rapidly developing lethal anemia with extensive damages in the spleen. Forced expression of miR-125a resulted in elevated cellular tyrosine phosphorylation and hypersensitivity toward hematopoietic cytokines. Furthermore, we demonstrate that miR-125a targets multiple protein phosphatases. Our data demonstrate that miR-125a-induced MPN is addicted to its sustained overexpression, and highlight the complex nature of oncogenic miRNA dependence in an early neoplastic state.
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http://dx.doi.org/10.1073/pnas.1213196109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478612PMC
October 2012

Hypoxia inducible factor-1α-mediated activation of survivin in cervical cancer cells.

J Obstet Gynaecol Res 2013 Feb 26;39(2):555-63. Epub 2012 Aug 26.

Department of Haematology, Shanghai Jiao Tong University Affiliated Shanghai First People's Hospital, Shanghai, China.

Aim: Hypoxia, a characteristic of almost all types of solid tumors, has been associated with poor outcome in a number of human malignancies. The aim of this study was to investigate the molecular mechanisms involved in hypoxia-induced activation of the human survivin gene promoter in cervical HeLa cells.

Material And Methods: Immunohistochemical staining was used to detect the expression of HIF-1α and survivin in cervical cancer samples and normal cervical samples. Under normoxic and hypoxic conditions, the expression of hypoxia inducible factor (HIF)-1α and survivin in cervical cancer HeLa cells was detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Luciferase reporter assays was used to investigate the molecular mechanisms in hypoxia-induced survivin activation. We also studied the effect of HIF-1α overexpression on the expression of survivin in cervical cancer HeLa cells.

Results: Significant HIF-1α and survivin overexpression is associated with cervical cancer, and HIF-1α protein expression is strongly correlated with survivin protein expression. In cervical cancer cell line (HeLa), hypoxia upregulated both HIF-1α and survivin expression. Moreover, luciferase reporter assays using survivin core promoter demonstrated that survivin transcription was activated under hypoxia conditions and was associated with HIF-1α overexpression. The transcriptional activation of reporter genes in response to hypoxia is independent of potential HIF-1α-responsive element, located between -86 and -82 regions. HIF-1α overexpression significantly activated survivin expression.

Conclusion: Our results demonstrate that survivin expression is upregulated following the induction of HIF-1α by hypoxia resulting from tumor formation, possibly leading to tumor progression. These findings have potential implication in developing novel cancer therapy targeting HIF-1.
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http://dx.doi.org/10.1111/j.1447-0756.2012.01995.xDOI Listing
February 2013

Effect of stem cell factor and granulocyte-macrophage colony-stimulating factor-induced bone marrow stem cell mobilization on recovery from acute tubular necrosis in rats.

Ren Fail 2012 20;34(3):350-7. Epub 2012 Jan 20.

Division of Pediatric Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.

Background: Acute tubular necrosis (ATN) is the most common reason for acute kidney injury (AKI), and there is still an absence of effective therapies.

Objective: To assess the value of bone marrow cell mobilization by stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy in rats with gentamicin-induced ATN.

Methods: ATN was induced in male Sprague-Dawley (SD) rats with five daily high-dose intraperitoneal injections of gentamicin. Subcutaneous injections of SCF and GM-CSF were administered simultaneously and these cytokines were observed on days 2, 5, 10, 17, 24, and 31. Peripheral blood and renal tissue CD34+ cell count, mortality rate, blood urea nitrogen (BUN), serum creatinine (SCr), creatinine clearance rate (CCr), and histopathologic lesion scores were determined. Twelve hours after bone marrow ablation (BMA) by lethal X-ray radiation, specific pathogen-free (SPF) ATN rats were given five daily injections of SCF and GM-CSF. BUN, SCr, and histopathologic lesion scores were evaluated on days 2, 5, and 10.

Results: Peripheral blood CD34+ cell count increased significantly in ATN rats between 2 and 10 days after SCF and GM-CSF injection. Mortality was reduced from 34.7% in the ATN group to 18.6% in the ATN+CSF. In addition, cytokines administration significantly decreased SCr and BUN. Moreover, cytokines rapidly ameliorated tubular injury. There was no significant effect on ATN rats after BMA.

Conclusions: This study demonstrated that SCF and GM-CSF effectively mobilized bone marrow cells in ATN rats, and cytokines administration partially prevented gentamicin-induced ATN. These results suggest that bone marrow stem cell (BMSC) mobilization may be an effective therapy for ATN.
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http://dx.doi.org/10.3109/0886022X.2011.647340DOI Listing
July 2012
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