Objective To determine the effects and mechanisms of somatostatin analogues (sandostatin) on pancreatic repair and regeneration in caerulein induced pancreatitis. Methods Acute pancreatitis was induced by intra abdominal infusion of caerulein in rats, sandostatin was administered intra abdominally at the time of induction of pancreatitis and 24, 48 and 72 hours after. Rats were sacrificed at 6, 24, 48, 72 and 96 hours after the operation. The mRNA expression for Transforming growth factor ? 1 (TGF ? 1) was evaluated by reverse transcription polymerase chain reaction, pancreatic tissue DNA synthesis was measured by 3H thymidine method in vitro and protein content was detected by Lowry's method. Results The serum amylase level was decreased significantly in the sandostatin treated group. Expression of TGF ? 1 mRNA was undetectable in the normal pancreas and the treated group at 6 hours. TGF ? 2 was observed at 24 hours after the induction of pancreatitis, reaching maximum at 72 hours. It could be detected in the sandostatin treated group at 6 hours, reaching maximum at 24 hours, the expression of TGF ? 1 was increased significantly in the sandostatin treated group as compared with the non treated group at 24, 48 hours. Pancreatic tissue DNA synthesis showed a significant decrease during the first 72 hours following the induction of pancreatitis and a marked increase was observed at 96 hours after treatment with sandostatin. Within 48 hours of the induction of pancreatitis, total protein content in pancreatic tissue declined, and there was a significant increase in the sandostatin treated group at 48 hours, reaching maximum at 96 hours. Conclusions Effects of somatostatin analogues (sandostatin) on pancreatic tissue regeneration in acute pancreatitis in rats might be attributed to the enhancement of TGF ? 1 gene expression which subsequently stimulates formation of extracellular matrix components, increases protein content and DNA synthesis, thus accelerates pancreatic repair and regeneration.

Objective To observe the activation of pancreatic stellate cells (PSC) during the formation of pancreatic fibrosis induced by the pancreatic injection of trinitrobenzene sulfonic acid (TNBS). Meanwhile, the effects of PSC-related factors, such as transforming growth factor ? 1 (TGF-? 1), collagen Ⅰ and MMP-2 on the pathogenesis of pancreatic fibrosis in rats were also evaluated. Methods Pancreatic fibrosis model in rats was induced by the injection of 2% TNBS in ethanolate-phosphate buffer solution into the pancreatic duct. The rats were sacrificed and the pancreata were removed at the 72nd hour, 3rd week, 4th week, 5th week, 6th week and 7th week after the operation respectively. Expressions of ?-smooth muscle actin (?-SMA), transforming growth factor ? 1 (TGF-? 1), collagen Ⅰ and MMP-2 were determined by either immunohistochemistry or RT-PCR, or Western blot respectively. The ultrastructure of pancreas was studied by electron microscope at different time points. Results The inflammation, swelling and necrosis were the major pathological changes of the pancreas at the early stage after the injection of 2% TNBS. Subsequently, the fibrotic manifestations such as proliferation of the fibrosis, atrophy of vesicles, deposition of collagen because prominent at the 3rd week after the operation, which peaked at 4th week. The expression of TGF-? 1 was increased significantly at the 3rd week after the operation and reached maximum at the 4th week. The expression of ?-SMA, which indicated the activation of PSC, could be detected at the 3rd week and also reached the peak value at the 4th week. After wards, it was decreased gradually. During the first 72 hours, the expression of MMP-2 mRNA was increased significantly and then was fluctuated but still higher than that in normal rats. The deposition of type Ⅰ collagen was increased in the areas of fibrotic tissues. Conclusions PSC might involve in the courses of the development and progression of TNBS induced pancreatic fibrosis in rats. This action was achieved via the activation of PSC by TGF-? 1, the production of those extracellular matrix metabolic associated enzymes such as the synthesis of collagen Ⅰ and the secretion of MMP-2.

To investigate the effects of Losartan,an angiotensinⅡ(AngⅡ)receptor(AT_1) antagonist,on pancreatic stellate cells(PSCs)and its possible mechanisms.Methods (1)PSCs were isolated from pancreatic cancerous samples to test the expressions of AT_1 and collagenⅠafter incubated with AngⅡor/and Losartan.(2)Ninety S-D rats were divided into normal group,control group and treatment group,with 30 rats in each.The rats in control and treatment groups were induced pancreatic fibrosis by injection of 2% trinitrobenenze sulfonic acid(TNBS)into biliopancreatic duct.Rats in treat- ment group were then treated with Losartan by garage daily and rats in control group were only given distilled water.The rats were sacrificed on day 3,7,14,21 and 28,respectively,and pancreas were removed.The histological abnormalities were observed by electron microscope.The mRNAs of trans- forming growth factor?_1(TGF?_1)and procollagenⅠwere detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of TGF?_1 and?-smooth muscle actin(?-SMA)proteins was assessed by immunohistochemistry and the level of?-SMA protein was quantified by Western blot. Results In vitro,there existed AT_1 expression in PSCs,and Losartan reduced expression of collagenⅠ.Losartan treatment reversed the histological abnormalities observed by electron microscope,com- pared to treatment with distill water.The expression of?-SMA,TGF?_1 and procollagenⅠwere signifi- cantly higher in the control group than those in normal group and were reduced by Losartan to different extent in treatment group.Conclusion AT_1 antagonist can inhibit the activation and the profibrogenic action of PSCs by blocking AT_1 receptor-mediated pathways.

Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break (DSB) signaling. P53-binding protein 1 (53BP1) plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining (NHEJ)-mediated DSB repair pathway that rejoins DSB ends. New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination (HR) signaling. This review focuses on the up- and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair, which in turn promotes the sensitivity of poly(ADP-ribose) polymerase inhibitor (PARPi) in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.

To propose the architectural layout for the big general hospital in the face of public health emergencies, we analyzed the conditions, methods, problems and countermeasures for the reconstruction of the isolation ward from the existing medical building layout of a general hospital. The affected areas met the requirements of isolation ward in the reconstruction, and realized the corresponding partition and separation of people. But the cost of occupying the medical room should be concerned. General hospital should be alerted to potential risks of public health emergencies. The characteristics of different construction types, defects, and the function of the hospital should be considered in the construction, rebuilding, and expansion of the hospital, which shouldnot only meet the needs of the development of the hospital daily usage but also consider dealing with emergent public health events. We can adopt the reasonable layout, including setting up a firewall-like device between the channel and the floor, an ordinary ward at ordinary times, and an independent space for emergency by pulling down the gate. This strategy can not only avoid the problem of low utilization rate of the space occupied by the corresponding area in the ward for diseases spread by air and droplets, maximizing the efficiency of the medical site, but also avoid the problem of emergency response to the temporary reconstruction.
Emergencies ; Emergency Service, Hospital ; Facility Design and Construction ; Hospitals, General ; Humans ; Public Health