1.Abnormal T-cell receptor signal pathway in murine autoimmue cardiom-yophy induced with adenine nucleotide translocase
Jing YUAN ; Yuhua LIAO ; Zhaohui WANG ; Jinghui ZHANG ; Zhongping LIU ; Jihua DONG ; Jinping WANG
Chinese Journal of Pathophysiology 1986;0(02):-
AIM: To explore the molecular mechanism in the pathogenesis of dilated cardiomyopathy (DCM) by analyzing the expression of T cell signaling molecules in mice with autoimmune DCM. METHODS: Mouse DCM model was induced by immunizing the animals with adenine nucleotide translocase (ANT) synthetic peptides. P56lck in T cells was detected with real-time fluorescent quantitative PCR in both DCM-group and the sham-immunized controls. At the same time, flow cytometry was used for quantity of Th cell intracellular cytokine IFN-? and IL-4, ELISA for examining the level of serum anti-ANT antibody, immune histochemistry for investigating the expression of CD45 in Th cells. RESULTS: The mRNA expression of P56lck ( 1 369.51 ?874.05 vs 47.93?10.21, P
2.Analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy.
Zhaohui, WANG ; Yuhua, LIAO ; Jing, YUAN ; Jinghui, ZHANG ; Jihua, DONG ; Jinping, WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2008;28(4):409-14
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6-8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-gamma and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-gamma, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P<0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P<0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
3.Clinical outcome of castrate-resistant prostate cancer patients with bone metastasis treated with thalidomide combined with docetaxel
Jing FENG ; Shaoguang LIAO ; Huihua CHENG ; Zhichao FU ; Huachun LUO ; Wenmin YING ; Jinping ZHOU
China Oncology 2017;27(4):287-292
Background and purpose: Docetaxel plus prednisone chemotherapy can improve the patients' survival for castrate-resistant prostate cancer. Angiogenesis inhibitors can also inhibit the growth of tumor. The curative effect of combined treatment is still not clear. This study aimed to evaluate the efficacy of docetaxel plus prednisone combined with thalidomide in treating castrate-resistant prostate cancer (CRPC) patients with bone metastasis. Methods:A total number of 78 CRPC patients were selected in Fuzhou General Hospital from Dec. 2008 to Jun. 2015. Seventy-eight patients were divided into two groups: 40 patients in chemotherapy group (docetaxel plus prednisone) and 38 patients in combined treatment group (docetaxel plus prednisone combined with thalidomide). A total number of 78 subjects were evaluated by the effective rate, the remission rate of bone pain, the prostate specific antigen (PSA) progression-free surviv-al, the overall survival and adverse effect. Results: The response rate (65.79%) and the remission rate of bone pain (86.84%) in combined treatment group were both higher than those in chemotherapy group (40.00% and 60.00%, P<0.05). The PSA progression-free survival (4.13 months), progression-free survival (4.25 months) and the overall survival (18.06 months) in combined treatment group were all longer than those in chemotherapy group (3.54, 3.75 and 16.26 months). The PSA pro-gression-free survival was significantly longer in combined treatment group (P<0.05). There was no significant difference in the overall survival between two groups (P>0.05). The rates of adverse effects including peripheral neuritis and lethargy in combined treatment group (26.32% and 55.26%) were higher than those in chemotherapy group (5.00% and 17.50%, P<0.05). Conclusion: Thalidomide combined with docetaxel plus prednisone in CRPC patients with bone metastasis can prolong the PSA progression-free survival and overall survival. The adverse effects are mild. It may become a new choice of treatment for CRPC.
4.Effectiveness of chest orthosis in early treatment of chest trauma
Bin SONG ; Yongzhou SHI ; Chen LI ; Liangyu ZHANG ; Jinping LIAO ; Mingzhi CHEN
Clinical Medicine of China 2012;28(10):1098-1100
Objective To evaluate the clinical effect of the chest orthosis on patients with multiple rib or(and) sternal fracture in early period of closed chest trauma.Methods Patients with multiple fractured of ribs or (and) sternal fracture were divided into control group (n =16)treated with the traditional fixation methods ( thoracic girdle added with folding towels) and experimental group ( n =30 ) treated with chest orthosis between January 2009 and December 2011.Correlated parameters of these patients in the two groups,including pain,indexes of blood gas analysis,pulmonary complications and hospitalization time were evaluated.Results There were significant differences on visual analogue scale(VAS) [ (4.45 ±2.23) vs (8.15 ±2.02),t =2.921,P <0.01 ],blood gas analysis including PaO2 [ 88.16 ± 9.12) mm Hg vs (77.22 ± 6.24 ) mm Hg,t =2.413,P <0.05] andPaCO2[ (40.91 ±3.40)mm Hg vs (46.06 ±5.40)mm Hg,t =2.335,P<0.05] between experimental group and control group.The incidence rate of pulmonary complications in experimental group was significantly lower than that in control group [ 17% ( 5/30 ) vs 44% ( 7/16 ),x2 =23.478,P < 0.05 ].And hospitalization time in experimental group was significantly shorter compared with control group[ (7.26 ± 4.17) d vs ( 14.26 ±3.53)d,t =2.430,P <0.05].Conclusion The chest orthosis in early treatment of chest trauma can reduce the pain and improve the condition of patients,and it is a simple,effective and cheap method with significant clinical effect.
5.Effect of using laparoscopic trocar for rapidly closed thoracic drainage on serious pneumothorax
Bin SONG ; Jinping LIAO ; Yongzhou SHI ; Chen LI ; Liangyu ZHANG ; Zhenyun SHU ; Mingzhi CHEN
Clinical Medicine of China 2011;27(5):502-505
Objective To explore a rapid,simple and effective therapy for serious pneumothorax which could be used in pre-hospital and in-hospital first-aid.Methods Sixty-seven patients were randomly divided into the observation group and control group .Patients in the observation group were treated using laparoscopic trocar for rapidly closed thoracic drainage,and patients in the control group were treated by using the traditional large caliber drainage tube and the intercostal incision method of conventional closed thoracic drainage.The operation time,remaining time of drainage,length of stay,effective rate,and complications,including of postoperative pain,hemorrhage,subcutaneous emphysema and infection were observed in both groups. Results The total effective rate was 94.1%(32/34) in the observation group,which was significantly higher than that in the control group(90.9%,30/33)(x2=1.876,P>0.05).No significant difference was found on the remaining time of drainage and length of stay between the two groups(remaining time of drainage:[4.56±1.65]d vs.[6.26±3.45]d;length of stay:(6.0±2.6)d vs.(6.7±2.2)d ,t=1.335 and 0.779,respectively,Ps>0.05).The operation time of using laparoscopic trocar was significantly lower than that of the control group((5.00±1.28)min vs.(15.00±4.03)min,t=3.031,P<0.05).The incision length was(0.95±0.11)cm in the observational group,which was significantly lower than that in the control group((2.41±0.52)cm ,t=2.585,P<0.05).Postoperative pain occurred in 14.7%(5/34) of patients in the observational group,which was significantly lower than that in the control group(87.9%(29/33))(t=2.983,P<0.05).In the observational group no hemorrhage and infection occurred,whereas in the control group the hemorrhage and infection rate was 36%(12/33) and 33%(11/33),respectively(x2=5.880 and 3.687,respectively,Ps<0.05). Conclusion The use of laparoscopic trocar for rapidly closed thoracic drainage in the treatment of serious pneu-mothorax is simple,easy,convenient,effective and reliable,with few complications.This therapy is suitable for using in pre-hospital and in-hospital first-aid.
6.Effect of Shenfu injection on cardiac arteries syndrome and its influence on C - reactive protein and mean arterial pressure
Mingzhi CHEN ; Yongzhou SHI ; Haixian PENG ; Jinping LIAO ; Zhiyuan DAI ; Bin SONG
Chinese Journal of Primary Medicine and Pharmacy 2018;25(22):2872-2875
Objective To investigate the clinical effect of Shenfu injection in the treatment of patients with post - cardiac arrest syndrome(PCAS),to analyze the patients' blood C - reactive protein (CRP) and early mean arterial pressure. Methods From September 2013 to September 2016,80 patients with PCAS in the No. 98 Hospital of PLA were randomly divided into study group and control group according to the digital table,with 40 cases in each group. The study group was treated by Shenfu injection,the control group was treated by saline. The changes of CRP,mean arterial pressure and GCS score at 4h,12h,1d,2d and 3d after resuscitation and the 90d survival rate were observed. Results At 4h,12h,1d,2d and 3d after resuscitation,the peripheral blood CRP levels in the study group were (22. 01 ±2. 16)mg/ L,(34. 68 ± 4. 95)mg/ L,(62. 51 ± 3. 68)mg/ L,(98. 65 ± 6. 57)mg/ L,(100. 67 ± 10. 03)mg/ L, respectively,which in the control group were (25. 16 ± 3. 54)mg/ L,(41. 52 ± 5. 31)mg/ L,(75. 09 ± 4. 58)mg/ L, (120. 48 ± 10. 61)mg/ L,(128. 26 ± 9. 64)mg/ L,respectively,there were statistically significant differences between the two groups(t = 4. 804,5. 959,13. 542,11. 063,12. 543,all P < 0. 01). At 4h,12h,1d,2d and 3d after resuscita-tion,the mean arterial pressure in the study group were (78. 03 ± 8. 65)mmHg,(88. 34 ± 10. 20)mmHg,(97. 05 ± 9. 57)mmHg,(105. 29 ± 10. 45)mmHg,(112. 14 ± 9. 46) mmHg,respectively,which were higher than those in the control group [(68. 21 ± 8. 03)mmHg,(74. 01 ± 10. 59) mmHg,(83. 09 ± 11. 25) mmHg,(98. 25 ± 9. 17) mmHg, (104. 68 ± 3. 14)mmHg](t = 5. 262,6. 164,5. 978,3. 203,4. 733,all P < 0. 01). At 4h,12h,1d,2d and 3d after resuscitation,the GCS scores of the study group were (5. 21 ± 1. 12) points, (5. 78 ± 2. 05) points, (6. 85 ± 1. 68)points,(7. 91 ± 2. 57)points,(9. 98 ± 2. 07) points,respectively,which were higher than those of the control group [(4. 01 ± 2. 14) points, (4. 22 ± 3. 75) points, (4. 39 ± 3. 89) points, (4. 41 ± 2. 86) points, (5. 06 ± 4. 14)points](t = 3. 142,2. 309,3. 672,5. 757,6. 723,all P < 0. 05). The survival rate of the study group was 50%(20 / 40) at 90d after resuscitation,which was higher than that of the control group [23% (9 / 40)](χ2 = 6. 545,P =0. 011). Conclusion Shenfu injection has protective effect on the function of patients with CRP after surgery,and can improve the prognosis of patients,it is worthy of clinical use.
7.Clinical significance and pathogenic role of anti-cardiac myosin autoantibody in dilated cardiomyopathy.
Zhaohui WANG ; Yuhua LIAO ; Jihua DONG ; Shuli LI ; Jinping WANG ; Michael L X FU
Chinese Medical Journal 2003;116(4):499-502
OBJECTIVEIn order to explore the possible roles played by the autoimmune mechanism in the progression of myocarditis into dilated cardiomyopathy (DCM) using an animal model, we investigated whether autoimmune myocarditis might develop into DCM.
METHODSExperimental Balb/C mice (n = 20) were immunized with cardiac myosin with Freund's complete adjuvant at days 0, 7 and 30. The control Balb/C mice (n = 10) were immunized with Freund's complete adjuvant in the same mannere. Serum and myocardium samples were collected after the first immunization at days 15, 21 and 120. The anti-myosin antibody was examined by enzyme-linked immunosorbent assay and immunoblotting.
RESULTSPathological findings demonstrated that there was myocardial necrosis or inflammatory infiltration during acute stages and fibrosis mainly in the late phase of experimental group, but the myocardial lesions were not found in the control group. Autoimmunity could induce myocarditis and DCM in the absence of viral infection. High titer anti-myosin IgG antibodies were found in the experimental group, but not in the control group. Furthermore, the anti-myosin heavy chain (200 KD) antibody was positive in 21 of 48 patients with DCM and viral myocarditis, but only 4 of 20 patients with coronary heart disease, including 1 case and 3 cases that reacted with heavy and light chains (27.5 KD), respectively. The antibodies were not detected in healthy donors.
CONCLUSIONCardiac myosin might be an autoantigen that provokes autoimmunity and leads to the transformation of myocarditis into DCM. Detection of anti-myosin heavy chain antibody might contribute to diagnosis for DCM and viral myocarditis.
Adult ; Aged ; Animals ; Autoantibodies ; blood ; Autoimmune Diseases ; complications ; Cardiac Myosins ; immunology ; Cardiomyopathy, Dilated ; etiology ; immunology ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Myocarditis ; complications ; Myocardium ; pathology
8.Analysis of Specific Th1/Th2 Helper Cell Responses and IgG Subtype Antibodies in Anti-CD4 Monoclonal Antibody Treated Mice with Autoimmune Cardiomyopathy
WANG ZHAOHUI ; LIAO YUHUA ; YUAN JING ; ZHANG JINGHUI ; DONG JIHUA ; WANG JINPING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2008;28(4):409-414
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6-8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM)group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P<0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P<0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced,to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
9. Pre- and post-orthotopic heart transplantation electrocardiogram characteristics of 998 patients
Hongquan GUAN ; Zhijian CHEN ; You ZHOU ; Jie LIU ; Weixin SUN ; Jie YUAN ; Yuhua LIAO ; Nianguo DONG ; Jinping LIU ; Kaige FENG ; Qing ZHANG ; Xin ZHAO ; Cheng QIAN ; Fen HU
Chinese Journal of Cardiology 2017;45(4):299-306
Objective:
To analyze pre- and post-operation electrocardiograms (ECGs) features of patients underwent orthotopic heart transplantation (OHT), and provide evidences for identifying and analyzing post OHT ECGs.
Methods:
Nine hundreds and ninty-eight pre- and post- OHT standard 12-leads ECGs from 110 consecutive patients, who underwent OHT in our hospital from May 2008 to May 2014, were analyzed.
Results:
The mean heart rate(HR)was (86.9±16.4) beats per minute before OHT, and (100.0±0.4) beats per minute after OHT. P wave′s amplitude, duration, amplitude multiplied by duration of donor heart in lead Ⅱ were (0.124±0.069)mV, (111.1±17.2)ms, (14.34±9.51)mV·ms before OHT; (0.054±0.037)mV, (86.9±27.0)ms, (5.02±4.03)mV·ms at 1 month after OHT; (0.073±0.049)mV, (93.9±17.5) ms, (7.00±4.81)mV·ms at 6 years after OHT. ECGs rotation occurred in 83.64%(92/110) patients after OHT, and prevalence of clockwise rotation was 76.36%(84/110). Sinus tachycardia was evidenced in 99.09%(109/110) patients after OHT, and incomplete right bundle branch block was present in 60.91%(67/110) patients after OHT. Pseudo complete atrioventricular block mostly occurred at 2 days after OHT. Prevalence of double sinus rhythm was 27.95%(263/941) post OHT, 40% of them occurred between the 1st and the 2nd month post OHT; the atrial rate of recipient hearts was (104.0±10.2) beats per minucte between the 3rd and the 6th month post OHT, and was (95.3±4.2) beats per minucte between the 4th year and the 5th year. P wave′s amplitude, duration, amplitude multiplied by duration of recipient heart in lead Ⅱ were (0.066±0.055) mV, (52.8±34.7) ms, (4.67±4.95) mV·ms at 1 month after OHT, (0.043±0.040)mV, (44.4±40.5) ms , (3.11±3.61) mV·ms between the 1st year and 2nd year after OHT. The absolute value of P-wave(originating from the donor heart) terminal force in chest leads increased in 48.99%(461/941) patients post OHT, the P-wave terminal force of V1 , V2 and V3 were -0.044(-0.066, -0.028), -0.060(-0.087, -0.038), -0.035(-0.056, 0) mm·s. Notched P wave in chest leads was presented in 10.31%(97/941) patients post OHT. PR segment depression in chest leads occurred in 60.24%(100/166) patients between the 3rd month and the 6th month, the incidence of PR segment depression in V1 , V2 and V3 was 21.04%(198/941), 37.41%(352/941) and 28.69%(270/941), respectively.
Conclusions
OHT is related to significantly changed ECGs. The mean HR increased significantly after OHT, then decreased gradually after half a year to one year, but it was still higher than preoperative mean HR after five or six years; the P waves of donor heart were usually inconspicuous or small in first month after OHT, and they became bigger after 2 months, and their duration and amplitude then became relatively steady afterwards. ECGs rotation, especially the clockwise rotation, was common post OHT. A variety of arrhythmias originating from the donor heart including sinus tachycardia and incomplete right bundle branch block could be found. Pseudo complete atrioventricular block could also be found in the early phase after OHT. With the extension of time, the incidence of double sinus rhythm reduced gradually. The atrial rate and P wave of recipient heart presented with a tendency to become lower. The absolute value of P-waves(originating from the donor heart) terminal force in chest leads (mainly V1, V2 and V3) increased, notched P waves in chest leads (mainly V1, V2) and PR segments depression in chest leads (mainly V2, V3 and V4) also belong to typical post OHT ECGs features.
10.Effect of mild hypothermia on behaviors of rats with intracerebral hemorrhage and the possible mechanism.
Yu PENG ; Yun LIN ; Xiaolin HOU ; Xiaoling LIAO ; Jinping LIU
Journal of Southern Medical University 2020;40(9):1359-1364
OBJECTIVE:
To explore the effect of mild hypothermia on inflammatory response and angiogenesis in brain tissues of rats with intracerebral hemorrhage (ICH) and its possible mechanism for improving behavioral deficits of the rats After ICH.
METHODS:
A total of 120 healthy male SD rats were randomly divided into sham operation group, ICH group and mild hypothermia group. Rat models of ICH were established in the latter two groups by stereotactic injection of autogenous blood in the brain, and the rats in the sham operation group received injection of normal saline in the same manner. At 15 min after modeling, the rats in hypothermia group were subjected to mild hypothermia (30-32 ℃) for 8 h followed by rewarming (37-38 ℃); the body temperature was maintained at 37-38 ℃ in the other two groups. At 2, 4, 7, 14 and 21 days after the treatment, Longa scoring, balance beam scoring and Berderson scoring were used to evaluate the behavioral deficits of the rats. Immunohistochemical staining was used to detect the protein expressions of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the brain tissue of the rats, and the mRNA expressions of α subunit of hypoxia-inducible factor 1 (HIF1-α) and vascular endothelial growth factor (VEGF) were detected using RT- PCR.
RESULTS:
At 2, 4, 7, 14 and 21 days after the treatment, the behavioral scores of the rats were significantly higher in ICH group and mild induced hypothermia group than in the sham operation group ( < 0.05 or 0.01). The protein expressions of TNF-α and NF-κB and mRNA expressions of HIF1-α and VEGF were significantly higher in ICH group and mild hypothermia group than in the sham operation group ( < 0.01). The behavioral scores were significantly lower in mild hypothermia group than in ICH group ( < 0.05), and the protein expressions of TNF-α and NF-κB were lower and the mRNA expressions of HIF1- α and VEGF were higher in mild hypothermia group than in ICH group ( < 0.05 or 0.01).
CONCLUSIONS
Mild hypothermia can improve behavioral deficits in rats with ICH possibly by antagonizing brain inflammation and promoting angiogenesis.