2.Homology modeling and application of 3 D structure of Cav1.2 channel
Ming LEI ; Jingyang SU ; Zhuo LI ; Shan YAN ; Xuefei SUN ; Tong ZHU ; Liying HAO
Chinese Pharmacological Bulletin 2017;33(1):90-94
Aim To construct 3 D structure model of cardiac Cav1.2 channel and check its accuracy and re-liability.Methods Homology model of Cav1.2 chan-nel α1 subunit was constructed using SWISS-MODEL server.The model was submitted to an online testing server built by University of California and scored by it.The binding of Cav1.2 channel with blocker or drug was simulated by MOE software molecular docking pro-gram to check the model′s accuracy and reliability.Re-sults Both the target sequence Cav1.2 α1 C and the template sequence Cav1.1 α1 S searched by SWISS-MODEL server belonged to L-type Ca2+channel.Since the homology was 7 1.5% revealed by sequence align-ment,homology modeling was performed using automa-ted mode.L-type Ca2+ channel blockers Verapamil, Nifedipine and Diltiazem could bind to the 3 D structure model of Cav1.2 channel,while sodium channel bloc-ker TTX could not.Furthermore,active ingredient of traditional Chinese drug Praeruptorin A and Berberine could also bind to the 3D structure model of Cav1.2 channel.Conclusion The 3 D structure model of Cav1.2 channel was constructed successfully,which provides reliable materials for further studies and estab-lishes the foundation for the application of homology modeling in the study of 3 D structure prediction of ion channels.
3.Acute type A aortic dissection preoperative hypoxemia clinical analysis
Xiaoyan XING ; Lizhong SUN ; Junming ZHU ; Jun ZHENG ; Xudong PAN ; Ming ZHANG ; Hao WAN ; Nan LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(3):149-151
ObjectiveAnalyze preoperative clinical relevanted factors of acute type A aortic dissection with hypoxemia according to a group clinical data.MethodsFrom January 2011 to June 2011,we have collected 54 preoperative cases of acute type A aortic dissection,including 42 males,12 females,aged 28-73 years old,onset to treatment time is 0.4-14.0 days.General information:age,gender,time of onset,body mass index,hypertension,diabetes mellitus,smoking,drinking,heart ejection fraction,prothrombin time,quantitative fibrinogen,fibrinogen degradation products,D-dimer,C-reactive protein,procalcitonin,ICU time,length of hospital stay.According to the blood gas analysis of quiet state case without oxygen,with PaO2 < ( 100-age ×0.33 ±5) mm Hg is for the hypoxemia group,equal or higher than this is no-hypoxemia group.ResultsNo-hypoxemia group has 14 cases,11 males,3 females,average aged (51.14 ± 14.24) years old,including 12 operation patients ( no death) and 2 no-operation patients(2 cases death).Hypoxemia group has 40 cases,31 males,9 females,average aged (50.53 ± 9.73 ) years old,including 33 operation patients(2 cases death) and 7 no-operation patients(7 cases death).There is no significant difference in age,gender,time of onset,hypertension,diabetes mellitus,smoking,drinking,cardiac ejection fraction,prothrombin time and fibrinogen.There is statistically significant on body mass index,fibrinogen degradation products,D-dimer,C-reactive protein,procalcitonin,ICU time and length of hospital stay time ( P < 0.05 ).ConclusionPreoperative hypoxemia with acute type A aortic dissection is associated with obesity,excessive inflammation and activation of coagulation and fibrinclytic system,and hypoxemia may prolong the time of operative patients with acute type A aortic dissection in ICU and hospital.
4.Study on Pharmacodynamics of Genistein Combined with Tripterygium Glycosides on Rheumatoid Arthritis Treatment of Ovariectomized Rats
Di WANG ; Ming ZHANG ; Pingping SUN ; Hao AI ; Jianzhao NIU ; Jian LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(6):1343-1347
This study was aimed to observe the pharmacodynamics of genistein combined with tripterygium gly-cosides ( GTW ) in the rheumatoid arthritis ( RA ) treatment of ovariectomized rats . SD rats were randomly divid-ed into four groups , which were the sham-operation group , model group , Methotrexate ( MTX ) treatment group ( 2.7 mg/kg ) , and genistein ( 30 mg/kg ) combined with GTW ( 70 mg/kg ) treatment group . There were ten rats in each group . Except the sham-operation group , rats in other groups were ovariectomized and immunized by collagen type II to prepare collagen induced arthritis ( CIA ) model . The intragastric administration of drugs was given once a day for two weeks . The arthritis index , joints swelling degree , and levels of anti-Col II , IL-6 and IL-10 in serum were tested . The results showed that the arthritis index , joints swelling degree , and levels of anti-Col II , IL-6 and IL-10 in serum were all significantly increased in the model group ( P < 0 . 05 or P< 0 . 01 ) . Compared with the model group , the arthritis index and joints swelling degree of both MTX and genistein combined with GTW were significantly decreased . The level of anti-Col II in serum of the MTX treatment group was significantly decreased ( P < 0 . 05 ) . However , there were no significant changes on levels of IL-6 and IL-10 . The levels of anti-Col II and IL-6 in serum of the genistein combined with GTW were significantly decreased ( P < 0 . 05 ) . The level of IL-10 was significantly increased ( P < 0 . 01 ) . It was conclud-ed that genistein combined with GTW can significantly inhibit the pathological progress of CIA on ovariec-tomized rats . Compared with MTX , the genistein combined with GTW received a better regulating effect on the expression of IL-6 and IL-10 . The results suggested that phytoestrogen combined with GTW played a good therapeutic effect on gonadal dysfunction type of RA . It provided novel strategies and experimental evidences on postmenopausal RA treatment in the clinical practice .
5.Clinical analysis of laparoscopic complications in urologic surgery
Yu-Ping ZHU ; Hao CHEN ; Ming ZHU ; Lin QI ; Lin-Yu ZHOU ; You-Wen SUN
Chinese Journal of Urology 2001;0(07):-
Objective To evaluate the causes,prevention and treatment ot laparoscopic comphca- tions in urologic surgery.Methods From May 2000 to May 2004,135 urologic laparoscopies were per- formed,including 17 transperitoneal laparoscopies and 118 retroperitoneal laparoscopies.Of the135 cases,26 had adrenal adenoma extirpation;31 had roof-removal and decompression of renal cyst;25 had radical ne- phrectomy;6 had pyeloplasty;2 had partial resection of renal capsula and encapsulation of the great omen- tum;2 had partial nephrectomy;4 had pelviureteral resection;13 had ligation of renal pedicle lymphatic ves- sel;2 had ureterolysis;7 had ureterolithotomy;12 had ligation of spermophlebectasis;5 had exploration,re- duction and fixation of undescended testis.The intra-and post-operative complications were retrospectively reviewed and clinically analyzed.Results Overall,14 cases(10.4%)had complications.Intraoperative complications occurred in 10 cases,including 6 cases of peritoneal injuries,which were clamped during oper- ation;4 of vascular injuries,which resulted in conversion to open surgery.Postoperative complications oc- curred in 4 cases,including 2 of subcutaneous emphysema,which was spontaneously absorbed at 5 and 7 d after operation;1 of incision seepage,which was drained for 40 d and then disappeared;and 1 of urine reten- tion,for which urethral catheterization was kept for 3 d and then the patient had voluntary voiding.No death occurred in this series.Conclusions Understanding the characteristics of laparoscopic complications in u- rologic surgery and systematic training of the surgeons can reduce the occurrence of complications.
6.Barbiturate infusion for intractable intracranial hypertension and its effect on brain tissue oxygen
Ming SUN ; Jiheng HAO ; Qingju ZHAO ; Xiaoying SHANG ; Tao XING ; Dianfeng HU
Journal of Chinese Physician 2010;12(10):1329-1331
Objective To examine the barbiturate infusion for intractable intracranial hypertension and its effect on brain tissue oxygen ( PbtO2 ). Method 60 patients with intractable intracranial hypertension were divided into tow groups, experimental group and control group. PbtO2 and intracranial pressure (ICP) were continuous monitored. Follow-up was more than 3 months and the prognosis was compared between two groups. Results When pentobarbital administration began, the mean PbtO2 [ 72 h: (26. 7 ±6. 7)mmHg] at 24h, 48h and 72h in experimental group were significantly higher than that of control group [ 72 h: ( 21. 1 ± 7. 2) mmHg ] ( P < 0. 05 ). The mean ICP [ 5 d: (2. 48 ± 1.11 ) kPa ] in the third and fifth day of experimental group were lower than that of control group [ 5 d: (3. 12 ± 1.09 ) kPa ]. Prognosis of pentobarbital group was better than control group( P < 0. 05 ). Conclusions Pentobarbital can effectively reduce intracranial pressure in patients with refractory intracranial hypertension and improve brain tissue oxygen. PbtO2 is an ideal monitoring marker, and it can predict prognosis to a certain extent.
7.Asiatic acid induces apoptosis in T98 G human glioblastoma cells by changing autophagy
Huan LI ; Fuqin GUAN ; Yu CHEN ; Min YIN ; Hao SUN ; Ming WANG ; Xu FENG ; Yu SHAN
Chinese Pharmacological Bulletin 2015;(10):1363-1367,1368
Aim To investigate the effect of asiatic acid on apoptosis and autophagy in human glioblastoma T98G cells. Methods MTT colorimetry was employed to assay the cellular proliferating activity. The fluores-cence microscope and Hoechst 33258 staining were used to detect the morphological changes. The cell ap-optosis and autophagy were analyzed by flow cytometry with Annexin-V/7-AAD and MDC staining respective-ly. The expressions of associated proteins were detected by Western blot to analyze the mechanism of apoptosis and autophagy. Results MTT assay showed that the growth of T 9 8 G cells was inhibited by asiatic acid ( IC50 =46. 3 μmol · L-1 ) . Annexin V/7-AAD stai-ning and Western blot revealed that asiatic acid in-duced apoptosis in T98 G cells by reducing the expres-sion of Akt, decreasing the mitochondrial membrane potential, and increasing the expression of Caspase-3. MDC staining and Western blot showed that the per-centage of MDC-positive cells was decreased and the expressions of Beclin-1 , LC3-II and Atgs were inhibi-ted by asiatic acid treatment. 5 μmol·L-1 chloroquine was used to up-regulate the expressions of LC3-Ⅱand Beclin-1 . Asiatic acid-inhibited autophagy was blocked and the total apoptotic rate was reduced remarkably. Conclusion Asiatic acid suppresses T98 G cells pro-liferation by inducing apoptosis and inhibiting cell au-tophagy, and the very role of inhibiting autophagy could promote apoptosis to a certain extent.
8.The study on the criterion-related validity of examination of computer-based case simulations
Peng QIN ; Yinyin GAO ; Ming HAO ; Tianming ZUO ; Yang ZHANG ; Baozhi SUN
Chinese Journal of Medical Education Research 2006;0(12):-
This paper gives the statistical analysis on the examination of Computer-Based Case Simulation to test 350 undergraduate clinical medical students of 5th or 6th year students,and analyses the statistical items of examination,then gives some discussion and reasonable suggestions.Finally,the author makes a series of discussion and views in the application of the medical education evaluations in future.
9.A preliminary study on the mutation of TLR4 gene in patients with invasive aspergillosis
Chen CHEN ; Xiaoyong XU ; Hao XIE ; Huiming SUN ; Fei CHEN ; Ming FANG ; Beilei ZHAO
Journal of Medical Postgraduates 2015;(9):944-948
Objective Toll-like receptor ( TLR) gene family is the most important pathogen recognition receptor and animal experiment have found TLR4 mice is inclined to infect aspergillosis ( IA) .The study was to investigate the variation of TLR4 gene in Chinese Han nationality and its relation with the susceptibility of IA. Methods 25 patients diagnosed with proven IA from June 2011 to December 2012 in our hospital were enrolled, among which 17 were males.Their average age was 52.4 ±12.3, and 12 pa-tients had underlying diseases, the others had no underlying diseases.The control group consisted of 103 normal persons, among which 70 were males.Their average age was 56.0 ±17.2.All of the subjects were Chinese Han population.DNA was extracted from periph-eral blood.Polymerase chain reaction ( PCR) was applied to amplify the coding sequence of TLR4 gene followed by sequencing.The sequencing result was compared with TLR4 coding sequence in NCBI GenBank along with the analysis on amino acid change caused by genetic mutation and its effect on protein function.Comparison analysis was made on genetic mutation rate between IA group and con-trol group. Results Two missense mutations,TLR4 219 C>G and 1420 C>T, were identified in TLR4.The prediction result of protein structure showed 219 C>G resulted in the change of functional area for TLR4 to recognize pathogen and 1420 C>T caused no change in domains.The variation rate of TLR4 in IA group was 8%( 2/25 ) and both the patients had no underlying diseases. No mutation has been founded in control group and the difference between two groups was of statistical significance (P=0.037). Conclusion Two missense mutations (219 C>G and 1420 C>T) have been detec-ted in encoding area of TLR4 gene of IA patients.Variation in the cod-ing region of TLR4 gene may increase the susceptibility to IA.
10.Effect and clinical significance of immunological state upon telomerase activation of bone marrow mononuclear cells in hemopoietic microenvironment of immune related hematocytopenia (IRHS)
Lifei SUN ; Qiangqiang WU ; Bing HAN ; Hongfeng HAO ; Gang XU ; Yanhui DU ; Hui MING ; Guichen WANG ; Jinbiao ZHANG
Chinese Journal of Immunology 2014;(7):956-962
Objective:To study the effect of immunological molecules expressive state upon the telomerase activation ( TA) of bone marrow mononuclear cells ( BMMNC ) in the hemopoietic microenvironment of patients with immune related hematocytopenia ( IRHS) ,and to explore the immunologic mechanism as well as the clinical significance of hematoclasis in marrow of IRHS patients .Methods:①TRAP-PCR-ELISA method was performed to detect the TA of BMMNC in marrow of 366 IRHS patients before and after therapy.②The molecules HLA-DR,anti-hunman IgG,FcγⅡR,mannose receptor ( MR),IL-17A and its receptor ( IL-17AR) were analysed by immunochemistry and immunofluorescence staining .③The flow cytometric ( FCM) was used to analyse the proportion of CD3+CD4+T cells as well as CD3+CD8+T cells ,CD3-CD19+B cells and CD3-CD16/56+NK cells in peripheral blood lymphocyte.60 cases of health examination were selected as the control group , and 30 cases hypoferric anemia patients were selected as disease control.The differences between patient group and control group were analysed with statistic method .Immunochemistry and immunofluo-rescence staining were performed to in situ analyze the activation-characteristics of immunocyte in bone marrow slides of IRHS ,and the dependablity of cellular immunologic injury was also checked.Results: ①The levels of TA was 0.261 7 ±0.021 6 before treatment , higher than the disease control group (0.061 6±0.031 3 ,P<0.01).Among of them HLA-B27+patients were higher than HLA-B27-patients (0.301 3±0.020 6 vs.0.192 3±0.012 9,P<0.05).Serious IRP patients with HLA-B27+IgG+were obviously higher than HLA-B27-IgG+patients (0.401 6±0.017 2 vs.0.221 1±0.011 0,P<0.01).②In marrow of HLA-B27+IgG+patients,both cell immunity and humoral immunity were in disorder in the hemopoietic microenvironment ,and immonocyte in marrow expressed HLA-DR, FcγⅡR,IL-17A,IL-17RA and MR,and Th,Ts,B cell and NK cell in peripheral blood increased in different degree ,inducing the in-flammation of haemocyte and lead to destruction.③Humoral immunity was in the dominant level in morrow;humoral immunity of HLA-B27-IgG+patients,immonocyte expressed FcγⅡR in high level,but IL-17A was seldom expressed,only CD19+B cell was increased slightly ,the antibody dependent cellular cytotoxicity ( ADCC) was the main mode of destruction.After therapy glucocorticoids associated with ciclosporin A ,the TA level of BMMNC decreased to 0 with devitalization.Conclusion: The telomerase activation of bone marrow mononuclear cells in IRHS is related with the immune state of hemopoietic microenvironment and the pathologic lesion degree of hema -topoietic cell in marrow.It is viral infection and immunological activation as well as a variety of inflammatory factors play a part in the immunologic injury that might be an important factor of the enhancement in TA.