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1.
Sci Rep ; 14(1): 10482, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714855

RESUMO

The mitogen-activated protein kinase (MAPK) pathway plays a critical role in tumor development and immunotherapy. Nevertheless, additional research is necessary to comprehend the relationship between the MAPK pathway and the prognosis of bladder cancer (BLCA), as well as its influence on the tumor immune microenvironment. To create prognostic models, we screened ten genes associated with the MAPK pathway using COX and least absolute shrinkage and selection operator (LASSO) regression analysis. These models were validated in the Genomic Data Commons (GEO) cohort and further examined for immune infiltration, somatic mutation, and drug sensitivity characteristics. Finally, the findings were validated using The Human Protein Atlas (HPA) database and through Quantitative Real-time PCR (qRT-PCR). Patients were classified into high-risk and low-risk groups based on the prognosis-related genes of the MAPK pathway. The high-risk group had poorer overall survival than the low-risk group and showed increased immune infiltration compared to the low-risk group. Additionally, the nomograms built using the risk scores and clinical factors exhibited high accuracy in predicting the survival of BLCA patients. The prognostic profiling of MAPK pathway-associated genes represents a potent clinical prediction tool, serving as the foundation for precise clinical treatment of BLCA.


Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Prognóstico , Sistema de Sinalização das MAP Quinases/genética , Masculino , Feminino , Nomogramas , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Idoso , Pessoa de Meia-Idade
2.
Sci Rep ; 14(1): 10468, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714870

RESUMO

Inflammatory age (iAge) is a vital concept for understanding the intricate interplay between chronic inflammation and aging in the context of cancer. However, the importance of iAge-clock-related genes (iAge-CRGs) across cancers remains unexplored. This study aimed to explore the mechanisms and applications of these genes across diverse cancer types. We analyzed profiling data from over 10,000 individuals, covering 33 cancer types, 750 small molecule drugs, and 24 immune cell types. We focused on DCBLD2's function at the single-cell level and computed an iAge-CRG score using GSVA. This score was correlated with cancer pathways, immune infiltration, and survival. A signature was then derived using univariate Cox and LASSO regression, followed by ROC curve analysis, nomogram construction, decision curve analysis, and immunocytochemistry. Our comprehensive analysis revealed epigenetic, genomic, and immunogenomic alterations in iAge-CRGs, especially DCBLD2, leading to abnormal expression. Aberrant DCBLD2 expression strongly correlated with cancer-associated fibroblast infiltration and prognosis in multiple cancers. Based on GSVA results, we developed a risk model using five iAge-CRGs, which proved to be an independent prognostic index for uveal melanoma (UVM) patients. We also systematically evaluated the correlation between the iAge-related signature risk score and immune cell infiltration. iAge-CRGs, particularly DCBLD2, emerge as potential targets for enhancing immunotherapy outcomes. The strong correlation between abnormal DCBLD2 expression, cancer-associated fibroblast infiltration, and patient survival across various cancers underscores their significance. Our five-gene risk signature offers an independent prognostic tool for UVM patients, highlighting the crucial role of these genes in suppressing the immune response in UVM.Kindly check and confirm whether the corresponding affiliation is correctly identified.I identified the affiliation is correctly.thank you.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.I confirm the abstract is correctly ,thank you.


Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Prognóstico , Neoplasias/genética , Neoplasias/imunologia , Biomarcadores Tumorais/genética , Inflamação/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Envelhecimento/genética , Envelhecimento/imunologia , Multiômica
3.
BMC Nephrol ; 25(1): 157, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714960

RESUMO

BACKGROUND: This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. METHODS: This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. RESULTS: A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan-Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients. CONCLUSION: Longer dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.


Assuntos
Diálise Peritoneal , Calcificação Vascular , Humanos , Diálise Peritoneal/efeitos adversos , Masculino , Feminino , Calcificação Vascular/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Idoso , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Estudos de Coortes , Hormônio Paratireóideo/sangue , Adulto , Aorta Abdominal/diagnóstico por imagem , Albumina Sérica/metabolismo , Albumina Sérica/análise , Cálcio/sangue
4.
BMC Pediatr ; 24(1): 316, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714959

RESUMO

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.


Assuntos
Histiocitose de Células de Langerhans , Hepatopatias , Humanos , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , Criança , Hepatopatias/etiologia , Resultado do Tratamento , Adolescente , Prognóstico
5.
BMC Cancer ; 24(1): 568, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714979

RESUMO

PURPOSE: The index composed of preoperative lymphocytes, albumin, and neutrophils (LANR), a new composite score based on inflammatory response and nutritional status, has been reported to be associated with the prognosis of multiple types of cancer, but the role of LANR in the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. PATIENTS AND METHODS: The data of 142 patients with PDAC who underwent radical resection in the Affiliated Hospital of Jiangnan University from January 2015 to December 2018 were retrospectively analyzed. Receiver Operating Characteristic (ROC) curves were generated to determine the optimal cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting survival. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis.  RESULTS: The optimal cut-off value of LANR was 18.145, and a low preoperative LANR was significantly correlated with the location of the tumor (p = 0.047). Multivariate analysis showed that tumor differentiation degree (HR:2.357, 95%CI:1.388-4.003,p = 0.002), lymph node metastasis (HR:1.755, 95%CI: 1.115-2.763, p = 0.015), TNM stage (HR:4.686, 95%CI: 2.958-7.425, p < 0.001), preoperative cancer antigen 19 - 9 levels (HR:1.001, 95%CI: 1.000-1.001, p < 0.001) and preoperative LANR (HR:0.221, 95%CI: 0.111-0.441, p < 0.001) were independent risk factors for a poor prognosis in patients undergoing radical resection of PDAC. CONCLUSION: This study found that preoperative LANR can be used to assess the prognosis of radical resection in patients with PDAC; those with low preoperative LANR had a worse outcome.


Assuntos
Carcinoma Ductal Pancreático , Linfócitos , Neutrófilos , Neoplasias Pancreáticas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/mortalidade , Estimativa de Kaplan-Meier , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Curva ROC , Albumina Sérica/análise , Albumina Sérica/metabolismo , Idoso de 80 Anos ou mais
6.
BMC Cancer ; 24(1): 570, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714987

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide and is associated with high morbidity and mortality rates. However, the specific biomarkers used to predict the postoperative prognosis of patients with gastric cancer remain unknown. Recent research has shown that the tumor microenvironment (TME) has an increasingly positive effect on anti-tumor activity. This study aims to build signatures to study the effect of certain genes on gastric cancer. METHODS: Expression profiles of 37 T cell-related genes and their TME characteristics were comprehensively analyzed. A risk signature was constructed and validated based on the screened T cell-related genes, and the roles of hub genes in GC were experimentally validated. RESULTS: A novel T cell-related gene signature was constructed based on CD5, ABCA8, SERPINE2, ESM1, SERPINA5, and NMU. The high-risk group indicated lower overall survival (OS), poorer immune efficacy, and higher drug resistance, with SERPINE2 promoting GC cell proliferation, according to experiments. SERPINE2 and CXCL12 were significantly correlated, indicating poor OS via the Youjiang cohort. CONCLUSIONS: This study identified T cell-related genes in patients with stomach adenocarcinoma (STAD) for prognosis estimation and proposed potential immunotherapeutic targets for STAD.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Linfócitos T Reguladores/imunologia , Perfilação da Expressão Gênica , Masculino , Feminino
7.
BMC Endocr Disord ; 24(1): 61, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715016

RESUMO

Hypopituitarism is a relatively rare complication of hemorrhagic fever with renal syndrome. However, almost all available reported cases were total anterior pituitary hypofunction, isolated growth-hormone deficiency, or isolated gonadotropin deficiency. Here, we firstly describe a patient with partial hypopituitarism with ACTH deficiency as the main manifestation as a complication of hemorrhagic fever with renal syndrome.


Assuntos
Febre Hemorrágica com Síndrome Renal , Hipopituitarismo , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/diagnóstico , Hipopituitarismo/complicações , Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico , Masculino , Hormônio Adrenocorticotrópico/deficiência , Hormônio Adrenocorticotrópico/sangue , Adulto , Prognóstico , Insuficiência Adrenal
8.
World J Surg Oncol ; 22(1): 124, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715036

RESUMO

BACKGROUND: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. METHODS: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. RESULTS: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). CONCLUSION: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.


Assuntos
Neoplasias Retais , Estomas Cirúrgicos , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Estomas Cirúrgicos/efeitos adversos , Idoso , Prognóstico , Fatores de Risco , Seguimentos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Protectomia/métodos , Protectomia/efeitos adversos , Idoso de 80 Anos ou mais
9.
Cardiovasc Diabetol ; 23(1): 156, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715129

RESUMO

BACKGROUND: Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population. METHODS: This study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses. RESULTS: The mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (< 8.6 [median level]) and hsCRP < 1 mg/L, those concurrently with a higher TyG and hsCRP had the highest risk of overall cardiovascular disease (adjusted hazard ratio [aHR], 1.300; 95% CI 1.155-1.462), coronary heart disease (aHR, 1.294; 95% CI 1.130-1.481) and stroke (aHR, 1.333; 95% CI 1.093-1.628), which were predominant among those aged 70 years or below. High hsCRP significantly mediated 13.4% of the association between the TyG index and cardiovascular disease, while TyG simultaneously mediated 7.9% of the association between hsCRP and cardiovascular risk. CONCLUSIONS: The findings highlight the coexposure effects and mutual mediation between the TyG index and hsCRP on cardiovascular diseases. Joint assessments of the TyG index and hsCRP should be underlined for the residual risk stratification and primary prevention of cardiovascular diseases, especially for middle-aged adults.


Assuntos
Biomarcadores , Glicemia , Proteína C-Reativa , Doenças Cardiovasculares , Triglicerídeos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Idoso , China/epidemiologia , Medição de Risco , Glicemia/metabolismo , Triglicerídeos/sangue , Estudos Longitudinais , Fatores de Tempo , Prognóstico , Resistência à Insulina , Mediadores da Inflamação/sangue , Incidência , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/epidemiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas
10.
Clin Respir J ; 18(5): e13757, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715380

RESUMO

OBJECTIVE: This research was aimed to comprehensively investigate the expression levels, diagnostic and prognostic implications, and the relationship with immune infiltration of G2 and S phase-expressed-1 (GTSE1) across 33 tumor types, including lung adenocarcinoma (LUAD), through gene expression profiling. METHODS: GTSE1 mRNA expression data together with clinical information were acquired from Xena database of The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) database for this study. The Wilcoxon rank-sum test was used to detect differences in GTSE1 expression between groups. The ability of GTSE1 to accurately predict cancer status was evaluated by calculating the area under the curve (AUC) value for the receiver operating characteristic curve. Additionally, we investigated the predictive value of GTSE1 in individuals diagnosed with neoplasms using univariate Cox regression analysis as well as Kaplan-Meier curves. Furthermore, the correlation between GTSE1 expression and levels of immune infiltration was assessed by utilizing the Tumor Immune Estimate Resource (TIMER) database to calculate the Spearman rank correlation coefficient. Finally, the pan-cancer analysis findings were validated by examining the association between GTSE1 expression and prognosis among patients with LUAD. RESULTS: GTSE1 exhibited significantly increased expression levels in a wide range of tumor tissues in contrast with normal tissues (p < 0.05). The expression of GTSE1 in various tumors was associated with clinical features, overall survival, and disease-specific survival (p < 0.05). In immune infiltration analyses, a strong correlation of the level of immune infiltration with the expression of GTSE1 was observed. Furthermore, GTSE1 demonstrated good discriminative and diagnostic value for most tumors. Additional experiments confirmed the relationship between elevated GTSE1 expression and unfavorable prognosis in individuals diagnosed with LUAD. These findings indicated the crucial role of GTSE1 expression level in influencing the development and immune infiltration of different types of tumors. CONCLUSIONS: GTSE1 might be a potential biomarker for the prognosis of pan-cancer. Meanwhile, it represented a promising target for immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Prognóstico
11.
Brain Behav ; 14(5): e3537, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715443

RESUMO

OBJECTIVE: Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90-day interval in AIS patients. METHODS: A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). RESULTS: Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90-day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90-day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p-overall = .011). CONCLUSIONS: Including RC as a contributing element may refine the prediction of poor 90-day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.


Assuntos
Colesterol , AVC Isquêmico , Humanos , Masculino , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Colesterol/sangue , Fatores de Risco , LDL-Colesterol/sangue
12.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 257-263, 2024 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-38716597

RESUMO

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.


Assuntos
Deleção de Genes , Fator de Transcrição Ikaros , Neoplasia Residual , Humanos , Fator de Transcrição Ikaros/genética , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida
13.
Cancer Med ; 13(9): e7209, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716651

RESUMO

OBJECTIVE: Precision medicine is transforming cancer treatment, yet the perspectives of surgeons who often play a critical role in the delivery of precision medicine remain understudied. METHODS: We conducted semi-structured interviews with 13 surgeons involved in a precision medicine trial for children with poor prognosis cancer. We explored knowledge of genetics, confidence with somatic and germline results, ratings of benefit to stakeholders and willingness to undertake surgical procedures. RESULTS: Surgeons generally had positive attitudes towards precision medicine but expressed concerns about families' unrealistic expectations, mixed opinions on the benefits and the use of research-only biopsies. Most surgeons rated their genetics knowledge as 'good' (69%) and felt 'very confident' in identifying genetic specialists (66%), but 'not confident' (66.6%) in making treatment recommendations. Surgeons' willingness to undertake a procedure was influenced by potential patient benefit. CONCLUSIONS: Our findings support the need for more workforce and training support for surgeons to fully engage with precision medicine.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias , Medicina de Precisão , Cirurgiões , Humanos , Medicina de Precisão/métodos , Neoplasias/terapia , Neoplasias/genética , Neoplasias/psicologia , Feminino , Masculino , Prognóstico , Criança , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Família/psicologia
14.
PLoS Comput Biol ; 20(5): e1012024, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38717988

RESUMO

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.


Assuntos
Biomarcadores Tumorais , Biologia Computacional , Bases de Dados Genéticas , Internet , Neoplasias , Software , Humanos , Neoplasias/genética , Neoplasias/mortalidade , Análise de Sobrevida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Prognóstico , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética
15.
Front Immunol ; 15: 1372692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720884

RESUMO

Background: The tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and "MCPcounter" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes. Results: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells. Conclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.


Assuntos
Biomarcadores Tumorais , Imunoterapia , Sarcoma , Microambiente Tumoral , Humanos , Sarcoma/genética , Sarcoma/terapia , Sarcoma/imunologia , Sarcoma/diagnóstico , Biomarcadores Tumorais/genética , Prognóstico , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Perfilação da Expressão Gênica , Análise de Célula Única
16.
Front Endocrinol (Lausanne) ; 15: 1354426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721144

RESUMO

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.


Assuntos
Autoanticorpos , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adulto , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Pessoa de Meia-Idade , Autoanticorpos/sangue , Estudos Retrospectivos , Prognóstico , Adulto Jovem , Adolescente , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Biomarcadores Tumorais/sangue , Tireoidectomia , Tireoglobulina/imunologia , Tireoglobulina/sangue , Radioisótopos do Iodo/uso terapêutico , Seguimentos
17.
Acta Biochim Pol ; 71: 12433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721304

RESUMO

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6 months after implantation. During the 3-6 months of observation level of OPN increased in patients with CIs (<50 years > 50 years) and HIs (<50 years) (CI: <50 years F = 36.457, p < 0.001; >50 years F = 30.104, p < 0.001; HI < 50 years F = 2.246, p < 0.001), ALP increased in patients with CIs (<50 years: F = 19.58, p < 0.001; >50 years: F = 12.01; p = 0.001) and HIs (<50 years) (F = 18.51, p < 0.001), OC increased in patients <50 years (CI: F = 33.72, p < 0.001; HI: F = 55.57, p < 0.001), but in patients >50 years - on the 3 days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3 months of the observation in patients <50 years (CI: F = 4.63, p = 0.037; HI: F = 2.8927, p = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50 years) during 1-6 months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50 years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.


Assuntos
Fosfatase Alcalina , Biomarcadores , Implantes Dentários , Líquido do Sulco Gengival , Osseointegração , Osteocalcina , Osteopontina , Osteoprotegerina , Humanos , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Feminino , Masculino , Osteoprotegerina/metabolismo , Líquido do Sulco Gengival/metabolismo , Fosfatase Alcalina/metabolismo , Osteocalcina/metabolismo , Adulto , Osteopontina/metabolismo , Prognóstico , Óxido Nítrico/metabolismo , Implantação Dentária/métodos , Fatores de Tempo
18.
Allergol Immunopathol (Madr) ; 52(3): 17-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721951

RESUMO

BACKGROUND: This study aims to investigate the relevance of platelet aggregation markers, specifically arachidonic acid (AA) and adenosine diphosphate (ADP), in relation to the prognosis of sepsis patients. METHODS: A cohort of 40 sepsis patients was included and stratified, based on their 28-day post-treatment prognosis, into two groups: a survival group (n = 31) and a severe sepsis group (n = 9. Then, their various clinical parameters, including patient demographics, platelet counts (PLT), inflammatory markers, and platelet aggregation rates (PAR) induced by AA and ADP between the two groups, were compared. Long-term health implications of sepsis were assessed using the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, and logistic regression analysis was conducted to evaluate the prognostic significance of PAR in sepsis patients. RESULTS: Patients with severe sepsis exhibited significantly elevated levels of procalcitonin (PCT), platelet adhesion rates, and PAR induced by ADP (P < 0.05), but having lower PLT (P < 0.05), compared to those in the survival group. Logistic regression analysis demonstrated that PAR induced by ADP was a protective factor in predicting prognosis in sepsis patients (P < 0.01). CONCLUSIONS: Activation of platelets in sepsis intensifies inflammatory response. Patients with sepsis whose ADP-induced PAR was < 60% displayed significant impairment in platelet aggregation function, and had higher mortality rate. Monitoring ADP-induced PAR is crucial for management of sepsis.


Assuntos
Difosfato de Adenosina , Agregação Plaquetária , Sepse , Humanos , Sepse/mortalidade , Sepse/diagnóstico , Sepse/sangue , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Difosfato de Adenosina/farmacologia , Ácido Araquidônico/sangue , Biomarcadores/sangue , Plaquetas/imunologia , Adulto
19.
Clin Transplant ; 38(5): e15329, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722085

RESUMO

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.


Assuntos
Vírus BK , Rejeição de Enxerto , Sobrevivência de Enxerto , Testes de Função Renal , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Viremia , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Feminino , Masculino , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/complicações , Pessoa de Meia-Idade , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Seguimentos , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Viremia/imunologia , Viremia/virologia , Prognóstico , Fatores de Risco , Taxa de Filtração Glomerular , Adulto , Complicações Pós-Operatórias , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/imunologia , Nefropatias/virologia , Nefropatias/imunologia , Nefropatias/cirurgia , Transplantados
20.
J Invest Surg ; 37(1): 2350358, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38724045

RESUMO

OBJECTIVES: Hypermetabolism is associated with clinical prognosis of cancer patients. The aim of this study was to explore the association between basal metabolic rate (BMR) and postoperative clinical outcomes in gastric cancer patients. METHODS: We collected data of 958 gastric cancer patients admitted at our center from June 2014 to December 2018. The optimal cutoff value of BMR (BMR ≤1149 kcal/day) was obtained using the X-tile plot. Logistic and Cox regression analyses were then performed to evaluate the relevant influencing factors of clinical outcomes. Finally, R software was utilized to construct the nomogram. RESULTS: A total of 213 patients were defined as having a lower basal metabolic rate (LBMR). Univariate and multivariate analyses showed that gastric cancer patients with LBMR were more prone to postoperative complications and had poor long-term overall survival (OS). The established nomogram had good predictive power to assess the risk of OS in gastric cancer patients after radical gastrectomy (c-index was 0.764). CONCLUSIONS: Overall, LBMR on admission is associated with the occurrence of postoperative complications in gastric cancer patients, and this population has a poorer long-term survival. Therefore, there should be more focus on the perioperative management of patients with this risk factor before surgery.


Assuntos
Metabolismo Basal , Gastrectomia , Nomogramas , Complicações Pós-Operatórias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Risco , Resultado do Tratamento , Adulto
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