1.Role of the IGF-1/PI3K pathway and the molecular mechanism of Fuzhenghuayu therapy in a spontaneous recovery rat model of liver fibrosis.
Bo-rong WU ; Yan-li ZHENG ; Xian-liang SANG ; Meng JIN ; Wei-zhen WANG ; Qing-shan ZHANG ; Su-xian ZHAO ; Li KONG
Chinese Journal of Hepatology 2013;21(9):674-678
OBJECTIVETo determine the role of IGF-1/PI3K pathway and investigate the molecular mechanism of Fuzhenghuayu (FZHY) therapy in a spontaneous recovery rat model of liver fibrosis.
METHODSThe liver fibrosis model was induced in male Wistar rats by administering 8 weeks of twice weekly CCL4 intraperitoneal injections without (untreated model) or with once daily FZHY (treated model). Normal, untreated rats served as the control group. At weeks 4, 6 and 8 (fibrosis) and 10, 12 and 14 (spontaneous recovery) after modeling initiation, effects on protein (a-SMA, IGF-1, PI3K) and mRNA (IGF-1, PI3K) expression levels were evaluated by immunohistochemistry and RT-PCR, respectively. Serum markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and liver cell damage (alkaline hydrolysis, HYP) were measured. Histology was performed to assess the degree of inflammation and fibrosis (Ishak scoring system).
RESULTSIn the untreated model group, progression of liver fibrosis (weeks 4, 6 and 8) was accompanied by gradual increases in inflammation, necrosis, serum ALT and AST, and hepatic expression of a-SMA protein and IGF-1 and PI3K protein and mRNA; however, during the spontaneous recovery period (weeks 10, 12 and 14) the IGF-1 and PI3K protein and mRNA levels rapidly decreased and the HYP level, Ishak score, and a-SMA hepatic expression also decreased. The FZHY-treated model group showed significantly lower fibrosis-related up-regulation of IGF-1 and PI3K protein and mRNA expression, HYP level, Ishak score, and a-SMA hepatic expression at each time point (vs. untreated model group).
CONCLUSIONThe IGF-1/PI3K pathway may contribute to progression of liver fibrosis. The mechanism by which FZHY prevents liver fibrosis in a rat model may involve blocking of the IGF/PI3K pathway and inhibiting HSC activation.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects
2.Diagnosis and treatment of primitive neuroectodermal tumors of pancreas.
Xin-ting SANG ; Nai-xin LIANG ; Yi-lei MAO ; Xin LU ; Zhi-ying YANG ; Shou-xian ZHONG ; Jie-fu HUANG
Acta Academiae Medicinae Sinicae 2006;28(2):191-195
OBJECTIVETo improve the diagnosis and treatment of primitive neuroectodermal tumors (PNET) of the pancreas.
METHODSOne patient with PNET of the pancreas was reported in this article. The corresponding literatures on the diagnosis and treatment was reviewed.
RESULTSThe patient was diagnosed as pancreatic PNET by her clinical, microscopic, and immunohistochemical features as well as cytogenetic analysis after the resection of the tumor located in the uncinate process in PUMC Hospital. Radiochemotherapy was given after the operation for 8 months and no recurrence was observed. Since PNET of pancreas have no specific clinical symptoms and most patients have jaundice and/or abdominal pain, the diagnosis depended on the immunohistochemical features of positive P30/32(MIC2) and at least two of the neural markers. The cytogenetic analysis showed translocation mainly harbored the characteristic t (11; 22) (q24; q12). Since pancreatic PNET were highly aggressive, early chemotherapy, close follow-up, and immediate surgical interventions were required as early as possible.
CONCLUSIONPNET can occur in pancreas, and diagnosis and treatment should be made as early as possible to improve the outcome.
Child ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Neuroectodermal Tumors, Primitive ; diagnosis ; therapy ; Pancreatic Neoplasms ; diagnosis ; therapy
3.Epicardial isolation of pulmonary veins with ethanol in open chest dogs.
Xian-Dong YIN ; Man NING ; Cai-Hua SANG ; Cheng-Long MIAO ; Cui LIANG ; Ri-Bo TANG ; De-Yong LONG ; Rong-Hui YU ; Xing-Peng LIU ; Jian-Zeng DONG ; Chang-Sheng MA
Chinese Medical Journal 2011;124(11):1714-1719
BACKGROUNDRadiofrequency (RF) ablation has become a widely accepted treatment for atrial fibrillation (AF). This study aimed to identify the efficacy and safety of pulmonary vein (PV) ablation with ethanol and to explore an alternative energy source for catheter ablation of AF.
METHODSTwelve open-chest mongrel dogs were randomized into ethanol ablation group and control group. Both the injections and electrophysiological mapping procedures were performed epicardialy. In ethanol ablation group (n = 6), injections were performed to circumferentially ablate the root of each PV (0.2 ml each site, 3 mm apart) with 95% ethanol using an 1 ml injector. In control group (n = 6), saline was injected other than ethanol. PV isolation was confirmed with a circular catheter immediately after the procedure and at follow up of 30 days. PV isolation was defined as the absence of PV potentials at each electrode of the circular catheter positioned at the PV side of the lesions, as well as complete conduction block into left atrium (LA) during PV pacing.
RESULTSPV electrical isolation with complete bidirectional conduction block was achieved with ethanol immediately and at 30 days in 95% of PVs, while saline injection caused only transient conduction changes between LA and PVs. In ethanol group, histologic analysis showed transmural lesions at 30 days. And there was no evidence of PV stenosis or thrombus formation. Mean LA diameter was not significantly different between baseline and 30 days.
CONCLUSIONEthanol is a safe energy source to effectively isolate PV in canine model and may be promising in endocardial ablation procedure of AF patients in the future.
Animals ; Catheter Ablation ; methods ; Dogs ; Electrophysiology ; Ethanol ; Pulmonary Veins ; physiology ; surgery ; Random Allocation
4.Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center.
Nian-sang LUO ; Wo-liang YUAN ; Yong-qing LIN ; Yang-xin CHEN ; Xiao-qun MAO ; Shuang-lun XIE ; Min-yi KONG ; Shu-xian ZHOU ; Jing-feng WANG
Chinese Medical Journal 2010;123(17):2295-2298
BACKGROUNDCardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However, the possible adverse effects of CRT are often ignored by clinicians.
METHODA retrospective analysis of CRT over a 6-year period was made in a single cardiac center.
RESULTSFifty-four patients were treated with CRT(D) device, aged (57 ± 11) years, with left ventricular ejection fraction of (32.1 ± 9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy, and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.
CONCLUSIONSNew-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.
Cardiac Resynchronization Therapy ; adverse effects ; Humans ; Perioperative Period ; Retrospective Studies ; Tachycardia, Ventricular ; etiology ; Ventricular Fibrillation ; etiology