AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence ...BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research.AIM To develop a visual risk profile model to explore factors influencing DR after surgery.METHODS We retrospectively selected 151 patients with DR undergoing PPV.The patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after surgery.Independent risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction curve.RESULTS After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model.The area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,respectively.The AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,respectively.CONCLUSION A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy.This study can help formulate relevant preventive and treatment measures.展开更多
AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcer...AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.展开更多
BACKGROUND Duodenal web is a rare congenital malformation,exceedingly uncommon in adults,and often misdiagnosed due to the subtle imaging features.CASE SUMMARY By analyzing the clinical diagnosis process and various i...BACKGROUND Duodenal web is a rare congenital malformation,exceedingly uncommon in adults,and often misdiagnosed due to the subtle imaging features.CASE SUMMARY By analyzing the clinical diagnosis process and various imaging findings of a patient from our institution,this case report emphasizes the necessity of upper gastrointestinal series in diagnosing duodenal webs,outlines its typical radiographic features,and provides a literature review on the etiology,clinical presentation,and management of this condition.CONCLUSION This case report emphasizes the necessity of upper gastrointestinal series in diagnosing duodenal webs.展开更多
AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHO...AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.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 detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional o...AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.展开更多
· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptid...· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.展开更多
AIM:To determine the difference of surgical induced astigmatism between conventional 20-gauge sutured vitrectomy and 23-gauge transconjunctival sutureless vitrectomy,and the influence of corneal pachymetry and intraoc...AIM:To determine the difference of surgical induced astigmatism between conventional 20-gauge sutured vitrectomy and 23-gauge transconjunctival sutureless vitrectomy,and the influence of corneal pachymetry and intraocular pressure(IOP)on surgical induced astigmatism in diabetic patients.METHODS:This retrospective,consecutive case series consisted of 40 eyes of 38 diabetic subjects who underwent either 20-gauge or 23-gauge vitrectomy.The corneal curvature and thickness were measured with Scheimpflug imaging before surgery and 1wk;1,3mo after surgery.We compared the surgical induced astigmatism(SIA)on the true net power in 23-gauge group with that in 20-gauge group.We determined the correlation between corneal thickness change ratio,IOP and SIA measured by Pentacam.RESULTS:The mean SIAs were 1.082±0.085 D(mean±SEM),0.689±0.070 D and 0.459±0.063 D at postoperative 1wk;1,3mo respectively in diabetic subjects.The vitrectomy induced astigmatisms were declined significantly with time(F2,36=33.629,P=0.000)postoperatively.The 23-gauge surgery group induced significantly less astigmatism than 20-gauge surgery group(F1,37=11.046,P=0.020).Corneal thickness in diabetes elevated after surgery(F3,78=10.532,P=0.000).The linear regression analysis at postoperatively 1wk went as:SIA=-4.519+4.931 change ratio(Port3)+0.026IOP(R2=0.46,P=0.000),whereas the rate of cornealthickness change and IOP showed no correlation with the change of astigmatism at postoperatively 1 and 3mo.CONCLUSION:There are significant serial changes in both 20-gauge and 23-gauge group in diabetic subjects.23-gauge induce less astigmatism than 20-gauge and become stable more rapidly than 20-gauge.The elevation of corneal thickness and IOP was associated with increased astigmatim at the early postoperative stage both in 23-gauge and 20-gauge surgery group.展开更多
Fracability is a property that indicates how easy reservoir rocks can be fractured in hydraulic fracturing operations.It is a key parameter for fracturing design and evaluation.In order to utilize continuous logging d...Fracability is a property that indicates how easy reservoir rocks can be fractured in hydraulic fracturing operations.It is a key parameter for fracturing design and evaluation.In order to utilize continuous logging data to predict fracability,synchronous tests of dynamic and static mechanical parameters of rocks under different confining pressures were conducted on13 tight sandstone samples derived from the central Junggar Basin,China.A modified formula between dynamic and static mechanical parameters was established.Fracability of the tight reservoir in the Junggar Basin was then evaluated based on brittleness index,fracture toughness,and fracability index.The effectiveness of fracturing was analyzed combined with the oil testing curve after hydraulic fracturing.The results show that:(1)The distribution of oil-bearing formations in the studied area coincides well with stratum of higher fracability index.(2)The critical fracability index is determined to be 0.3,three formations are selected as fracturing candidates,and a thin mudstone interbed is identified in the oil-bearing formation.(3)Well testing curve verifies the reliability of the fracability evaluation method and the accuracy of the modified formula between dynamic and static mechanical parameters.This study provides useful information for improving fracturing operations of tight oil and gas reservoirs.展开更多
Rock damage appears in brittle shale even prior to peak stress(i.e.,before failure)due to the occurrence of microcracks in these rocks.In this work,a coupled hydromechanical model was built by incorporating the mechan...Rock damage appears in brittle shale even prior to peak stress(i.e.,before failure)due to the occurrence of microcracks in these rocks.In this work,a coupled hydromechanical model was built by incorporating the mechanical and fluid seepage induced stresses around a wellbore during drilling.The borehole instability mechanism of hard-brittle shale was studied.The results show that even if a well is simply drilled into a hard-brittle shale formation,the formation around the borehole can be subjected to rock damage.The maximum failure ratio of the formation around the borehole increases with drilling time.A lower drilling fluid density corresponds to a faster increase in the failure ratio of the borehole with time and a shorter period of borehole collapse.When the initial drilling fluid density is too low,serious rock damage occurs in the formation around the borehole.Even though a high-density drilling fluid is used after drilling,long-term borehole stability is difficult to maintain.While drilling in hard-brittle shale,drilling fluid with a proper density should be used rather than increasing the density of the drilling fluid only after borehole collapse occurs,which is more favorable for maintaining long-term borehole stability.展开更多
AIM:To report the effectiveness of intravitreal implantation of dexamethasone implant(Ozurdex)after phacoemulsification and intraocular lens implantation in refractory uveitis patients.METHODS:This single-center retro...AIM:To report the effectiveness of intravitreal implantation of dexamethasone implant(Ozurdex)after phacoemulsification and intraocular lens implantation in refractory uveitis patients.METHODS:This single-center retrospective study conducted for refractory pan-uveitis patients who underwent cataract surgery combined with intravitreal Ozurdex implantation.The main outcome measurements were bestcorrected visual acuity(BCVA),central retinal thickness(CRT),grade of anterior chamber cell(AAC),intraocular pressure(IOP),and systemic/ocular adverse events.RESULTS:Ten eyes of 7 patients were included.BCVA showed significant improvement at 1 mo(P=0.004),3 mo(P=0.0004),and 6 mo(P=0.001)post operation.There were no statistically significant differences in the postoperative CRT among follow-up groups(P>0.05).No significant differences were observed in the baseline IOP when compared to 1,3,and 6 mo(all P>0.05)post operation.One patient developed a transient elevated IOP post injection.Two eyes(20%)developed posterior capsular opacifications and underwent neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy.In six patients(8 eyes,71.4%),the systemic steroid usage was reduced to below 10 mg/d.The patients experienced a mean of 1.4±0.52 recurrences of inflammation in the 6 mo before operation and 0.7±0.48 in the 6 mon post operation.The mean recurrence time was 13±0.58 wk(range 12-14 wk)post operation.In five of seven patients(7 out of 10 eyes),inflammation relapse was developed postoperatively.Only one patient(2 eyes)needed increased amounts of oral corticosteroids.Intraocular inflammation recurrence in the remaining patients was controlled by topical steroids.CONCLUSION:Ozurdex is considered a safe and effective approach to control postoperative inflammation in cataract surgery for patients with refractory uveitis in our study.After the disappearance of Ozurdex’s antiinflammatory effects over time,in most cases the recurrent inflammation can be controlled by topical steroids.展开更多
OBJECTIVE Paeoniflorin(PF) and albiflorin(AF) are the major active components of total peony glucosides(TPG) from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory,antioxidation an...OBJECTIVE Paeoniflorin(PF) and albiflorin(AF) are the major active components of total peony glucosides(TPG) from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory,antioxidation and anti-hypertension effects.The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiplereaction monitoring(MRM) scanning via electrospray ionization(ESI) source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG.RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad.ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC,MRT and t1/2 of the drug PF,and reduce the values of CL of PF.From a comparison of the main pharmacokinetic parameters among AF alone,AF combined with PF and AF in TPG,the values of the MRT and t1/2 of AF in TPG were greater than that of AF alone,and there were statistically signifi.cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats,suggesting that there was a decreased exposure of PF in rats under hypoxia.The multiple active components in TPG may lead to DDIs between some P-gp substrates.CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute.The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.展开更多
AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospec...AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A(18 patients), with the peeling area within one-half of the optic disc macular distance as the radius;group B(18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity(BCVA), light-adaptive electroretinography, macular hole(MH) closure rate, central macular thickness(CMT), retinal nerve fiber layer(RNFL) and ganglion cell complex(GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study(ETDRS) ring] before and 1, 3, and 6mo after surgery.RESULTS: The closure rate was 94.4%(17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo(P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery(P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery(P=0.038).CONCLUSION: Enlarging the extent of ILM peeling doesn’t affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.展开更多
Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagn...Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagnosed at an advanced stage and have a poor prognosis.Germline mutations in the BRCA1 DNA repair associated gene(BRCA1)and the BRCA2 DNA repair associated gene(BRCA2)account for 20%–25%of epithelial ovarian cancer(EOC).BRCA1 germline mutations are more common in Chinese EOC patients.Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient.Whole-exome sequencing was performed on two EOC patients and an unaffected individual.Variant validation was also performed in all available members by Sanger sequencing.Results A heterozygous splice site variant,c.4358-2A>G in the BRCA1 gene,was identified.Bioinformatic analysis showed that the variant may change the splicing machinery.Conclusion The BRCA1 splice site variant,c.4358-2A>G was identified as the likely genetic cause for EOC,and may also be associated with the increased risk of rectal adenocarcinoma in the family.The findings were beneficial for genetic counseling,helpful for cancer prevention in other family members,and may facilitate therapy decision-making in the future to reduce cancer lethality.展开更多
AIM:To assist with retinal vein occlusion(RVO)screening,artificial intelligence(AI)methods based on deep learning(DL)have been developed to alleviate the pressure experienced by ophthalmologists and discover and treat...AIM:To assist with retinal vein occlusion(RVO)screening,artificial intelligence(AI)methods based on deep learning(DL)have been developed to alleviate the pressure experienced by ophthalmologists and discover and treat RVO as early as possible.METHODS:A total of 8600 color fundus photographs(CFPs)were included for training,validation,and testing of disease recognition models and lesion segmentation models.Four disease recognition and four lesion segmentation models were established and compared.Finally,one disease recognition model and one lesion segmentation model were selected as superior.Additionally,224 CFPs from 130 patients were included as an external test set to determine the abilities of the two selected models.RESULTS:Using the Inception-v3 model for disease identification,the mean sensitivity,specificity,and F1 for the three disease types and normal CFPs were 0.93,0.99,and 0.95,respectively,and the mean area under the curve(AUC)was 0.99.Using the DeepLab-v3 model for lesion segmentation,the mean sensitivity,specificity,and F1 for four lesion types(abnormally dilated and tortuous blood vessels,cotton-wool spots,flame-shaped hemorrhages,and hard exudates)were 0.74,0.97,and 0.83,respectively.CONCLUSION:DL models show good performance when recognizing RVO and identifying lesions using CFPs.Because of the increasing number of RVO patients and increasing demand for trained ophthalmologists,DL models will be helpful for diagnosing RVO early in life and reducing vision impairment.展开更多
Nitric oxide(NO)is a second messenger playing crucial roles in the signaling of a variety of cellular functions.Due to its pathophysiological significance,various NO modulators have been developed to explore NO pathwa...Nitric oxide(NO)is a second messenger playing crucial roles in the signaling of a variety of cellular functions.Due to its pathophysiological significance,various NO modulators have been developed to explore NO pathways and some have been used as therapies.These modulators are often used directly to observe pharmacological effects in cell lines,but their actual effect on intracellular NO level is seldom analyzed.Herein,facilitated by a selective and sensitive fluorescence probe,we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase(eNOS)inhibitor N(u)-nitro-L-arginine methyl ester(L-NAME)failing to decrease intracellular free NO level in EA.hy926 cells while NO donor diethylamine-NONOate(DEA$NONOate)and eNOS activator calcimycin(A23187)failing to increase free NO level in human umbilical vein endothelial cell line(HUV-EC-C),although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells(primary HUVECs)and RAW 264.7 macrophage cells.Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase(NOS)level and the endogenous glutathione(GSH)level.Genetically manipulating eNOS level in both cells restores the expected response,while decreasing GSH level restores the ability of DEA$NONOate to increase NO level in HUV-EC-C.These results reveal that the cellular microenvironment has a profound impact on pharmacological effect.Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironmentdependent pharmacological effects.展开更多
AIM:To evaluate the effect of miRNA-451 on rhesus macaque choroid-retinal endothelial(RF/6A)cell function and proteome profile.METHODS:The RF/6A cells were transfected with miRNA-451 mimic and inhibitor.The role of mi...AIM:To evaluate the effect of miRNA-451 on rhesus macaque choroid-retinal endothelial(RF/6A)cell function and proteome profile.METHODS:The RF/6A cells were transfected with miRNA-451 mimic and inhibitor.The role of miRNA-451 on proliferation ability was evaluated by CCK-8 assay.Furthermore,iTRAQ quantitative proteomic analysis was applied to comprehensively illuminate the change of cellular proteins and biological function between different groups.RESULTS:In miRNA-451 overexpression group,cell proliferation of RF/6A decreased both at 24 h and 48 h;while in miRNA-451 inhibition group,on the contrary,RF/6A cell proliferation was increased at 48 h.Based on iTRAQ quantitative proteomic analysis,23 differentially expressed proteins(DEPs)were detected in the comparison of miRNA-451 mimic and mimic control-transfected RF/6A cells,and 30 DEPs were identified in the comparison of RF/6A cells transfected with miRNA-451 inhibitor and inhibitor control.DEPs such as GORASP2,KRT1,SLC7 A2,RIC8 A,DDX42,CAP1,PCBP2 might be closely related to the inhibitory effect of miRNA-451 on RF/6A cell proliferation,while PCYT1 A,MGAT1,TUBB,MCU,SIL1,BID,MSH6 might account for the positive effect of miRNA-451 inhibitor on RF/6A cell growth.PTPN1,as the only protein exhibiting an opposite trend between miRNA-451 mimic and inhibitortransfected cells,was most likely accountable for the inhibition of miRNA-451 mimic on RF/6A cell growth,and the promotion of miRNA-451 inhibitor on RF/6A cell proliferation.CONCLUSION:miRNA-451 overexpression can suppress the growth of RF/6A cells while knockdown of miRNA-451 can promote RF/6A cell viability.Among all DEPs,increased PTPN1 is most likely to account for the negative regulation of miRNA-451 on RF/6A proliferation.miRNA-451 can be a protective factor for neovascular disease of fundus via regulating choroid retinal endothelial cell function.展开更多
OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in v...OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phenazinemethosulfate(PMS)assay,hoechst 33358 staining,annexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomerase I(TOP I)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322DNA relaxation assays and molecular docking.TOPⅠand TOPⅡexpression levels in C6 cells were also determined.RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).It was showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cel s in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠ and Ⅱ.Lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡin molecular docking study.Also,lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠ and TOPⅡ activities,as wel as TOPⅡ expression.展开更多
AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on fou...AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017.HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg.Clinical response,relapse rate,change of visual acuity,and other metrics were evaluated.RESULTS:All four patients presented with responses to HUC-MSCs treatment,with three males and one female.The numbers of uveitis attacks per year after the HUCMSCs treatment(0,2,0,0 respectively)all decreased compared with the numbers before the treatment(3,6,4,4 respectively).The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation,and three patients discontinued their oral medicine at the last visit.The best corrected visual acuity(BCVA)of 3 patients was improved to varying degrees,and the BCVA of 1 patient remained at 20/20(Snellen chart)from the first to the last consultation.CONCLUSION:The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.展开更多
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金Supported by the Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-037A.
文摘BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research.AIM To develop a visual risk profile model to explore factors influencing DR after surgery.METHODS We retrospectively selected 151 patients with DR undergoing PPV.The patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after surgery.Independent risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction curve.RESULTS After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model.The area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,respectively.The AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,respectively.CONCLUSION A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy.This study can help formulate relevant preventive and treatment measures.
基金Supported by National Natural Science Foundation of China(No.82171085).
文摘AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.
文摘BACKGROUND Duodenal web is a rare congenital malformation,exceedingly uncommon in adults,and often misdiagnosed due to the subtle imaging features.CASE SUMMARY By analyzing the clinical diagnosis process and various imaging findings of a patient from our institution,this case report emphasizes the necessity of upper gastrointestinal series in diagnosing duodenal webs,outlines its typical radiographic features,and provides a literature review on the etiology,clinical presentation,and management of this condition.CONCLUSION This case report emphasizes the necessity of upper gastrointestinal series in diagnosing duodenal webs.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.
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 Shanxi China Scientific and Technological Project(No.2007031096-1)Ph.D.Program Foundation of Ministry of Education of China(No.20111202110008)
文摘AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.
基金Supported by National Natural Science Foundation of China(No.81371005)
文摘· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.
基金Supported by National Natural Science Foundation of China (No.31100991) Natural Science Foundation of Tianjin, China (No.15JCQNJ11400)
文摘AIM:To determine the difference of surgical induced astigmatism between conventional 20-gauge sutured vitrectomy and 23-gauge transconjunctival sutureless vitrectomy,and the influence of corneal pachymetry and intraocular pressure(IOP)on surgical induced astigmatism in diabetic patients.METHODS:This retrospective,consecutive case series consisted of 40 eyes of 38 diabetic subjects who underwent either 20-gauge or 23-gauge vitrectomy.The corneal curvature and thickness were measured with Scheimpflug imaging before surgery and 1wk;1,3mo after surgery.We compared the surgical induced astigmatism(SIA)on the true net power in 23-gauge group with that in 20-gauge group.We determined the correlation between corneal thickness change ratio,IOP and SIA measured by Pentacam.RESULTS:The mean SIAs were 1.082±0.085 D(mean±SEM),0.689±0.070 D and 0.459±0.063 D at postoperative 1wk;1,3mo respectively in diabetic subjects.The vitrectomy induced astigmatisms were declined significantly with time(F2,36=33.629,P=0.000)postoperatively.The 23-gauge surgery group induced significantly less astigmatism than 20-gauge surgery group(F1,37=11.046,P=0.020).Corneal thickness in diabetes elevated after surgery(F3,78=10.532,P=0.000).The linear regression analysis at postoperatively 1wk went as:SIA=-4.519+4.931 change ratio(Port3)+0.026IOP(R2=0.46,P=0.000),whereas the rate of cornealthickness change and IOP showed no correlation with the change of astigmatism at postoperatively 1 and 3mo.CONCLUSION:There are significant serial changes in both 20-gauge and 23-gauge group in diabetic subjects.23-gauge induce less astigmatism than 20-gauge and become stable more rapidly than 20-gauge.The elevation of corneal thickness and IOP was associated with increased astigmatim at the early postoperative stage both in 23-gauge and 20-gauge surgery group.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(2016ZX05002-002)the National Natural Science Foundation of China(41972138).
文摘Fracability is a property that indicates how easy reservoir rocks can be fractured in hydraulic fracturing operations.It is a key parameter for fracturing design and evaluation.In order to utilize continuous logging data to predict fracability,synchronous tests of dynamic and static mechanical parameters of rocks under different confining pressures were conducted on13 tight sandstone samples derived from the central Junggar Basin,China.A modified formula between dynamic and static mechanical parameters was established.Fracability of the tight reservoir in the Junggar Basin was then evaluated based on brittleness index,fracture toughness,and fracability index.The effectiveness of fracturing was analyzed combined with the oil testing curve after hydraulic fracturing.The results show that:(1)The distribution of oil-bearing formations in the studied area coincides well with stratum of higher fracability index.(2)The critical fracability index is determined to be 0.3,three formations are selected as fracturing candidates,and a thin mudstone interbed is identified in the oil-bearing formation.(3)Well testing curve verifies the reliability of the fracability evaluation method and the accuracy of the modified formula between dynamic and static mechanical parameters.This study provides useful information for improving fracturing operations of tight oil and gas reservoirs.
基金financially supported by the National Natural Scienceof China(52074224,U1762216)the Key Research and Development Program of Shandong Province(2019GGX103025)
文摘Rock damage appears in brittle shale even prior to peak stress(i.e.,before failure)due to the occurrence of microcracks in these rocks.In this work,a coupled hydromechanical model was built by incorporating the mechanical and fluid seepage induced stresses around a wellbore during drilling.The borehole instability mechanism of hard-brittle shale was studied.The results show that even if a well is simply drilled into a hard-brittle shale formation,the formation around the borehole can be subjected to rock damage.The maximum failure ratio of the formation around the borehole increases with drilling time.A lower drilling fluid density corresponds to a faster increase in the failure ratio of the borehole with time and a shorter period of borehole collapse.When the initial drilling fluid density is too low,serious rock damage occurs in the formation around the borehole.Even though a high-density drilling fluid is used after drilling,long-term borehole stability is difficult to maintain.While drilling in hard-brittle shale,drilling fluid with a proper density should be used rather than increasing the density of the drilling fluid only after borehole collapse occurs,which is more favorable for maintaining long-term borehole stability.
基金Supported by National Natural Science Foundation of China(No.81870651No.81671642)。
文摘AIM:To report the effectiveness of intravitreal implantation of dexamethasone implant(Ozurdex)after phacoemulsification and intraocular lens implantation in refractory uveitis patients.METHODS:This single-center retrospective study conducted for refractory pan-uveitis patients who underwent cataract surgery combined with intravitreal Ozurdex implantation.The main outcome measurements were bestcorrected visual acuity(BCVA),central retinal thickness(CRT),grade of anterior chamber cell(AAC),intraocular pressure(IOP),and systemic/ocular adverse events.RESULTS:Ten eyes of 7 patients were included.BCVA showed significant improvement at 1 mo(P=0.004),3 mo(P=0.0004),and 6 mo(P=0.001)post operation.There were no statistically significant differences in the postoperative CRT among follow-up groups(P>0.05).No significant differences were observed in the baseline IOP when compared to 1,3,and 6 mo(all P>0.05)post operation.One patient developed a transient elevated IOP post injection.Two eyes(20%)developed posterior capsular opacifications and underwent neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy.In six patients(8 eyes,71.4%),the systemic steroid usage was reduced to below 10 mg/d.The patients experienced a mean of 1.4±0.52 recurrences of inflammation in the 6 mo before operation and 0.7±0.48 in the 6 mon post operation.The mean recurrence time was 13±0.58 wk(range 12-14 wk)post operation.In five of seven patients(7 out of 10 eyes),inflammation relapse was developed postoperatively.Only one patient(2 eyes)needed increased amounts of oral corticosteroids.Intraocular inflammation recurrence in the remaining patients was controlled by topical steroids.CONCLUSION:Ozurdex is considered a safe and effective approach to control postoperative inflammation in cataract surgery for patients with refractory uveitis in our study.After the disappearance of Ozurdex’s antiinflammatory effects over time,in most cases the recurrent inflammation can be controlled by topical steroids.
文摘OBJECTIVE Paeoniflorin(PF) and albiflorin(AF) are the major active components of total peony glucosides(TPG) from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory,antioxidation and anti-hypertension effects.The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiplereaction monitoring(MRM) scanning via electrospray ionization(ESI) source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG.RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad.ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC,MRT and t1/2 of the drug PF,and reduce the values of CL of PF.From a comparison of the main pharmacokinetic parameters among AF alone,AF combined with PF and AF in TPG,the values of the MRT and t1/2 of AF in TPG were greater than that of AF alone,and there were statistically signifi.cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats,suggesting that there was a decreased exposure of PF in rats under hypoxia.The multiple active components in TPG may lead to DDIs between some P-gp substrates.CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute.The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.
基金Supported by a grant from the Natural Science Foundation of Tianjin City (No.20JCZXJC00040)Tianjin Key Medical Discipline (No.Specialty) Construction Project (No.TJYXZDXK-037A)。
文摘AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A(18 patients), with the peeling area within one-half of the optic disc macular distance as the radius;group B(18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity(BCVA), light-adaptive electroretinography, macular hole(MH) closure rate, central macular thickness(CMT), retinal nerve fiber layer(RNFL) and ganglion cell complex(GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study(ETDRS) ring] before and 1, 3, and 6mo after surgery.RESULTS: The closure rate was 94.4%(17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo(P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery(P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery(P=0.038).CONCLUSION: Enlarging the extent of ILM peeling doesn’t affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.
基金the National Natural Science Foundation of China(No.81800219 and No.81873686)Natural Science Foundation of Hunan Province(No.2019JJ50927,No.2020JJ3057 and No.2020JJ4830)the Lotus Scholars Program of Hunan Province,and the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagnosed at an advanced stage and have a poor prognosis.Germline mutations in the BRCA1 DNA repair associated gene(BRCA1)and the BRCA2 DNA repair associated gene(BRCA2)account for 20%–25%of epithelial ovarian cancer(EOC).BRCA1 germline mutations are more common in Chinese EOC patients.Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient.Whole-exome sequencing was performed on two EOC patients and an unaffected individual.Variant validation was also performed in all available members by Sanger sequencing.Results A heterozygous splice site variant,c.4358-2A>G in the BRCA1 gene,was identified.Bioinformatic analysis showed that the variant may change the splicing machinery.Conclusion The BRCA1 splice site variant,c.4358-2A>G was identified as the likely genetic cause for EOC,and may also be associated with the increased risk of rectal adenocarcinoma in the family.The findings were beneficial for genetic counseling,helpful for cancer prevention in other family members,and may facilitate therapy decision-making in the future to reduce cancer lethality.
基金Tianjin Science and Technology Project(No.BHXQKJXM-SF-2018-05)Tianjin Clinical Key Discipline(Specialty)Construction Project(No.TJLCZDXKM008).
文摘AIM:To assist with retinal vein occlusion(RVO)screening,artificial intelligence(AI)methods based on deep learning(DL)have been developed to alleviate the pressure experienced by ophthalmologists and discover and treat RVO as early as possible.METHODS:A total of 8600 color fundus photographs(CFPs)were included for training,validation,and testing of disease recognition models and lesion segmentation models.Four disease recognition and four lesion segmentation models were established and compared.Finally,one disease recognition model and one lesion segmentation model were selected as superior.Additionally,224 CFPs from 130 patients were included as an external test set to determine the abilities of the two selected models.RESULTS:Using the Inception-v3 model for disease identification,the mean sensitivity,specificity,and F1 for the three disease types and normal CFPs were 0.93,0.99,and 0.95,respectively,and the mean area under the curve(AUC)was 0.99.Using the DeepLab-v3 model for lesion segmentation,the mean sensitivity,specificity,and F1 for four lesion types(abnormally dilated and tortuous blood vessels,cotton-wool spots,flame-shaped hemorrhages,and hard exudates)were 0.74,0.97,and 0.83,respectively.CONCLUSION:DL models show good performance when recognizing RVO and identifying lesions using CFPs.Because of the increasing number of RVO patients and increasing demand for trained ophthalmologists,DL models will be helpful for diagnosing RVO early in life and reducing vision impairment.
基金We greatly appreciate the financial support from the National Natural Science Foundations of China(21778048,81673489,31871414,U1703235)the National Key R&D Program of China(2019ZX09201001-003-010)+1 种基金the Natural Science Foundation of Zhejiang Province,China(LR18H300001)Shanghai Science and Technology Development Funds(19YF1457500).
文摘Nitric oxide(NO)is a second messenger playing crucial roles in the signaling of a variety of cellular functions.Due to its pathophysiological significance,various NO modulators have been developed to explore NO pathways and some have been used as therapies.These modulators are often used directly to observe pharmacological effects in cell lines,but their actual effect on intracellular NO level is seldom analyzed.Herein,facilitated by a selective and sensitive fluorescence probe,we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase(eNOS)inhibitor N(u)-nitro-L-arginine methyl ester(L-NAME)failing to decrease intracellular free NO level in EA.hy926 cells while NO donor diethylamine-NONOate(DEA$NONOate)and eNOS activator calcimycin(A23187)failing to increase free NO level in human umbilical vein endothelial cell line(HUV-EC-C),although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells(primary HUVECs)and RAW 264.7 macrophage cells.Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase(NOS)level and the endogenous glutathione(GSH)level.Genetically manipulating eNOS level in both cells restores the expected response,while decreasing GSH level restores the ability of DEA$NONOate to increase NO level in HUV-EC-C.These results reveal that the cellular microenvironment has a profound impact on pharmacological effect.Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironmentdependent pharmacological effects.
基金Supported by grants from National Natural Science Foundation of China(No.81900891)Global Ophthalmology Awards Program 2020(No.482667)。
文摘AIM:To evaluate the effect of miRNA-451 on rhesus macaque choroid-retinal endothelial(RF/6A)cell function and proteome profile.METHODS:The RF/6A cells were transfected with miRNA-451 mimic and inhibitor.The role of miRNA-451 on proliferation ability was evaluated by CCK-8 assay.Furthermore,iTRAQ quantitative proteomic analysis was applied to comprehensively illuminate the change of cellular proteins and biological function between different groups.RESULTS:In miRNA-451 overexpression group,cell proliferation of RF/6A decreased both at 24 h and 48 h;while in miRNA-451 inhibition group,on the contrary,RF/6A cell proliferation was increased at 48 h.Based on iTRAQ quantitative proteomic analysis,23 differentially expressed proteins(DEPs)were detected in the comparison of miRNA-451 mimic and mimic control-transfected RF/6A cells,and 30 DEPs were identified in the comparison of RF/6A cells transfected with miRNA-451 inhibitor and inhibitor control.DEPs such as GORASP2,KRT1,SLC7 A2,RIC8 A,DDX42,CAP1,PCBP2 might be closely related to the inhibitory effect of miRNA-451 on RF/6A cell proliferation,while PCYT1 A,MGAT1,TUBB,MCU,SIL1,BID,MSH6 might account for the positive effect of miRNA-451 inhibitor on RF/6A cell growth.PTPN1,as the only protein exhibiting an opposite trend between miRNA-451 mimic and inhibitortransfected cells,was most likely accountable for the inhibition of miRNA-451 mimic on RF/6A cell growth,and the promotion of miRNA-451 inhibitor on RF/6A cell proliferation.CONCLUSION:miRNA-451 overexpression can suppress the growth of RF/6A cells while knockdown of miRNA-451 can promote RF/6A cell viability.Among all DEPs,increased PTPN1 is most likely to account for the negative regulation of miRNA-451 on RF/6A proliferation.miRNA-451 can be a protective factor for neovascular disease of fundus via regulating choroid retinal endothelial cell function.
文摘OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phenazinemethosulfate(PMS)assay,hoechst 33358 staining,annexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomerase I(TOP I)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322DNA relaxation assays and molecular docking.TOPⅠand TOPⅡexpression levels in C6 cells were also determined.RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).It was showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cel s in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠ and Ⅱ.Lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡin molecular docking study.Also,lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠ and TOPⅡ activities,as wel as TOPⅡ expression.
文摘AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017.HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg.Clinical response,relapse rate,change of visual acuity,and other metrics were evaluated.RESULTS:All four patients presented with responses to HUC-MSCs treatment,with three males and one female.The numbers of uveitis attacks per year after the HUCMSCs treatment(0,2,0,0 respectively)all decreased compared with the numbers before the treatment(3,6,4,4 respectively).The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation,and three patients discontinued their oral medicine at the last visit.The best corrected visual acuity(BCVA)of 3 patients was improved to varying degrees,and the BCVA of 1 patient remained at 20/20(Snellen chart)from the first to the last consultation.CONCLUSION:The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.
