Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

Thermal-contact capacity of one-dimensional attractive Gaudin-Yang model

Tan's contact C is an important quantity measuring the two-body correlations at short distances in a dilute system.Here we make use of the technique of exactly solved models to study the thermal-contact capacity K_(T),i.e.,the derivative of C with respect to temperature in the attractive Gaudin-Yang model.It is found that K_(T) is useful in identifying the low temperature phase diagram,and using the obtained analytical expression of K_(T),we study its critical behavior and the scaling law.Especially,we show K_(T) versus temperature and thus the non-monotonic tendency of C in a tiny interval,for both spin-balanced and imbalanced phases.Such a phenomenon is merely observed in multi-component systems such as SU(2)Fermi gases and spinor bosons,indicating the crossover from the Tomonaga-Luttinger liquid to the spin-coherent liquid.

糖尿病前期成年人综合健康生活方式与糖尿病、心血管疾病、癌症和死亡的关联--来自中、美、英三个国家的四个队列研究

在糖尿病前期人群中,采取健康的生活方式可以有效预防糖尿病的发生。然而,健康生活方式与心血管疾病(cardiovascular disease,CVD)、癌症和死亡的长期风险之间的关联尚未阐明。本文旨在探究糖尿病前期人群中综合健康生活方式与上述多种健康结局之间的关联。本研究纳入的121254名糖尿病前期参与者来自以下4个前瞻性队列,包括中国的东风-同济队列(Dongfeng-Tongji,DFTJ)和开滦研究,英国生物银行(UK Biobank,UKB)和美国的国家健康与营养调查(National Health and Nutrition Examination Survey,NHANES;仅用于死亡分析)。随访期间,共诊断了18333例新发糖尿病病例、10829例新发心血管疾病病例、6926例新发癌症病例和9877例全因死亡。本文基于5个因素(从不吸烟或戒烟超过10年、适量饮酒、充足的体力活动、健康膳食和理想的腰围)构建综合健康生活方式评分。各因素均被分为健康水平(赋1分)和不健康水平(赋0分),评分的加和为综合健康生活方式评分(0~5分)。首先,采用Cox比例风险回归模型计算每个队列中综合健康生活方式评分与健康结局之间的关联;然后,通过随机效应模型的荟萃分析合并各独立队列结果的多变量校正的风险比(hazard ratio,HR)和95%置信区间(confidence interval,CI)。与生活方式最不健康(评分为0~1分)的研究对象相比,生活方式最健康(评分为4~5分)的研究对象具有更低的糖尿病、心血管疾病、癌症和死亡风险,合并的HR(95%CI)分别为0.57(0.48~0.69)、0.67(0.62~0.73)、0.80(0.73~0.88)和0.54(0.42~0.70)。根据研究对象的基线人口学特征和代谢健康状况进行亚组分析的结果也与主要分析的结果一致。总而言之,本研究对来自三个国家的4个队列的合并分析表明,在糖尿病前期人群中,坚持更健康的生活方式与糖尿病及主要并发症的发生风险降低有关。本研究的发现为临床指南和公共卫生政策提供了可靠证据。

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.

Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis

Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.

Effect of Physical Activity on Hospital Service Use and Expenditures of Patients with Coronary Heart Disease: Results from Dongfeng-Tongji Cohort Study in China

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

Protective effects of a novel drug RC28-E blocking both VEGF and FGF2 on early diabetic rat retina

AIM： To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS： The streptozotocin （STZ）-induced diabetic rats were randomly divided into 6 groups： diabetes mellitus （DM） group （saline, 3 μL/eye）; RC28-E at low （0.33 μg/μL, 3 μL）, medium （1 μg/μL, 3 μL）, and high （3 μg/μL, 3 μL） dose groups; vascular endothelial growth factor （VEGF） Trap group （1 μg/μL, 3 μL）; fibroblast growth factor （FGF） Trap group （1 μg/μL, 3 μL）. Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein （GFAP） expression was examined by immunofluorescence. Blood-retinal barrier （BRB） breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy （TEM）. Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay （ELISA）. The retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）, tumor necrosis factor-α （TNF-α）, VEGF and FGF genes was examined by quantitative polymerase chain reaction （qPCR）. RESULTS： TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap （all P〈0.05）, the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap （P〈0.01）. GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina （P〈0.01）. TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs. CONCLUSION： Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy （DR）.

Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats

Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

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.

Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases

Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles(EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique antiinflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.

Therapeutic effects of mesenchymal stem cells administered at later phase of recurrent experimental autoimmune uveitis

AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.

Inhibition of LncRNA Vof-16 expression promotes nerve regeneration and functional recovery after spinal cord injury

Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16(lncRNA Vof-16)was upregulated after spinal cord injury,but its precise role in spinal cord injury remains unclear.Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis.PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus.The overexpression of lncRNA Vof-16 inhibited PC12 cell survival,proliferation,migration,and neurite extension,whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells.Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6,tumor necrosis factor-α,and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells.Furthermore,we established rat models of spinal cord injury using the complete transection at T10.Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury.At 7 days after spinal cord injury,rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension.At 8 weeks after spinal cord injury,rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb.Notably,lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-αand Caspase-3 expression in treated animals.Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends.These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis.The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury.The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University,China.

Hot deformation map and its application of GH4706 alloy

The hot deformation behaviors of GH4706 alloy were investigated using compression tests in a deformation temperature range from 900℃ to 1200℃ with a strain rate range of 0.001-1 s-1. Hot processing maps were developed on the basis of the dynamic material model and compression data. A three-dimensional distribution of power dissipation parameter （η） with strain rate and temperature reveals that η decreases in sensitivity with an increase in strain rate and a decrease in temperature. Microstructure studies show that the grain size of GH4706 alloy increases when η is larger than 0.32, and the microstructure exhibits local deformation when r/is smaller than 0.23. The hot processing map at the strain of 0.7 exposes a domain peak at 7=0.32 for the temperature between 940℃ and 970℃ with the strain rate from 0.015 s-1 to 0.003 s-1, and these are the optimum parameters for hot working.

Effects of annealing treatments on forming performance of zirconium alloys

The effects of annealing treatments(ATs)on the microstructure of Zr-Sn-Nb alloy strips were studied.Based on the characteristics of strips for nuclear fuel assemblies,punching experiments were carried out and the formability of zirconium alloy strips was quantitatively evaluated.The results indicate that the proportions of small-angle grain boundaries of the zirconium alloy under conditions of annealing treatment at 580°C(ATⅠ)and annealing treatment at 620°C(ATⅡ)are 14.3%and 23.2%,respectively,while that of the as-received material is 12.4%.And the forming limit margin fields of the zirconium alloy under ATⅠcan reach 0.43%,while the values of the as-received material and the ATⅡare-0.35%and-2.8%,respectively.The annealing process affects the evolution process of the strip recrystallization texture and the grain size.Moreover,the total texture and pole density are closely related to the degree of anisotropy of the strip.Besides,the small-angle grain boundary affects the strain path and crack expansion of the necking unit during the strip punching process,while the grain size affects the hardening exponent of the material.

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.

Orolingual angioedema during thrombolysis in acute ischemic stroke:A case report

Dear editor,According to the World Health Organization,ischemic heart disease and stroke were the top 2leading causes of death in 2019.[1]In the past few years,intravenous recombinant tissue-type plasminogen activator(rt-PA)has been a significantly effective treatment to increase survival and reduce mortality in acute ischemic stroke.[2,3]However,as the number of patients who receive alteplase is increasing,a rare but potentially life-threatening adverse complication of alteplase administration is becoming more common-orolingual angioedema(OA).[4-6]

Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with macular edema secondary to uveitis

AIM:To assess the correlation between disorganization of the retinal inner layers(DRIL)and best-corrected visual acuity(BCVA)in patients with uveitis and macular edema(UME)who underwent systemic treatment using optical coherence tomography(OCT).METHODS:A retrospective clinical study of 23 patients(30 eyes)with DRIL and 23 patients(31 eyes)without DRIL secondary to UME were included.All patients underwent comprehensive ophthalmic examinations at baseline,3,6,and 12 mo after local and systemic treatment.The OCTbased parameters included foveal center point thickness(FCPT),mean thickness(MT),and diameters of DRIL in horizontal and vertical directions.BCVA and OCT-based parameters were compared between the two groups.The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis.RESULTS:At the initial visit,the mean baseline FCPT was 441.03±128.68μm in the eyes with DRIL and 337.26±99.31μm in the eyes without DRIL(P=0.001).No significant differences were observed in MT(P=0.357).The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61μm at baseline,respectively.There was significant improvement in BCVA and OCT-based parameters at 3,6,and 12 mo in all cases(P<0.001 for each timepoint).In addition,significant differences were detected in BCVA and OCT parameters between eyes with and without DRIL at each time point(P<0.01 for each timepoint).A greater DRIL range at baseline was associated with a worse baseline BCVA(transverse diameter of DRIL:r=0.875,P<0.001;vertical diameter of DRIL:r=0.622,P<0.001).The transverse diameter of baseline DRIL was found to be significantly correlated with the final BCVA(P=0.003).CONCLUSION:The improvement in BCVA is associated with DRIL in patients with UME.DRIL is an easy-todetermine and robust imaging biomarker that could help predict BCVA prognosis in eyes with UME.

Achromatopsia caused by novel missense mutations in the CNGA3 gene

AIMTo identify the genetic defects in a Chinese family with achromatopsia.METHODSA 2.5-year-old boy, who displayed nystagmus, photophobia, and hyperopia since early infancy, was clinically evaluated. To further confirm and localize the causative mutations in this family, targeted region capture and next-generation sequencing of candidate genes, such as CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H were performed using a custom-made capture array.RESULTSSlit-lamp examination showed no specific findings in the anterior segments. The optic discs and maculae were normal on fundoscopy. The unaffected family members reported no ocular complaints. Clinical signs and symptoms were consistent with a clinical impression of autosomal recessive achromatopsia. The results of sequence analysis revealed two novel missense mutations in CNGA3, c.633T&#x0003e;A (p.D211E) and c.1006G&#x0003e;T (p.V336F), with an autosomal recessive mode of inheritance.CONCLUSIONGenetic analysis of a Chinese family confirmed the clinical diagnosis of achromatopsia. Two novel mutations were identified in CNGA3, which extended the mutation spectrum of this disorder.

STUDIES ON THE INTERFACIAL ADHESION BETWEEN FUNCTIONALIZED POLYPROPYLENE AND POLYAMIDE 1010

The interface behavior of polyamide 1010 (PA1010) and polypropylene (PP) was studied. In order to improve their interfacial adhesion, functional PP was prepared by means of grafting glycidyl methacrylate (GMA) on PP main chains and used instead of plain PP. Several technological characterizations were performed here on their interfaces. ESCA was used to confirm that some kind of reaction occurred between end groups of PA1010 and epoxy species of PP-g-GMA. The peel test was adopted to measure interfacial adhesion. It was found that the fracture energy of interfaces between PA1010 and PP-g-GMA was dramatically increased with the content of GMA. Their interfaces were observed as being blurred by using SEM and TEM and a crack that could be seen in the case of the interfaces of the PA1010 and the plain PP disappeared.

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.