Objective To explore the effect of lysophosphatidic acid(LPA)on blood-brain barrier(BBB) permeability and its possible mechanism.Methods LPA or LPA+suramin(L+S)were stereotaxically injected into the right eaudate nucleus in SD rats in vivo.Evans blue(EB)was used to quantitatively measure the permeability of BBB at different time points.The expression of matrix metalloproteinase-9 was detected by immunohistochemistry technique.The pathological ultrastruetural changes of BBB were assessed by transmission electron microscopy.Results The BBB permeability began to increase after LPA administered into ipsilateral eaudate nucleus,and reached the peak at 24h.Then the permeability of BBB gradually lowered after 48h.In comparison with the same time points of control group,there were quite significant differences(P＜0.01).After L+S was injected,the change of BBB permeability had differences in comparison with those of LPA group in the same time points,(P＜0.05).MMP-9 positive cells were mainly vascular endothelial cells.The numbers of MMP-9 positive blood vessels grew at 6h in LPA group,and the expression of it reached maximum at 24h,then the number of it decreased at 48h,showing significant statistical differences in comparison with the L+S group(P＜0.01),It was observed microscopically that ultrastrueture of BBB of the LPA group was changed sharply,such as basement membrane roughed and fragmented,astroeyte end-feet swolled markedly and perivaseular space enlarged obviously.But there were no remarkable changes in BBB in L+S group.Conclusion LPA can induce increase of BBB permeability and its possible mechanism is the strong expression of MMP-9 protein produeted by endothelial cells through the mediation of LPA receptor,leading to degradation of basement membrane.

AIM:To report the safty and efficiency of intravitreal injection of bevacizumab (Avastin) in patients with macular edema (ME) due to branch retinal vein occlusion (BRVO).METHODS: A consecutive series of patients with ME due to BRVO who were treated with intravitreal bevacizumab injection (2.5g/0.1L) were retrospectively studied. Patients underwent complete ophthalmoscopic examination, including Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and/or flurescence angiographic testing at baseline and follow-up visits.RESULTS: There were 32 eyes of 32 consecutive patients who received at least one intravitreal bevacizumab injections (range from 1 to 3). The mean length of follow-up was 4.7 (range from 3 to 8) months. The mean visual acuity improved from 20/200- at baseline to 20/100- at 1 month and 20/100+ at 3 months and last follow-up (P＜0.01). The mean central 1mm macular thickness was 483μm at baseline and decreased to 275, 314,and 301μm at 1 month,3 months, and last follow-up (P＜0.01)respectively.No adverse side effects were observed following injections in any eyes.CONCLUSION: Intravitreal bevacizumab (Avastin) showed a marked decrease in ME secondary to BRVO, improvement in visual acuity and lack of adverse side effects.

Background A main cause of visual impairment in proliferative diabetic retinopathy (PDR) is vitreous hemorrhage and retinal detachment due to contraction of fibrovascular membrane.To explore the pathogenic mechanism of fibrovascular membrane is a new target for the prevention and management of PDR.Objective This study was to determine the change in expression of vascular endothelial growth factor (VEGF),connective tissue growth factor(CTGF) and pigment epithelium derived factor(PEDF) in the proliferative membranes of patients with PDR after intravitreal injection of avastin,an anti-VEGF agent.Methods This study was approved by the Medical Ethic Committee of Tianjin Medical College,and written informed consent was obtained from each patient before enrollment.A prospective randomized-controlled study was designed.Twenty-six eyes of 24 patients with PDR scheduled for surgery were enrolled from January to June,2008 in Tianjin Medical College Eye Hospital.The patients were randomized into the simple vitrectomy group and avastin injection combined with vitrectomy group,with matched gender,age and disease duration.1.25 mg (0.05 ml) of avastin was intravitreally injected prior to surgery,and vitrectomy was performed 10 days after injection in the avastin injection combined with vitrectomy group,and only vitrectomy was given in the simple vitrectomy group.Preretinal membrane was collected during the surgery.Expression of VEGF,CTGF and PEDF in the preretinal membranes was assayed by immunochemistry.Results VEGF,CTGF and PEDF were expressed in the cytoplasm.The rate of VEGF expression in the preretinal membranes was 30.77％ in the avastin injection combined with vitrectomy group,showing a significant reduction in comparison with the simple vitrectomy group(100.00％)(U =4.000,P＜0.01).The rate of expression CTGF was remarkable elevated in the avastin injection combined with vitrectomy group compared with the simple vitrectomy group (92.31％ vs.62.54％)(U=7.500,P=0.048).However,no significant difference was found in the expression rate of PEDF between the two groups(100.00％ vs.92.31％) (U =65.500,P =0.299).Conclusions The results suggest that intravitreal injection of anti-VEGF drugs resulted in the decrease of VEGF expression and increased CTGF expression in proliferative membranes from patients with PDR.

Objective To establish a determination method for leuprolide acetate microspheres. Methods HPLC was performed on Inertsil ODS-SP (150×4.6 mm×5μm) with mobile phase consist of 0.1 mol/L of Ammonium Dihydrogen Phosphate(adjust its pH to 7.00±0.05 with Ammonium Hydroxide) and Acetonitrile in ratio of 3:1(V/V),and the flow rate was 1.0 mL/min.The wavelength was 220 nm and column temperature was 30℃. The injection volume was 20 μL. Results The linear range of leuprolide acetate was 20.0-160.0μg/mL (r=0.9999) with an average recovery of 99.80%,RSD=0.63%(n=9). Conclusion The method of HPLC was accurate,reliable and specific, which could be used to determinate the assay of leuprolide acetate microspheres and for quality control of microspheres.

Alanine Transaminase ; blood ; DNA, Viral ; blood ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; virology ; Humans

5 mm and ≤8 mm in 4 cases.The mean value was 4.2 mm. Four patients noticed reduction in their vision and two had diplopia.Those patients were examined by CT or MR.Direct venography was performed in each patient.After the diagnosis of OVM was confirmed, intralesional injection of BLE was performed.The efficacy of the treatment and complications were observed during the following 8 to 42 months(mean 23 months).Results The BLE were successfully injected in all the patients.All patients had resolution of proptosis and diplopia.Three patients gained improvement of visual acuity.The periorbital swelling occurred in all patients after operation and resolved within 1 week without special treatment.Other complications,such as orbital hemorrhage and periorbital scar,were not observed during following-up.Conclusion Intralesional injection with BLE is convenient,safe and efficient for the treatment of OVM.

Objective To observe the effects of 75 gram glucose oral tolerance test (75 g OGTT) and standard mixed meal test (SMMT) on insulin secretion function of the islets of Langerhans and plasma free fatty acid (FFA) in patients with type 2 diabetes mellitus.Methods Seventy-six patients with type 2 diabetes without using insulin and with no obvious complications were recruited for 75 g OGTT following overnight fasting on the first day and SMMT (bread 50 g,egg 50 g and milk 250 ml) on the 7th day.Blood specimens were collected from each patients before the tests and 30 min,60 min,120 min and 180 min after glucose or meal load to measure their levels of plasma glucose,serum insulin,C peptide,FFA and lipids (total cholesterol,triglyceride,high-density and low-density lipoprotein cholesterol).Results No difference in fasting plasma glucose,serum insulin,C peptide,FFA and lipids between 75 g OGTT and SMMT was found.Postprandial plasma glucose 30 min,60 min,120 min and 180 min after 75 g OGTT was significantly higher than that after SMMT,with (15.3?3.5) vs (9.9?3.4) mmol/L,(18.2?4.8) vs (12.8?4.0) mmol/L,(16.3?5.8) vs (12.2?4.9) mmol/L and (10.6?5.4) vs (9.5?4.5) mmol/L (F=28.1,P

Emerging evidence has indicated that circular RNAs (circRNAs) play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors.However,the clinical role of circRNAs in bladder cancer (BC) and the molecular mechanisms have yet to be fully understood.In this study,the clinical specimens were obtained and the expression level of a circRNA BCRC4 was detected by real-time PCR in both BC tissues and cell line.The circular RNA over-expression plasmid was constructed and transfected into BC cells and related cell line.The cell cycles and apoptosis were observed using inverted microscope and flow cytometry.Western blotting was used to compare the relative protein expression of groups with different treatments.It was found that circRNA BCRC4 expression was lower in BC tissues than in adjacent normal tissues.Furthermore,consequences of fomed-expression of BCRC4 promoted apoptosis and inhibited viability of T24T and UMUC3 cells,and up-regulated BCRC4-inereased miR-101 level,which suppressed EZH2 expression in both RNA and protein levels.In addition,gambogic acid (GA) is a promising natural anticancer compound for BC therapy,and GA treatment increased the BCRC4 expression in T24T and UMUC3 cells in a dose-dependent manner.Altogether,our findings suggest that BCRC4 functions as a tumor suppressor in BC,and mediates anticancer function,at least in part,by up-regulating the expression of miR-101.Targeting this newly identified circRNA may help us develop a novel strategy for treating human BC.

Objectives: To observe the impact of cannulation strategies on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) complications. Methods: A total of 37 patients with refractory heart failure (HF) treated in our hospital from 2007 to 2016 were enrolled. All patients received VA-ECMO with ipsilateral femoral artery and vein cannulation and they were divided into 2 groups: Direct cannulation group, patients received open surgery for femoral artery and vein cannulation directly, based on downstream leg ischemia condition, ARROW sheath was used in ECMO pipeline to establish collateral circulation, n=21 and "Chimney technique" group, patients received femoral vessel cannulation as a graft of 8 mm Dacron artificial vessel was end-to-side anastomosed to the host femoral artery, then was connected to the host femoral vein directly, n=16. Prior ECMO clinical condition, time of cannulation, duration of VA-ECMO, the mean amounts of daily bleeding and transfusion, downstream leg ischemia condition and in-hospital mortality were observed and compared between 2 groups. Results: Compared with Direct cannulation group, "Chimney technique" group showed the longer time of cannulation (83.54±13.2) min vs (67.33±22.4) min, P<0.05, less patients with downstream leg ischemia (6.2% vs 23.8%), less amounts of daily bleeding (210.78±180.22) ml vs (560.76±220.23) ml and transfusion (3.11±1.65) U vs (6.37±2.44) U, all P<0.01; the in-hospital mortality was similar between 2 groups (62.5% vs 61.9%), P>0.05. Conclusions: "Chimney technique" of VA-ECMO improved the downstream leg ischemia and bleeding, while the in-hospital mortality was similar to direct cannulation in relevant patients.

Purpose::In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC.Methods::This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0.Results::The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature ( OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time ( OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer ( OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis-DIC ( r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged ( p < 0.05). Conclusions::The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.