Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activiti...Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activities of cells.The aim of this study was to investigate the prognostic significance of Cuproptosis-associated lncRNAs in osteosarcoma.Methods:The Gene expression profiling of osteosarcoma samples versus normal samples and corresponding clinical data were downloaded from the public databases UCSC Xena and GTEx,and the cuproptosis gene was obtained from the published literature,the prognostic model of osteosarcoma cuproptosis-related lncRNA was constructed by using coexpression network,minimum absolute contraction and selection algorithm(LASSO)and Cox regression model.Receiver operating characteristic(ROC)curves and nomograms were used to assess the predictive power of the model.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the relationship between osteosarcoma immune cells and function in different risk groups.Results:181 cuproptosis-related lncRNAs were obtained by co-expression analysis of 19 cuproptosis genes collected.Ten lncRNAs were screened out by differential analysis and single-factor Cox analysis.Three cuproptosis-related lncrnas(AC124798.1,AC090152.1,AC090559.1)were screened by Lasso and multivariate Cox regression to construct the prognostic model.Patients were divided into high and low risk groups based on the median risk score.The results of overall survival,risk score distribution and survival status in the lowrisk group were better than those in the high-risk group,and were verified in the internal data.Univariate and multivariate Cox regression analyses showed that risk score was an independent prognostic factor.Nomograms and ROC curves showed that the prognostic model had good predictive ability.The results of ssGSEA suggest that immune cells and function may be inhibited in the high-risk group.Conclusion:The 3 cuproptosis-related lncRNAs may be helpful to guide the prognosis of osteosarcoma patients and provide some theoretical basis for clinical decision.展开更多
BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, rec...BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, reconstitute gut microbiota, and improve cognition in animal models of AD. A Phase 3 trial was conducted to assess efficacy and safety of GV-971. METHODS We conducted a Phase 3, double-blind placebo-controlled trial in patients with mild-to-moderate AD. Participants were randomized to receive placebo or GV-971(900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer′s Disease Assessment Scale(ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician′s Interview-Based Impression of Change(CIBIC+), Alzheimer′s Disease Cooperative Study-Activities of Daily Living(ADCS-ADL) scale, and Neuropsychiatric Inventory(NPI). The effect of GV-971 on the cerebral glucose metabolic rate was examined by 18 Fluorine-FDG PET in a subgroup. Safety and tolerability were monitored. RESULTS 818 participants were randomized, of which 408 were assigned to GV-971 and 410 to placebo. A significant drug-placebo difference in favor of GV-971 was present at each measurement time-point on the ADAS-Cog12. The difference between groups with regard to the change from baseline was-2.15 points(95% confidence interval,-3.07 to-1.23;P<0.0001;effect size 0.531) after 36 weeks treatment. There was a trend towards benefit on CIBIC+(P=0.0588) but not on the ADCS-ADL(P=0.5712), NPI(P=0.8004), or the CMRglu. TEAE incidence77% and 76%, comparable between the two groups. Two deaths occurred in the GV-971 group;these were determined not to be related to GV-971. CONCLUSION GV-971 demonstrated significant efficacy in improving cognition and showed sustained improvement across al observation periods. GV-971 was safe and well tolerated.展开更多
基金National Natural Science Foundation Project of China (No.81860793)Natural Science Foundation Project of Guangxi Province (No.2020JJA140375)Guangxi Graduate Education Innovation Program (No.YCSY2022027)。
文摘Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activities of cells.The aim of this study was to investigate the prognostic significance of Cuproptosis-associated lncRNAs in osteosarcoma.Methods:The Gene expression profiling of osteosarcoma samples versus normal samples and corresponding clinical data were downloaded from the public databases UCSC Xena and GTEx,and the cuproptosis gene was obtained from the published literature,the prognostic model of osteosarcoma cuproptosis-related lncRNA was constructed by using coexpression network,minimum absolute contraction and selection algorithm(LASSO)and Cox regression model.Receiver operating characteristic(ROC)curves and nomograms were used to assess the predictive power of the model.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the relationship between osteosarcoma immune cells and function in different risk groups.Results:181 cuproptosis-related lncRNAs were obtained by co-expression analysis of 19 cuproptosis genes collected.Ten lncRNAs were screened out by differential analysis and single-factor Cox analysis.Three cuproptosis-related lncrnas(AC124798.1,AC090152.1,AC090559.1)were screened by Lasso and multivariate Cox regression to construct the prognostic model.Patients were divided into high and low risk groups based on the median risk score.The results of overall survival,risk score distribution and survival status in the lowrisk group were better than those in the high-risk group,and were verified in the internal data.Univariate and multivariate Cox regression analyses showed that risk score was an independent prognostic factor.Nomograms and ROC curves showed that the prognostic model had good predictive ability.The results of ssGSEA suggest that immune cells and function may be inhibited in the high-risk group.Conclusion:The 3 cuproptosis-related lncRNAs may be helpful to guide the prognosis of osteosarcoma patients and provide some theoretical basis for clinical decision.
文摘BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, reconstitute gut microbiota, and improve cognition in animal models of AD. A Phase 3 trial was conducted to assess efficacy and safety of GV-971. METHODS We conducted a Phase 3, double-blind placebo-controlled trial in patients with mild-to-moderate AD. Participants were randomized to receive placebo or GV-971(900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer′s Disease Assessment Scale(ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician′s Interview-Based Impression of Change(CIBIC+), Alzheimer′s Disease Cooperative Study-Activities of Daily Living(ADCS-ADL) scale, and Neuropsychiatric Inventory(NPI). The effect of GV-971 on the cerebral glucose metabolic rate was examined by 18 Fluorine-FDG PET in a subgroup. Safety and tolerability were monitored. RESULTS 818 participants were randomized, of which 408 were assigned to GV-971 and 410 to placebo. A significant drug-placebo difference in favor of GV-971 was present at each measurement time-point on the ADAS-Cog12. The difference between groups with regard to the change from baseline was-2.15 points(95% confidence interval,-3.07 to-1.23;P<0.0001;effect size 0.531) after 36 weeks treatment. There was a trend towards benefit on CIBIC+(P=0.0588) but not on the ADCS-ADL(P=0.5712), NPI(P=0.8004), or the CMRglu. TEAE incidence77% and 76%, comparable between the two groups. Two deaths occurred in the GV-971 group;these were determined not to be related to GV-971. CONCLUSION GV-971 demonstrated significant efficacy in improving cognition and showed sustained improvement across al observation periods. GV-971 was safe and well tolerated.
