Publications by authors named "Qianyi Lu"

38 Publications

Increased levels of alphaB-crystallin in vitreous fluid of patients with proliferative diabetic retinopathy and correlation with vascular endothelial growth factor.

Clin Exp Ophthalmol 2017 May 27;45(4):379-384. Epub 2017 Jan 27.

Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Background: AlphaB-crystallin has been shown to have angiogenic properties. The purpose of this study was to determine the levels of alphaB-crystallin in the vitreous fluid of patients with proliferative diabetic retinopathy and to confirm the association between the expression level of alphaB-crystallin and vascular endothelial growth factor.

Methods: Vitreous samples were collected before vitrectomy from 46 eyes of 46 consecutive patients with proliferative diabetic retinopathy, and 19 patients without diabetes mellitus had vitrectomy for idiopathic macular hole. The concentrations of alphaB-crystallin and vascular endothelial growth factor were measured via enzyme-linked immunosorbent assay.

Results: The vitreous level (mean ± SD) of alphaB-crystallin was significantly higher in patients with proliferative diabetic retinopathy (317.3 ± 151.7 ng/mL) than in control patients (idiopathic macular hole, 8.3 ± 6.1 ng/mL) (P < 0.0001). The vitreous concentration of vascular endothelial growth factor was also significantly higher in patients with proliferative diabetic retinopathy (860.1 ± 566.4 pg/mL) than in control patients (9 pg/mL) (P < 0.0001). Meanwhile, both the expression levels of alphaB-crystallin and vascular endothelial growth factor were significantly higher in eyes with active proliferative diabetic retinopathy than in those with inactive proliferative diabetic retinopathy. Also, the vitreous concentration of alphaB-crystallin correlated significantly with that of vascular endothelial growth factor in vitreous fluid of proliferative diabetic retinopathy ([correlation coefficient], R = 0.78, P < 0.001).

Conclusions: These results suggest a significant increase of alphaB-crystallin in the vitreous fluid of patients with proliferative diabetic retinopathy and present a crucial association between alphaB-crystallin and vascular endothelial growth factor with angiogenic activity in proliferative diabetic retinopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ceo.12891DOI Listing
May 2017

Diabetes Onset at 31-45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes.

Sci Rep 2016 11 29;6:38113. Epub 2016 Nov 29.

Department of Ophthalmology, Shanghai First People's Hospital of Nanjing Medical University, Shanghai 200080, China.

This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People's Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31-45 years (odds ratio [OR] 1.815 [1.139-2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31-45 years within each group. A diabetes onset age of 31-45 years is an independent risk factor for DR development in Chinese type 2 DM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep38113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126680PMC
November 2016

Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

Inflamm Res 2017 Feb 26;66(2):157-166. Epub 2016 Oct 26.

Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.

Objective And Design: Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR.

Methods: Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference.

Results: In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis.

Conclusions: Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00011-016-1002-6DOI Listing
February 2017

Prognostic value of endocrine treatment-related symptoms in patients with breast cancer: a meta-analysis.

Breast Cancer Res Treat 2016 11 23;160(2):197-209. Epub 2016 Sep 23.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.

Purpose: Endocrine therapy is associated with improved disease-free survival (DFS) in hormone receptor-positive breast cancer, but it is also associated with many adverse events. The aim of this study was to clarify the association between endocrine treatment-related symptoms and treatment efficacy in patients receiving adjuvant endocrine therapy.

Method: EMBASE, Web of Science, PubMed, and CENTRAL databases were searched for studies that compared treatment efficacy between patients in whom adverse events did and did not occur during hormone therapy. Hazard ratios (HRs) and associated 95 % confidence intervals (CIs) for DFS and overall survival were estimated and pooled using random-effects models.

Results: Of 4665 citations identified, ten studies incorporating 32,192 patients were included in the meta-analysis. The presence of endocrine treatment-related symptoms was associated with improved DFS (HR 0.76; 95 % CI 0.68-0.85). Similar results were observed in patients with vasomotor symptoms (HR 0.76; 95 % CI 0.66-0.87) or musculoskeletal symptoms (HR 0.75; 95 % CI 0.60-0.94), in patients taking an aromatase inhibitor (HR 0.69; 95 % CI 0.57-0.85) or tamoxifen (HR 0.74; 95 % CI 0.60-0.93), and in patients with symptoms at 3-month (HR 0.74; 95 % CI 0.66-0.83), 6-month (HR 0.80; 95 % CI 0.66-0.96), or 12-month follow-up visits (HR 0.75; 95 % CI 0.68-0.83). However, no significant difference in overall survival was observed between patients with or without endocrine treatment-related symptoms (HR 0.82; 95 % CI 0.60-1.11). Sensitivity analysis excluding studies with heterogeneous factors yielded consistent results. No evidence of publication bias was observed.

Conclusion: In our meta-analysis, endocrine treatment-related symptoms were shown to correlate with superior DFS and may therefore be useful in predicting treatment efficacy in patients with breast cancer receiving hormone therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-016-3995-5DOI Listing
November 2016

Preoperative intravitreal injection of ranibizumab for patients with severe proliferative diabetic retinopathy contributes to a decreased risk of postoperative neovascular glaucoma.

Acta Ophthalmol 2016 Jun 24;94(4):414-5. Epub 2016 Mar 24.

Department of Ophthalmology, First People's Hospital of Shanghai, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.13019DOI Listing
June 2016

miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway.

Diabetologia 2016 Mar 19;59(3):644-54. Epub 2015 Dec 19.

Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.

Aims/hypothesis: The mechanisms underlying the cellular metabolic memory induced by high glucose remain unclear. Here, we sought to determine the effects of microRNAs (miRNAs) on metabolic memory in diabetic retinopathy.

Methods: The miRNA microarray was used to examine human retinal endothelial cells (HRECs) following exposure to normal glucose (N) or high glucose (H) for 1 week or transient H for 2 days followed by N for another 5 days (H→N). Levels of sirtuin 1 (SIRT1) and acetylated-nuclear factor κB (Ac-NF-κB) were examined following transfection with miR-23b-3p inhibitor or with SIRT1 small interfering (si)RNA in the H→N group, and the apoptotic HRECs were determined by flow cytometry. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of miR-23b-3p inhibitor. Chromatin immunoprecipitation (ChIP) analysis was performed to detect binding of NF-κB p65 to the potential binding site of the miR-23b-27b-24-1 gene promoter in HRECs.

Results: High glucose increased miR-23b-3p expression, even after the return to normal glucose. Luciferase assays identified SIRT1 as a target mRNA of miR-23b-3p. Reduced miR-23b-3p expression inhibited Ac-NF-κB expression by rescuing SIRT1 expression and also relieved the effect of metabolic memory induced by high glucose in HRECs. The results were confirmed in the retina using a diabetic rat model of metabolic memory. High glucose facilitated the recruitment of NF-κB p65 and promoted transcription of the miR-23b-27b-24-1 gene, which can be suppressed by decreasing miR-23b-3p expression.

Conclusions/interpretation: These studies identify a novel mechanism whereby miR-23b-3p regulates high-glucose-induced cellular metabolic memory in diabetic retinopathy through a SIRT1-dependent signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-015-3832-0DOI Listing
March 2016

ANGPTL-4 correlates with vascular endothelial growth factor in patients with proliferative diabetic retinopathy.

Graefes Arch Clin Exp Ophthalmol 2016 Jul 20;254(7):1281-8. Epub 2015 Oct 20.

Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100 Haining Road, Shanghai, 200080, China.

Purpose: To investigate the relationship between angiopoietin-like protein 4 (ANGPTL-4) and vascular endothelial growth factor (VEGF) in the serum and vitreous of eyes in patients with proliferative diabetic retinopathy (PDR).

Methods: Thirty-five eyes of 35 patients with PDR, 20 eyes of 20 patients with non-proliferative diabetic retinopathy, 20 eyes of 20 patients with diabetes but no diabetic retinopathy, and 14 eyes of 14 nondiabetic patients with an idiopathic macular hole (IMH) were recruited from Shanghai First People's Hospital. The ANGPTL-4 and VEGF concentrations were determined using enzyme-linked immunosorbent assays. Group means were compared using one-way analysis of variance with GraphPad Prism 4.0 and SPSS ver. 17.0. The research followed the tenets of the Declaration of Helsinki.

Results: The ANGPTL-4 and VEGF levels were significantly higher in the vitreous and serum of patients with PDR compared with patients with IMH. There were significant correlations between the ANGPTL-4 and VEGF levels in the vitreous and serum of patients with PDR. The vitreous and serum ANGPTL-4 levels were also significantly correlated in patients with PDR. The ANGPTL-4 in both the vitreous and serum correlated with the serum triglyceride and high-density lipoprotein cholesterol levels.

Conclusions: The ANGPTL-4 levels were markedly elevated and the ANGPTL-4 expression was directly correlated with the VEGF expression in the vitreous and serum of patients with PDR. The vitreous and serum ANGPTL-4 levels were also significantly correlated with serum lipids in patients with PDR. Our results suggest that the ANGPTL-4 may be used as a new therapeutic target for the treatment of PDR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-015-3187-8DOI Listing
July 2016

RhoA/mDia-1/profilin-1 signaling targets microvascular endothelial dysfunction in diabetic retinopathy.

Graefes Arch Clin Exp Ophthalmol 2015 May 20;253(5):669-80. Epub 2015 Mar 20.

Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, No.100 Haining Road, Shanghai, 200080, China.

Background: Diabetic retinopathy (DR) is a major cause of blindness in the working-age populations of developed countries, and effective treatments and prevention measures have long been the foci of study. Patients with DR invariably demonstrate impairments of the retinal microvascular endothelium. Many observational and preclinical studies have shown that angiogenesis and apoptosis play crucial roles in the pathogenesis of DR. Increasing evidence suggests that in DR, the small guanosine-5'-triphosphate-binding protein RhoA activates its downstream targets mammalian Diaphanous homolog 1 (mDia-1) and profilin-1, thus affecting important cellular functions, including cell morphology, motility, secretion, proliferation, and gene expression. However, the specific underlying mechanism of disease remains unclear.

Conclusion: This review focuses on the RhoA/mDia-1/profilin-1 signaling pathway that specifically triggers endothelial dysfunction in diabetic patients. Recently, RhoA and profilin-1 signaling has attracted a great deal of attention in the context of diabetes-related research. However, the precise molecular mechanism by which the RhoA/mDia-1/profilin-1 pathway is involved in progression of microvascular endothelial dysfunction (MVED) during DR has not been determined. This review briefly describes each feature of the cascade before exploring the most recent findings on how the pathway may trigger endothelial dysfunction in DR. When the underlying mechanisms are understood, novel therapies seeking to restore the endothelial homeostasis comprised in DR will become possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-015-2985-3DOI Listing
May 2015
-->