Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Artesunate is a derivative of artemisinin,and due to its high solubility,and it has a broader application in clinical settings.Extensive research has confirmed that artemisinin-based drugs show significant activities ...Artesunate is a derivative of artemisinin,and due to its high solubility,and it has a broader application in clinical settings.Extensive research has confirmed that artemisinin-based drugs show significant activities in antiinflammatory,anti-tumor,anti-viral,and anti-angiogenesis aspects,suggesting that artesunate might have potential in treating retinal diseases.Currently,the etiology of most retinal diseases is not fully understood,and there is a lack of effective treatment methods.This paper summarized the research progress of artesunate in the treatment of retinal diseases,including retinoblastoma,choroidal melanoma,diabetic retinopathy,central retinal vein occlusion,proliferative retinopathy,and ocular neovascularization.In addition,the potential applications and future research directions of artesunate in the treatment of retinal diseases were also discussed.展开更多
AIM:To report the incidence of epiretinal membrane(ERM)formation following panretinal photocoagulation(PRP)as the treatment for diabetic retinopathy(DR).METHODS:Retrospective cross-sectional study of patient charts be...AIM:To report the incidence of epiretinal membrane(ERM)formation following panretinal photocoagulation(PRP)as the treatment for diabetic retinopathy(DR).METHODS:Retrospective cross-sectional study of patient charts between January 1^(st),2010 to January 1^(st),2017 with at least 1y follow-up data.All 809 patients treated with PRP for DR were evaluated for exclusion criteria and 73 eyes remained after exclusion for confounding variables related to ERM formation such as other procedures or diseases.Outcomes were determined through medical record review and masked review of optical coherence tomography(OCT)images.Cohen’s kappa was completed to determine if there was an agreement between masked retinal specialists on OCT evaluations.Univariate logistic regression was used to determine the unadjusted odds ratio for patient and procedural characteristics on the formation of ERMs.Multiple logistic regression was then completed on select variables that met the cutoff of 0.25 for a statistically significant contribution by the Wald test with the sequential addition of clinical variables that contributed positively to the model.RESULTS:Among the 73 eyes studied,9.6%formed an ERM with an average time to formation of 1.4y.The minimum power uses during PRP was found to be statistically significant between non-ERM formers and ERM formers(P=0.044).When adjusting for all selected variables aside from minimum power used,multiple logistic regression determined that for every 10 mW increase in minimum power used during PRP,there is an increase in log odds of 1.009(SE:0.003,P=0.014).CONCLUSION:The incidence of ERM formation in 2y following treatment of DR with PRP is roughly 1 in every 10 eyes treated.展开更多
Aerial organs in rice,including leaves,stems,and grains,are crucial for photosynthesis,lodging resistance,and yield.Therefore,an in-depth study on the development of these organs can lay a foundation for achieving hig...Aerial organs in rice,including leaves,stems,and grains,are crucial for photosynthesis,lodging resistance,and yield.Therefore,an in-depth study on the development of these organs can lay a foundation for achieving high and stable rice yields.In this study,we isolated a novel slender aerial organ mutant sao,which is characterized by a significant reduction in the width of leaves,stems,and grains.Histological analysis revealed that the slender phenotype of aerial organs in sao is caused by impaired cell proliferation and elongation.展开更多
AIM:To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS:Retrospect...AIM:To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS:Retrospective,noncomparative,interventional study.Ten surgical pearls were summarized and adapted from the ancient Chinese philosophy.Totally 346 cases(443 eyes)that underwent pars plana vitrectomy(PPV)at our hospial from January 2016 to February 2024 were selected.Flexible combinations of these pearls were applied according to the specific condition of each patient during surgeries.The efficacy and safety were analyzed,as well as the application frequencies according to the existence of tractional retinal detachment or not.RESULTS:A total of 473 times of surgeries were performed on all the patients.According to ancient Chinese allusions,ten surgical pearls were summarized from these surgeries.All PPVs went smoothly with the application of different combinations.Finally,almost all proliferative membranes were successfully peeled except for 10 patients(11 eyes),who went through strategy No.10(minimal membranectomy)that,only necessary relaxation incisions were made with most of the proliferative membranes left on purpose.The final visual acuities were mostly improved or stable(1.92±0.83 LogMAR preoperatively vs 1.16±0.85 LogMAR postoperatively,P<0.01).Postoperative complications mainly included early inflammatory responses in the anterior chamber and nuclear sclerosis.Recurrent vitreous hemorrhage,retinal detachment,and hyphema or neovascular glaucoma occurred in 1.9%(9/473),3.2%(15/473),0.4%(2/473)and 0.4%(2/473)times of PPVs,respectively.After 12/473(2.5%)times of PPVs,retinal detachment at the macular area still existed,and multiple times of subsequent PPVs were conducted.Final retinal attachment at the macular area was realized in 98.9%eyes.Those 5 unattached eyes were with heavily reproliferated membranes and subsequent tractional retinal detachment recurrence under the oil,and three of them were scleral buckled additionally.CONCLUSION:These 10 surgical strategies and technique pearls were mostly effective and safe in the management of severe PDR patients.They were relatively easy to be memorized and applicated once the meaning of each Chinese idiom was understood.One can use different combinations flexibly according to a patient’s specific condition.展开更多
AIM:To evaluate the efficacy of second-stage phacoemulsification(PE)of complicated initial cataract after vitreoretinal surgery(VRS)in patients with advanced proliferative diabetic retinopathy(PDR).METHODS:Totally 216...AIM:To evaluate the efficacy of second-stage phacoemulsification(PE)of complicated initial cataract after vitreoretinal surgery(VRS)in patients with advanced proliferative diabetic retinopathy(PDR).METHODS:Totally 216 patients with PDR and complicated initial cataract who underwent surgery were included.These patients were divided into four groups according to their management.In the 1st group patients were subjected to a two–step surgical procedure:VRS with silicone oil tamponade was performed as the first step,followed by the second step,PE+intraocular lens(IOL)implantation+silicone oil removal.In the 2nd group PE was performed simultaneously with VRS and silicone oil tamponade.The second step differed in the removal of silicone oil from the vitreous cavity.Patients Ia(n=17)and IIa(n=17)subgroups had their tear liquid samples being examined before surgery and on the 2nd day after the 1st phase.In subgroups Ib and IIb,an angiogenesis inhibitor was implanted 10-14d before VRS at a dose of 0.5 mg once.In the 3rd group patients were subjected to a two–step surgical procedure:VRS with gas tamponade performed as the 1st step in their treatment;followed by the 2nd step,PE and the IOL implantation.In the 4th group PE performed simultaneously with VRS with gas tamponade.RESULTS:Patients in subgroup Ia and group III had better functional results than those in subgroup IIa and group IV,respectively(P<0.001).More marked inflammatory response(2-3 points)was statistically significant in patients of the IIa subgroup(P<0.001)and group IV(P<0.001)in comparison with the patients in the Ia and group III respectively.The IIa subgroup(n=9;14.5%)showed higher incidence of neovascular glaucoma(NVG)than the Ia(n=2;3.2%),P=0.027.There also was a higher rate of NVG in group IV(n=6;19.3%)compared to group III(n=1;3.1%),P=0.04.Subgroup IIa revealed a 2 to 2.5 times higher concentration of interleukin 8(IL-8),monocyte chemoattractant protein 1(MCP-1),and inter-cellular adhesion molecule 1(ICAM-1)compared to subgroup Ia.CONCLUSION:PE of initial cataract at the second stage after VRS in patients with advanced PDR provides a sparing approach to surgical treatment in this category of patients and allows to improve anatomical and functional results of VRS.In addition,it contributes to reduction of number and severity of postoperative complications.展开更多
Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatenin...Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.展开更多
AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to ex...AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to explore the causal relationships between 91 CIPs and various severities of DR:background DR(BDR)or non-proliferative DR(NPDR),and proliferative DR(PDR).Single-nucleotide polymorphisms(SNPs)related to the 91 CIPs as exposure factors were identified.These SNPs were selected from an extensive genome-wide association study(GWAS)analyzing large genomic datasets.Genetic variation data of various DR phenotypes provided by the FinnGen collaboration were utilized as outcomes.Inverse-variance weighting(IVW)was used as the main MR analysis.Robustness of study results was evaluated through a series of sensitivity analyses,employing the MR-pleiotropy-test and mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)to confirm the absence of pleiotropy.RESULTS:In a bidirectional MR analysis,we uncovered a complex relationship between CIPs and DR.Elevated levels of tumor necrosis factor ligand superfamily member 14(TNFSF14),latency associated peptide transforming growth factors beta-1(LAP-TGF-beta1),interleukin-10(IL-10),and vascular endothelial growth factor A(VEGF-A)were associated with a reduced risk of NPDR.Conversely,elevated levels of fibroblast growth factor 23(FGF-23)were associated with an increased risk of NPDR.Concentrations of adenosine deaminase(ADA),matrix metalloproteinase-10(MMP-10),eotaxin,and IL-10 showed elevated levels and were linked to a reduced risk of NPDR.On the other hand,the levels of oncostatin-M,beta-nerve growth factor(β-NGF),and interleukin-7(IL-7)were elevated and associated with an increased risk of SNPDR.Elevated levels of ADA,MMP-10,and macrophage colony-stimulating factor 1(CSF1)were linked to a lower likelihood of PDR.Conversely,elevated levels of Caspase 8 and glial cell line-derived neurotrophic factor(GDNF)were associated with an increased risk of PDR.In reverse MR analysis,DR affected the expression of these factors.CONCLUSION:Our research demonstrates evidence supporting a potential causal link between key inflammatory factors and the risk and prognosis of various DR phenotypes.These findings emphasize the regulation of inflammatory factors responses as a strategic approach for preventing and managing DR.Altogether,our results validate the pathogenic role of inflammatory factors dysregulation in DR and support the rationale for exploring immunotherapeutic targets further.展开更多
AIM:To investigate the change of diabetic macular edema(DME)post vitrectomy and its risk factors.METHODS:This retrospective study included 365 eyes of 330 patients who underwent vitrectomy for proliferative diabetic r...AIM:To investigate the change of diabetic macular edema(DME)post vitrectomy and its risk factors.METHODS:This retrospective study included 365 eyes of 330 patients who underwent vitrectomy for proliferative diabetic retinopathy(PDR)with gradable optical coherence tomography(OCT)imaging from January 2018 to March 2022.The incidence of post vitrectomy DME(PV-DME)was defined as patients with a central retinal thickness(CRT)>300µm by OCT among patients without preoperative DME.RESULTS:The cumulative incidence of PV-DME at 3mo was 40.1%(89/222),with its majority subtype of single diffused retinal thickening(66.2%)followed by single cystoid macular edema(27.0%).Multivariate Cox regression analysis indicated that a thicker preoperative CRT[hazard ratio(HR)=1.01,95%confidence interval(CI)1.00-1.02]and intraoperative internal limiting membrane peeling(HR=3.18,95%CI 1.85-5.47)were associated with the presence of PV-DME,while intraoperative intravitreal injection of triamcinolone acetonide(HR=0.28,95%CI 0.13-0.57)was protective against PV-DME.In eyes with preoperative DME(n=143),the CRT decreased gradually from 468.3±177.7μm preoperatively to 409.5±151.0μm(P=0.027),377.4±141.9μm(P<0.001),and 368.0±157.6μm(P<0.001)at 7d,1 and 3mo postoperatively,respectively.Multivariate linear regression analysis indicated that only a thicker preoperative CRT(β=0.77,95%CI 0.63-0.92)was associated with a decreasing postoperative CRT.CONCLUSION:PV-DME is a very common postoperative complication in patients with PDR.Triamcinolone acetonide could prevent its formation.Attention should be paid to patients with a thicker preoperative CRT and internal limiting membrane peeling.展开更多
BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological ...BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological characteristics and long-term outcomes in terms of remission,requirement of kidney replacement therapy(KRT),and patient survival.METHODS A retrospective analysis was conducted on biopsy-proven focal or diffuse PLN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation and followed up at the renal clinic for a minimum of 5 years.All patients were induced with a combination of intravenous cyclophosphamide and corticosteroids for 6 months,followed by maintenance treatment with azathioprine(AZA)or mycophenolate mofetil(MMF).Data were analyzed using Statistical Package for the Social Sciences,version 22.0.P≤0.05 was considered statistically significant.RESULTS The mean age at the onset of systemic lupus erythematosus was 24.12 years±8.89 years,and at LN onset,26.63 years±8.61 years.There was a female predominance of 184(88.9%)cases.Among baseline characteristics,reduced estimated glomerular filtration rate,presence of hypertension,requirement of KRT,and underlying renal histology(International Society of Nephrology/Renal Pathology Society class IV than class III)were significantly associated with end-stage kidney disease(ESKD)and mortality.The renal outcomes were negatively correlated with age,duration of symptoms,and 24-hour urinary protein excretion.The overall remission rate was 89.8%at the end of induction therapy.At 5 years,141(68.11%)patients were in complete and partial remission(94[45.4%]and 47[22.7%],respectively).In total,19(9.2%)patients required KRT on presentation,and at 5 years,38(18.4%)patients developed ESKD,and 28(13.5%)patients died.Thirty-four(16.4%)patients had a renal relapse,more with AZA than MMF(30[88.2%]vs 4[11.76%],respectively;P=0.04).Renal survival at 6 months was 89.8%,while at 5 years,it was 68.11%,showing a significant improvement in patients who did not need KRT at the time of presentation(P<0.0001).CONCLUSION Baseline renal functions,requirement of KRT,and diffuse proliferative disease were the most relevant prognostic factors for kidney survival among this cohort.Short-term renal outcomes were good.Long-term outcomes were poorer with AZA-based maintenance therapy than with MMF,with more ESKD and mortality.展开更多
OBJECTIVE Geldanamycin,a natural product of Streptomyces geldanus,binds the heat shock protein 90(Hsp90),a cell chaperone protein that interacts with Bcl-2.In this study,we investigated whether geldanamycin(GA)inhibit...OBJECTIVE Geldanamycin,a natural product of Streptomyces geldanus,binds the heat shock protein 90(Hsp90),a cell chaperone protein that interacts with Bcl-2.In this study,we investigated whether geldanamycin(GA)inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2 expression. METHODS HeLa cells,a human cervical cell line,were cultured in vitro and treated with different concentrations of GA(0,0.02,0.2, 2,10μmol/L)for 24 h.or were treated for different lengths of time at a GA concentration of 10μmol/L.Proliferation of the cells was analyzed by an MTT assay,and cell apoptosis was determined by staining the cells with annexin V.In addition,cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction(PCR),and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots. RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner.The inhibition was a result of increased cellular apoptotic levels.Further analyses showed that while the mRNA and protein expression levels of Hsp90 were not affected,GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation. CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2,probably through interaction and functional inhibition of Hsp90.展开更多
Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer mem...Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.展开更多
AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search o...AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2 DM patients. Effect size(ES) with 95% confidence interval(CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2 DM patients, respectively. RESULTS: There were 41 references and 48 995 T2 DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2 DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2 DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2 DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients(45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients(74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2 DM from India was higher than patients fromother locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2 DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2 DM patients, and we also recommend suitable interventions to prevent its progression.展开更多
AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic sig...AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (＞40%) and low (≤40%) expression. Areas of extensive proliferation (＞50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P＜0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.展开更多
AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface ...AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR).METHODSThis study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively.RESULTSIn PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis.CONCLUSIONWe found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.展开更多
Diabetic retinopathy(DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important managemen...Diabetic retinopathy(DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor(VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema(DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation(PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.展开更多
AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) an...AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as induced by connective tissue growth factor(CTGF) or transforming growth factor-β (TGF-β) in a human retinal pigment epithelial cell line, ARPE-19. METHODS:The effect of Y27632 on the CTGF or TGF-β induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19 cells were treated with CTGF (1, 10, 100ng/mL)and TGF-β (10ng/mL) in serum free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK inhibitor, Y27632, to analyze the signaling contributing to ECM production. ·RESULTS:Treatment of ARPE-19 cells in culture with TGF-β or CTGF induced an ECM change from a cobblestone morphology to a more elongated swirl pattern indicating a mesenchymal phenotype. RT-qPCR analysis and different gene expression analysis demonstrated an upregulation in expression of genes associated with cytoskeletal structure and motility. CTGFor TGF-β significantly increased expression of fibronectin mRNA (P =0.006, P =0.003 respectively), laminin mRNA (P =0.006, P =0.005), MMP-2 mRNA (P =0.006, P =0.001), COL1A1 mRNA (P =0.001, P =0.001), COL1A2 mRNA (P = 0.001, P =0.001). Preincubation of ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF-β induced fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P = 0.003, P =0.002), COL1A1 (P =0.006, P =0.003), and COL1A2 (P =0.006, P =0.004) gene expression, but not laminin (P =0.375, P =0.516). CONCLUSION:Our study demonstrated that both TGF-β and CTGF upregulate the expression of ECM components including fibronectin, laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway. During this process, ARPE-19 cells were shown to change from an epithelial to a mesenchymal phenotype in vitro. Y27632, a ROCK inhibitor, inhibited the transcription of fibronectin, MMP-2 and type I collagen, but not laminin. The data from our work suggest a role for CTGF as a profibrotic mediator. Inhibiting the RhoA/ROCK pathway represents a potential target to prevent the fibrosis of retinal pigment epithelial (RPE) cells. This might lead to a novel therapeutic approach to preventing the onset of early proliferative vitreoretinopathy(PVR).展开更多
AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimenta...AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.展开更多
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金Supported by the Ministry of National Natural Science Foundation of China(No.82260210)General Project of Jiangxi Provincial Traditional Chinese Medicine Science and Technology Plan(No.2023B1368)Jiangxi Provincial Health Science and Technology Program(No.202510055).
文摘Artesunate is a derivative of artemisinin,and due to its high solubility,and it has a broader application in clinical settings.Extensive research has confirmed that artemisinin-based drugs show significant activities in antiinflammatory,anti-tumor,anti-viral,and anti-angiogenesis aspects,suggesting that artesunate might have potential in treating retinal diseases.Currently,the etiology of most retinal diseases is not fully understood,and there is a lack of effective treatment methods.This paper summarized the research progress of artesunate in the treatment of retinal diseases,including retinoblastoma,choroidal melanoma,diabetic retinopathy,central retinal vein occlusion,proliferative retinopathy,and ocular neovascularization.In addition,the potential applications and future research directions of artesunate in the treatment of retinal diseases were also discussed.
文摘AIM:To report the incidence of epiretinal membrane(ERM)formation following panretinal photocoagulation(PRP)as the treatment for diabetic retinopathy(DR).METHODS:Retrospective cross-sectional study of patient charts between January 1^(st),2010 to January 1^(st),2017 with at least 1y follow-up data.All 809 patients treated with PRP for DR were evaluated for exclusion criteria and 73 eyes remained after exclusion for confounding variables related to ERM formation such as other procedures or diseases.Outcomes were determined through medical record review and masked review of optical coherence tomography(OCT)images.Cohen’s kappa was completed to determine if there was an agreement between masked retinal specialists on OCT evaluations.Univariate logistic regression was used to determine the unadjusted odds ratio for patient and procedural characteristics on the formation of ERMs.Multiple logistic regression was then completed on select variables that met the cutoff of 0.25 for a statistically significant contribution by the Wald test with the sequential addition of clinical variables that contributed positively to the model.RESULTS:Among the 73 eyes studied,9.6%formed an ERM with an average time to formation of 1.4y.The minimum power uses during PRP was found to be statistically significant between non-ERM formers and ERM formers(P=0.044).When adjusting for all selected variables aside from minimum power used,multiple logistic regression determined that for every 10 mW increase in minimum power used during PRP,there is an increase in log odds of 1.009(SE:0.003,P=0.014).CONCLUSION:The incidence of ERM formation in 2y following treatment of DR with PRP is roughly 1 in every 10 eyes treated.
基金supported by the Sichuan Science and Technology Program,China(Grant No.2024JDRC0064)the Chongqing Talent Program Foundation,China(Grant No.cstc2024ycjh-bgzxm0063)+1 种基金the National Natural Science Foundation of China(Grant No.32470354)the Sichuan Science and Technology Innovation and Entrepreneurship Seedling Foundation,China(Grant No.2024JDRC0064).
文摘Aerial organs in rice,including leaves,stems,and grains,are crucial for photosynthesis,lodging resistance,and yield.Therefore,an in-depth study on the development of these organs can lay a foundation for achieving high and stable rice yields.In this study,we isolated a novel slender aerial organ mutant sao,which is characterized by a significant reduction in the width of leaves,stems,and grains.Histological analysis revealed that the slender phenotype of aerial organs in sao is caused by impaired cell proliferation and elongation.
文摘AIM:To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS:Retrospective,noncomparative,interventional study.Ten surgical pearls were summarized and adapted from the ancient Chinese philosophy.Totally 346 cases(443 eyes)that underwent pars plana vitrectomy(PPV)at our hospial from January 2016 to February 2024 were selected.Flexible combinations of these pearls were applied according to the specific condition of each patient during surgeries.The efficacy and safety were analyzed,as well as the application frequencies according to the existence of tractional retinal detachment or not.RESULTS:A total of 473 times of surgeries were performed on all the patients.According to ancient Chinese allusions,ten surgical pearls were summarized from these surgeries.All PPVs went smoothly with the application of different combinations.Finally,almost all proliferative membranes were successfully peeled except for 10 patients(11 eyes),who went through strategy No.10(minimal membranectomy)that,only necessary relaxation incisions were made with most of the proliferative membranes left on purpose.The final visual acuities were mostly improved or stable(1.92±0.83 LogMAR preoperatively vs 1.16±0.85 LogMAR postoperatively,P<0.01).Postoperative complications mainly included early inflammatory responses in the anterior chamber and nuclear sclerosis.Recurrent vitreous hemorrhage,retinal detachment,and hyphema or neovascular glaucoma occurred in 1.9%(9/473),3.2%(15/473),0.4%(2/473)and 0.4%(2/473)times of PPVs,respectively.After 12/473(2.5%)times of PPVs,retinal detachment at the macular area still existed,and multiple times of subsequent PPVs were conducted.Final retinal attachment at the macular area was realized in 98.9%eyes.Those 5 unattached eyes were with heavily reproliferated membranes and subsequent tractional retinal detachment recurrence under the oil,and three of them were scleral buckled additionally.CONCLUSION:These 10 surgical strategies and technique pearls were mostly effective and safe in the management of severe PDR patients.They were relatively easy to be memorized and applicated once the meaning of each Chinese idiom was understood.One can use different combinations flexibly according to a patient’s specific condition.
文摘AIM:To evaluate the efficacy of second-stage phacoemulsification(PE)of complicated initial cataract after vitreoretinal surgery(VRS)in patients with advanced proliferative diabetic retinopathy(PDR).METHODS:Totally 216 patients with PDR and complicated initial cataract who underwent surgery were included.These patients were divided into four groups according to their management.In the 1st group patients were subjected to a two–step surgical procedure:VRS with silicone oil tamponade was performed as the first step,followed by the second step,PE+intraocular lens(IOL)implantation+silicone oil removal.In the 2nd group PE was performed simultaneously with VRS and silicone oil tamponade.The second step differed in the removal of silicone oil from the vitreous cavity.Patients Ia(n=17)and IIa(n=17)subgroups had their tear liquid samples being examined before surgery and on the 2nd day after the 1st phase.In subgroups Ib and IIb,an angiogenesis inhibitor was implanted 10-14d before VRS at a dose of 0.5 mg once.In the 3rd group patients were subjected to a two–step surgical procedure:VRS with gas tamponade performed as the 1st step in their treatment;followed by the 2nd step,PE and the IOL implantation.In the 4th group PE performed simultaneously with VRS with gas tamponade.RESULTS:Patients in subgroup Ia and group III had better functional results than those in subgroup IIa and group IV,respectively(P<0.001).More marked inflammatory response(2-3 points)was statistically significant in patients of the IIa subgroup(P<0.001)and group IV(P<0.001)in comparison with the patients in the Ia and group III respectively.The IIa subgroup(n=9;14.5%)showed higher incidence of neovascular glaucoma(NVG)than the Ia(n=2;3.2%),P=0.027.There also was a higher rate of NVG in group IV(n=6;19.3%)compared to group III(n=1;3.1%),P=0.04.Subgroup IIa revealed a 2 to 2.5 times higher concentration of interleukin 8(IL-8),monocyte chemoattractant protein 1(MCP-1),and inter-cellular adhesion molecule 1(ICAM-1)compared to subgroup Ia.CONCLUSION:PE of initial cataract at the second stage after VRS in patients with advanced PDR provides a sparing approach to surgical treatment in this category of patients and allows to improve anatomical and functional results of VRS.In addition,it contributes to reduction of number and severity of postoperative complications.
文摘Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.
基金Supported by Natural Science Foundation of Hubei Province(No.2023AFC019,No.2020CFB240)Hubei Key Laboratories Opening Project(No.2023KFH019,No.2021KFY055)Fundamental Research Funds for Central Universities(No.2042020kf0065).
文摘AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to explore the causal relationships between 91 CIPs and various severities of DR:background DR(BDR)or non-proliferative DR(NPDR),and proliferative DR(PDR).Single-nucleotide polymorphisms(SNPs)related to the 91 CIPs as exposure factors were identified.These SNPs were selected from an extensive genome-wide association study(GWAS)analyzing large genomic datasets.Genetic variation data of various DR phenotypes provided by the FinnGen collaboration were utilized as outcomes.Inverse-variance weighting(IVW)was used as the main MR analysis.Robustness of study results was evaluated through a series of sensitivity analyses,employing the MR-pleiotropy-test and mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)to confirm the absence of pleiotropy.RESULTS:In a bidirectional MR analysis,we uncovered a complex relationship between CIPs and DR.Elevated levels of tumor necrosis factor ligand superfamily member 14(TNFSF14),latency associated peptide transforming growth factors beta-1(LAP-TGF-beta1),interleukin-10(IL-10),and vascular endothelial growth factor A(VEGF-A)were associated with a reduced risk of NPDR.Conversely,elevated levels of fibroblast growth factor 23(FGF-23)were associated with an increased risk of NPDR.Concentrations of adenosine deaminase(ADA),matrix metalloproteinase-10(MMP-10),eotaxin,and IL-10 showed elevated levels and were linked to a reduced risk of NPDR.On the other hand,the levels of oncostatin-M,beta-nerve growth factor(β-NGF),and interleukin-7(IL-7)were elevated and associated with an increased risk of SNPDR.Elevated levels of ADA,MMP-10,and macrophage colony-stimulating factor 1(CSF1)were linked to a lower likelihood of PDR.Conversely,elevated levels of Caspase 8 and glial cell line-derived neurotrophic factor(GDNF)were associated with an increased risk of PDR.In reverse MR analysis,DR affected the expression of these factors.CONCLUSION:Our research demonstrates evidence supporting a potential causal link between key inflammatory factors and the risk and prognosis of various DR phenotypes.These findings emphasize the regulation of inflammatory factors responses as a strategic approach for preventing and managing DR.Altogether,our results validate the pathogenic role of inflammatory factors dysregulation in DR and support the rationale for exploring immunotherapeutic targets further.
基金Supported by Zhejiang Provincial Highlevel Health Talents Training Project(No.CZ-RC2022010)Wenzhou Basic Medical and Health Technology Project(No.Y2023173)Innovation Project of School of Ophthalmology and Optometry,Eye Hospital of Wenzhou Medical University(No.YNCX3201905).
文摘AIM:To investigate the change of diabetic macular edema(DME)post vitrectomy and its risk factors.METHODS:This retrospective study included 365 eyes of 330 patients who underwent vitrectomy for proliferative diabetic retinopathy(PDR)with gradable optical coherence tomography(OCT)imaging from January 2018 to March 2022.The incidence of post vitrectomy DME(PV-DME)was defined as patients with a central retinal thickness(CRT)>300µm by OCT among patients without preoperative DME.RESULTS:The cumulative incidence of PV-DME at 3mo was 40.1%(89/222),with its majority subtype of single diffused retinal thickening(66.2%)followed by single cystoid macular edema(27.0%).Multivariate Cox regression analysis indicated that a thicker preoperative CRT[hazard ratio(HR)=1.01,95%confidence interval(CI)1.00-1.02]and intraoperative internal limiting membrane peeling(HR=3.18,95%CI 1.85-5.47)were associated with the presence of PV-DME,while intraoperative intravitreal injection of triamcinolone acetonide(HR=0.28,95%CI 0.13-0.57)was protective against PV-DME.In eyes with preoperative DME(n=143),the CRT decreased gradually from 468.3±177.7μm preoperatively to 409.5±151.0μm(P=0.027),377.4±141.9μm(P<0.001),and 368.0±157.6μm(P<0.001)at 7d,1 and 3mo postoperatively,respectively.Multivariate linear regression analysis indicated that only a thicker preoperative CRT(β=0.77,95%CI 0.63-0.92)was associated with a decreasing postoperative CRT.CONCLUSION:PV-DME is a very common postoperative complication in patients with PDR.Triamcinolone acetonide could prevent its formation.Attention should be paid to patients with a thicker preoperative CRT and internal limiting membrane peeling.
文摘BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological characteristics and long-term outcomes in terms of remission,requirement of kidney replacement therapy(KRT),and patient survival.METHODS A retrospective analysis was conducted on biopsy-proven focal or diffuse PLN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation and followed up at the renal clinic for a minimum of 5 years.All patients were induced with a combination of intravenous cyclophosphamide and corticosteroids for 6 months,followed by maintenance treatment with azathioprine(AZA)or mycophenolate mofetil(MMF).Data were analyzed using Statistical Package for the Social Sciences,version 22.0.P≤0.05 was considered statistically significant.RESULTS The mean age at the onset of systemic lupus erythematosus was 24.12 years±8.89 years,and at LN onset,26.63 years±8.61 years.There was a female predominance of 184(88.9%)cases.Among baseline characteristics,reduced estimated glomerular filtration rate,presence of hypertension,requirement of KRT,and underlying renal histology(International Society of Nephrology/Renal Pathology Society class IV than class III)were significantly associated with end-stage kidney disease(ESKD)and mortality.The renal outcomes were negatively correlated with age,duration of symptoms,and 24-hour urinary protein excretion.The overall remission rate was 89.8%at the end of induction therapy.At 5 years,141(68.11%)patients were in complete and partial remission(94[45.4%]and 47[22.7%],respectively).In total,19(9.2%)patients required KRT on presentation,and at 5 years,38(18.4%)patients developed ESKD,and 28(13.5%)patients died.Thirty-four(16.4%)patients had a renal relapse,more with AZA than MMF(30[88.2%]vs 4[11.76%],respectively;P=0.04).Renal survival at 6 months was 89.8%,while at 5 years,it was 68.11%,showing a significant improvement in patients who did not need KRT at the time of presentation(P<0.0001).CONCLUSION Baseline renal functions,requirement of KRT,and diffuse proliferative disease were the most relevant prognostic factors for kidney survival among this cohort.Short-term renal outcomes were good.Long-term outcomes were poorer with AZA-based maintenance therapy than with MMF,with more ESKD and mortality.
文摘OBJECTIVE Geldanamycin,a natural product of Streptomyces geldanus,binds the heat shock protein 90(Hsp90),a cell chaperone protein that interacts with Bcl-2.In this study,we investigated whether geldanamycin(GA)inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2 expression. METHODS HeLa cells,a human cervical cell line,were cultured in vitro and treated with different concentrations of GA(0,0.02,0.2, 2,10μmol/L)for 24 h.or were treated for different lengths of time at a GA concentration of 10μmol/L.Proliferation of the cells was analyzed by an MTT assay,and cell apoptosis was determined by staining the cells with annexin V.In addition,cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction(PCR),and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots. RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner.The inhibition was a result of increased cellular apoptotic levels.Further analyses showed that while the mRNA and protein expression levels of Hsp90 were not affected,GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation. CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2,probably through interaction and functional inhibition of Hsp90.
基金Supported by National Natural Science Foundation of China,No.81373465
文摘Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.
文摘AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2 DM patients. Effect size(ES) with 95% confidence interval(CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2 DM patients, respectively. RESULTS: There were 41 references and 48 995 T2 DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2 DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2 DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2 DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients(45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients(74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2 DM from India was higher than patients fromother locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2 DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2 DM patients, and we also recommend suitable interventions to prevent its progression.
基金Supported by the Emil Aaltonen Foundation and Turku University Research Foundation
文摘AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (＞40%) and low (≤40%) expression. Areas of extensive proliferation (＞50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P＜0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.
基金Supported by Public Interest Research on Social Development Projects in Zhejiang Province (No.2011c23019)
文摘AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR).METHODSThis study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively.RESULTSIn PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis.CONCLUSIONWe found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.
文摘Diabetic retinopathy(DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor(VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema(DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation(PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.
文摘AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as induced by connective tissue growth factor(CTGF) or transforming growth factor-β (TGF-β) in a human retinal pigment epithelial cell line, ARPE-19. METHODS:The effect of Y27632 on the CTGF or TGF-β induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19 cells were treated with CTGF (1, 10, 100ng/mL)and TGF-β (10ng/mL) in serum free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK inhibitor, Y27632, to analyze the signaling contributing to ECM production. ·RESULTS:Treatment of ARPE-19 cells in culture with TGF-β or CTGF induced an ECM change from a cobblestone morphology to a more elongated swirl pattern indicating a mesenchymal phenotype. RT-qPCR analysis and different gene expression analysis demonstrated an upregulation in expression of genes associated with cytoskeletal structure and motility. CTGFor TGF-β significantly increased expression of fibronectin mRNA (P =0.006, P =0.003 respectively), laminin mRNA (P =0.006, P =0.005), MMP-2 mRNA (P =0.006, P =0.001), COL1A1 mRNA (P =0.001, P =0.001), COL1A2 mRNA (P = 0.001, P =0.001). Preincubation of ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF-β induced fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P = 0.003, P =0.002), COL1A1 (P =0.006, P =0.003), and COL1A2 (P =0.006, P =0.004) gene expression, but not laminin (P =0.375, P =0.516). CONCLUSION:Our study demonstrated that both TGF-β and CTGF upregulate the expression of ECM components including fibronectin, laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway. During this process, ARPE-19 cells were shown to change from an epithelial to a mesenchymal phenotype in vitro. Y27632, a ROCK inhibitor, inhibited the transcription of fibronectin, MMP-2 and type I collagen, but not laminin. The data from our work suggest a role for CTGF as a profibrotic mediator. Inhibiting the RhoA/ROCK pathway represents a potential target to prevent the fibrosis of retinal pigment epithelial (RPE) cells. This might lead to a novel therapeutic approach to preventing the onset of early proliferative vitreoretinopathy(PVR).
基金Supported by the National Natural Science Foundation of China(No.81371039)Shanghai Natural Science Foundation(No.18ZR1440200)
文摘AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.
