Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Proliferative vitreoretinopathy and its relationship with inflammatory serum biomarkers

AIM:To analyze if a relationship between levels ofinflammatory serum biomarkers and severity of primaryproliferative vitreoretinopathy(PVR)exists.METHODS:A retrospective case-control study.Thehealthy adult patients with rhegmatogenous retinaldetachment and primary PVR were included in the PVRgroup.For the control group,healthy adults who underwentcataract surgery were included.The grade of PVR wasclassified according to the Retinal Society TerminologyCommittee.Blood samples were obtained before surgery,and processed in MYTHIC 18.Measures of interest wereneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyteratio(PLR),and lymphocyte-to-monocyte ratio(LMR),thetime between the decrease in visual acuity and surgery,PVRgrade,type of surgery,final best corrected visual acuity,andrate of re-detachment.RESULTS:Totally 240 patients were included,120 ineach group,79(65.8%)and 56(46.7%)were male in thePVR and control group,respectively.PVR A had greaterlevels of monocytes(0.28±0.18 vs 0.12±0.32,P=0.002),neutrophils(4.59±1.51 vs 3.92±1.27,P=0.006),and LMR(9.32±4.42 vs 7.43±3.90,P=0.01).PVR B had a greatermonocyte count(0.30±0.13 vs 0.12±0.32,P=0.001),andPVR C demonstrated higher levels in monocytes(0.27±0.12vs 0.12±0.32,P=0.004),neutrophils(4.39±1.13 vs3.92±1.27,P=0.004),and LMR(9.63±3.24 vs 7.43±3.90,P=0.002)compared to control,respectively.An LMR cut-offvalue of 9.38 predicted PVR with a sensibility of 54.2%andspecificity of 77.5%and NLR cut-off of 1.70 predicted PVRwith a sensibility of 62%and specificity of 54.2%.CONCLUSION:Patients with primary PVR demonstrategreater neutrophil,monocyte,and LMR levels than thecontrol group.Cut-off values obtained from ratios could beuseful in a clinical setting when no posterior view of thefundus is possible due to media opacity.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

AIM:To analyze the distribution of fibrovascular proliferative membranes(FVPMs)in proliferative diabetic retinopathy(PDR)patients that treated with pars plana vitrectomy(PPV),and to evaluate the outcomes separately.METHODS:This was a retrospective and cross-sectional study.Consecutive 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April 2020.According to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type group.All patients were followed up for over one year.General characteristics,operation-related variables,postoperative parameters and complications were recorded.RESULTS:Among 103 eyes recruited,the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different(both P<0.01),with 95(92.23%)FVPMs located in the nasal quadrants,and 74(71.84%)in the inferior.The eyes with a central FVPM required the longest operation time,with silicon oil used in most patients,generally combined with tractional retinal detachment(RD)and rhegmatogenous RD,the worst postoperative bestcorrected visual acuity(BCVA)and the highest rates of recurrent RD(all P<0.05).FVPM type,age of onset diabetes mellitus,preoperative BCVA,and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement(all P<0.05).Compared with the central type group,the arcade type group had higher rates of BCVA improvement.CONCLUSION:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels.Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Study on crustal thickness and the prediction of prolific depressions:the Bohai Basin as an example

The deep crustal structure is closely related to oil and gas reserves.Predicting the oil and gas enrichment of depressions based on the Moho depth and crustal thickness is a promising research topic with significant implications for guiding exploration in petroliferous basins.In this study,seismic data were used as a constraint on the use of satellite gravity anomaly inversion to obtain the distribution of Moho depth and crustal thickness in the Bohai Basin.Stretching factors were calculated to analyze the differential distribution of deep crustal structural activity.Four indicators,including the minimum Moho depth,minimum crustal thickness,sum of Moho stretching factors,and sum of crustal stretching factors,were selected.Principal component analysis was applied to reduce the dimensionality of the multi-indicator system and obtain an oil and gas enrichment score for quantitative prediction of favorable prolific depressions.The deviation between the inverted Moho depth and seismic constraints was small;thus,the data effectively reflect the variations in the characteristics of each depression.The analysis revealed significant statistical features related to the minimum Moho depth/crustal thickness and the sum of Moho/crustal stretching factors associated with prolific depressions.Based on the oil and gas enrichment score,the depressions were classified into four categories related to their different deep crustal structural characteristics.Highly active ClassⅠ,ClassⅡ,and ClassⅢdepressions are predicted to be favorable prolific depressions.This study expands the research on quantitatively predicting favorable prolific depressions in the Bohai Basin using the deep crustal structure and can contribute to reducing production costs and improving exploration efficiency in future explorations.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract:a randomized clinical trial

●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.

Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness(SFCT)in proliferative diabetic retinopathy(PDR).AIM To investigate the relationship between the SFCT and age in Chinese patients with PDR.METHODS This was a cross-sectional retrospective study.The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR.Contralateral eyes that met the criteria were included in the study.All necessary laboratory tests were performed at the time of admission.Central macular thickness(CMT)and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography.CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software.RESULTS The final analysis included a total of 234 individuals with PDR.The average age was 55.60 years old±10.03 years old,and 57.69%of the population was male.Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR[β=-2.44,95%confidence interval(95%CI):-3.46 to-1.42;P<0.0001].In the fully adjusted model,the correlation between SFCT and age remained steady(β=-1.68,95%CI:-2.97 to-0.39;P=0.0117).Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear,with an inflection point at 54 years of age.CONCLUSION Our findings suggest that age is a key determinant of choroidal thickness.The non-linear link between SFCT and age in PDR patients should be taken into account.

Nomogram for predicting non-proliferative vitreoretinopathy probability after vitrectomy in eyes with rhegmatogenous retinal detachment

AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

Chronic hypotony management using endoscopy-assisted vitrectomy after severe ocular trauma or vitrectomy

·AIM: To report outcomes of endoscopy-assisted vitrectomy(EAV) in patients with chronic hypotony following severe ocular trauma or vitrectomy.·METHODS: This was a retrospective, noncomparative case series. Ciliary bodies were evaluated using ultrasound biomicroscopy pre-operatively and direct visualisation intraoperatively. All selected individuals(seven patients/seven eyes) underwent EAV. Removal of ciliary membrane and traction, gas/silicone oil tamponade(GT/SOT), and scleral buckling(SB) were performed in selected eyes. Outcome measurements mainly included intraocular pressure(IOP) and best-corrected visual acuity(BCVA).·RESULTS: Seven eyes from 7 male aphakic patients with a mean age of 45(range, 20-68)y were included in this study;the average follow-up time was 12(9-15)mo. GT was performed in 2 eyes;membrane peeling(MP) and SOT in 2 eyes;and MP, SOT, and SB in 3 eyes. The mean preand post-operative IOP were 4.5(range, 4.0±0.11 to 4.8±0.2) mm Hg and 9.9(range, 5.6±0.17 to 12.1±0.2) mm Hg at 52wk(12mo), respectively. BCVA improved in six eyes;one eye still showed light perception, and no bulbi phthisis was observed.·CONCLUSION: Endoscopy offers improved judgment and recognition and has an improved prognosis for chronic hypotony. Therefore, endoscopy can be an effective and promising operative technique for chronic traumatic hypotony management.

Preparation and application of a novel monoclonal antibody specific for the heat shock protein 60 of Lawsonia intracellularis

Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.

Cux1^(+)proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics

Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

Surgical treatment for proliferative diabetic retinopathy with ocular albinism

Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase activities and melanin biosynthesis resulting in little or no production of the pigment melanin。

Risk factors and prognosis of pediatric rhegmatogenous retinal detachment in Egypt:a university hospital based study

AIM:To study and compare the predisposing factors and clinical features of pediatric,adult,and elderly rhegmatogenous retinal detachment(RRD).METHODS:This is an observational analytic crosssectional study in which patients with RRD admitted for surgery during 6mo period were divided into 3 age groups:pediatric(<18y),adult(18-60y),and elderly(>60y).Patients’demographic data,clinical features,RRD predisposing factors/features including myopia(axial length≥26.5 mm),aphakia/pseudophakia,blunt trauma,peripheral retinal degenerations,history of RRD in the fellow eye,and surgical interventions/findings were recorded and analyzed.RESULTS:Totally 142 patients(142 eyes)were studied:26(18.31%)pediatrics,86(60.56%)adults,and 30(21.13%)elderly.Elderly patients had a significantly higher intraocular pressures and cataracts compared to the other 2 groups(P=0.04).The RRD extent was larger in pediatric group(mostly 4 quadrants)compared to adults and elderly(mostly 2 quadrants),but it was not statistically insignificant(P=0.242).There were not statistically significantly differences in proliferative vitreoretinopathy(PVR)rate,posterior vitreous detachment(PVD)rate,number,site,shape,and size of breaks in three groups.All three groups had macular detachment in all eyes.Myopia and peripheral retinal degenerations were found to be more significant in adults(P=0.049,P=0.035,respectively),while blunt trauma was higher but insignificant in pediatric eyes(P=0.052).Pars plana vitrectomy(PPV)with silicone oil as a tamponade was the most used surgery in all groups.CONCLUSION:There are no significant difference in PVR rate in pediatric eyes but a significant higher rate of total RRD.Blunt trauma is more frequent in pediatrics eyes while myopia and/or peripheral retinal degenerations are more frequent in older ages.The rate of PPV as a choice for surgery is similar among all age groups.

Predictive factors of epiretinal membrane in complicated rhegmatogenous retinal detachment tamponaded with silicone oil

AIM:To determine the incidence and predictive factors for epiretinal membrane(ERM)formation in eyes with complicated primary rhegmatogenous retinal detachment(RRD)tamponaded with silicone oil(SO).METHODS:This retrospective case-control study included 141 consecutive patients with(51 eyes)and without(90 eyes)ERM formation after primary pars plana vitrectomy(PPV)and SO tamponade for complicated RRD.The risk factors for ERM were assessed using logistic regression analysis.RESULTS:The prevalence of postoperative ERM was 36.2%(51/141).Multivariate logistic regression analysis showed that the risk factors for ERM in SO-tamponaded eyes included preoperative proliferative vitreoretinopathy[PVR;odds ratio(OR),2.578;95%confidence interval(CI)1.580–4.205,P<0.001],preoperative choroidal detachment(OR,4.454;95%CI 1.369–14.498,P=0.013),and photocoagulation energy(OR,2.700;95%CI 1.047–6.962,P=0.040).The duration of the preoperative symptoms,intraocular SO tamponade time,giant retinal tear,preoperative vitreous hemorrhage,preoperative bestcorrected visual acuity,number of breaks,quadrants of RRD,axial length,and photocoagulation points were not predictive factors for ERM formation.CONCLUSION:Preoperative PVR,choroidal detachment,and photocoagulation energy are risk factors of ERM formation after complicated RRD repair.Better ophthalmic care as well as patient education are necessary for such patients with risk factors.

Cerebral proliferative angiopathy in pediatric age presenting as neurological disorders:A case report

BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.