Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma

BACKGROUND Cuproptosis has recently been considered a novel form of programmed cell death.To date,long-chain non-coding RNAs(lncRNAs)crucial to the regulation of this process remain unelucidated.AIM To identify lncRNAs linked to cuproptosis in order to estimate patients'prognoses for hepatocellular carcinoma(HCC).METHODS Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma(TCGA-LIHC),a co-expression network of cuproptosis-related genes and lncRNAs was constructed.For HCC prognosis,we developed a cuproptosisrelated lncRNA signature(CupRLSig)using univariate Cox,lasso,and multivariate Cox regression analyses.Kaplan-Meier analysis was used to compare overall survival among high-and low-risk groups stratified by median CupRLSig risk score.Furthermore,comparisons of functional annotation,immune infiltration,somatic mutation,tumor mutation burden(TMB),and pharmacologic options were made between high-and low-risk groups.RESULTS Three hundred and forty-three patients with complete follow-up data were recruited in the analysis.Pearson correlation analysis identified 157 cuproptosis-related lncRNAs related to 14 cuproptosis genes.Next,we divided the TCGA-LIHC sample into a training set and a validation set.In univariate Cox regression analysis,27 LncRNAs with prognostic value were identified in the training set.After lasso regression,the multivariate Cox regression model determined the identified risk equation as follows:Risk score=(0.2659×PICSAR expression)+(0.4374×FOXD2-AS1 expression)+(-0.3467×AP001065.1 expression).The CupRLSig high-risk group was associated with poor overall survival(hazard ratio=1.162,95%CI=1.063-1.270;P<0.001)after the patients were divided into two groups depending upon their median risk score.Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as the validation set.The area under the curve of 0.741 was found to be a better predictor of HCC prognosis as compared to other clinicopathological variables.Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses(median survival of 30 mo vs 102 mo of low-risk combinations with low TMB group).The low-risk group had more activated natural killer cells(NK cells,P=0.032 by Wilcoxon rank sum test)and fewer regulatory T cells(Tregs,P=0.021)infiltration than the high-risk group.This finding could explain why the low-risk group has a better prognosis.Interestingly,when checkpoint gene expression(CD276,CTLA-4,and PDCD-1)and tumor immune dysfunction and rejection(TIDE)scores are considered,highrisk patients may respond better to immunotherapy.Finally,most drugs commonly used in preclinical and clinical systemic therapy for HCC,such as 5-fluorouracil,gemcitabine,paclitaxel,imatinib,sunitinib,rapamycin,and XL-184(cabozantinib),were found to be more efficacious in the low-risk group;erlotinib,an exception,was more efficacious in the high-risk group.CONCLUSION The lncRNA signature,CupRLSig,constructed in this study is valuable in prognostic estimation of HCC.Importantly,CupRLSig also predicts the level of immune infiltration and potential efficacy of tumor immunotherapy.

Effects of early rehabilitation in improvement of paediatric burnt hands function

BACKGROUND Hands are one of the most common burn sites in children.Hypertrophic scar contractures in hands after wound healing result in further reductions in their range of motion(ROM),motility,and fine motor activities.Rehabilitation can improve the function of hands.But the optimal time of rehabilitation intervention is still unclear.Therefore,this study was designed to investigate the effects of early rehabilitation management of paediatric burnt hands and to compare the efficacy between early and later rehabilitation intervention.AIM To investigate the effects of early rehabilitation management of paediatric burnt hands.METHODS A total of 52 children with burnt hands were allocated into the early intervention group(≤1 mo from onset)and a late intervention group(>1 mo from onset)between January 2016 and December 2017.The children received the same rehabilitation programme including skin care,scar massage,passive ROM exercises,active ROM exercises,compression therapy,orthotic devices wearing and game or music therapy.Rehabilitation assessments were performed before and after the rehabilitation treatment.RESULTS In the early intervention group,the ROM of the hands was significantly improved after rehabilitation(P=0.001).But in the late group the effect was not significant statistically(P=0.142).In the early group,38.5%of the patients showed significant improvement,while in the late group,69.2%of the patients showed no significant improvement.The time from onset to posttraumatic rehabilitation(P=0.0007)and length of hospital stay(P=0.003)were negatively correlated with the hand function improvement.The length of rehabilitation stay was positively correlated with the hand function improvement(P=0.005).CONCLUSION These findings suggest that early rehabilitation might show better results in terms of ROM.