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BACKGROUND: Leptomeningeal metastases (LM) were rare in gastric cancer (GC), and GC patients with LM (GCLM) generally suffer from poor prognosis. Nevertheless, the clinical utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) was underinvestigated in GCLM. METHODS: We retrospectively studied 15 GCLM patients, and all patients had paired primary tumor tissue samples and post-LM CSF samples while 5 patients also had post-LM plasma samples. All samples were analyzed using next-generation sequencing (NGS), and the molecular and clinical features were correlated with clinical outcomes. RESULTS: CSF had higher mutation allele frequency (P = 0.015), more somatic mutations (P = 0.032), and more copy-number variations (P < 0.001) than tumor or plasma samples. Multiple genetic alterations and aberrant signal pathways were enriched in post-LM CSF, including CCNE1 amplification and cell cycle-related genes, and CCNE1 amplification was significantly associated with patients' overall survival (P = 0.0062). More potential LM progression-related markers were detected in CSF samples than in tumor samples, including PREX2 mutation (P = 0.014), IGF1R mutation (P = 0.034), AR mutation (P = 0.038), SMARCB1 deletion (P < 0.001), SMAD4 deletion (P = 0.0034), and TGF-beta pathway aberration (P = 0.0038). Additionally, improvement in intracranial pressure (P < 0.001), improvement in CSF cytology (P = 0.0038), and relatively low levels of CSF ctDNA (P = 0.0098) were significantly associated with better PFS. Lastly, we reported a GCLM case whose CSF ctDNA dynamic changes were well correlated with his clinical assessment. CONCLUSIONS: CSF ctDNA could more sensitively detect molecular markers and metastasis-related mechanisms than tumor tissues in GCLM patients, and our study sheds light on utilizing CSF ctDNA in prognostic estimation and clinical assessment in GCLM.
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Ácidos Nucleicos Livres , Neoplasias Pulmonares , Neoplasias Meníngeas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Estudos Retrospectivos , Neoplasias Meníngeas/genética , Mutação/genética , Genômica , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/patologiaRESUMO
OBJECTIVES: Frequent gout attacks in the initial introduction of urate-lowering therapy (ULT) are significant causes of poor drug adherence and ULT discontinuation. Initial low-dose urate-lowering drugs may be effective in reducing gout flares, however, robust evidence is sparse. The aim of this study was therefore to assess the association of initial dose urate-lowering drugs with gout flares in adult males with gout during the initial introduction of ULT. METHODS: This cohort study obtained data on consecutive gout patients from a single-center gout cohort study from August 2017 to October 2020. A standard questionnaire was applied to collect demographic and clinical information, and biochemical parameters were tested on the same day. The primary end point was to estimate the association of initial dose febuxostat with gout flares, using cox hazard models with inverse probability of treatment weighting (IPTW). RESULTS: A total of 582 gout patients were included in this study. During 6-week follow-up, 71 (12.2%) patients suffered gout flares. In the main analysis using cox hazard models with IPTW, compared with colchicine prophylaxis, initial low-dose febuxostat alone had no statistical significance with the increased risk of gout flares [hazard ratio (HR), 1.26; 95% CI, 0.58-2.72], while initial high-dose febuxostat was associated with an increased risk of gout flares (HR, 3.08; 95% CI, 1.34-7.07). CONCLUSIONS: This observational study demonstrated that initial low-dose febuxostat was equally effective in preventing gout flares as colchicine prophylaxis, while initial high-dose febuxostat alone was associated with an increased risk of gout flares.
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BACKGROUND: The current radiologic criteria for assessing intraoperative superior mesenteric-portal vein (SMPV) involvement (i.e., presence of tumor-SMPV contact >180° or venous deformity) in pancreatic ductal adenocarcinoma (PDAC) are highly specific but insufficiently sensitive. Therefore, development of improved markers for a more accurate prediction is essential. This study aimed to develop a risk score model to estimate SMPV involvement in PDAC using radiomics analysis of computed tomography (CT) images. METHODS: Data from two institution-based cohorts of PDAC patients undergoing preoperative CT scans were used to develop (n = 173) and validate (n = 156) a radiomics-based risk score of SMPV involvement using clinical and imaging variables. A radiomics signature was developed based on 2436 radiomic features extracted from the semi-automatic three-dimensional segmentation ofn CT images. The SMPV involvement risk score was built using multivariate logistic regression and compared with the current radiologic criteria. RESULTS: The study surgically identified SMPV involvement in 59 (34.1%) and 57(36.5 %) patients with PDAC in the development and validation cohorts, respectively. A 12-feature-based radiomics signature achieved areas under receiver operating characteristics curves (AUCs) of 0.89 or greater for estimating SMPV involvement. Multivariate regression identified the radiomics signature and SMPV deformity as associated with SMPV involvement. The risk score model had significantly improved AUC (0.928 vs. 0.768; P < 0.001) and sensitivity (84.2% vs. 66.7%; P = 0.025) in the radiologic evaluation. CONCLUSIONS: The novel risk score in this study, combining radiomics signature and venous deformity, demonstrated promising performance for estimating SMPV involvement preoperatively for patients with PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Veia Porta/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Tomografia Computadorizada por Raios X/métodos , Fatores de Risco , Neoplasias PancreáticasRESUMO
Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.
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Vacinas contra COVID-19 , COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunogenicidade da Vacina , Estudos Prospectivos , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
OBJECTIVE: Iron depletion may be a novel therapeutic strategy for cancer. This study aimed to assess the inhibition effects of deferasirox (DFX), an oral iron chelator, on cervical cancer. METHODS: In this study, we performed immunohistochemical analysis, enzyme-linked immunoassay, cell viability and invasive ability assay, cell cycle and apoptosis analysis, protein expression investigation, molecular mechanism investigation, and in vivo murine xenograft model to evaluate the impact of DFX on cervical cancer. RESULTS: The cervical cancer cell lines viability decreased and cell apoptosis was induced after DFX incubation. Additionally, DFX promoted cell cycle arrest by regulating the expression of cell cycle regulators cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) in cervical cancer cell lines. DFX also decreased cell invasion by upregulating the expression of NDRG1 and downregulating c-Myc. The activation of Akt and the MEK/ERK signaling pathway was inhibited by DFX. DFX also significantly suppressed xenograft tumor growth, decreased the levels of ferritin in serum and tumor tissue, reduced iron deposits and reactive oxygen species (ROS) levels in xenografts of DFX-treated group compared with the control group, with no serious side effects. CONCLUSION: Present study demonstrated the inhibitory effect of DFX against cervical cancer, and provided a potential therapeutic agent for cervical cancer.
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Quelantes de Ferro , Neoplasias do Colo do Útero , Animais , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Deferasirox/farmacologia , Feminino , Humanos , Ferro , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Camundongos , Triazóis/farmacologia , Triazóis/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.
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Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19 , Imunogenicidade da Vacina/imunologia , Hepatopatia Gordurosa não Alcoólica , Vacinação , Vacinas de Produtos Inativados , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , China/epidemiologia , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Vacinação/métodos , Vacinação/estatística & dados numéricos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversosRESUMO
A novel approach to solve optimal control problems dealing simultaneously with fractional differential equations and time delay is proposed in this work. More precisely, a set of global radial basis functions are firstly used to approximate the states and control variables in the problem. Then, a collocation method is applied to convert the time-delay fractional optimal control problem to a nonlinear programming one. By solving the resulting challenge, the unknown coefficients of the original one will be finally obtained. In this way, the proposed strategy introduces a very tunable framework for direct trajectory optimization, according to the discretization procedure and the range of arbitrary nodes. The algorithm's performance has been analyzed for several non-trivial examples, and the obtained results have shown that this scheme is more accurate, robust, and efficient than most previous methods.
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Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.
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Linfócitos T CD8-Positivos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , RNA-Seq/métodos , Biomarcadores Tumorais/genética , Análise de Célula Única/métodos , Regulação Neoplásica da Expressão Gênica , Análise da Expressão Gênica de Célula ÚnicaRESUMO
The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin ß4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma.
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As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Microambiente Tumoral , Carcinogênese , IntegrinasRESUMO
Introduction: It is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC. Methods: We obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts. Results: High riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.
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Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Neoplasias Ovarianas/genética , Nomogramas , Linfócitos T CD4-Positivos , Calibragem , Microambiente Tumoral/genéticaRESUMO
[This corrects the article DOI: 10.3389/fonc.2022.986867.].
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We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002-1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003-1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006-1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009-1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029-1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.
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Encefalopatia Hepática , Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Encefalopatia Hepática/etiologia , Amônia , Creatinina , Nomogramas , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Retrospectivos , Hipertensão Portal/etiologia , Hipertensão Portal/cirurgia , Verde de IndocianinaRESUMO
BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.
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Gosserrelina , Neoplasias da Próstata , Humanos , Masculino , Antineoplásicos Hormonais/uso terapêutico , População do Leste Asiático , Hormônio Liberador de Gonadotropina/agonistas , Gosserrelina/uso terapêutico , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , TestosteronaRESUMO
Oxygen carriers can significantly enhance the performance of chemical looping combustion at low energy-cost CO2 capture. Based on the density functional theory, a microscopic model of the metal Fe, Al-doped NiO oxygen carrier was established. The results indicate that the intermediate state energy and the reaction energy reduce due to electronic interaction of the Al-doped surface. With the progress of the reaction, the NiO-Al surface promotes the oxidation process of CO, indicating that the activity of the NiO surface enhanced, which is attributed to the electronic and steric effects of the Al-O structure. For the decomposition of CO on the OC surface, doping with other atoms is beneficial to suppress the carbon deposition, which is related to the steric hindrance caused by doping with other atoms. Besides, doping with iron and aluminum atoms is more conducive to the movement of OC bulk crystal lattice oxygen to the surface, thereby promoting subsequent reactions. Therefore, it is feasible to improve the reactivity of the Ni-based OC by doping metal Al, and its modification effect is closely related to the characteristics of the components.
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Epithelial ovarian cancer (EOC) is the leading killer among women with gynecologic malignancies. Homologous recombination deficiency (HRD) has attracted increasing attention due to its significant implication in the prediction of prognosis and response to treatments. In addition to the germline and somatic mutations of homologous recombination (HR) repair genes, to widely and deeply understand the molecular characteristics of HRD, we sought to screen the long non-coding RNAs (lncRNAs) with regard to HR repair genes and to establish a prognostic risk model for EOC. Herein, we retrieved the transcriptome data from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA) databases. HR-related lncRNAs (HRRlncRNAs) associated with prognosis were identified by co-expression and univariate Cox regression analyses. The least absolute shrinkage and selection operator (LASSO) and multivariate stepwise Cox regression were performed to construct an HRRlncRNA risk model containing AC138904.1, AP001001.1, AL603832.1, AC138932.1, and AC040169.1. Next, Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), nomogram, calibration, and DCA curves were made to verify and evaluate the model. Gene set enrichment analysis (GSEA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in the risk groups were also analyzed. The calibration plots showed a good concordance with the prognosis prediction. ROCs of 1-, 3-, and 5-year survival confirmed the well-predictive efficacy of this model in EOC. The risk score was used to divide the patients into high-risk and low-risk subgroups. The low-risk group patients tended to exhibit a lower immune infiltration status and a higher HRD score. Furthermore, consensus clustering analysis was employed to divide patients with EOC into three clusters based on the expression of the five HRRlncRNAs, which exhibited a significant difference in checkpoints' expression levels and the tumor microenvironment (TME) status. Taken together, the results of this project supported that the five HRRlncRNA models might function as a biomarker and prognostic indicator with respect to predicting the PARP inhibitor and immune treatment in EOC.
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BACKGROUND: Acute kidney injury (AKI) is a common complication, especially among postoperative critically ill patients. Early identification of AKI is essential for reducing mortality. METHODS: Multicenter data were used to develop an AKI prediction model for critically ill postoperative patients. A total of 1731 patients admitted to intensive care units (ICUs) were divided into a development set (n=1196) and a validation set (n=535) according to the principle of 7:3 randomization. Multivariate logistic regression analysis was performed on the predictors identified by univariate analysis, and a nomogram was created based on the predictors. The area under the receiver operating characteristic curve (AUROC) was used to assess the discrimination of the model. Calibration curves were generated, and the Hosmer-Lemeshow (HL) goodness of fit test was carried out. Decision curve analysis (DCA) was performed to assess the net clinical benefit. RESULTS: The final model included 7 predictors: age, emergency surgery, abnormal basal creatinine level (BCr), chronic kidney disease (CKD), use of nephrotoxic drugs, diuretic use, and the Sequential Organ Failure Assessment (SOFA) score. A nomogram was drawn based on the predictors. The AUROC of the model in the development set was 0.725 (95% confidence interval (CI): 0.696-0.754). In the validation set, the AUROC was 0.706 (95% CI: 0.656-0.744). The model showed good discrimination (>70%) in both sets, and the HL test indicated that the model fit was good (P>0.05). DCA showed that our model is clinically useful. CONCLUSION: The novel prediction model can be used to identify high-risk postoperative patients and provide a scientific and effective basis for clinicians to identify AKI early with a nomogram.
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Objective: To develop a nomogram for predicting post-hepatectomy liver failure (PHLF) in patients with resectable hepatocellular carcinoma (HCC) based on portal hypertension, the extent of resection, ALT, total bilirubin, and platelet count. Methods: Patients with HCC hospitalized from January 2015 to December 2020 were included in a retrospective cohort study. 595 HCC patients were divided into a training cohort (n=416) and a validation cohort (n=179) by random sampling. Univariate and multivariable analyses were performed to identify the independent variables to predict PHLF. The nomogram models for predicting the overall risk of PHLF and the risk of PHLF B+C were constructed based on the independent variables. Comparisons were made by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) with traditional models, such as FIB-4 score, APRI score, CP class (Child-Pugh), MELD score (model of end-stage liver disease), and ALBI score (albumin-bilirubin) to analyze the accuracy and superiority of the nomogram. Results: We discovered that portal hypertension (yes vs no) (OR=1.677,95% CI:1.817-4.083, p=0.002), the extent of liver resection (OR=1.872,95% CI:3.937-47.096, p=0.001), ALT (OR=1.003,95% CI:1.003-1.016, P=0.003), total bilirubin (OR=1.036,95% CI:1.031-1.184, p=0.005), and platelet count (OR= 1.004, 95% CI:0.982-0.998, p=0.020) were independent risk factors for PHLF using multifactorial analysis. The nomogram models were constructed using well-fit calibration curves for each of these five covariates. When compared to the FIB4, ALBI, MELD, and CP score, our nomogram models have a better predictive value for predicting the overall risk of PHLF or the risk of PHLF B+C. The validation cohort's results were consistent. DCA also confirmed the conclusion. Conclusion: Our models, in the form of static nomogram or web application, were developed to predict PHLF overall risk and PHLF B+C risk in patients with HCC, with a high prediction sensitivity and specificity performance than other commonly used scoring systems.