Objective To investigate the effects and mechanisms of G protein-coupled receptor 91 (GPR91) on blood-retinal barrier (BRB) in diabetic rats.Methods A lentiviral vector of shRNA targeting rat GPR91 and scrambled shRNA were constructed.Healthy male Sprague-Dawley (SD) rats were selected in this study.The 60 rats were randomized into 4 groups and treated as follows:(1) control group (Group A,n=15),the rats received injections of an equal volume of 0.1％ citrate buffer;(2) streptozocin (STZ) group (Group B,n=15),the rats received injections of STZ;(3) LV.shScrambled group (Group C,n=15),diabetic rats received an intravitreal injection of 1 μl 1 × 10s TU/ml scrambled shRNA lentiviral particles at 2 weeks after the induction of diabetes;(4) LV.shGPRg1 group (Group D,n=15),diabetic rats received an intravitreal injection of 1 μl 1 × 108 TU/ml pGCSIL-GFP-shGPR91 lentiviral particles.At 12 weeks after intravitreal injection,immunohistochemistry and Western blot were used to assess the expression of GPRg1,p-extracellular signal-regulated kinase(ERK)1/2,t-ERK1/2,p-Jun N-terminal kinase (JNK),t-JNK,p-p38 mitogen-activated protein kinase (MAPK) and t-p38 MAPK.Haematoxylin and eosin (HE) staining and Evans blue dye were used to assess the structure and function of the retinal vessel.Immunohistochemistry enzyme-linked immunosorbent assay (ELISA) was used to test the protein level of VEGF.Results Immunohistochemistry staining showed that GPR91 was predominantly localized to the cell bodies of the ganglion cell layer.Western blot showed that GPR91 expression in Group D decreased significantly compared with Group C (F=39.31,P＜0.01).HE staining showed that the retina tissue in Group B and C developed telangiectatic vessels in the inner layer of retina,while the telangiectatic vessels attenuated in Group D.It was also demonstrated in Evans blue dye that the microvascular leakage in Group D decreased by (33.8±4.11)％ compared with Group C and there was significant difference (F =30.35,P＜0.05).The results of ELISA showed the VEGF secretion of Group B and C increased compared with Group A and the VEGF expression in Group D was significantly down regulated after silencing GPR91 gene (F=253.15,P＜0.05).The results of Western blot indicated that compared with Group A,the expressions of p-ERK1/2,p-JNK and p-p38 MAPK were significantly upregulated (q=6.38,2.94,3.45;P＜0.05).Meanwhile,the activation of ERK1/2 was inhibited by GPR91 shRNA and the difference was statistically significant (F=22.50,P＜0.05).Conclusions The intravitreal injection of GPR91 shRNA attenuated the leakage of BRB in diabetic rats.GPR91 regulated the VEGF release and the leakage of BRB possibly through the ERK1/2 signaling pathway.

The neuroretinal injuries of diabetic retinopathy (DR) include retinal neuronal damage and reactive gliosis,both of which are induced by hyperglycemia and presented as early features of DR.They promote to develop mutually and accelerate the progression of DR.The molecular mechanisms study of neuronal damage mainly focuses on the alterations of extracellular environment and related signaling pathways,include inflammation,oxidative stress,endoplasmic reticulum stress,the formation of advanced glycation end products,glutamate toxicity and so on.These alterations mainly result in neuronal apoptosis and autophagy.The damaged neurons activate the glial cells with apparent changes in morphology,cell counts and the level of intracellular protein expression.In non-proliferative DR,glial cells are moderately hypertrophic and slightly increased in numbers.In proliferative DR,there is a significant rise in glial cell number with enhanced level of inflammatory factors and vascular active substances which lead a further neuronal damage.Signaling pathways of extracellular signal-regulated kinase 1/2,c-Fos and p38 mitogen-activated protein kinase are associated with their activation.Researches on the molecular mechanisms and signaling pathways of the DR will promote controlling the DR progression at the cellular level.

Objective To explore the effects of bundle care on improving the tolerance of enteral nutrition (EN) in postoperative patients with gastric carcinoma. Methods Totally 180 patients who received laparoscopic surgery for gastric carcinoma in the Department of Gastrointestinal Surgery of Anhui Provincial Hospital from May 2016 to January 2017 were equally divided into a control group and an observation group according to the random number table. Patients in the control group received conventional nursing with enteral nutrition, while patients in the observation group received bundle care on the basis of conventional nursing. The time of first anal exhaust, time of oral intake, incidence of gastrointestinal complications, completion of daily EN consumption, duration of hospital stays, hospital expenses and satisfaction after surgery were then compared between the patients in the two groups. Results The time of first anal exhaust and oral intake of the patients in the observation group was (62.77±17.29) and (62.77±10.11)h, respectively, earlier than that of the patients in the control group, [(68.30±23.11) and (67.29±17.92)h; t=2.03, 2.08; P< 0.05]. The incidence of sickness or emesis, abdominal distension and diarrhea of the patients in observation group was (4.44%, 11.11%, 5.56%), lower than that of the patients in the control group, [(13.33%, 22.22%, 5.56%); χ2=4.39, 4.72, 4.77; P<0.05]. The completion rate of daily EN consumption of the patients in the observation group was (98.74±1.07)%, better than that of the patients in the control group [(93.71±1.24)%, t=27.57,P< 0.01]. The average duration of hospital stays of the patients in the observation group was(7.12±1.36) days, shorter than that of the patients in the control group [(9.02±2.21) days; t=6.95,P<0.01]. The hospital expense of the patients in the observation group was (38 100±11 200) RMB, less than that of the patients in the control group, [(41 200±10 900) RMB; t=2.25,P< 0.05]. The patients in the observation group showed higher satisfaction 3 days after surgery and at discharge than the patients in the control group (P<0.05). Conclusions Bundle care can help to improve the EN tolerance, shorten the time of anal exhaust and the duration of hospital stays, reduce hospital expenses, and enhance patients' satisfaction in the process of early enteral nutrition after surgery.