经巩膜睫状体光凝与睫状体冷冻治疗绝对期青光眼的疗效比较

目的:探讨经巩膜二极管睫状体光凝(CPC)与睫状体冷冻(CCT)对绝对期青光眼的降眼压(IOP)效果及术后并发症的比较。方法:前瞻性病例观察研究。纳入天津市眼科医院收治的绝对期青光眼85例,随机分成两组行CPC或CCT手术治疗,观察术前,术后1、3d,1、2wk,1、3、6mo的IOP、抗青光眼药物数量、眼前节炎症反应,利用视觉模拟评分标准(VAS)评价术后眼球疼痛感。比较手术前后的所有指标及两种手术方式成功率的差异。结果:与CPC组相比,CCT组的IOP在术后1、3d,1、2wk,1mo较术前下降少,VAS评分在术后3d,1、2wk,1mo较术前下降少,抗青药物数量对数值在术后1、3d,1、2wk较术前下降少(P<0.05)。与CPC组相比,CCT组术后3d,1、2wk,1、3、6mo完全成功率较术后1d升高,但只有术后3、6mo有差异(P<0.05)。与CPC组相比,CCT组前房闪辉分级在术后3d,1、2wk,1mo较术前上升更多,结膜充血分级在术后1、3d,1、2wk较术前上升更多,角膜水肿分级在术后3d,1、2wk,1mo较术前上升更多,炎症反应更重(P<0.05)。结论:与CPC相比,CCT术后降IOP速度较慢,眼前节反应及眼部疼痛感较重且持续时间较长,术后需将抗炎药物及抗青光眼药物使用的时间延长。

Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

瞄准：为了在肺损害的致病调查原子因素 kappa B (NF-kappaB ) 的角色，导致了旁边肠的 ischemia/reperfusion (I/R ) ，和它细胞间的粘附 molecule-1 (ICAM-1 ) 上的效果表示和嗜中性的渗入。方法：24 只 Wistar 老鼠随机被划分成控制， I/R 和吡咯烷 dithiocarbamate (PDTC ) 处理组，在各个的 n=8。I/R 组和 PDTC 治疗组织为 2 h 为 1 h 和灌注堵塞的收到的优异 mys 伤寒动脉(SMA ) 。PDTC 组在外科前与 2% 100 mg/kg PDTC 1 h 的腹膜内注射被管理。肺组织学和支气管 alveolus 肺液体(BALF ) 蛋白质是 assayed。浆液 IL-6，肺 malondialdehyde (MDA ) 和象 NF-kappaB 和 ICAM-1 的表示水平一样的 myeloperoxidase (军邮局) 被测量。结果：肺损害由肠的 I/R 导致了，被浮肿，出血和嗜中性的渗入以及由 BALF 的重要升起描绘蛋白质。比作控制组，在 I/R 显著地增加的浆液 IL-6 和肺 MDA 和军邮局的层次组织(P=0.001 ) 。NF-kappaB p65 和 ICAM-1 的强壮的积极表示被观察。在 PDTC 的管理以后，象 NF-kappaB 和 ICAM-1 一样的浆液 IL-6，肺 MDA 和军邮局的水平显著地减少了(P【0.05 ) 什么时候与 I/R 相比组。结论：NF-kappaB 的激活在肠的 I/R 直在调整嗜中性的渗入和肺 ICAM-1 表示上面导致的肺损害的致病起一个重要作用。NF-kappaB 的一个禁止者能阻止肺损害的 PDTC 通过禁止 NF-kappaB 的活动由肠的 I/R 导致了。

Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion via AMPK/SIRT-1/autophagy pathway

AIM To evaluate whether fish oil(FO) can protect liver injury induced by intestinal ischemia/reperfusion(I/R) via the AMPK/SIRT-1/autophagy pathway.METHODS Ischemia in wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion. Blood andtissue samples were collected for analyses. AMPK, SIRT-1, and Beclin-1 expression was determined in lipopolysaccharide(LPS)-stimulated HepG2 cells with or without FO emulsion treatment.RESULTS Intestinal I/R induced significant liver morphological changes and increased serum alanine aminotransferase and aspartate aminotransferase levels. Expression of p-AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis factor-α(TNF-α) and malonaldehyde(MDA) were increased. FO emulsion blocked the changes of the above indicators effectively. Besides, in LPS-stimulated HepG2 cells, small interfering RNA(siRNA) targeting AMPK impaired the FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-α and MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease of TNF-α and MDA.CONCLUSION Our study indicates that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway.

Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p

BACKGROUND Recent studies have demonstrated that circular RNA AKT3(circAKT3)plays a crucial role in regulating the malignant phenotypes of tumor cells.However,the potential effects of circAKT3 on esophageal cancer have not been investigated.AIM To illuminate the role of circAKT3 in malignant behaviors of esophageal cancer cells and its underlying mechanism.METHODS Clinical samples were collected to detect the expression of circAKT3.The role of circAKT3 in proliferation,migration,invasion,and apoptosis of esophageal cancer cells was evaluated using Cell Counting Kit-8,wound healing assays,Transwell assays,and fluorescence analysis,respectively.The target of circAKT3 was screened and identified using an online database and luciferase reporter assay.A xenograft nude mouse model was established to investigate the role of circAKT3 in vivo.RESULTS In vitro assays showed that proliferative,migratory,and invasive capacities of esophageal cancer cells were significantly enhanced by circAKT3 overexpression.Furthermore,miR-17-5p was screened as the target of circAKT3,and miR-17-5p antagonized the effects of circAKT3 on esophageal cancer cells.Moreover,we identified RHOC and STAT3 as the direct target molecules of miR-17-5p,and circAKT3 facilitated expression of RHOC and STAT3 by inhibiting miR-17-5p.In vivo assays showed circAKT3 knockdown inhibited growth of esophageal cancer.CONCLUSION CircAKT3 contributed to the malignant behaviors of esophageal cancer in vitro and in vivo by sponging miR-17-5p thus providing a potential target for treatment of esophageal cancer.

PTEN-induced kinase 1-induced dynamin-related protein 1 Ser637 phosphorylation reduces mitochondrial fission and protects against intestinal ischemia reperfusion injury

BACKGROUND Intestinal ischemia reperfusion(I/R)occurs in various diseases,such as trauma and intestinal transplantation.Excessive reactive oxygen species(ROS)accumulation and subsequent apoptotic cell death in intestinal epithelia are important causes of I/R injury.PTEN-induced putative kinase 1(PINK1)and phosphorylation of dynamin-related protein 1(DRP1)are critical regulators of ROS and apoptosis.However,the correlation of PINK1 and DRP1 and their function in intestinal I/R injury have not been investigated.Thus,examining the PINK1/DRP1 pathway may help to identify a protective strategy and improve the patient prognosis.AIM To clarify the mechanism of the PINK1/DRP1 pathway in intestinal I/R injury.METHODS Male C57BL/6 mice were used to generate an intestinal I/R model via superior mesenteric artery occlusion followed by reperfusion.Chiu’s score was used to evaluate intestinal mucosa damage.The mitochondrial fission inhibitor mdivi-1 was administered by intraperitoneal injection.Caco-2 cells were incubated in vitro in hypoxia/reoxygenation conditions.Small interfering RNAs and overexpression plasmids were transfected to regulate PINK1 expression.The protein expression levels of PINK1,DRP1,p-DRP1 and cleaved caspase 3 were measured by Western blotting.Cell viability was evaluated using a Cell Counting Kit-8 assay and cell apoptosis was analyzed by TUNEL staining.Mitochondrial fission and ROS were tested by MitoTracker and MitoSOX respectively.RESULTS Intestinal I/R and Caco-2 cell hypoxia/reoxygenation decreased the expression of PINK1 and p-DRP1 Ser637.Pretreatment with mdivi-1 inhibited mitochondrial fission,ROS generation,and apoptosis and ameliorated cell injury in intestinal I/R.Upon PINK1 knockdown or overexpression in vitro,we found that p-DRP1 Ser637 expression and DRP1 recruitment to the mitochondria were associated with PINK1.Furthermore,we verified the physical combination of PINK1 and p-DRP1 Ser637.CONCLUSION PINK1 is correlated with mitochondrial fission and apoptosis by regulating DRP1 phosphorylation in intestinal I/R.These results suggest that the PINK1/DRP1 pathway is involved in intestinal I/R injury,and provide a new approach for prevention and treatment.

Protection of Veratrum nigrum L.var.ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver

AIM: To investigate the protective effects and possible mechanisms of Veratrum nigrum L.var. ussuriense Nakai alkaloids (VnA) on hepatic ischemia/reperfusion (I/R) injury in rats. METHODS: Forty male Wistar rats were randomly divided into four experimental groups (n = 10 in each): (A) Control group (the sham operation group); (B) I/R group (pretreated with normal saline); (C) Small-dose (10 mg/kg) VnA pretreatment group; (D) Large-dose (20 mg/kg) VnA pretreatment group. Hepatic ischemia/ reperfusion (Hepatic I/R) was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and nitric oxide (NO) content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (ES) were detected by immunohistochemical examinations and Western blot analyses. RESULTS: The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine aminotransferase (ALT: 74.53 ± 2.58 IU/L vs 1512.54 ± 200.76 IU/L, P < 0.01) and lactic dehydrogenase (LDH: 473.48 ± 52.17 IU/L vs 5821.53 ± 163.69 IU/L, P < 0.01), as well as the levels of MPO (1.97 ± 0.11U/g vs 2.57 ± 0.13 U/g, P < 0.01) and NO (69.37 ± 1.52 mmol/g protein vs 78.39 ± 2.28 mmol/g protein, P < 0.01) in the liver tissue, all of which were reduced by pretreatment with VnA, respectively (ALT: 1512.54 ± 200.76 IU/L vs 977.93 ± 89.62 IU/L, 909.81 ± 132.76 IU/L, P < 0.01, P < 0.01; LDH: 5821.53 ± 163.69 IU/L vs 3015.44 ± 253.01 IU/L, 2448.75 ± 169.4 IU/L, P < 0.01, P < 0.01; MPO: 2.57 ± 0.13 U/g vs 2.13 ± 0.13 U/g, 2.07 ± 0.05 U/g, P < 0.01, P < 0.01; NO: 78.39 ± 2.28 mmol/g protein vs 71.11 ± 1.73 mmol/g protein, 68.58 ± 1.95 mmol/g protein, P < 0.05, P < 0.01). The activity of SOD (361.75 ± 16.22 U/mg protein vs 263.19 ± 12.10 U/mg protein, P < 0.01) in the liver tissue was decreased after I/R, which was enhanced by VnA pretreatment (263.19 ± 12.10 U/mg protein vs 299.40 ± 10.80 U/mg protein, 302.09 ± 14.80 U/mg protein, P < 0.05, P < 0.05). Simultaneously, the histological evidence of liver hemorrhage, polymorphonuclear neutrophil infiltration and the overexpression of ICAM-1 and E-selectin in the liver tissue were observed, all of which were attenuated in the VnA pretreated groups.CONCLUSION: The results demonstrate that VnA pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of antioxidant capacity, reduction of inflammatory responses and suppressed expression of ICAM-1 and E-selectin.

Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury

BACKGROUND Intestinal ischemia reperfusion(I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22(USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice.AIM To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury.METHODS An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion.Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo. siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22,Cyclin D1, and proliferating cell nuclear antigen(PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival(viability) and cell cycle were evaluated using the Cell Counting Kit-8and flow cytometry, respectively.RESULTS USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro, which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group(P < 0.05), while opposite results were observed in the USP22 overexpression group(P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration.CONCLUSION USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury.

Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of micro RNA-137

BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.

Overexpression of Gli1 in cancer interstitial tissues predicts early relapse after radical operation of breast cancer

Breast cancer is a significant global public health problem. Despite major advances in adjuvant therapy, therapeutic options for patients with unresectable metastatic disease, recurrent disease or triple negative breast cancer are limited. Approximately 39,840 patients died of this disease in the USA in 2010 （1）, emphasizing the need for new therapies. A better understanding of the mechanisms that underlie the development of breast cancer would help to identify novel molecular targets for its treatment and determine more accurate clinicopathological prognostic factors.

Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion

AIM:To investigate the possible protective effects of carnosol on liver injury induced by intestinal ischemia reperfusion (I/R). METHODS: Rats were divided randomly into three experimental groups:sham, intestinal I/R and carnosol treatment (n=18 each). The intestinal I/R model was established by clamping the superior mesenteric artery for 1h. In the carnosol treatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg carnosol 1h before the operation. At 2, 4 and 6h after reperfusion, rats were killed and blood, intestine and liver tissue samples were obtained. Intestine and liverhistology was investigated. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and interleukin (IL)-6 were measured. Liver tissue superoxide dismutase (SOD) and myeloperoxidase (MPO) activity were assayed. The liver intercellular adhesion molecule-1 (ICAM-1) and nuclear factor κB (NF-κB) were determined by immunohistochemical analysis and western blot analysis. RESULTS: Intestinal I/R induced intestine and liver injury, characterized byhistological changes, as well as a significant increase in serum AST and ALT levels. The activity of SOD in the liver tissue decreased after I/R, which was enhanced by carnosol pretreatment. In addition, compared with the control group, carnosol markedly reduced liver tissue MPO activity and serum IL-6 level, which was in parallel with the decreased level of liver ICAM-1 and NF-κB expression. CONCLUSION: Our results indicate that carnosol pretreatment attenuates liver injury induced by intestinal I/R, attributable to the antioxidant effect and inhibition of the NF-κB pathway.

Expression and role of inducible nitric oxide synthase in ischemia-reperfusion liver in rats

OBJECTIVE: To investigate the expression and the role of iNOS expression in hepatic ischemia-reperfusion (L/R) injury. METHODS: Male Wistar rats were subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS mRNA expression in liver tissue was assessed by Western blot and RT-PCR analysis respectively at different time points after reperfusion. The effects of L-NAME (Nω-nitro-L-arginine methyl ester, a nonselective NOS inhibitor) or AE-ITU (aminoethytl-isothiourea, a relative selective inhibitor of iNOS) treatment were also evaluated. RESULTS: High levels of iNOS protein and mRNA expression were detected in the liver tissue subjected to I/R, but not in the sham-operated rats. iNOS protein and iNOS mRNA expression reached a maximum on the first day after reperfusion and decreased later. The levels of iNOS protein and iNOS mRNA disappeared on 7th, 3rd day after reperfusion respectively. The high iNOS expression was correlated with hepatic dysfunction. L-NAME administration worsened hepatic dysfunction induced by hepatic I/R. In contrast, AE-ITU administration showed mild protective effects against hepatic dysfunction induced by hepatic I/R. CONCLUSION: Ischemia-reperfusion may induce or up-regulate the expression of iNOS protein and iNOS mRNA, which is detrimental to hepatic I/R injury.