Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

OBJECTIVE: To study the protective effect of anthocyanins extracted from Vaccinium Uliginosum (VU) on retinal 661W cells against microwave radiation induced retinal injury. METHODS: 661W cells were divided into 6 groups, including control, model [661W cells radiated by microwave (30 mW/cm², 1 h)] and VU groups [661W cells pretreated with anthocyanins extracted from VU (25, 50, 100 and 200 µg/mL, respectively) for 48 h, and radiated by microwave 30 mW/cm², 1 h]. After treatment with different interventions, the cell apoptosis index (AI) was determined using Heochst staining; contents of malonaldehyde (MDA), glutataione (GSH), and activity of superoxide dismutase (SOD) were measured. mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1(HO-1) were detected by real time quantitative polymerase chain reaction, and the expression of HO-1 protein was examined by Western blot analysis. Nucleus and cytoplasm were separated and Nrf2 protein expression was further verified by Western blot analysis. RESULTS: There was significant difference in AI among the groups (F=322.83, P<;0.05). Compared with the control group, AI was significantly higher in the model group and was lower in 4 VU-pretreated groups (P<;0.05). Linear regression analysis showed the decline of AI was in a dose-dependent manner with VU treatment (r=0.8419, P<;0.05). The MDA and GSH contents of 661W cells in VU-treated groups were significantly lower than the model group (P<;0.05). Compared with the model group, the SOD activity in the VU-treated groups (50, 100 and 200 µg/mL) was significantly higher (all P<;0.05). The Nrf2 and HO-1 mRNA expressions were slightly increased after irradiation, and obviously increased in 100 µg/mL VU-treated group. After irradiation, the relative expressions of HO-1 and Nrf2 proteins in nucleus were slightly increased (P<;0.05), and the changes in cytoplasm were not obvious, whereas it was significantly increased in both nucleus and cytoplasm in the VU treatment groups. CONCLUSIONS Anthocyanins extracted from VU could reduce apoptosis, stabilize cell membrane, and alleviate oxidant injury of mouse retinal photoreceptor 661W cells. The mechanism might be through activating Nrf2/HO-1 signal pathway and inducing HO-1 transcription and translation.
Animals ; Anthocyanins/therapeutic use* ; Blueberry Plants/metabolism* ; Heme Oxygenase-1/metabolism* ; Mice ; Microwaves ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; RNA, Messenger/metabolism* ; Superoxide Dismutase/metabolism*

· AIM:To investigate the efficacy of the combined treatment of Conbercept and panretinal photocoagulation (PRP) for neovascular glaucoma (NVG) with central retinal vein occlusion (CRVO).· METHODS:The clinical data of 100 NVG patients with CRVO treated in our hospital from May 2014 to May 2017 were retrospectively analyzed.In those,50 patients treated with glaucoma filtering surgery combined with PRP were selected as control group,and based on this,50 patients treated with intravitreal injection of conbercept were included in the observation group.The best corrected visual acuity (BCVA) before treatment,and after 7d,1,3,and 6mo treatment were compared.The intraocular pressure IOP of each period with the non-contact tonometer were also compared,the effect of surgery was evaluated by slit-lamp examination of neovascularization combined with intraocular pressure,and then recurrence rate and complication was recorded during 6mo follow-up.· RESULTS:No statistically significant difference was found between preoperative and after surgery at each time point (P＞0.05).The intraocular pressure of the two groups was significantly lower than that of before the surgery,the observation group was significantly lower than that of the control group 7d and 1mo after surgery,and the difference was statistically significant (P＜0.05).There was no statistically significant difference on lOP the 3 and 6mo after surgery between two groups (P＞0.05).The operation success rate was 100％ in the observation group and was 92％ in the control group,the difference was statistically significant (P＜ 0.05).The complete success rate of the observation group was 84％,which was significantly higher than 66％ of the control group,the difference was statistically significant (P＜ 0.05).The hyphema and recurrence rate of the observation group were significantly lower than those of the control group,the difference was statistically significant (P＜0.05).There was no significant difference in the incidence of shallow anterior chamber and low intraocular pressure (P＞0.05).· CONCLUSION:Preoperative intravitreal injection of conbercept combined with panretinal photocoagulation for neovascular glaucoma after central retinal vein occlusion make the pressure recovery and neovascularization time shorter with better surgical results,and can control the anterior chamber hemorrhage and reduce the recurrence rate.

·AIM: To investigate the visual acuity after cataract extraction and vitrectomy with gas tamponade for idiopathic macular hole (IMH) at different stages. ·METHODS: In this study, 75 IMH patients ( 75 eyes ) treated in our hospital from August 2014 to August 2016 were enrolled and underwent cataract extraction, vitrectomy and C3F8gas tamponade. Patients were divided into stage Ⅱ Group ( 18 cases ), stage Ⅲ ( 36 cases) and stageⅣ(21 cases) according to Gass stages, and macular hole closure at 2 and 4wk postoperatively were compared. The routine visual acuity examination before and after surgery were performed, and the visual acuity in each group were compared. The optical coherence tomography ( OCT) was used to measure the macular thickness before and after surgery. ·RESULTS: The closure rate of macular hole in stage Ⅱwas significantly higher than that of stage Ⅲ and IV at the 1mo after operation, that at the stage Ⅲ was significantly higher than that of stageⅣgroup, and the difference was statistically significant (P<0. 05). There was no significant difference in the rate of closure of macular hole between stage Ⅱ and stage Ⅲ at 3mo after operation (P>0. 05). The proportion of eyes with visual acuity of finger counting, 0. 02-0. 08, 0. 10-0. 20, 0. 25-0. 40 and ≥0. 50 was statistically significant different before and after surgery(P<0. 05). The improvement rate of visual acuity was 94% in stage Ⅱ, which was significantly higher than that in stage Ⅲ (83%) and stage Ⅳ (67%). The macular thickness of the stage Ⅱ and Ⅲ was significantly lower after the surgery, but there was no significant difference in the stage Ⅳ before and after surgery (P>0. 05), the decreasing range of the stage Ⅱ and Ⅲ was not statistically significantly different (P>0. 05), which were significantly higher than that of the stage Ⅳ, the difference was statistically significant (P<0. 05). ·CONCLUSION: Cataract extraction, vitrectomy and C3F8 gas tamponade surgery is conducive to the vision recovery after idiopathic macular hole, but the effects with different Gass staging are different, surgery should be performed as early as possible to improve macular hole closure and eyesight recovery.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

Objective To investigate the effects of HLA-B27 in disease activity and the clinical features of axial spondyloarthritis(SpA). Methods Clinical data of 112 patients with axial SpA was collected and studied prospectively. Clinical manifestations and laboratory examination results of 82 HLA-B27 positive and 30 HLA-B27 negative patients with axial SpA were analyzed. Data source was from Chinese Rheumatism Data Center. Results (1)The average age of onset of HLA-B27 negative patients was significantly later than that of the positive patients , and there was no significant difference in the course of disease and the proportion of male and female patients. (2)The ratio of severe lesion of hip ,peripheral arthritis ,attachment inflammation and systemic symptoms of HLA-B27 negative group were significantly lower than those of HLA-B27 positive group. Familial aggregation phenomenon,uveitis and spine radiology changes in two groups had no significant difference.(3)The changes of disease activity index including erythrocyte sedimentation rate and C-reactive protein increased in HLA-B 27 negative group was significantly lower than those in HLA-B27 positive group. Conclusion There is strong correlation between axial SpA and HLA-B27. The average age of onset of HLA-B27 negative patients was significantly later than that of the positive patients. HLA-B27 negative patients manifested severe symptoms and worse prognosis.

Optic neuritis refers to all inflammatory diseases in the optic nerve. The most common type is demyelinating optic neuritis. Biomarkers can indicate its pathophysiological process and thus are useful in disease diagnosis and treatment. This article reviews the known biomarkers for demyelinating optic neuritis.
Biomarkers ; Demyelinating Diseases ; Humans ; Optic Neuritis

BACKGROUNDIn vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.

METHODSCNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.

RESULTSThe CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R 2 =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001).

CONCLUSIONSThere is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection. The result might provide a useful evaluation of CNV both for the studies using CNV models induced by subretinal injection and human AMD studies.

Animals ; Choroidal Neovascularization ; pathology ; physiopathology ; Disease Models, Animal ; Fluorescein Angiography ; Humans ; Mice ; Mice, Inbred C57BL ; Tomography, Optical Coherence

Objective To evaluate uncertainty for the determination of oxcarbazepine active metabolite (10-hydroxycarbazepine) in human se-rum by solid phase extraction -HPLC.Methods The uncertainty caused in the whole process of determination was analyzed.Sources of uncertainty were established and simplified, then each component of un-certainty, combined uncertainty and expanded uncertainty were calculat-ed by using the method validation data in accordance with the evaluation procedure.Results The expanded uncertainty for low, medium and high concentrations (3.18, 12.73, 50.91 μg· mL-1 ) of 10-hydroxy-carbazepine was 0.24, 0.44 and 1.66 μg· mL-1 , respectively ( k =2, P=95%).Conclusion The uncertainty of this method was mainly caused by calibration curve fitting ( especially low level of sample ) , serum drug extraction, serum sample preparation, HPLC error and measuring repeatability.

OBJECTIVEConsidering the difficulty in classifying some cases with eye trauma by Birmingham Eye Trauma Terminology (BETT) in our epidemiological study, we introduce a new classification for epidemiological study of mechanical eye injuries based on BETT.

METHODSA retrospective investigation was carried out in 31 hospitals from January 2005 to December 2010. All medical records of inpatients with eye injuries were reviewed. A total of 10 718 patients (11 227 eyes) were diagnosed as mechanical eye injuries. All mechanical eye injuries were tried to be classified using BETT. While some eye injuries were difficult to categorize. We recorded the injury type and case number. A new classification based on BETT was also used for the same project.

RESULTSOf 10 718 patients (11 227 eyes) with mechanical eye injuries, the following cases cannot be classified by BETT: 1 488 patients (1 559 eyes) with merely orbital or ocular adnexa injury, 1 961 (2 054) globe injuries associated with orbital or ocular adnexa injury, 271 (284) ocular surface foreign body (OSFB) or ocular wall foreign body (OWFB), 77 (89) contusion, 9 (11) lamellar laceration associated with OSFB or OWFB, 29 (30) rupture associated with OSFB, OWFB or intraocular foreign body and 60 (62) lace- ration associated with OSFB or OWFB. While according to our new classification, all eye injuries can be categorized without any difficulty.

CONCLUSIONDifficulty in classifying some eye injuries in epidemiological study by BETT brings some trouble to our study, which can be solved by our new eye injury classification to some extent. It is hoped that other ophthalmologists present better ones to make the classification more perfect.

Adolescent ; Eye Injuries ; classification ; epidemiology ; Humans ; Retrospective Studies ; Young Adult