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PubMed | China Japan Friendship Hospital, Academy of Military Medicine science, BGI Shenzhen, Chinese Institute of Clinical Medical Sciences and 5 more.
Type: Journal Article | Journal: Cell research | Year: 2014

The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP(+) cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature cells in vitro.


Gong W.,Jilin University | Gong W.,Academy of Military Medicine science | Jiang Y.,Academy of Military Medicine science | Za Y.,Guangdong Center for Animal Disease Control | And 7 more authors.
Virus Research | Year: 2010

Phylogenetic studies have revealed a profound understanding about the biodiversity of rabies viruses in China, but little is known about their evolutionary dynamics in the country. In the present study, the complete G gene sequences of 33 rabies virus isolates (RABVs) isolated from distinct Chinese provinces were determined and phylogenetic analysis was conducted using these G sequences and 93 others retrieved from GenBank representing China and Southeast Asia. Further evolutionary history of RABV was estimated using a Bayesian Markov chain Monte Carlo method to understand the temporal and spatial dynamics of this virus. Results showed that rabies viruses in China and Southeast Asia share a common ancestor and form 2 clades with each being further divided into 3 lineages. The time of the most recent common ancestor of current RABV strains was estimated to be year 1654 (1514-1812) and the viruses circulating in Southeast Asia likely derived from China. © 2010 Elsevier B.V.


Wang C.,CAS Institute of Zoology | Zhang Y.,Academy of Military Medicine science | Wu B.,CAS Institute of Zoology | Liu S.,Centers for Disease Control and Prevention | And 8 more authors.
PLoS ONE | Year: 2013

The 2009 influenza pandemic had a tremendous social and economic impact. To study the genetic diversity and evolution of the 2009 H1N1 virus, a mutation network for the non-structural (NS) gene of the virus was constructed. Strains of the 2009 H1N1 pandemic influenza A virus could be divided into two categories based on the V123I mutation in the NS1 gene: G1 (characterized as 123 Val) and G2 (characterized as 123 Ile). Sequence homology analysis indicated that one type of NS sequence, primarily isolated from Mexico, was likely the original type in this pandemic. The two genotypes of the virus presented distinctive clustering features in their geographic distributions. These results provide additional insight into the genetics and evolution of human pandemic influenza H1N1. © 2013 Wang et al.


PubMed | Academy of Military Medicine science, Centers for Disease Control and Prevention, CAS Institute of Zoology and Kafr El Sheikh University
Type: | Journal: Scientific reports | Year: 2016

Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs. In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out. We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV. Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-B pathway. ssc-miR-30d-R_1 significantly reduced viral infections and pathological changes in pig lungs in vivo. Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.


Hu K.-X.,Academy of Military Medicine science | Wang M.-H.,Academy of Military Medicine science | Fan C.,Qingdao Hiser Medical Center | Wang L.,Academy of Military Medicine science | And 2 more authors.
International Immunopharmacology | Year: 2011

The results of haploidentical hematopoietic stem cell transplantation (HSCT) have been disappointing due to the high incidence of severe graft-versus-host disease (GVHD) and infectious complications. It is well known that mesenchymal stem cells (MSCs) can prevent severe acute GVHD in HSCT. However, there is a controversy concerning whether MSC-mediated suppression of T cell functions is accompanied by inducing T cells maturation effects after HSCT. The CB6F1 (H-2bd) female mice irradiated with 8 Gy 60Co γ-rays were divided into two groups: mice in the MSCs group were infused with MSCs labeled with cm-DiI and mononuclear cells from the bone marrow and spleen of BALB/c (H-2d) mice; the control group was infused with only the mononuclear cells of BALB/c (H-2d) mice. After transplantation, chimerisms of donor MSCs were observed in the recipients. The recovery of the T-lymphocyte subpopulation, the proliferative activity of T-cells after stimulation with ConA, the mixed lymphocytes' reaction between donor and recipient and three parts, and the number of apoptosis thymus cells were compared in two groups. The results showed that MSCs preferentially homed to the thymus and grew there, a more rapid recovery of T-cells in the peripheral blood, and decreased the apoptosis of the thymocytes. Thus MSCs may affect the thymus in order to improve T-cells maturation and immune system recovery. © 2011 Elsevier B.V.


Zhou H.,Chinese Institute of Basic Medical Sciences | Guo M.,Academy of Military Medicine Science | Bian C.,Chinese Institute of Basic Medical Sciences | Sun Z.,Chinese Institute of Basic Medical Sciences | And 4 more authors.
Biology of Blood and Marrow Transplantation | Year: 2010

The success of treatment for sclerodermatous chronic graft-versus-host disease (ScGVHD) remains disappointing. The immunomodulatory ability of bone marrow (BM)-derived mesenchymal stem cells (MSCs) shows promise in treating GVHD, especially given its previous success in treating patients with acute GVHD (aGVHD). The potential efficacy and safety issues for treating cGVHD, particularly ScGVHD, remain to be clarified, however. Here, we report 4 patients with ScGVHD who received MSCs expanded ex vivo from unrelated donors by intra-BM injection. After MSC infusion, the ratio of helper T lymphocyte (Th) 1 cells to Th2 cells was dramatically reversed, with an increase in Th1 and a decrease in Th2 achieving a new balance. Correspondingly, symptoms gradually improved in all 4 patients. During the course of MSC treatment, the patients' vital signs and laboratory results remained normal. At the time of this report, none of the 4 patients had experienced recurrence of leukemia. Although this study alone cannot guarantee the application of MSCs in ScGVHD, our findings strongly suggest that this treatment is therapeutically practicable, with no detectable side effects. This approach may provide new insight into the clinical treatment of ScGVHD, with the aim of greatly increasing the survival rate in patients with leukemia who undergo allogeneic BM transplantation (BMT). © 2010 American Society for Blood and Marrow Transplantation.


Jing-Feng W.,Academy of Military Medicine Science | Jing-Feng W.,Tianjin Key Laboratory of Risk Assessment and Control for Environment and Food Safety | Zhi-Gang Q.,Academy of Military Medicine Science | Zhi-Gang Q.,Tianjin Key Laboratory of Risk Assessment and Control for Environment and Food Safety | And 9 more authors.
PLoS ONE | Year: 2012

The goal of this study is to investigate the effect of inoculating granules on reducing membrane fouling. In order to evaluate the differences in performance between flocculent sludge and aerobic granular sludge in membrane reactors (MBRs), two reactors were run in parallel and various parameters related to membrane fouling were measured. The results indicated that specific resistance to the fouling layer was five times greater than that of mixed liquor sludge in the granular MBR. The floc sludge more easily formed a compact layer on the membrane surface, and increased membrane resistance. Specifically, the floc sludge had a higher moisture content, extracellular polymeric substances concentration, and negative surface charge. In contrast, aerobic granules could improve structural integrity and strength, which contributed to the preferable permeate performance. Therefore, inoculating aerobic granules in a MBR presents an effective method of reducing the membrane fouling associated with floc sludge the perspective of from the morphological characteristics of microbial aggregates. © 2012 Jing-Feng et al.


Zhou H.,Chinese Academy of Sciences | Guo M.,Academy of Military Medicine Science | Sun Q.-Y.,Academy of Military Medicine Science | Huang S.,Chinese Academy of Sciences | And 5 more authors.
Journal of Clinical Rehabilitative Tissue Engineering Research | Year: 2010

BACKGROUND: The immunomodulatory ability of bone marrow mesenchymal stem cells (BMSCs) gives it a promising future in treating graft-versus-host disease (GVHD), especially with previous success in treating patients with acute GVHD. However, there are fewer reports concerning BMSCs in treating chronic GVHD, particularly for sclerodermatous chronic graft-versus-host disease (ScGVHD). OBJECTIVE: To evaluate the efficacy and safety of treatment of BMSCs for ScGVHD, and to primarily explore the immunological mechanism of clinical efficacy. METHODS: Four ScGVHD patients at the Affiliated Hospital of Academy of Military Medicine Science, between September 2006 and August 2008, were enrolled for this trial. The median patient age was 41 years, 1 female and 3 male. The patients received BMSCs infusion at a dose of (1.0-2.0)×107 cells every time by intrabone marrow injection from the anterosuperior iliac spine and BMSCs from the same donor for the same patient were infused more than once. Concomitant medications for ScGVHD were individualized for each patient, but all were current standard medicines and the doses were significantly tapered. RESULTS AND CONCLUTION: After BMSCs infusion, the ratio of Th1 to Th2 was dramatically overturned, with an increase of Th1 and a decrease of Th2 reaching at a new balance. Correspondingly, symptoms of all the four patients gradually improved. During the course of BMSCs treatment, the life signs and laboratory results from the recipients remained normal. By the time of this report, there has been no recurrence of leukemia in the four patients. Although this study alone cannot guarantee the application of BMSCs in ScGVHD, the results are strongly in favor of the idea that the BMSCs treatment for ScGVHD patients is therapeutically practical without any detectable side effects, which may provide a new insight into the matter of treating ScGVHD clinically, thus will greatly increase the survival rate of leukemia after allogeneic bone marrow transplantation.


Hu K.X.,Academy of Military Medicine science | Sun Q.Y.,Academy of Military Medicine science | Guo M.,Academy of Military Medicine science | Ai H.S.,Academy of Military Medicine science
British Journal of Radiology | Year: 2010

The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage ofMSCs inmicewith total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 γ-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow,were observed in the MSC-treated groups.MSCs induced recovery of CFU-GMand CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 x 10 8 kg -1 of MSCs increasedmortality. These results indicate that MSCs protected and treated irradiatedmice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome. © 2010 The British Institute of Radiology.


PubMed | Academy of Military Medicine science
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

11588 Background: The objective of this retrospective study was to discuss the clinical feature, the therapeutic results and the prognostic factors of breast cancer in elder women throughout a study of 464 women patients aged more than 60 years.We reviewed the epidemioclinical records of all the patients of our hospital. Nonmetastatic and operable patients were treated with surgery (conservative or radical) followed by an adjuvant treatment (chemotherapy, radiotherapy, endocrine therapy) indicated according to the prognostic factors. Locally advanced or metastasis tumors were treated with chemotherapy. Overall survival was calculated according to the Kaplan-Meier method. The multivariate analysis was performed according to the Cox model.The mean age was of 65.2 years. The 5 years overall survival of elder patients was of 77.04%. Pejorative prognostic factors in univariate analysis and multivariate analysis were: clinical phase, N+, adjuvant radiation treatment and adjuvant endocrine therapy.Clinical presentation and outcome of breast cancer in our elder patients aged more than 60 years seems to be better prognostic than those of younger patients. No significant financial relationships to disclose.

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