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Objective To investigate the effect of pathologically elevated-cyclic stretch induced by hypertension on mitochondrial biogenesis of vascular smooth muscle cells (VSMCs), and the role of PGC1α in this process. Methods The Flexcell-5000T stretch loading system in vitro was applied to VSMCs with a frequency of 1. 25 Hz and an amplitude of 5% or 15% to simulate the mechanical environment under normal physiological or hypertensive pathological conditions respectively. Western blotting and qPCR were used to detect the expression of PGC1α, citrate synthase and mitochondrial DNA (mtDNA) copy number in VSMCs under normal physiological or hypertensive pathological conditions. VSMCs were treated with PGC1α specific activator ZLN005 to promote PGC1α expression or specific interfering fragment siRNA to inhibit PGC1α expression in order to detect the effect on citrate synthase and mtDNA copy number. Results Compared with 5% physiological cyclic stretch, 15% pathologically elevated-cyclic stretch significantly suppressed the expression of PGC1α, citrate synthase and mtDNA copy number in VSMCs. Compared with control group, the protein expression of PGC1α was significantly decreased and increased respectively. When VSMCs transfected with PGC1α siRNA or incubated PGC1α activator ZLN005, the expression of citrate synthase and mtDNA copy number were also significantly down regulated and up-regulated in VSMCs accordingly. Under physiological cyclic stretch conditions, the protein level of PGC1α was significantly down-regulated by PGC1α siRNA, which also significantly down-regulated citrate synthase expression and mtDNA copy number. The protein expression of PGC1α was significantly up-regulated by ZLN005, which also enhanced the expression of citrate synthase and mtDNA copy number. Conclusions The pathological cyclic stretch induced by hypertension significantly down-regulated the expression of citrate synthase and mtDNA copy number via suppressing the expression of PGC1α, resulting in mitochondrial dysfunction of VSMCs. PGC1α may be a potential therapeutic target molecule to alleviate the progression of hypertension.
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Objective To explore the role of adenosine monophosphate-activated protein kinase (AMPK), a key regulator of cellular energy metabolism, in vascular smooth muscle cell (VSMC) migration in response to physiological cyclic stretch. Methods The Flexcell-5000T mechanical loading system was applied with a physiological cyclic stretch at 10% amplitude and 1.25 Hz frequency to primary rat VSMCs, to simulate mechanical stimulation of VSMCs in vivo. The protein expression of p-AMPK in VSMCs was detected by Western blotting, and VSMC migration was detected by wound healing test. Results Compared with the static group, physiological cyclic stretch loading for 24 h significantly decreased the area of wound healing, indicating that physiological cyclic stretch inhibited VSMC migration. The protein expression of p-AMPK in VSMCs was increased significantly after physiological cyclic stretch loading for 3 h, and was decreased significantly after 24 h. Under physiological cyclic stretch loading conditions, incubating AMPK inhibitor could significantly reduce the protein expression of p-AMPK after 3 h, and promote VSMC migration after 24 h; incubating AMPK activator AICAR under static conditions significantly increased the protein expression of p-AMPK after 3 h, and weakened VSMC migration after 24 h. Conclusions Physiological cyclic stretch inhibits VSMC migration by increasing the protein expression of p-AMPK, indicating that VSMC migration regulated by physiological cyclic stretch is of great significance for maintaining vascular homeostasis.
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Objective To Investigate the safety and clinical significance of self-made wrapper tube assisted endoscopic mucosal resection for upper esophageal mucosal endometriosis.Methods A total of 53 patients with upper esophageal mucosal endometriosis and the corresponding symptoms, which was confirmed by endoscopy and pathology, underwent endoscopic treatment.The endoscope was inserted into the esophagus together with wrapper tube.Then the endoscope was retreated into the wrapper tube and pulled back together with the tube.When the tip of the wrapper tube reached at the oral side of the lesion, it was fixed, and submucosal resection was performed.All patients were followed up to 6 months.Results All lesions were completely resected, which was achieved by one session in 45 patients, by two in 5, and by three in 3 other patients, with a mean procedure time at 6.5 minutes (4.5-7.5).Symptoms were relieved in 43 patients (81.1%) at 3 months after the procedure, and in 45 patients (85%) at 6 months.No local recurrence was observed under endoscopy and biopsy.No complications including esophageal stenosis, perforation or cardiopulmonary accidence were recorded. Conclusion For upper esophageal mucosal endometriosis presented with local symptoms, wrapper tube assisted endoscopic mucosal resection is safe, less invasive, easy to manipulate and effective.
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Objective To evaluate the wrapper tube in emergency endoscopy for gastro-esophageal variceal hemorrhage. Methods A total of 62 patients diagnosed as having gastro-esophageal variceal bleeding were enrolled as the treatment group to accept wrapper tube assisted emergency endoscopic sclerotherapy. The therapeutic effect was compared with another group of 62 patients who also had gastro-esophageal variceal hemorrhage while treated by conventional emergency endoscopic sclerotherapy (control group). Results The rate of hemostasis with wrapper tube was 100%, which was significantly higher than that of the control group (80. 65%, P ＜0. 05). The rate of gastro-esophageal varices remission after sclerotherapy in treatment group was 59.32%, which was also significantly higher than that of the control group (7. 25%, P ＜ 0. 05 ). The rates of chest pain, esophageal ulcer, length of hospitalization, and total medical cost in treatment group were significantly lower than those of control group ( P ＜ 0. 05 ). Conclusion Wrapper tube in emergency endoscopy for gastro-esophageal varices bleeding can improve therapeutic effect and relieve patients' economic burden.
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Objective To investigate the effect of Intedeukin-18 (IL-18) on Th1/Th2 balance and its antitumor mechanism in C57BL/6 mice Lewis lung cancer model. Methods 24 C57BL/6 mice were randomly divided into three equal groups: group A(IL-18 injec-tion group, n = 8), group B (Lewis lung cancer model, n = 8) and group C (normal control group, n = 8). The Lewis lung cancer cells were cultured and implanted subcutaneously into the group A and group B. IL-18 and NS were given to group A and B respectively by intrap-eritoneal injection on the 7th day (once every day, 7 times altogether), but group C was not given any treatment. Enzyme-linked immunosor-bent assay (ELISA) was used to detect the Th1/Th2 cytokines. Health status in all the animals was evaluated; the volume and weight ofsubcutaneous tumors were measured. Results The concentration of IFN-γ in group A and C were significantly higher than those in group B (P <0.05), and the concentration of IL-4 in group A and C were significantly lower than those in group B (P<0.05), but there was no significant difference between group A and C (P>0.05). The tumor growth inhibitory rate was 75%. Conclusion IL-18 can effectively induced IFN-γ and inhibit IL-4 production, regulate Th1/Th2 balance in the C57BL/6 mice Lewis lung cancer model, and elicit the antitu-mor immunity of the host, which could obviously inhibit the growth of tumor cells and decelerate the proliferation of tumor cells.
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Objective To estimate the success rate of emergency endoscopic treatment in patients with esophagogastric variceal bleeding using self-made gastroscope outer casing and to investigate bow to prevent complications. Methods A total of 11 patients with esophagogastric variceal bleeding underwent endoscopic treatment with self-made gastroscope outer casing, which consisted of a wire reinforced plastic casing (1.05 cm in inner diameter, 1.35 cm in outer diameter and 50 cm in length), a 3.8 cm×3.8 cm balloon fixed on the casing head and its cavity connected to the gas pipeline placed in casing tail, an anti-reflux pad in the insert entrance of the endoscope tail as well.as a flushing hole. The endoscopy was introduced to the esophagus or stomch together with outer casing to wash and pump the hematocele out from the side of flushing hole. In patients with hemorrhagic lesion in esophageal vein, the balloon was used to press bleeding vein and intravascular sclerotherapy was performed simutanously. In those with hemorrhagic lesion in gastric vein, the balloon was pressed on esophageal vein near to the cardia and intravascular sclerotherapy was performed. Results During the process of examination, the hemorrhagic lesion was fully exposed because of flushing, and bleeding was controlted in all patients after sclerotherapy. No complication such as aspiration or perforation was seen. Conclusions For emergency endoscopic treatment of esophagogastric variceal bleeding, gastroscope outer casing is helpful in removing intragastric hematocele and maintaining a clear field of vision. It can be effectively improving the efficacy of sclerot herapy.
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Objective The efficacies of four cholangiogrphies were compaired with each other in preventing bile duct injury during the procedure of LC. Methods Four cholangiogrphies were used in LC:1. Cold light cholangiography (CLCP); 2. Methylenum coeruleum cholangioguaphy (MCCP); 3. Intraoperative cholangiography (IOCP); 4. Intraoperative endoscopic retrogarde cholangiopancreatography (IERCP). Results The images of CLCP and MCCP were direct and could help operator to identify bile duct structure in LC. The images of IPCP and IERCP were indirect and could not be so helpful. Conclusions CLCP is the only technique that clearly and directly shows the location of the extra hepatic biliary system and may be useful in selected cases with abnormal or uncertain anatomy for the prevention of bile duct injury.
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AIM: To express the synthesized human insul in like growth factor I (hIGF-1) gene in E.coli with high expression level a nd explore the way to increase the efficiency of factor Xa cleavage. METHODS: The gene of hIGF-1 was designed and synthesized accordi n g to the preference of E.coli. A fusion protein with a recognized site of fa ctor Xa between CBD (cellulose binding domain) and hIGF-1 was expressed and puri fied by cellulose affinity chromatography. MTT method was used to assay the bioa ctivity of CBD-IGF fusion protein. hIGF-1 was released by factor Xa. In order to improve the sensitivity of fusion protein to factor Xa, the short flexible pept ide (Gly-Thr-Gly- Gly-Gly-Ser-Gly) was added before the recognized site of fac tor Xa. RESULTS: SDS-PAGE results indicated that the CBD-IGF fusion prot ein was expressed and purified . Biological assay results indicated CBD-IGF fusi on protein could promote the growth of NIH3T3 cell. The short flexible peptide (Gly-Thr-Gly-Gly-Gly-Ser-Gly), which was added before the recognized site of f actor Xa, improved the sensitivity of fusion protein to factor Xa. CONCLUSION: CBD-IGF fusion protein with bioactivite are expresse d and purified. The amio acid sequences changes between the site recognize of fa ctor Xa can help to improve the cleavage efficiency of Factor Xa.