1.Humanized mouse models for liver disease research:a review
Acta Laboratorium Animalis Scientia Sinica 2014;(5):95-99
Liver diseases post great threats to human public health globally.Lacking of appropriate small animal models largely impeded the translational studies on human liver diseases, especially on viral hepatitis and related cirrhosis, hepatocellular carcinoma, etc.By human hepatocyte transplantation, the liver-humanized mice have significantly contribu-ted to the researches of human liver diseases.This review summarizes the currently widely used and representative human-ized mouse models, including uPA, FAH, TK-NOG, AFC8 mice and their applications in studies of human liver diseases.
2.An Exploration on Bilingual Teaching in Prothodontics
Chinese Journal of Medical Education Research 2003;0(02):-
To explore the feasibility and new teaching mode on bilingual teaching in stomatoloy,we carried out bilingual teaching in prothodontics among the four-year Bachelor degree students.Questionnaires about the understanding and evaluation of bilingual teaching were answered after the class.The study provided an important evidence for improving the quality of bilingual teaching in Stomatoloy.
3.Chemotherapy strategies in adult refractory/relapsed acute lymphoblastic leukemia
Fengru LIN ; Xiaonan GUO ; Jinhai REN
Journal of Leukemia & Lymphoma 2010;19(6):321-324
The treatment for adult refractory /relapsed acute lymphoblastic leukemia is a major challenge in clinical practice. Therapeutic strategies including high-dose single agent,intensified induction,new drugs,targeted therapy,and immunotherapy etc. may be of benefit to some patients. The post-remission treatments remain to be further developed.
4.Problems in the treatment of acute promyelocytic leukemia
Fengru LIN ; Xiaonan GUO ; Jinhai REN
Journal of Leukemia & Lymphoma 2011;20(1):11-14
Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is characterized by rapid progress, prone to developing DIC, and high mortality. Typical chromosome translocation with PMLRARα fusion gene occurs in more than 95% of APL cases. Since 1986, the outcome of APL has been significantly improved in our country by firstly using ATRA and ATO for treating APL, making APL of AML curable by chemotherapy only. Based on our limited experiences, we discussed the related problems in the treatment of APL.
5.Is it chronic eosinophilic leukemia or myeloid/lymphoid neoplasm with eosinophilia?
Fengru LIN ; Xiaonan GUO ; Jinhai REN
Journal of Leukemia & Lymphoma 2009;18(11):641-642
In 2008, WHO classified chronic eosinophilic leukemia with rearranged PDGFRA、PDGFRB or FGFRI as myeloid / lymphoid neoplasm with eosinophilia and PDGFRA、PDGFRB or FGFR1rearrangement and CEL without these abnormalities but with other abnormal clonality as CEL not otherwise specified (CEL-NOS). The article expresses authors' opinion.
6.Interleukin-1 receptor type 1 signaling induces excessive inflammatory responses in H1N1 influenza ;virus infection
Rongrong REN ; Xiaonan REN ; Boyin QIN ; Mengjiao YUAN ; Hua YANG ; Chao WANG ; Shun LI ; Xiaohui ZHOU
Chinese Journal of Microbiology and Immunology 2016;36(12):887-893
Objective To investigate the role of interleukin-1 receptor type 1 (IL-1R1) signaling in H1N1 influenza virus infection. Methods IL-1R1 knockout ( IL-1R1-/-) mice and wild type ( WT) mice were infected intranasally with 2×104 TCID50(50% tissue culture infective dose) of influenza virus H1N1 PR8. Changes in clinical signs, survivals and bodyweights of those mice were monitored daily for 14 consecutive days. Three mice from each group were sacrificed at 3, 7 and 14 days post infection (d. p. i), from which whole lungs were harvested. A part of the lobes was fixed in 4% paraformaldehyde for histopatho-logical assessment and the rest were split and stored at-80 centigrade for further analysis. Real-time quanti-tative PCR and cytometric bead array ( CBA) were performed to detect viral loads in lungs and inflammatory cytokines in supernatants of lung homogenates. Results The mice in both groups showed severe symptoms after the infection of PR8. The maximum bodyweight loss of IL-1R1-/- mice [(24. 22±0. 80) % at 8 d. p. i] was lower than that of WT mice [(28. 03±1. 51)% at 9 d. p. i] (P<0. 05). The IL-1R1-/- mice with PR8 infection showed a higher survival rate (90%) as compared with that of the control group (40%) (P<0. 05). No statistical differences in virus loads were observed between the two groups at 3, 7 and 14 d. p. i. The lung weight to body weight ratio of IL-1R1-/-mice [(1. 42±0. 03) %] was lower than that of WT mice [(1. 79±0. 08) %] at 3 d. p. i (P<0. 05). Pathological changes in IL-1R1-/- mice were less severe than those in WT mice. CBA detection assay revealed that the proinflammatory cytokines in lungs of IL-1R1-/-mice were less than those in WT mice. Conclusion IL-1R1 signaling plays a pathogenic role in mice infec-ted with 2×104 TCID50 of influenza virus PR8 by promoting inflammatory responses.
7.Establishment of an Alb-cre/DTR mouse model of inducible liver injury
Xiaonan REN ; Rongrong REN ; Xue LIU ; Hua YANG ; Boyin QIN ; Xiaohui ZHOU
Acta Laboratorium Animalis Scientia Sinica 2016;24(2):134-138
Objective To analyze the Alb-cre/DTR mouse phenotype, and establish a model of induced liver damage to serve basic researches of liver diseases.Methods The introduced Alb-cre and DTR mice were crossed to obtain Alb-cre/DTR mice and the genomic DNAs were extracted from the tail tissue of the mice for genotying by PCR.Diphtheria toxin was intraperitoneally(i.p.)injected into the Alb-cre/DTR mice, then the body weights were monitored and the sera were collected for the detection of serum ALT and AST levels.Results By crossing Alb-cre and DTR mice we obtained the Alb-cre and DTR double transgenic mouse.The intraperitoneal injection of diphtheria toxin in a dose of 0.625 ng/g body weight significantly induced liver injury in these mice, as showed by the elevated levels of ALT and AST, the gross appearance of liver damage and the pathological changes such as necrosis in the liver tissue.Conclusions We have ob-tained a novel mouse strain of Alb-cre/DTR by crossing Alb-cre and DTR mice.Liver damages in those Alb-cre/DTR mice can be induced by injection of diphtheria toxin.This established mouse model of inducible liver damage is a useful platform for the studies of liver damage and recovery, as well as liver transplantation.
8.Epitope competition weakens specific T cell response to subdominant epitopes
Xiaonan REN ; Yanqin REN ; Jing WANG ; Zhidong HU ; Yanmin WAN ; Jianqing XU
Chinese Journal of Microbiology and Immunology 2013;(6):440-444
Objective To elucidate the influences of epitope competition on the frequency and average intensity of specific T cell response.Methods C57BL/6 mice were immunized with either single epitope DNA vaccines (pSV-gag92 or pSV-env203) or fusion gene DNA vaccine (pSV-gag/env).Gag92and Env203 epitope-specific CD8 T cell responses were analyzed by intracellular cytokine staining assay.Results Gag92-specific IFN-γ+CD8 T cells that were induced by pSV-gag92 accounted for 0.415 00% ±0.045 88% of the total CD8 T cells,which was much more than that induced by pSV-gag/env of 0.058 67% + 0.019 64%.Moreover,the mean fluorescence intensity of Gag92-specific TNF-α-IFN-γ+CD8 T cells (296.70+14.08) elicited by pSV-gag/env was significantly lower than that of Env203-specific TNF-α-IFN-γ+CD8 T cells (818.00+49.34).Conclusion Epitope competition could significantly decrease both the frequency and the average intensity of specific T cell response to subdominant epitopes.
9.Effects of allogeneic compact bone derived-mesenchymal stem cell on proliferation,differentiation and chemokine receptor expression of T cells
Shukai QIAO ; Xiaonan GUO ; Jinhai REN ; Xiaoling GUO ; Yujie GUO ; Shengxin CAI
Chinese Journal of Immunology 2016;(1):37-41
Objective:To observe the effects of allogeneic compact bone derived-mesenchymal stem cells ( CB-MSCs) on pro-liferation and differentiation of T cells,and investigate the molecular mechanisms of the immunosuppressive ability.Methods:With an established co-culture system of CB-MSCs and mouse spleen lymphocytes ( SP) in vitro,we observed the effects of CB-MSCs on prolif-eration,apoptosis and cell cycle of SP by MTS/PES assay and flow cytometry.Also,we measured the effects of CB-MSCs on regulatory T cells ( Treg) ratio and expressions of CCR5,CCR7 and CXCR3 in SP.Results:CB-MSCs could obviously inhibit the PHA-stimulated SP proliferation with a dose-dependent manner;MSCs could significantly inhibit the spontaneous apoptosis of SP and induce SP cell cycle G0/G1 phase arrest.After co-culture with SP,CB-MSCs could obviously increase the proportion of Treg in SP,down-regulate the expression of CXCR3 and CCR5,as well as up-regulate the expression of CCR7.Conclusion: Allogeneic CB-MSCs can significantly inhibit cell proliferation of SP,the mechanisms mainly involved the G0/G1 cell cycle arrest rather than apoptosis induction.In addition, CB-MSCs can exert immunomodulatory effects by increasing the Treg ratio,regulating the expressions of chemokine receptors.
10.Effects of dezocine on diabetic neuropathic pain and expression of NMDA receptor subunit 2B in spinal dorsal horns of rats
Peng LIU ; Qianqian CAO ; Shuhong YANG ; Rui DONG ; Huiping BAI ; Wei REN ; Xiaonan ZHAO ; Xiuli WANG
Chinese Journal of Anesthesiology 2014;(3):315-318
Objective To evaluate the effects of dezocine on diabetic neuropathic pain (DNP ) and expression of NMDA receptor subunit 2B (NR2B) in the spinal dorsal horns of rats .Methods Forty-eight male Sprague-Dawley rats , aged 4 weeks , weighing 150-170 g , with DNP induced by intraperitoneal injection of streptozocin (STZ) 50 mg/kg (successful induction of diabetes was defined as blood glucose >16.7 mmol/L) , were randomly divided into 2 groups ( n=24 each) using a random number table:DNP group and dezocine group (group D) .Twenty-four normal rats were chosen and served as normal control group (group C) .In group D , dezocine 2.52 mg/kg was injected intramuscularly once a day for 7 consecutive days starting from 2nd week after STZ injection ,while the rats in DNP and C groups received the equal volume of normal saline .Paw withdrawl threshold (PWT) to mechanical stimulation was measured before dezocine injection (T0 ) ,and on 1st ,3rd ,5th and 7th days after dezocine injection (T1-4 ) and on 7th day after the end of dezocine injection (T5 ) .Twelve rats in each group were sacrificed after measurement of PWT at T4 ,and T5 .The lumbar segments of the spinal cord were removed for determination of NR2B protein expression (by immuno-histochemistry and Western blot ) and NR2B mRNA expression (by RT-PCR ) in the spinal dorsal horns .Results Compared with group C ,the PWT at T0-5 in group DNP and at T0 and T5 in group D was significantly decreased , and the expression of NR2B protein and mRNA at T4 ,5 in DNP group and at T5 in D group was up-regulated ( P<0.05) .Compared with group DNP ,the PWT was significantly increased at T1-4 ,the expression of NR2B protein and mRNA was down-regulated at T4 ( P<0.05) ,and no significant changes were found in the parameters mentioned above at T5 in group D ( P>0.05) . The PWT was significantly lower at T0 and T5 ,and the expression of NR2B protein and mRNA was higher at T5 than at T4 in group D ( P<0.05 ) .Conclusion Dezocine can effectively relieve DNP in rats and inhibition of NR2B expression in the spinal dorsal horns is involved in the mechanism .