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China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.
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Dióxido de Carbono , Pegada de Carbono , Aço , China , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , Metalurgia , Monitoramento Ambiental , Indústrias , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/prevenção & controleRESUMO
BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Neoplasias Gastrointestinais , Neutropenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Neoplasias Gastrointestinais/tratamento farmacológico , Neutropenia/prevenção & controle , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Adulto , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Irinotecano/uso terapêutico , Irinotecano/efeitos adversos , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , China/epidemiologiaRESUMO
Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.
Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.
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Objective: To discuss the effectiveness of breast reconstruction with dual plane prosthesis implantation or anterior pectoralis prosthesis implantation under endoscopy by using prospective comparative study, in order to provide a reference for clinical surgical selection. Methods: A total of 54 female patients with breast cancer admitted between January 2023 and December 2023 and met the selection criteria were selected as research subjects. According to the random number table, 54 patients were divided into trial group and control group with 27 cases in each. The patients in the trial group and control group were treated with dual plane prosthesis implantation and anterior pectoralis prosthesis implantation for breast reconstruction after glandular resection under endoscopy, respectively. There was no significant difference between the two groups ( P>0.05) in the terms of age, body mass index, affected side, breast clinical stages, molecular typing, disease duration, breast volume of healthy side, breast ptosis of affected side, and preoperative Breast-Q score (social mental health, sexual health, breast satisfaction, chest somatic health). The operation-related indicators (operation time, total volume of drainage within 7 days after operation, extubation time, and hospital stay), occurrence of complications, breast reconstruction efficacy related indicators (transverse and longitudinal distance difference), and the pre- and post-operative differences (change values) of Breast-Q scores for each item were compared between the two groups. Results: There was no significant difference in operation time, total volume of drainage within 7 days after operation, extubation time, and hospital stay between the two groups ( P>0.05). All patients of the two groups were followed up 3-12 months (mean, 6.3 months). Three patients (11.11%) in trial group and 5 patients (18.52%) in control group experienced complications, and there was no significant difference in the occurrence of complications ( P>0.05). At 7 days after operation, the transverse and longitudinal distance differences were significantly less in trial group than in control group ( P<0.05). The Breast-Q scores of the two groups at 7 days after operation were significantly higher in all items than those before operation ( P<0.05), but there was no significant difference in all change values between the two groups ( P>0.05). Conclusion: For patients with breast cancer, comparison of breast reconstruction with anterior pectoralis prosthesis implantation, breast reconstruction with dual plane prosthesis implantation has better breast reconstruction effectiveness and higher safety.
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Implante Mamário , Implantes de Mama , Neoplasias da Mama , Endoscopia , Mamoplastia , Músculos Peitorais , Humanos , Feminino , Endoscopia/métodos , Estudos Prospectivos , Neoplasias da Mama/cirurgia , Implante Mamário/métodos , Músculos Peitorais/cirurgia , Mamoplastia/métodos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Satisfação do Paciente , Mastectomia/métodos , Pessoa de Meia-IdadeAssuntos
Fundo Gástrico , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Fundo Gástrico/cirurgia , Ligadura/métodos , Gastroscopia/métodos , Feminino , Masculino , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Pessoa de Meia-Idade , Suturas , Técnicas de SuturaRESUMO
BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignant tumor of the bile duct, with a poor prognosis and a high mortality rate. Currently, there is a lack of effective targeted treatment methods and reliable biomarkers for prognosis. METHODS: We downloaded RNA-seq and clinical data of CCA from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as training and test sets. The apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB) database. We used univariate/multivariate Cox regression and Lasso regression analyses to construct a riskscore prognostic model. Based on the median riskscore, we clustered the patients into high-risk (HR) and low-risk (LR) groups. We carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in HR and LR groups. The single sample gene set enrichment analysis (ssGSEA) was employed to analyze the immune infiltration of the HR and LR groups. The CellMiner database was utilized to predict drugs and perform molecular docking on drugs and target proteins. RESULTS: We identified 8 genes with prognostic significance to construct a prognostic model. Results of GO and KEGG demonstrated that DEGs were mainly enriched in biological functions such as fatty acid metabolic processes and pathways such as the cAMP signaling pathway. Results of ssGSEA uncovered that immune cells such as DCs and Macrophages in the HR group, as well as immune functions such as Check-point and Parainflammation, were considerably higher than those in the LR group. Drug sensitivity prediction and results of molecular docking revealed that Rigosertib targeted the prognostic genes MAP3K1. HYPOTHEMYCIN and AMG900 effectively targeted JUN. CONCLUSION: Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.
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BACKGROUND: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. METHODS: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). RESULTS: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. CONCLUSION: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.
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Disfunção Cognitiva , Modelos Animais de Doenças , Lipopolissacarídeos , MicroRNAs , NF-kappa B , Pirrolidinas , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório , Tiocarbamatos , Animais , MicroRNAs/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Ratos , Tiocarbamatos/farmacologia , Tiocarbamatos/uso terapêutico , NF-kappa B/metabolismo , Masculino , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
Background: Cataract surgery and laser peripheral iridotomy (LPI) are effective approaches for preventing primary angle closure diseases (PACDs), as well as acute primary angle closure (APAC). Due to the development of population screening and increases in cataract surgery rates, this study aimed to examine trends in the admission rates of PACD among the urban population in China. Methods: This cross-sectional study examined patients who were admitted to a hospital for PACD, and who underwent cataract surgery or LPI operations. The data were obtained from the Yinzhou Regional Health Information Platform (YRHIP) from 2011 to 2021. The annual rates of PACD and APAC admissions, cataract surgery and LPI were analyzed, with the number of cases used as numerators and the annual resident population in Yinzhou district used as denominators. Results: A total of 2,979 patients with PACD admissions, 1,023 patients with APAC admissions, 53,635 patients who underwent cataract surgery and 16,450 patients who underwent LPI were included. The number of annual admissions for PACD gradually increased from 22 cases (1.6/100000) in 2011 to 387 cases (30.8/100000) in 2016, after which it decreased to 232 cases (16.2/100000) in 2019 and then increased to 505 cases (30.6/100000) in 2021. The number of cataract surgeries gradually increased from 1728 (127.7/100000) in 2011 to 7002 (424.9/100000) in 2021. Similarly, the number of LPI gradually increased from 109 (8.0/100000) in 2011 to 3704 (224.8/100000) in 2021. Conclusion: The admission rates of PACD for the urban population in China have declined in recent years after a long increasing trend in the rates of cataract surgery and LPI. However, it increased rapidly during the COVID-19 epidemic. The national health database should be further utilized to investigate temporal trends in the prevalence of PACD.
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Extração de Catarata , Glaucoma de Ângulo Fechado , População Urbana , Humanos , Glaucoma de Ângulo Fechado/epidemiologia , Glaucoma de Ângulo Fechado/cirurgia , China/epidemiologia , Estudos Transversais , Masculino , Feminino , Idoso , Extração de Catarata/estatística & dados numéricos , Extração de Catarata/tendências , Pessoa de Meia-Idade , População Urbana/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Idoso de 80 Anos ou mais , Adulto , Admissão do Paciente/estatística & dados numéricos , Admissão do Paciente/tendênciasRESUMO
BACKGROUND: Our previous studies have shown that lipoxin A4 (LXA4) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology. OBJECTIVE: By analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren-Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA4 on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA. METHODS: The association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture. We overexpressed and knocked down LPAR3 in vitro to explore its potential mechanism in FLSs. A rat model of monosodium iodoacetate (MIA)-induced KOA was constructed and intervened with moderate-intensity treadmill exercise and intraperitoneal injection of PHTPP to investigate the effects of the LXA4 intracellular receptor ESR2 on exercise therapy. RESULTS: ESR2, LPAR3, and GPX4 levels in the synovium decreased with increasing KL grade. After LXA4 intervention in the co-culture system, GPX4, LPAR3, and ESR2 were upregulated in FLSs, collagen II was upregulated in chondrocytes, and MMP3 and ADAM9 were downregulated. LPAR3 overexpression upregulated the expression of GPX4, Nrf2, and SOD1 in FLSs, while downregulating the expression of MMP13 and MMP3; LPAR3 knockdown reversed these changes. Moderate-intensity platform training improved the behavioral manifestations of pain in KOA rats, whereas PHTPP treatment partially reversed the improvement in synovial and cartilage pathologies induced by platform training. CONCLUSION: LXA4 inhibited FLSs ferroptosis by activating the ESR2/LPAR3/Nrf2 axis, thereby alleviating the pain and pathological progression of KOA. This study brings a new target for the treatment of KOA and also leads to a deeper understanding of the potential mechanisms of exercise therapy for KOA.
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Ferroptose , Lipoxinas , Fator 2 Relacionado a NF-E2 , Osteoartrite do Joelho , Sinoviócitos , Animais , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/patologia , Ratos , Lipoxinas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sinoviócitos/metabolismo , Humanos , Masculino , Modelos Animais de Doenças , Fibroblastos/metabolismo , Transdução de Sinais , Ratos Sprague-Dawley , Membrana Sinovial/metabolismo , Progressão da DoençaRESUMO
BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.
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Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood. In this study, we first found that ER stress could dramatically elevate m6A methylation levels through XBP1s-dependent transcriptional upregulation of METTL3/METTL14 in breast cancer (BC) cells. Further MeRIP sequencing and relevant validation results confirmed that ER stress caused m6A methylation enrichment on target genes for ER-phagy. Mechanistically, METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and p62, thus enhancing their mRNA stability. Of note, we further confirmed that the chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase m6A methylation for ER-phagy. Furthermore, the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice. Thus, our data built a novel bridge on the crosstalk between ER stress, m6A methylation and ER-phagy. Most importantly, our work provides novel evidence of METTL3 and METTL14 as potential therapeutic targets for PTX sensitization in breast cancer.
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Neoplasias da Mama , Estresse do Retículo Endoplasmático , Metiltransferases , Paclitaxel , Proteína 1 de Ligação a X-Box , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Paclitaxel/farmacologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Metiltransferases/genética , Metiltransferases/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/farmacologia , Autofagia/efeitos dos fármacos , Metilação , Camundongos Nus , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologiaRESUMO
LINC00624 is a long noncoding RNA (lncRNA) which was seldom investigated before. The goal of our study is to clarify the expression and underlying network of LINC00624 in hepatocellular carcinoma (HCC). Here, both HCC and normal living cell lines were employed. Real-time quantitative PCR and western blot were used to determine the pattern of genes and proteins. Colony formation, flow cytometry and western blot tests were used to determine cell proliferation and apoptosis, respectively. Dual luciferase was used to verify molecule-molecule interactions. LINC00624 expression was increased in HCC cell lines and miR-342-3p was decreased. Elimination of LINC00624 increased proliferation while decreasing cell apoptosis. LINC00624 acted as a molecular sponge for miR-342-3p, hence facilitating DNAJC5 expression. Functional tests demonstrated that miR-342-3p suppression could reverse the effect of LINC00624 silence and overexpression of DNAJC5 significantly mitigated the biological consequences of miR-342-3p. These finding demonstrated that LINC00624 aggravated HCC progression by modulating proliferation and apoptosis via targeting miR-342-3p/DNAJC5 axis. These data support that inhibition of LINC00624 may a potential treatment strategies of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não CodificanteRESUMO
AIMS: To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS: In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. RESULTS: Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033). CONCLUSION: In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Proteína C-Reativa , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , PulmãoRESUMO
The steel industry is one of the most carbon-intensive industries in China. To analyze the carbon emission and carbon reduction potential of the steel industry in the life cycle, a carbon emission accounting model was built from the perspective of the life cycle. Taking the year 2020 as an example, an empirical analysis was carried out to predict and evaluate the carbon reduction potential of the steel industry in the life cycle by optimizing four variables, namely, scrap usage, fossil fuel combustion, electric power carbon footprint factor, and clean transportation proportion. At the same time, sensitivity analysis was used to determine the key degree of factors affecting carbon emission reduction in the life cycle of steel. The results showed that in 2020, the total life cycle CO2 emissions of the steel industry in China was approximately 2.404 billion tons, of which the acquisition and processing of raw materials were the key links in the carbon emissions of the steel industry, accounting for more than 98% of the total life cycle CO2 emissions of the steel industry. From the analysis of CO2 emission source categories, fossil fuel savings and outsourcing power cleaning were the top priorities of carbon reduction in the steel industry. By 2025, the steel industry could achieve 20%, 6%, 5%, and 1% carbon emission reduction potential by respectively promoting low-carbon technology, optimizing the power structure, increasing the number of steel scraps, and increasing the proportion of clean transportation. The fossil fuel combustion had the most significant impact on the life cycle CO2 emissions of the steel industry, followed by the electric power carbon footprint factor and scrap steelmaking usage. With regard to low-carbon technologies in the steel industry, in the short term, the promotion of low-carbon technologies in the steel rolling process and blast furnace ironmaking process should be the main focus. Later, with the gradual increase in the proportion of electric furnace steelmaking, the promotion of low-carbon technologies in the electric furnace steelmaking process will significantly improve the carbon emission reduction potential of the steel industry throughout its life cycle.
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The role of pyrotinib in the treatment of HER2-positive metastatic breast cancer (MBC) has been well-established. This multicenter, single-arm phase II trial (NCT03876587) aimed to assess the benefit of pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC. Women with HER2-positive MBC who had not undergone HER2 blockade or chemotherapy for metastatic disease were enrolled in the study and received daily oral pyrotinib 400 mg plus intravenous docetaxel 75 mg/m2 every 3 weeks. The primary endpoint was the objective response rate (ORR), secondary endpoints included progression-free survival (PFS), duration of response (DoR), clinical benefit rate (CBR), overall survival (OS) and safety. From June 2019 to June 2021, 79 patients were enrolled. The confirmed ORR was 79.7% (95% confidence interval [CI], 70.8-88.6), and the CBR was 87.3% (95%CI, 80.0-94.6) in the intention-to-treat population. The pre-specified primary endpoint was met. The median DoR was 15.9 months (interquartile range, 8.3-19.5); the median PFS was 16.0 months (95% CI, 11.2-20.8), and the median OS was not reached. The most common grade ≥3 treatment-related adverse events observed were leukopenia (29.1%), neutropenia (27.8%), and diarrhea (21.5%). This study demonstrates that pyrotinib plus docetaxel show an acceptable safety profile and promising antitumor activity as a first-line treatment option for patients with HER2-positive MBC.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Docetaxel/uso terapêutico , Trastuzumab/uso terapêutico , Receptor ErbB-2/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Introduction: Small cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations. Methods: A total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases. Results: The median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1-84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7-10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort. Discussion: The findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.
RESUMO
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive with poor prognosis. Long non-coding RNAs (lncRNAs), a group of non-coding RNAs, play important roles in the progression of PDAC. This study aimed to investigate the potential involvement of lncRNA CCAT2 in PDAC tumorigenesis. Methods Expression of CCAT2 was detected by quantitative real-time PCR (qRT-PCR) in 80 human PDAC tissues and three PDAC cell lines. The effects of CCAT2 silencing in PANC-1 cells on cell proliferation and invasion were studied using MTT assay and transwell assay, respectively. The effect of CCAT2 silencing on tumorigenesis was assessed by PANC-1 xenograft in vivo. Using si-KRAS, the role of KRAS to regulate CCAT2 was evaluated by qRT-PCR and luciferase reporter assay. The involvement of MEK/ERK and PI3K/AKT signaling in CCAT2 regulation was investigated by pathway inhibitors PD98059 and LY294002, respectively. Results CCAT2 was significantly elevated in high-grade PDAC tissues and higher CCAT2 expression was correlated with lower survival rate in PDAC patients. CCAT2 was up-regulated in PDAC cell lines, as compared with normal pancreatic cells. Silencing of CCAT2 inhibited cell proliferation and invasion in PANC-1 cells in vitro, and attenuated tumorigenesis of PANC-1 xenograft in vivo. Furthermore, CCAT2 was regulated by KRAS through MEK/ERK signaling pathway. Conclusions CCAT2 is an oncogenic lncRNA in PDAC likely regulated by the KRAS-MEK/ERK pathway. It could be a potential diagnostic biomarker and therapeutic target for PDAC.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Ductal Pancreático/genética , RNA Longo não Codificante/genética , Mutação/genética , Prognóstico , Carcinoma Ductal Pancreático/patologia , Reação em Cadeia da Polimerase em Tempo Real , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To compare the therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis to provide a basis for clinical practice. METHODS: Data from 83 patients with rheumatoid arthritis undergoing total knee arthroplasty were retrospectively analyzed. The 83 patients were divided into a drainage blood reinfusion group (DR group, n = 45) and a temporary clamping drainage group (CD group, n = 38). In the DR group, postoperative drainage blood was used for autotransfusion. In the CD group, closed drainage was adopted, and the drainage tube was clamped for 2 h postoperatively followed by patency. The postoperative drainage amount, hemoglobin level, rate and average volume of allogeneic blood transfusion, swelling and ecchymosis of the affected knee joint, time to straight-leg raising and range of active knee flexion were compared between the two groups. RESULTS: The total drainage volume was higher in the DR group than in the CD group (P = 0.000). The average volume of postoperative allogeneic blood transfusion (P = 0.000) and the decrease in the hemoglobin level 24 h after total knee arthroplasty (P = 0.012) were lower in the DR group than in the CD group. Swelling and ecchymosis of the affected knee joint, time to straight-leg raising and the range of active knee flexion were improved in the DR group compared with the CD group (all P<0.05). CONCLUSION: Compared with temporary clamping drainage, drainage blood reinfusion after total knee arthroplasty can reduce the allogeneic blood transfusion volume and is conducive to early rehabilitation in patients with rheumatoid arthritis. .