Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

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.

Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: a systematic review and Metaanalysis

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.

Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

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.

Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

· 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.

Modified method for fracability evaluation of tight sandstones based on interval transit time

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.

Surgical induced astigmatism correlated with corneal pachymetry and intraocular pressure: transconjunctival sutureless 23-gauge versus 20-gauge sutured vitrectomy in diabetes mellitus

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.

Utilizing dexamethasone intravitreal implant to control postoperative inflammation in refractory uveitis undergoing cataract surgery

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.

Time-dependent borehole stability in hard-brittle shale

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.

Enhancement of exposure and reduction of elimination for paeoniflorin or albiflorin via co-administration with total peony glucosides and hypoxic pharmacokinetics comparison

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.

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery

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.

A BRCA1 Splice Site Variant Responsible for Familial Ovarian Cancer in a Han-Chinese Family

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.

Artificial intelligence can assist with diagnosing retinal vein occlusion

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.

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system

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.

miRNA-451 regulates rhesus choroid-retinal endothelial cell function and proteome profile

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.

Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomeraseⅠ and topoisomeraseⅡ

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.

Human umbilical cord-derived mesenchymal stem cells treatment for refractory uveitis: a case series

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.

Myopia with X-linked retinitis pigmentosa results from a novel gross deletion of RPGR gene

AIM: To identify mutations with whole exome sequencing(WES) in a Chinese X-linked retinitis pigmentosa(XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to Sure Select Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiS eq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation.RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29113 del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp(D10 Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa(RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP.CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.

Multimodal imaging of the carriers of choroideremia and X-linked retinitis pigmentosa

Dear Editor,We are Dr. Zhi-Qing Li and Dr. Jin Yang, from the Neuro-ophthalmology and Medical Retinal Department of Tianjin Medical University Eye Hospital, Tianjin, China. We here present two cases of X-linked inheritable retinal diseases with genetic confirmation of the multimodal imaging findings of the patients, especially the female carriers. This study was approved by the institutional review board of Tianjin Medical University Eye Hospital, and the protocols adhered to the tenets of the Declaration of Helsinki. This letter mainly describes a novel imaging modality, multispectral imaging （MSI）, which appeared to be sensitive in detecting the pattern of chorioretinal degeneration and the tapetal-like reflex.

Pharmacokinetics and pharmacodynamics of cisatracurium in children undergoing cleft lip or cleft palate repair surgery

OBJECTIVE The aim of the study was to characterize the pharmacokinetics(PK) and pharmacodynamics(PD) profile of cisatracurium in 0-2 years and 2-5 years old children patients with cheilopalatognathus,to find if there are some connections between the different muscle relaxation action and different PK procedure.METHODS 14 children patients were divided into two groups,≤2 years and 2-5 years group,venous samples were taken before injection of a 0.15 mg·kg-1 dose of cisatracurium and then at 2,5,10,30,60,90,and 120 min.Cisatracurium plasma concentrations were determined by ultra-performance liquid chromatography/electrospray ionization/triple quadrupole tandem mass spectrometer system(UPLC/MS/MS).The degree of neuromuscular block was measured by train of four(TOF) testing.An indirect PK-PD link model with a sigmoid E max model was established using Win Nonlin software.The model were applied to PK and PD data analysis,respectively.RESULTS The TOF monitor parameters showed that cisatracurium works very quickly,the onset time were(2.64±0.93) min and(2.59 ± 0.90) min for ≤2 years and 2-5 years group respectively.Young children ≤2 years have longer muscle blocking duration time(62.5 ± 6.01 min vs 53.86 ± 12.18 min) and slower recovery index(32.14±7.10 min and 27.43±10.63 min) than those children in group of 2-5 years.More children ≤2 years have postoperative complication than that in 2-5 children.PK parameters showed that there were no statistical differences in blood concentration and pharmacokinetic parameters.While the concentration of cisatracurium in muscle site calculated by using PK/PD model were higher and longer for ≤2 year children than that of 2-5 year children.This means that cisatracurium could stay at high concentration for a longer time in younger children' muscle tissue.CONCLUSION As a result young children tend to have postoperative complications related to slower muscle recovery action and increased concentration in skeletal muscle.So more careful observation and monitor are needed for younger children,our study could be of use in clinical practice for the administration of cisatracurium to children patients.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients

AIM:To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction(MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a Lipi View interferometer.METHODS:Forty cases were randomized into control group A and treatment group B;the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery.The average non-invasive tear film break-up time(NITBUTav),first noninvasive tear film break-up time(NITBUTf),non-invasive measured tear meniscus height(NTMH),meibomian gland loss(MGL),lipid layer thickness(LLT)and partial blink rate(PBR)were measured preoperatively and 1wk,1 and 3mo postoperatively.RESULTS:The NITBUTav values of group A at 1wk(4.38±0.47),1mo(6.76±0.70),and 3mo(7.25±0.68)were significantly lower than those of group B(7.45±0.78,10.46±0.97,and 11.31±0.89;P=0.002,0.004,and 0.001,respectively).The NTMH values of group B at 1wk(0.20±0.01)and 1mo(0.22±0.01)were markedly higher than those of group A(0.15±0.01 and 0.15±0.01;P=0.008 and P<0.001,respectively);however,there was no difference at 3mo.The LLT of group B at 3mo[91.5(76.25-100.00)]significantly exceeded that of group A[65.00(54.50-91.25),P=0.017].No obvious intergroup difference was found in MGL or PBR(P>0.05).CONCLUSION:Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy.Preoperative cleaning,hot compresses,and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.