1.Role of TGF-β Expressed by Biliary Epithelial Cells in Pathogenesis of Cholestatic Liver Disease
Yao HE ; Baili CHEN ; Rongping YANG ; Zhirong ZENG ; Ming REN
Journal of Sun Yat-sen University(Medical Sciences) 2010;31(1):85-90,99
[Objective] To investigate the change of liver histology, proliferation of BDEC, and expression of TGF-β in different stages of liver chelestusis. [Methods] ①Rat cholestatic livers were induced by common bile duct ligation (BDL) and separated into 3 groups, namely control group (DO), 7 days after BDL group (DT), and 18 days after BDL group (D18). ② Histological changes of livers in different groups were evaluated based on Knodell HAI score. ③ Real-time PCR was used to detect the expression of TGF-β in liver tissue and isolated BDEC in different groups. ④ Statistically analyzing the correlation between Knedell HAl score and the levels of TGF-β_1 mRNA. ⑤ In vitro study was performed to investigate the effect of TGF-β_1 on an immortalized mouse intrahepatic bililary epithelial cell line (mIBEC). [Results] (I) Knedell HAI score and the proliferation of intrahepatic bile ducts increased as the liver cholestasis aggravated. ② The levels of TGF-β_1, TGF-β_2, and TGF-β_3 mRNA were significantly up-regulated in liver tissues and BDEC as the liver cholestasis aggravated. ③ Positive correlation was found between Knedell fibrotic score and the levels of TGF-β_1 mRNA in liver tissues and BDEC(r=0.9376, P<0.05 and r=0.9682, P < 0.01). ④ In vitro study showed that TGF-β_1 inhibited the proliferation of mIBEC. [Conclusion] ① Liver injury, biliary proliferation, and the levels of TGF-β mRNA expression increased as liver cholestasis aggravated. ② The interaction of TGF-β_1 and BDEC plays an important role in the pathogenesis of BDL induced cholestatic liver disease. ④ Up-regulated expression of TGF-β_1 mRNA in the proliferated BDEC participates in the formation of BDL induced cholestatic liver fibrosis.
2.Inhibitory Effect of CTLA-4Ig Fusion Protein on Atherosclerosis in ApoE-/- Mice
Jie CHEN ; Yujie LI ; Dongdan ZHENG ; Yan XIONG ; Xin LI ; Xiaoxing LIAO
Journal of Sun Yat-sen University(Medical Sciences) 2009;30(4):395-399,417
[Objective] To investigate the inhibitory effect of CTLA-4Ig fusion protein on atherosclerosis in the mice with an apolipoprotein-E gene defect fed on cholesterol diet.[Methods] Twenty-five male 10-week-old ApoE-/- mice were selected and fed on cholesterol diet for 4 weeks,5 out of which were executed at random as control group and their pathological sections were kept to observe the early fatty streaks.The other 20,divided into CTLA-4Ig treatment group,PBS group,IgG1 group,and blank group at random,5 in each.Three groups were given intraperitoneal injection of CTLA-4Ig (10 μg per time),PBS (100 μL per time),Rat-IgG1 (10 μg per time) respectively,twice a week,for 8 weeks.The blank group has no treatment.Followed by 8-week treatment,the whole aorta from the root to crotch of iliac artery was separated after anesthesia with the intraperitoneal injection of 1 % pentobarbital.Subsequently,the area ratio of plaque and lumen,the thickness ratio of endangium and tunica media,the lipid-soaking extent intra-plaque and the content of collagen fibrils and smooth muscle cells intra-plaque were analyzed by image-processing soft.[Results] After fed on cholesterol diet for 4 weeks,there were obviously atherosclerosis in the aorta in the ApoE-/- mice.There were typical atherosclerotic plaque in ApoE-/- mice fed on cholesterol diet after another 8 weeks.The area ratios of plaque and lumen in CTLA-4Ig group,PBS group,IgG1 group,and blank group were 0.27 ± 0.08,0.40 ± 0.08,0.43 ± 0.08,and 0.46 ± 0.10,and obviously increased than those in control group (0.05 ± 0.01,P < 0.05).The thickness ratios of endangium and tunica media in four groups were 2.6 ± 0.6,6.0 ± 0.9,5.7 ± 0.8,and 5.9 ± 0.6 and obviously increased than those in control group (0.5 ± 0.1,P < 0.05).The lipid-soaking extent intra-plaque in experimental groups were 26.0 ± 3.0,40.8 ± 5.7,40.6 ± 3.0,and 43.2 ± 5.7,and were obviously increased than those in control group (7.2 ± 1.4,P < 0.05 ).It was found that the area ratio of plaque and lumen,the thickness ratio of endangium and tunica media,and the lipid-soaking extent intra-plaque in CTLA-4Ig group were significantly lower than those in PBS group,IgG1 group,and blank group (P < 0.05),but there was no significant difference in those between the PBS group,IgG1 group,and blank group (P > 0.05).The content of collagen fibrils in CTLA-4Ig group were 16.0 ± 1.1 and higher than those in PBS group,IgG1 group,and blank group (8.6 ± 1.2,9.2 ± 1.5,and 9.0 ± 1.3,P < 0.05).The content of smooth muscle cells in plaque in CTLA-4Ig group were 11.8 ± 1.0 and higher than those in PBS group,IgG1 group,and blank group (7.8 ± 0.8,7.5 ± 0.9,and 7.3 ± 0.7,P < 0.05).There was no significant difference in content of collagen fibrils and smooth muscle cells between the PBS group,IgG1 group,and blank group (all P > 0.05).[Conclusion] CTLA-4Ig fusion protein could evidently inhibit the atherosclerosis progression and enhance the stability of plaque through increasing the content of collagen fibrils produced by smooth muscle cells intra-plaque in ApoE-/- mice fed on cholesterol diet.
3.Activation of Muscarinic Cholinergic Receptors Protects Cerebellar Granule Neurons from Dopamine-Induced Apoptosis via ERK Pathway
Xuemin WANG ; Pengxin QIU ; Xingwen SU ; Wenming LI ; Shoujian HUANG ; Guangmei YAN
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(3):161-164,169
【Objective】To investigate the molecular mechanism of dopamine (DA)-induced apoptosis in cultured cerebellar granule neurons (CGNs) and the effect of muscarinic cholinergic receptor (mAChR) agonist carbachol on it.【Methods】The apoptosis of neurons was measured by phase-contrast microscopy,Hoechst 33258 nucleus staining and DNA fragmentation agarose gel electrophoresis.The neuronal viability was measured by fluorescein diacetate (FDA) staining.The activation of extracellular signal-regulated protein kinase (ERK) was determined by Western blot.【Results】Dopamine increases the phosphorylation of ERK and induces apoptosis in CGNs,which is blocked by both carbachol and PD 98059.The protective effect and the inhibiting ERK phosphorylation of carbachol were blocked by atropine.【Conclusion】DA-induced apoptosis in CGNs may be mediated by activation of ERK.Carbachol protects CGNs from DA-induced apoptosis by activating mAChR and subsequent inhibition of activation of ERK.
4.Endometrial Carcinoma(EC) Accompanied with Multiple Primary Malignancy
Lizhi LIANG ; Daocheng LI ; Xin HUANG ; Qiuliang WU
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):76-78
【Objective】 To study the incidence, possible etiology, diagnosis and prognosis of endometrial carcinoma with multiple primary carcinom a. 【Method】 45 cases of EC with other primary tumors were eligible for the ret rospective study. 【Results】 Of 1389 cases with EC, the rate of EC accompanied wit h other primary carcinoma was 3.2% (45/1389); the interval between two tumors d iagnosed was ranged from 8 months to 19 years. The percentage of interval more t han 5 years accounted for 62% (16/26). Among these 45 patients, the percentage o f EC complicated by other reproductive tract tumor was 53%(24/45), of them, 19 were synchronous carcinoma. The rate of EC with breast cancer and colo-rectal carcinoma were 169%(7/45), and 11%(5/45) respectively. Clinical staging for pati ents with EC plus multiple primary malignancy were 30 with stage Ⅰ, 9 stage Ⅱ, 3 stage Ⅲ and 2 stage Ⅳ. All patients with first primary tumors were treated by radical treatment. While 8 cases were also treated by radiation and 6 cases t reated by chemotherapy. In this group, all multiple primary tumors were treated by radical therapy. The overall 5-year survival rate was 63%. 【Conclusions】 ①The possibility of second primary tumor, such as female reproductive tract tu mor , breast cancer, and colo-rectal carcinoma should be considered in the patients with EC. ②The etiology of EC with multiple primary tumor may be relevant to th e same embryonic histogenesis, estrogen receptor, radiotherapy and chemotherapy.
5.Etiology Analysis of Recurrent Early Spontaneous Abortion
Qiong WANG ; Minzhi WANG ; Yuepeng WU ; Hongwei SHEN
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):73-75
【Objective】 To identify the main factor or factors w hich contribute to recurrent early spontaneous abortion for clinical diagnosis a nd treatment. 【Methods】 69 cases received the screening examination including inherent, endocrine, anatomical, infective, immunological and contamination hist ory poison metabolic factors, then analyses all factors. 【Results】 Analysing the single factor effecting th e recurrent early spontaneous abortion in the above 7 factors, we found the immun ological factor was 86.2%. Furthermore the immunological factor had significant difference in the various aged groups. 【Conclusion】 Immunological factor is a main factor in recurrent early spontaneous abortion. The immunological factor b ecomes significantly important as the times of spontaneous abortion increasing.
6.The Morbidity Trend of the Preterm Delivery in Thirty Years and Sampling Analysis of the Obsterical Factors
Minling CHEN ; Shunying HUANG ; Zilian WANG
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):68-72
【Objective】 To investigate the morbidity trend of the preterm delivery.【Methods】 A retrospective study was done on the delivery data in our hospital from 1969 to 1998. Select the cases on annual August as the sam pling units, and divided those 253 cases into three decade groups, to analyze th e obsterical factors affecting the preterm delivery.【Results】 ① The morbidity of the preterm delivery in thirty years was 4.72%(95% CI 4.16, 5.32). ② The re were no obvious changes of the morbidity among the years, and had no seasonal aggregation. ③ The cesarean section rates in the third decade increased signif icantly than those in former two decades (P<0.05). ④ As time goes on, the i ncidence of premature rupture of membrane increased, and that of the preterm del ivery with no obvious complication decreased. The cases with the intrauterine fe tal distress and IVF-ET in the third decade were significantly increased. ⑤ Th e gestation age and birth weight increased significantly, especially in the thir d decade, but the neonatal mortality had no obvious change. 【Conclusions】 Ther e was no reduction of the morbidity of the preterm delivery, further studies sho uld be emphasized. It seems unlikely the increased of cesarean section rates wil l reduce the neonatal mortality. PROM is important factors affecting the preterm delivery, and the IVF women may be at higher risk of preterm delivery.
7.Risk Factors of HBV Intrauterine Transmission
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):61-63
【Objective】 To study the risk factors of Hepatitis B Virus intrauterine transmission. 【Method】 Cordal blood from 87 HBV carrier's newborns was tested for HBV markers and PCR-HBV-DNA. Maternal venous blood po stpartum was tested for HBV markers. 【Results】 HBV-DNA positive rate of corda l blood is 1.2%(1/86). Odds Ratio(OR) of positive maternal HBsAb, HBeAg, HBeAb and HBcAb for intrauterine infection are 0.697(0.586~0.786), 50.792(13.082 ~197.204), 0.103(0.032~0.338) and 2.261(0.587~8.712), respectively. Co rdal HBsAg positive rate of maternal HBeAg positive group was significantly high er than that of only HBsAg positive group (31.0% vs 3.92%), so was cordal HBeA g positive rate (72.4% vs 3.92%). Maternal HBeAg was significantly correla ted with cordal HBsAg, especially HBeAg. Newborn sex wasn′t correlated with intraut erine infection. 【Conclusion】 Positive maternal HBeAg was one risk factor of i ntrauterine HBV infection. Newborn sex wasn′t correlated with intrauterine infe ction.
8.Anti-Myocardial Ischemia Effect ant Its Mechanism of Traditiona l Chinese Medicine Composite Xinmaitong Capsule
Ruixiang QIU ; Jingbo HE ; Jun LAN ; Cuiyi KUANG ; Hongjian LIU ; Jun FENG
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):57-60
【Objective】 To assess the effects of traditional Chine se medicine composited Xinmaitong (XMT) capsule on treating ischemia cardiac dis ease. 【Methods】 Sixty coronary heart disease patients with myocardial ischemia were divided randomly into two groups. XMT group (30 cases) was treated with XM T and western medicine, and control group (30 cases) with western medicine. The changes of the scores of clinical symptoms, the total ischemia burden (TIB), the plasma endothelin (ET), the nitric oxide (NO), the super oxide dismutase (SOD), and the malonyldialdehyde (MDA) levels were observed before and after treatment . 【Results】 After treatment with XMT, the scores of clinical symptoms, TIB, ET and MDA levels were significantly decreased (P<0.01), the levels of NO and SOD were significantly increased (P<0.01) in XMT group. Comparing with contr ol group, these changes were statistically different (P<0.01). 【Conclusions 】 XMT capsule can act against myocardial ischemia effectively, one of the mecha nisms of which is protecting the function of vascular endothelium and resisting lipid peroxidation injury. The effect of adding XMT capsule on conventional trea tment with western medicine was better than that with western medicine only.
9.Slow Atrioventricular Nodal Pathway Ablation: Electrocardiogram Monitoring During Effective Delivery of Radiofrequency Energy
Yesong WANG ; Hong MA ; Jiangui HE ; Anli TANG ; Jun LIU ; Suhua WU ; Xinxue LIAO
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):54-56
【Objective】 To explore the significance of electrocard iogram monitoring during the effective application of radiofrequency energy to s low atrioventricular (AV) nodal pathway ablation. 【Methods】 Slow AV nodal pathway ablation was performed in 58 patients with slownfast AV nodal ree-trant tachyca rdi a (AVNRT). The changes of electrocardiogram were monitored during the effective application of low radiofrequency RF energy (15~25 W). A faster rate of junctio nal ectopy (>150 min-1), ventriculoatrial (VA) block in association with j unctional ectopy, and l ong P-R interval during sinus beat were considered as harbingers of atrioventri cular (AV) block. RF energy deliveries were discontinued as soon as the harbinge rs of AV block occurred. Otherwise, RF energy continued until junctional ectopie s were decreased or vanished. If junctionnal ectopies were not decreased, RF ene rgy continued lasted for 90~120 s. 【Results】 Slow AV nodal pathway ablation w as successful in all patients who had junctional ectopy during the effective del ivery of RF energy. The effective ablation time was (128±26) s. 54 patients exp erienced one time successful ablation, and 4 patients experienced two times abla tion. Unsustained AV block occurred in 6 patinets after RF energy deliveries whi ch were immediately terminated because of VA block in association with junctiona l ectopy in 4 patinets and long P-R interval during sinus beats in 2 patients. No patients developed permanent AV block. Recurrent AVNRT requiring second ablat ion occurred in 2 of 58 successfully ablated slow pathway during (18±16) months of follow-up. 【Conclusion】 RF energy deliveries could be instructed b y intracardiac electrocardiogram monitoring during AVNRT ablation, which could e nhance the successful rate of slow pathway ablation, reduce recurrence and avoide permanent AV block.
10.Study on Electrophysiological Properties of Atrial and Atriovent ricular Node in Patients with Paroxysmal Atrial Fibrillation
Journal of Sun Yat-sen University(Medical Sciences) 2001;22(1):51-53
【Objective】 To compare the difference of electrophy siological properties in atrial and atrioventricular node between patients with paroxysmal atrial fibrillation and normal adults, and to study the initiation ra te of atrial fibrillation in the two groups. 【Methods】 The electrophysiologica l preperties were detected by the technique of esophagus-atrial program pacing in 182 patients with paroxysmal atrial fibrillation and 30 normal adults. 【Resu lt】 ①The initiation rate of atrial fibrillation by the technique of esophagus -atrial pacing was 95.6%; ②In the state of normal sinus rhythm and in basic c ycle length, There was no difference in atrial and A-V node conduction function between the two groups; ③The atrial effective refrectory period (ERPA) was s ignificantly shortened and both atrial relative refrectory period (RRPA) and i ntra-atrial conduction delay (IACD) were significantly lengthened in the atrial fibrillation group when compared with the control group by using premature impu lse. 【Conclusion】 ①In patients with atrial fibrillation, the abnormalities of electrophysiological property would favor the development of micro-circus move ment; ②The esophagus-atrial pacing may be the useful method for identifing the clinical diagnosis of suspected atrial fibrillation but short of evidence of el etrocardiogram.