OBJECTIVETo investigate the effect of tanshinone II(A) on the expression of different components in the renin-angiotensin system of left ventricles of renal hypertensive rats.

METHODThe renal hypertension model was established in rats by the two-kidney-one-clip (2K1C) method. In the experiment, all of the rats were randomly divided into four groups (n = 15 per group) before the operation: the sham-operated (Sham) group, the hypertensive model (Model) group, the low-dose tanshinone II(A) group and the high-dose tanshinone II(A) group. At 5 week after the renal artery narrowing, the third and fourth groups were administered with 35 mg kg(-1) x d(-1) and 70 mg x kg(-1) x d(-1) of tanshinone II(A), respectively. The blood pressure in rats was determined by the standard tail-cuff method in each week after the operation. After the drug treatment for 8 weeks, all the rats were put to death, and their left ventricles were separated to determine the ratio of left ventricle weight to body weight (LVW/BW), the myocardial collagen content, and the expressions of different components in myocardial RAS, including angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin 1-type receptor (AT1R), Mas receptor mRNA expression and angiotensin II (Ang II) and angiotensin (1-7) [Ang (1-7)] content.

RESULTCompared with the sham group, the hypertensive model group exhibited a markable increase in the content of Ang II and Ang (1-7) and the mRNA expressions of ACE, ACE2, AT1R and Mas (P < 0.01). However, the treatment with tanshinone II(A) showed the does dependence, inhibited left ventricle hypertrophy, decreased myocardial Ang II content and the mRNA expression of ACE and AT, R in renal hypertensive rats (P < 0. 01) , further increased the myocardial Ang (1-7) content and the mRNA expression of ACE2 and Mas (P < 0.01) , but without any change in the blood pressure of hypertensive rats.

CONCLUSIONThe treatment with tanshinone II(A) could inhibit left ventricle hypertrophy of renal hypertensive rats. Its mechanism may be partially related to the expression of different components in the renin-angiotensin system for regulating myocardial tissues.

Angiotensin I ; genetics ; metabolism ; Angiotensin II ; genetics ; metabolism ; Animals ; Blood Pressure ; drug effects ; Diterpenes, Abietane ; administration & dosage ; Heart Ventricles ; drug effects ; metabolism ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; Peptide Fragments ; genetics ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Renin ; genetics ; metabolism ; Renin-Angiotensin System ; drug effects

Objective To observe the changes of body weight,fat mass and skeletal muscle mass of rats after 4 weeks of intermittent fasting,and explore relationship with autophagy in skeletal muscle,so as to provide theoretical basis for intermittent fasting.Method Twenty male Sprague Dawley rats were randomly divided into a control group (Con) and an intermittent fasting group (IF),each of 10.The rats of IF group were forbidden to eat food every Wednesday and Friday,and the body weight of both groups was recorded weekly.After 4 weeks,Dual-Energy X-Ray Absorption (DEXA) was used to analyze the body fat mass,then the bilateral soleus was separated to record the wet weight and measure the cross-sectional area of the soleus fibers by testing laminin with immunofluorescence confocal laser scanning microscope.The form of autophagic vacuole of soleus was observed using a transmission electron microscopy.The expression of autophagy-related protein LC3,p62 and regulating protein AMPK,pAMPK and ULK1 were measured using Western blotting.Result After 4 weeks of intermittent fasting,the weight and fat mass of IF were significantly lower than those of Con (P＜0.01),but there were no significant differences between them in wet weight and cross-sectional area of soleus (P＞0.05).The expressions of AMPK,p-AMPK,ULK1 in IF were significantly higher than those in Con (P＜0.01).Compared with Con,the expression of LC3-Ⅱ/LC3-Ⅰ of IF increased significantly,while the expression of p62 decreased significantly (P＜0.01).Conclusion Four weeks of intermittent fasting decreases the fat mass significantly,and control the weight efficiently.Intermittent fasting can maintain the skeletal muscle mass by promoting moderate autophagy through the AMPK-ULK1 pathway.It should be a potential lose weight method for further research.

Objective To construct a genetically-stable double auxotrophic,in which the uracil and leucine were mutated,using the Candida parapolymorpha ATCC26012 as materials.Methods Based on the physical and genetic engineering methods,the chromosome of the C.parapolymorpha strain was modified,where the ura3 and leu2 genes were directly mutated,to obtain the uracil and leucine double auxotrophic strain.Then the constructed strain was identified by the analysis of its biological properties,such as genetic stability,the change of the genes,and the physiologic and biochemical characteristics.Results The uracil and leucine double auxotrophic strain is obtained by screening.The biological identification results show that the obtained strain is genetically stable and the targeted genes are directly altered.In addition,the physiologic and biochemical analyses indicate that the auxotrophic can utilize various kinds of carbon and nitrogen nutrient sources,and its growth is good.Conclusion The successful construction of double auxotrophic mutant strains facilitated the genetic studies on C.parapolymorpha to meet various investigational purposes.Moreover,the constructed auxotrophic strains can be applied as advantageous host cells to express multiple proteins/antigens simultaneously,which is of great significance in the development of vaccines.

Objective To evaluate in vivo tracking of swine mesenchymal stem cells (MSCs) la-beled with super paramagnetic iron oxide (SPIO) in intraportal transplantation by a clinical 1.5T MR.Methods MSCs were isolated from swine and cultured as well as expanded, which were then incuba-ted with SPIO (Feridex I. V.). Prussian blue staining was performed for showing intracelluar irons.To establish a swine model of acute liver necrosis, 0.5 g/kg of D-galactosamine was administrated to 10 pigs. MSCs(labeled cells in six, unlabeled cells in four)were injected into liver via portal veins. MR imaging was performed with a clinical 1.5T MR immediately before and at 6 h, 3 d, 7 d, 14 d after transplantation, respectively. Results Prussian blue staining of SPIO labeled MSCs could be effec-tively labeled and the labeling efficiency was almost 100%. Signal intensity loss in liver by SPIO labe-ling on FFE sequence persisted until 14 days after transplantation. Histological analysis by Prussian blue staining showed homing of labeled MSCs in liver after 14 days, primarily distributing in hepatic sinusoids and liver parenchyma. Conclusion MSCs can be labeled with SPIO in vitro successfully.MRI can monitor magnetically labeled MSCs transplanted into liver.

Objective To explore the operative indication operation time and post-operative care for infants with large ventricular septal defects (VSD).Methods Eighty-eight infants who suffered from large VSD were selected,male 53 cases,female 35 cases,aged from 3 to 18 months[average (7.5-±2.9) months],weight from 5 to 13 kg [average (7.9 ± 1.9) kg].All patients underwent VSD repair and other accompanied anomaly corrections under cardiopulmonary bypass.Fifty-eight cases were operated through right atrium,14 cases through pulmonary artery and 16 cases through right ventricle.Patch repairs were done in all patients,78 cases given bovine pericardium patches,10 cases given self pericardium patches treated by Glutaral.Patients were sent to the intensive care unit after surgery,vasoactive drugs were used as a routine method.Antibotics were selected based on their sputum cultures postoperatively.Nutritional support was given in the earlier stage.Results There were no hospital death,average hospitalization days were (15.2 ± 5.9) days (from 11 to 32 days).The main complication were pneumonia (5 cases),bad coalesce of incision (4 cases),atelectasis (3 cases),minimal residual shunt of VSD (3 cases).All patients were discharged from hospital,76 cases were followed up from 1 to 12 months,2 cases had residual shunt of VSD,the residual shunt of the other case disappeared;76 patients had no clinical symptom,28 patients body weight returned to normal after 6 months of operation.There was no other complication and death.Conclusion Early surgical treatment for infants with large VSD is a safe and effective way with a better prognosis.

AimTo evaluate the efficiency of gene amplification technique used in detecting the specimens colleted from rodents to identify natural epidemic foci of scrub typlus. MethodMice of Kunining strain were experimentally infected by a certain amount of Oriential tsutsugamushi. The specimens of blood clot and spleen from the infected animals were detected by nested polymerase chain reaction(nPCR)specific to O. T sutsugamush at the day 3,6 and 9 of post-infection. Then the technique was used for detection of samples collected from field. As an infected index ,the specimen was considered to be positive only if a 88-bp DNA fragment from Sta 58kDa gene of O. Tsutsugamushi could be produced. According to the study ,it was estimated whether or not that the sampling area is a natural epidemic focus of the disease. ResultsThe specimens of both blood clot and spleen from the mica at day 3 of post-infecction showed negative to the specific PCR product ,but positive when detected at day 6 and hereafter. Of 111 spleen samples from the field collections in the northwest of Fujian province,one was positive, and another positive sample was in the 29 blood clots from Jiangxi province. It is demonstrated that these areas have been the natural epidemic foci. Conclusion The nPCR method is of highly sensitive and specific to be used in the etiologic study on specimens from field rats.

With the increase of morbidity and mortality, pancreatic cancer will not only become one of the leading causes of death in China, but also a major public health problem in the world. New onset cases of pancreatic cancer all around the world are expected to increase year by year. The prognosis of patients with pancreatic cancer is poor. The 5-year survival rate is only about 6%. The major reason for the poor prognosis is the lack of typical clinical symptoms in the early stage of disease, which makes it difficult to detect and control its relevant recurrence and metastasis. Moreover, lack of effective chemotherapy drugs and resistance to existing chemotherapy drugs are also important reasons for its dismal status. Radical resection surgery is still the most effective treatment. However, even after radical resection surgery, early recurrence and distant metastasis are still the main problems that bother patients. This article reviews recent high quality studies on pancreatic cancer including epidemiological investigation, advances in basic research, and clinical treatment.

Pancreatic cancer is a highly malignant, fast progressive digestive system neoplasm with poor prognosis, and the incidence has increased significantly in the recent years. The treatment mode of pancreatic cancer has been transformed from surgery-first approach to multidisciplinary approach including surgery, chemotherapy, radiotherapy and other comprehensive treatment modalities, accompanying with significant improvement in clinical efficacy. During the last decade, the molecular mechanism of pancreatic cancer has been explored in depth. Indeed, we had a clearer understanding of the disease, which provides clues for translation of basic research into clinical practice. This review summarized recent high quality studies on pancreatic cancer including pathogenic factor, advances in basic research, and clinical treatment.

Objective To observe the clinical efficacy of thread embedding at the holographic point Kidney of the second metacarpal bone in treating tinnitus.Method Eighty-two patients with tinnitus were randomized into a treatment group and a control group, 41 cases in each group. The treatment group was intervened by thread embedding at the holographic point Kidney of the second metacarpal bone, while the control group was by intragluteal injection with Mecobalamin 0.5 mg. The Tinnitus Handicap Inventory (THI) was compared before intervention and after 1 treatment course.Result The THI scores were significantly changed in both groups after intervention (P<0.01). The change of THI score after intervention in the treatment group was significantly different from that in the control group (P<0.05).Conclusion Thread embedding at the holographic point of the second metacarpal bone in an effective approach in treating tinnitus.

Objective:To evaluate the effect of Nutlin-3,a MDM2 antagonist,on the pyroptosis in SMMC-7721 cells.Methods: The expression of actived caspase-1(p20) and IL-1β was detected using Western blot analysis.Pyroptosis was investigated by a standard lactate dehydrogenase release assay(LDH).IL-1β content in the cell culture supernatant was quantified by ELISA.Results: Nutlin-3 up-regulated the expression level of actived caspase-1 and IL-1β in SMMC-7721 cells.Meanwhile,Nutlin-3 increased significantly the content of LDH and IL-1β in the cell culture supernatant(P<0.05).Conclusion: Nutlin-3 activated pro-caspase-1,promoted pyroptosis and IL-1β release in SMMC-7721 cells.