1.Research progress of Rett syndrome causing gene MECP2——The structure,function and modulation of MECP2
Journal of Peking University(Health Sciences) 2003;0(06):-
Rett syndrome(RTT),an X-linked dominant neurodevelopmental disorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-binding protein 2(MECP2).The 76 kb human MECP2 is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and different polyadenylation sites,and a 40 kb intergenic region separating MECP2 from the nearest upstream gene.There are two isoforms of MeCP2,MeCP2e1 and MeCP2e2.The differences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied.In contrast to initial report,recent studies show that MeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcription.Abstract:SUMM ARY Rett syndrome(RTT),an X-linked dom inant neurodevelopmental d isorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-bind ing protein 2(MECP2).The 76 kb humanMECP2is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and d ifferent polyadenylation sites,and a 40 kb intergenic region separatingMECP2from the nearest up-stream gene.There are two isoforms ofMeCP2,MeCP2e1 and MeCP2e2.The d ifferences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic re-gion were extensively stud ied.In contrast to initial report,recent stud ies show thatMeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcrip-tion.
2.Research progress of Rett syndrome causing gene MECP2-The structure, function and modulation of MECP2
Journal of Peking University(Health Sciences) 2009;41(6):712-715
SUMMARY Rett syndrome (RTT) , an X-linked dominant neurodevelopmental disorder characterized by regression of language, stereotype hand movement and loss of purposeful hand use, is primarily caused by mutation of menthyl-CpG-binding protein 2 ( MECP2 ). The 76 kb human MECP2 is characterized by three sab'ent features; a very large intron 2 (60 kb) , an 8. 5 kb 3'-UTR with highly conserved regions and different polyadenylation sites, and a 40 kb intergenic region separating MECP2 from the nearest upstream gene. There are two isoforms of MeCP2, MeCP2el and MeCP2e2. The differences between the two isoforms, the function of the 3'-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied. In contrast to initial report, recent studies show that MeCP2 binds not only to methylated promoters and silence transcription, but also to the sites outside of genes containing only a few of CpG islands. Furthermore, MeCP2 can function as both an activator and a repressor of transcription.
3.The research of lymphocyte proliferation using CFSE and FCM
Jingjing BAO ; Haixia LIN ; Jing MA
Chinese Pharmacological Bulletin 1986;0(06):-
Aim To quantitatively analyze the lymphocyte proliferation using the time-series data of carboxyfluorescein diacetate succinimidyl ester(CFSE).Methods The model of immune suppression in mice was created by cyclophosphamide and CFSE dye was used for staining the lymphocyte of both control group and treatment group animals. The data were analyzed through mathematical model-fitting.Results The first generation of cell proliferation of the control group and treatment group were 27.17 h and 22.88 h; cell death rates in each division were respectively 20% and 40%; the half-life of cells before the proliferation was respectively 31.53 h and 43.32 h.Conclusions The mathematical fitting of CFSE data can quantitatively analyze the mechanism of the drugs attecting the proliferation of lymphocyte.In this experiment the mechanism of cyclophosphamide inhibiting lymphocyte proliferation may be due to the increase of cell death rate of each division caused by cyclophosphamide.
4.Endoplasmic reticulum stress-mediated high-fat diet, palmitic acid-induced insulin resistance in skeletal muscle and interventional effects of fenofibrate
Yingying BAO ; Yunxia LU ; Guanjun CHEN ; Jingjing CHENG ; Qiu ZHANG
Chinese Pharmacological Bulletin 2014;(11):1557-1563
Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.
5.Weight analysis of influencing factors of human angle Kappa
Dan, CHENG ; Jingjing, XU ; Jinhua, BAO ; Jiandong, PAN ; Fan, LV
Chinese Journal of Experimental Ophthalmology 2014;32(5):425-429
Background Angle Kappa is the angle between the pupillary axis and visual axis,and it is a major consideration in corneal refractive surgery and strabismic surgery.Researches showed that age and refractive status affect angle Kappa value,and additionally,the measuring results of angle Kappa are associated with instruments.Objective This study was to investigate and weight the influences of axial length,anterior chamber depth and corneal curvature to angle Kappa.Methods A cross-sectional study was designed.Fifty health volunteers were included from Dec 2009 to Aug 2010,with the age of 18-38 years and average diopter of-1.0 D and best corrected visual acuity of 1.0.The horizontal and vertical angle Kappa was binocular measured with a testing machine designed by laboratory of School of Optometry & Ophthalmology Wenzhou Medical University.IOLMaster was employed to measure the ocular axial length,anterior chamber depth and corneal curvature radius.A multiple linear regression model was established to analyze the influences of axial length,anterior chamber depth and corneal curvature radius to angle Kappa.Results An efficacious regression equation was established as Y =15.554-0.587X1+0.724X2+ 0.232X3 with the independent variables as axial length(X1),anterior chamber depth (X2),corneal curvature (X3) and dependent variable as horizontal angle Kappa (Y) (R =0.788,R2 =0.621,P =0.000).Horizontal angle Kappa showed a negative correlation with axial length (b1 =-0.587,β1 =-1.002,P =0.000) and a positive correlation with anterior chamber depth (b2 =0.724,β32 =0.296,P =0.030).No significant correlation was found between corneal curvature radius and horizontal angle Kappa (b3 =-0.232,β3 =-0.068,P=0.338).A new regression equation was Y =14.235-0.622X1 + 0.824X2 after removed the corneal curvature variable (R =0.786,R2=0.618,P =0.000),with a negative correlation between horizontal angle Kappa and axial length (b1 =-0.622,β1 =-1.062,P<0.05) or positive correlation between horizontal angle Kappa and the anterior chamber depth (b2 =0.824,β2 =0.337,P<0.05).In addition,a multiple linear regression equation among 3 independent variables and dependent variable of vertical angle Kappa was Y =0.492-0.020X1 +0.038X2 +0.089X3 (R =0.436,R2 =0.191,P =0.000).However,no significant correlations were seen between vertical angle Kappa and axial length,anterior chamber depth or corneal curvature radius (all at P > 0.05).Conclusions Ocular axial length and anterior chamber depth have an obvious influence to horizontal but not vertical angle Kappa.Axial length appears to have more influence to horizontal angle Kappa than anterior chamber depth.
6.Preliminary exploration of Internet-based practice of stomatology hospitals
Jingjing LI ; Yulei HUANG ; Xiaohuan ZHANG ; Peng BAO ; Cuiyi YAN
Chinese Journal of Hospital Administration 2021;37(1):21-24
Internet-based practice of stomatology hospitals plays an important role in promoting hierarchical medical system and overcoming the social problems of " high costs and difficulties of medical services" . The authors introduced the practice of free online consultations at a tertiary stomatology hospital during this period. They also analyzed such characteristics of the practice as the doctors′ response rate, doctors′ response timeliness, as well as the specialties and timeframe distribution of patient consultations. The hospital provides online consultations on Guangdong cloud-based hospital platform in two modes. For example, the normal consultation mode operates in a many-many manner, with services provided by attendings and associate chief physicians appointed less than three years. In off hours, patients can also raise questions online. The expert consultation mode offers consultations during business hours in a one-to-one manner, with services provided by associate chief physicians appointed over three years and chief physicians. From February 10 to March 22 2020, 2 156 persons/times of consultations were served in the normal mode, and 1 043 persons/times received in the expert mode. The response timelines of the latter (16.19 min) was much better than the former (27.10 min). In terms of consultation workload of sub-specialties, oral medicine ranked the top (69.30%), while the consultations of the normal mode in work hours accounted for only 73.47% of total consultation workload. It is recommended to optimize resources deployment, introduce artificial intelligent inquiry service, explore an online-offline combined stomatological service, and improve performance management. These measures, when in place, can promote sustainable development of Internet-based stomatology hospitals.
7.Effects of Kruppel-like factor 6 on HepG2 and the development of liver in zebrafish
Hao CHEN ; Zhenguo YANG ; Shuilong WU ; Yongfu WU ; Yufei FENG ; Xiaoxia GAO ; Shiting BAO ; Jingjing ZHANG
Chinese Journal of Comparative Medicine 2017;27(5):42-50
Objective To investigate the effects of Kruppel-like factor 6 (KLF6) on the apoptotic and migration ability of HepG2 cell, and the developmental role of KLF6 on zebrafish liver.Methods Constructed plasmid with shRNA-KLF6 was transfected in HepG2 and L-02.The impacts of loss of KLF6 on HepG2 was investigated by Western bolt, apoptosis analyses, cell cycle detection and scratch experiment;KLF6 morpholino oligonucleotides was microinjected into the Tg(lfabp:eGFP) transgenic zebrafish embryos.The morphant phenotype of the liver was imaged and the protein expression of KLF6 after knockdown of KLF6 was analyzed by Immunofluorescence staining.Results The expression of KLF6 in L-02 was significantly higher than in HepG2.After knockout of KLF6, KLF6 protein expression and apoptosis were significantly reduced.In addition, the cell cycle mainly stated in S phase and the migration ability of HepG2 was enhanced.After klf6 knockdown in transgenic zebrafish larvae, the development of zebrafish liver was delayed and KLF6 expression was obviously decreased in the liver.Conclusions The reduction of KLF6 expression increased the proliferation and migration ability, and reduced the apoptosis of HepG2.Loss of KLF6 affects the development of zebrafish liver, which may open a possibility to use zebrafish as a liver cancer model and for anti-liver cancer drug screening.
8.Resveratrol improves vascular endothelial injury induced by high-calorie and high-cholestrol diet through reduced ERS and increased eNOS expression
Jingjing CHENG ; Li CHEN ; Chaofei LI ; Guanjun CHEN ; Yingying BAO ; Yunxia LU
Chinese Pharmacological Bulletin 2014;(12):1756-1762
Aim To study whether the mechanisms in-volved in resveratrol′s protective effects on vascular en-dothelial injury induced by high-calorie and high-chol-estrol diet are concerned with ERS and the change of eNOS expression. Methods Twenty-four male C57BL/6 mice were randomly divided into standard control diet (SCD),high-calorie and high-cholestrol diet(HCD)and HCD group treated with resveratrol (HCD +RES,400 mg·kg -1 ·d -1 ,1 2 weeks).Then the thoracic aorta was separated,embedded and sliced to analyze the pathological changes by HE and resor-cinol staining.The protein distribution of eNOS was measured with immunohistochemical analysis.The up-stream and downstream genes of ERS in thoracic aorta were detected by RT-PCR.After the pretreatment with different concentrations of resveratrol,the mouse aortic endothelial cells (MAECs)were treated with palmitic acid,then the changes of cell proliferation in each group were compared.Western blot,immunofluores-cence and immunohistochemistry were used to deter-mine the protein expressions of GRP78,CHOP and eNOS respectively.Results Mice fed with HCD showed thickening of thoracic aortic wall and disorgan-ized elastic fibers as compared with those in SCD group.The mRNA levels of ERS related genes were all increased obviously (P <0.05),while the protein expression of eNOS was decreased.Compared with HCDgroup,the thickened wall and the disorganized elasticfibers were improved significantly,the mRNA levels ofERS related genes were all decreased obviously (P <0.05)and the expression of eNOS protein was increased in HCD +RES group.Compared with NCgroup, the cell proliferation was significantly decreased,meanwhile GRP78 and CHOP was significantly increased (P <0.05)and the protein expression ofeNOS was decreased in PA group.The cell proliferation was increased significantly (P <0.05),the mRNA and protein expression of GRP78 and CHOP wasobviously decreased (P <0.05),meanwhile the protein expression of eNOS was increased in the mediumand large dose of RES pretreatment groups.Conclusion Resveratrol has obvious effects of improving endothelial damages induced by HCD and decreasing cellproliferateion of MAECs induced by PA, and themechanisms are possibly related with decreased ERSand increased level of eNOS protein.
10.Pathologic diagnosis and differential diagnosis of bizarre parosteal osteochondromatous proliferation
Xiaoqin JIANG ; Jingjing BAO ; Wenchao WANG ; Guihong DAI ; Fuxing LIU ; Xiaowei ZHU ; Xia JIAO ; Wei XIAO ; Hong YU
Cancer Research and Clinic 2017;29(3):188-190,196
Objective To study the clinicopathological features and differential diagnosis of bizarre parosteal osteochondromatous proliferation (BPOP). Methods The clinicopathological features of 3 patients with BPOP were analyzed , and related literature was reviewed. Results 3 patients included 2 males and 1 female with an average age 40 years old (24-53 years old). The lesions in three patients were located in the left side of the distal radius, the left side of the little finger inside and the right side of ulna coracoid, respectively. Histologically, characterized by unusual mineralized cartilaginous matrix (`blue bone'), the lesion was composed of a heterogeneous mixture of bone, cartilage and fibrous tissue. Conclusion BPOP is a rare benign surface osteocartilaginous lesion, and its diagnosis and differential diagnosis mainly depend on radiographic and histopathologic features.