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BACKGROUND: CFAP65 (cilia and flagella associated protein 65) is a fundamental protein in the development and formation of ciliated flagella, but few studies have focused on its role in cancer. This study aimed to investigate the prognostic significance of CFAP65 in colon cancer. METHODS: The functionally enriched genes related to CFAP65 were analyzed through the Gene Ontology (GO) database. Subsequently, CFAP65 expression levels in colon cancer were evaluated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) and immunoblotting in 20 pairs of frozen samples, including tumors and their matched paratumor tissue. Furthermore, protein expression of CFAP65 in 189 colon cancer patients were assessed via immunohistochemical staining. The correlations between CFAP65 expression and clinical features as well as long-term survival were statistically analyzed. RESULTS: CFAP65-related genes are significantly enriched on cellular processes of cell motility, ion channels, and GTPase-associated signaling. The expression of CFAP65 was significantly higher in colon cancer tissue compared to paratumor tissue. The proportion of high expression and low expression of CFAP65 in the clinical samples of colon cancer were 61.9% and 38.1%, respectively, and its expression level was not associated with the clinical parameters including gender, age, tumor location, histological differentiation, tumor stage, vascular invasion and mismatch repair deficiency. The five-year disease-free survival rate of the patients with CFAP65 low expression tumors was significantly lower than that those with high expression tumors (56.9% vs. 72.6%, P = 0.03), but the overall survival rate has no significant difference (69% vs. 78.6%, P = 0.171). The cox hazard regression analysis model showed that CFAP65 expression, tumor stage and tumor location were independent prognostic factors. CONCLUSIONS: In conclusion, we demonstrate CFAP65 is a potential predictive marker for tumor progression in colon cancer.
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Biomarcadores Tumorais , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Idoso , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Relevância Clínica , Proteínas de Membrana , Proteínas de NeoplasiasRESUMO
BACKGROUND: The main metastatic route for lung cancer is lymph node metastasis, and studies have shown that non-small cell lung cancer (NSCLC) has a high risk of lymph node infiltration. OBJECTIVE: This study aimed to compare the performance of handcrafted radiomics (HR) features and deep transfer learning (DTL) features in Computed Tomography (CT) of intratumoral and peritumoral regions in predicting the metastatic status of NSCLC lymph nodes in different machine learning classifier models. METHODS: We retrospectively collected data of 199 patients with pathologically confirmed NSCLC. All patients were divided into training (nâ=â159) and validation (nâ=â40) cohorts, respectively. The best HR and DTL features in the intratumoral and peritumoral regions were extracted and selected, respectively. Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Light Gradient Boosting Machine (Light GBM), Multilayer Perceptron (MLP), and Logistic Regression (LR) models were constructed, and the performance of the models was evaluated. RESULTS: Among the five models in the training and validation cohorts, the LR classifier model performed best in terms of HR and DTL features. The AUCs of the training cohort were 0.841 (95% CI: 0.776-0.907) and 0.955 (95% CI: 0.926-0.983), and the AUCs of the validation cohort were 0.812 (95% CI: 0.677-0.948) and 0.893 (95% CI: 0.795-0.991), respectively. The DTL signature was superior to the handcrafted radiomics signature. CONCLUSIONS: Compared with the radiomics signature, the DTL signature constructed based on intratumoral and peritumoral areas in CT can better predict NSCLC lymph node metastasis.
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Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Metástase Linfática , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Metástase Linfática/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Idoso , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , AdultoRESUMO
BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.
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Doença de Crohn , Enterite , Tuberculose Gastrointestinal , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Diagnóstico Diferencial , Parafina , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/patologia , Enterite/diagnóstico , Aprendizado de Máquina , Proteínas Mutadas de Ataxia TelangiectasiaRESUMO
With the increased awareness of early tumor detection, the importance of detecting and diagnosing esophageal cancer in its early stages has been underscored. Studies have consistently demonstrated the crucial role of methylation levels in circulating cell-free DNA (cfDNA) in identifying and diagnosing early-stage cancer. cfDNA methylation pertains to the methylation state within the genomic scope of cfDNA and is strongly associated with cancer development and progression. Several research teams have delved into the potential application of cfDNA methylation in identifying early-stage esophageal cancer and have achieved promising outcomes. Recent research supports the high sensitivity and specificity of cfDNA methylation in early esophageal cancer diagnosis, providing a more accurate and efficient approach for early detection and improved clinical management. Accordingly, this review aims to present an overview of methylation-based cfDNA research with a focus on the latest developments in the early detection of esophageal cancer. Additionally, this review summarizes advanced analytical technologies for cfDNA methylation that have significantly benefited from recent advancements in separation and detection techniques, such as methylated DNA immunoprecipitation sequencing (MeDIP-seq). Recent findings suggest that biomarkers based on cfDNA methylation may soon find successful applications in the early detection of esophageal cancer. However, large-scale prospective clinical trials are required to identify the potential of these biomarkers.
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Ácidos Nucleicos Livres , Neoplasias Esofágicas , Humanos , Metilação de DNA/genética , Estudos Prospectivos , Detecção Precoce de Câncer/métodos , Ácidos Nucleicos Livres/genética , Neoplasias Esofágicas/diagnóstico , BiomarcadoresRESUMO
1,4-dioxane is a potential carcinogen in water and is difficult to deal with due to its robust cycloether bond and complete miscibility with water. To remove 1,4-dioxane in an economically viable and environmentally friendly way, a series of carbon aerogels were synthesized as adsorbents for 1,4-dioxane. The experiment results showed that adsorption performances were closely related to the preparation conditions of carbon aerogels, such as the molar ratio, heating rate, pyrolysis temperature and residence time, which were carefully controlled. Scanning electron microscope analysis revealed the presence of a three-dimensional porous network structure in carbon aerogels. Brunauer-Emmett-Teller analysis results demonstrated an increase in specific surface area (673.89 m2/g) and total pore volume after carbonization, with an increase in mesoporous porosity and a decrease in microporosity. When considering each variable individually, the highest specific surface area of prepared carbon aerogels was achieved at a pyrolysis temperature of 800 °C, a holding time of 1 h, and a heating rate of 2 °C/min. Under optimal experimental conditions, the adsorption removal of 1,4-dioxane by carbon aerogels exceeded 95%, following quasi-second-order kinetics and Langmuir isothermal adsorption isotherms, indicating that monolayer adsorption on the surface of carbon aerogels occurred. The maximum adsorption capacity obtained was 67.28 mg/g at a temperature of 318 K, which was attributed to the presence of a large proportion of mesopores and abundant micropores simultaneously in carbon aerogels. Furthermore, with the interference of chlorinated solvents such as trichloroethylene (TCE), the removal efficiency of 1,4-dioxane had no obvious inhibition effect. Regeneration experiments showed that after five continuous cycles, the carbon aerogels still kept a comparable adsorption capacity, which illustrates its potential application in 1,4-dioxane-polluted water purification.
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Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge. By RNA-sequencing analysis, we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA. LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion. Silencing of LLNLR-299G3.1 with ASO (antisense oligonucleotide) resulted in opposite effects. Mechanistically, LLNLR-299G3.1 bound to cancer-associated RNA binding proteins and regulated the expression of cancer-related genes, including OSM, TNFRSF4, HRH3, and SSTR3. ChIRP-seq (chromatin isolation by RNA purification and sequencing) revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1. Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4. Therapeutically, intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide (pICSA-BP-ANPs) strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo. Overall, our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante , Gravidez , Animais , Humanos , Feminino , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Proliferação de Células/genética , Placenta/metabolismo , Placenta/patologia , Cromatina , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Movimento Celular/genéticaRESUMO
Objective: The aim of this study is to acquire pulmonary CT (Computed tomography) angiographic data for the purpose of creating a three-dimensional reconstruction. Additionally, we aim to analyze the features and deviations of the branches in both pulmonary lobes. This information is intended to serve as a more comprehensive and detailed reference for medical professionals when conducting preoperative evaluations and devising surgical plans. Method: Between August 2019 and December 2021, 420 patients were selected from the thoracic surgery department at the First Hospital of Jilin University, and underwent pulmonary 64 channel contrast enhanced CT examinations (Philips ICT 256). The images were acquired at a 1.5 mm slice thickness, and the DCM files that complied with DICOM (Digital Imaging and Communications in Medicine) standards were analysed for 3D (three dimensional) reconstruction using Mimics 22.0 software. The reconstructed pulmonary artery models were assessed by attending chest surgeons and radiologists with over 10 years of clinical experience. The two-dimensional image planes, as well as the coronary and sagittal planes, were utilized to evaluate the arteries. The study analyzed the characteristics and variations of the branches and courses of pulmonary arteries in each lobe of the lungs, with the exception of the subsegmental arterial system. Two chest surgeons and two radiologists with professional titles-all of whom had over a decade of clinical experience-jointly evaluated the 3D models of the pulmonary artery and similarly assessed the characteristics and variations of the branches and courses in each lobe of the lungs. Results: Significant variations were observed in the left superior pulmonary artery across the 420 subjects studied. In the left upper lobe, the blood supply of 4 arteries accounted for 50.5% (n = 212), while the blood supply of 2 arteries in the left lower lobe was the most common, accounting for 79.5% (n = 334). The greatest variation in the right pulmonary artery was observed in the branch supply of the right upper lobe mediastinal artery. In the majority of cases (77.9%), there were two arteries present, which was the most common configuration observed accounting for 64% (n = 269). In the right inferior lobe of the lung, there were typically 2-4 arteries, with 2 arteries being the most common configuration (observed in 79% of cases, n = 332). Conclusion: The three-dimensional reconstruction of pulmonary artery CT angiography enables clear observation of the branches and distribution of the pulmonary artery while also highlighting any variations. This technique holds significant clinical value for preoperative assessments regarding lesions and blood vessels.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Biomarcadores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Imunoterapia , Mutação , Biomarcadores Tumorais/genéticaRESUMO
Background: The aim of this study was to develop a nomogram model in combination with thromboelastography (TEG) to predict the development of venous thromboembolism (VTE) after lung cancer surgery. Methods: The data of 502 patients who underwent surgical treatment for lung cancer from December 2020 to December 2022 were retrospectively analyzed. Patients were then randomized into training and validation groups. Univariate and multivariate logistic regression analyses were carried out in the training group and independent risk factors were included in the nomogram to construct risk prediction models. The predictive capability of the model was assessed by the consistency index (C-index), receiver operating characteristic curves (ROC), the calibration plot and decision curve analysis (DCA). Results: The nomogram risk prediction model comprised of the following five independent risk factors: age, operation time, forced expiratory volume in one second and postoperative TEG parameters k value(K) and reaction time(R). The nomogram model demonstrated better predictive power than the modified Caprini model, with the C-index being greater. The calibration curve verified the consistency of nomogram between the two groups. Furthermore, DCA demonstrated the clinical value and potential for practical application of the nomogram. Conclusion: This study is the first to combine TEG and clinical risk factors to construct a nomogram to predict the occurrence of VTE in patients after lung cancer surgery. This model provides a simple and user-friendly method to assess the probability of VTE in postoperative lung cancer patients, enabling clinicians to develop individualized preventive anticoagulation strategies to reduce the incidence of such complications.
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Background: To analyze the prognosis and diagnostic value of relevant hematological indexes on the survival status of patients with esophageal squamous cell carcinoma after radical surgery. Methods: This study included 206 patients with esophageal cancer who underwent surgical R0 resection. The data, including the basic information, preoperative blood routine, albumin, fibrinogen, surgery-related information, postoperative pathology, and overall survival, of the patients were compared. Results: The survival and death groups showed a significant difference in overall survival (OS), the degree of differentiation, depth of infiltration, pathological stage, vascular infiltration, nerve infiltration, fibrinogen, white blood cell, neutrophils, platelet, and platelet hematocrit (P<0.05). Tumor located in the middle thorax, larger lesion length, deeper invasion, later pathological stage, vascular infiltration, nerve infiltration, lymph node metastasis, cardiovascular disease, and higher smoking grade were risk factors for poor prognosis of esophageal squamous cell carcinoma (ESCC) (P<0.05). Cardiovascular disease, lower differentiation, tumor located in the middle thorax, and nerve infiltration were independent risk factors for the reduction of survival time of patients with ESCC (P<0.05). Conclusions: History of cardiovascular disease, tumor located in the middle chest, poorly differentiated esophageal squamous cell carcinoma, visible nerve cancer invasion, hematocrit (HCT), mean erythrocyte hemoglobin concentration (MCHC), and hemoglobin (HB) are independent risk factors for the long-term survival of patients with ESCC.
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Leukapheresis is an effective adjuvant therapy for leukemia patients with hyperleukocytosis, but few studies have reported recent data with modern modalities and comparisons among different leukemia types. We conducted a retrospective study on leukapheresis among 420 patients with AML, ALL and CML in four local centers. WBC counts decreased significantly (p < 0.001) postleukapheresis in all three cohorts. Clearance efficiency was higher in acute leukemia patients than CML patients (p < 0.01). Concomitant leukocytoreduction drugs improved WBC reduction only in AML patients (p < 0.05). Leukocyte, hemoglobin and platelet levels preleukapheresis might affect the clearance efficiency in AML and/or ALL patients. Hematological toxicities were the major concerns, but most of them were mild, and only 11 patients died of all causes within one week postleukapheresis. In conclusion, leukapheresis can safely reduce the leukemic burden, especially for patients with acute leukemias.
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Leucaférese , Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Leucocitose/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Contagem de Leucócitos , Doença AgudaRESUMO
The effects of ISG15 or ISGylation on tumor progression have been widely revealed; however, its roles in glioma progression are largely unknown. This study aims to explore the roles and underlying mechanisms of ISG15 in glioma progression. Here, ISG15 level was found to be upregulated in glioma tissues compared to the paired/unpaired normal tissues, and positively correlated with the level of stemness markers in glioma tissues. Loss of functional experiments indicated that ISG15 positively regulated glioma cell stemness, as evident by the increase of sphere formation ability, ALDH activity, stemness marker expression, and tumor-initiating ability. Further mechanistic studies revealed that ISG15 directly interacted with Oct4 protein, a critical stemness promoter, induced the ISGylation of Oct4 protein, and thus enhanced Oct4 protein stability. Additionally, it was found that Oct4 was ISGylated at lysine 284 (K284), which has been confirmed to be the ubiquitination site of Oct4 protein, and ISG15 knockdown did not degrade K284R mutant Oct4. Furthermore, ISG15 knockdown-induced downregulation of glioma cell stemness was rescued by Oct4 overexpression, but not by K284R mutant Oct4. Altogether, we suggest that ISG15-induced ISGylation of Oct4 protein is essential for glioma cell stemness.
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Citocinas , Glioma , Fator 3 de Transcrição de Octâmero , Ubiquitinas , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo , Glioma/genética , Humanos , Células-Tronco Neoplásicas , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Estabilidade Proteica , Ubiquitinação , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMO
Objective: Esophageal squamous cell carcinoma (ESCC) causes many deaths worldwide every year. Fascin actin-bundling protein 1(FSCN1) has been reported to be a promoter of ESCC via its actin-binding function, however, its new role as an RNA-binding protein (RBP) has not been investigated. Here, we explored the RBP role of FSCN1 in the development of ESCC. Methods: Whole-genome expression sequencing was performed to screen for altered genes after FSCN1 knockdown. RNA immunoprecipitation was performed to determine the target mRNA of FSCN1 as an RBP. In vitro experiments with ECA-109 and KYSE-150 and ex vivo experiments in tumor-bearing mice were performed to investigate the effects of FSCN1 and Protein Tyrosine Kinase 6 (PTK6) on ESCC progression. Results: FSCN1 could downregulate mRNA and the protein level of PTK6. The binding position of PTK6 (PTK6-T2) pre-mRNA to FSCN1 was determined. PTK6-T2 blocked the binding between FSCN1 and the pre-mRNA of PTK6, and thus reversed the promotion effect of FSCN1 on ESCC tumor progression via the AKT/GSK3ß signaling pathway. Conclusion: A novel effect of FSCN1, RBP-binding with the pre-mRNA of PTK6, was confirmed to play an important role in ESCC progression. PTK6-T2, which is a specific inhibitor of FSCN1 binding to the pre-mRNA of PTK6, could impede the development of ESCC.
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Objective: To evaluate the clinical efficacy and safety of hydrogen inhalation in improving hearing loss in patients with long-term survival of nasopharyngeal carcinoma after radiotherapy. Methods: The eustachian tube dysfunction score, pure tone air conduction threshold, bone conduction threshold, the score of tympanogram and otoscope were prospectively observed in patients with deafness after radiotherapy only or combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Paired t test and one-way analysis of variance were used to analyze the data before and after treatment. Results: A total of 17 patients were observed. The median time from radiotherapy to now was 228 months, and the median time from the diagnose of deafness to now was 92 months. After 4 weeks of hydrogen inhalation, the score of eustachian tube dysfunction, air conduction and bone conduction hearing thresholds were significantly reduced, P values were 0.0293, 0.0027, 0.0404, respectively. The mean air-bone gap, the score of otoendoscopy and tympanogram were also decreased, but the differences were not significant (P = 0.2079, P = 0.0536, P = 0.1056). Patients with radiotherapy alone and concurrent chemo-radiotherapy had significantly lower air conduction hearing threshold after hydrogen absorption (P = 0.0142, P = 0.0495). The results of air and bone hearing thresholds before, 4 and 12 weeks after hydrogen inhalation showed a descending trend. The air and bone hearing thresholds before hydrogen inhalation were 74.69 ± 27.03 dB and 45.70 ± 21.58 dB, respectively. At the 12th week, the mean values of air and bone hearing thresholds were the lowest, which were 66.88 ± 20.88 dB and 40.94 ± 18.93 dB, respectively, but there was no significant difference in air and bone hearing thresholds among all groups (P = 0.6755, P = 0.7712). After hydrogen inhalation treatment, no adverse reactions such as nosebleed, chest pain, dyspnea, nausea, vomiting, dizziness, earache and allergic reaction were observed. Conclusion: This is the first prospective study on the effect of hydrogen inhalation on hearing improvement in patients with deafness after radiotherapy/chemotherapy for nasopharyngeal carcinoma, suggesting that continuous hydrogen inhalation may be an alternative rehabilitation therapy for these patients.
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BACKGROUND AND PURPOSE: Background - Up to now, the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy remain controversial. Purpose - To analyze the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy under an endoscope, and to provide evidence for preventing and controlling the occurrence and development of infections. METHODS: A total of 370 patients receiving endoscopic transsphenoidal pituitary adenomectomy in our hospital from January 2014 to October 2017 were selected. The risk factors related to postoperative intracranial infections were analyzed. The hospitalization lengths and expenditures of patients with and without intracranial infections were compared. RESULTS: Of the 370 patients, 18 underwent postoperative intracranial infections, with the infection rate of 4.86%. Intraoperative blood loss >120 mL, cerebrospinal leakage, diabetes, preoperative use of hormones, macroadenoma as well as surgical time >4 h all significantly increased the infection rate (P<0.05). Preoperative use of antibacterial agents prevented intracranial infection. Compared with patients without intracranial infections, the infected ones had significantly prolonged hospitalization length and increased expenditure (P<0.05). Discussion - It is of great clinical significance to analyze the risk factors related to intracranial infection after endoscopic transsphenoidal pituitary adenomectomy, aiming to prevent and to control the onset and progression of infection. CONCLUSION: Intracranial infections after endoscopic transsphenoidal pituitary adenomectomy were affected by many risk factors, also influencing the prognosis of patients and the economic burden.
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Adenoma/cirurgia , Endoscopia/métodos , Infecções/etiologia , Neoplasias Hipofisárias/cirurgia , Osso Esfenoide/cirurgia , Adenoma/patologia , Humanos , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias , Fatores de Risco , Procedimentos Cirúrgicos Operatórios , Resultado do TratamentoRESUMO
Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1st to September 25th, 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019.
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Imunidade Adaptativa/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Hidrogênio/administração & dosagem , Hidrogênio/farmacologia , Imunidade Inata/efeitos dos fármacos , Neoplasias Pulmonares/imunologia , Administração por Inalação , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Long non-coding RNAs (lncRNAs), some of the most abundant epigenetic regulators, play an important role in esophageal squamous cell carcinoma (ESCC). In the current study, the functions and mechanisms of the lncRNA LINC00673 were investigated. The expression levels of LINC00673 and its potential target genes were assessed by quantitative real-time polymerase chain reaction (qPCR) in ESCC surgical specimens and ESCC cell lines. RNA fluorescence in situ hybridization (RNA FISH) was employed to detect the subcellular location and the levels of LINC00673 in ESCC samples from patients with different survival times. LINC00673 function in ESCC carcinogenesis was also evaluated in vivo and in vitro. Cell cycle synchronization was performed using serum withdrawal; the cell cycle was monitored by fluorescence analysis and cellular DNA was detected by flow cytometry. The molecular mechanisms underlying LINC00673 were explored via Western blotting, chromatin immunoprecipitation (ChIP), and ChIP-PCR. Up-regulated LINC00673 was associated with poor prognosis in ESCC patients and promoted the proliferation of ESCC cells both in vitro and in vivo. Compared to the control group, depletion of LINC00673 in ESCC cells arrested the cell cycle, at least, at the G1/S checkpoint. Knockdown of LINC00673 significantly enhanced posttranscriptional expression of CDKN2C, and histone 3 lysine 27 trimethylation (H3K27me3) was enriched at the promoter region of CDKN2C. After inhibiting EZH2, the CDKN2C expression levels were increased. The present findings are the first to reveal that LINC00673 represses CDKN2C expression and promotes ESCC cell proliferation by elevating EZH2-mediated H3K27me3 levels. These data suggest that LINC00673 regulates the cell cycle in ESCC and that it is a promising target for clinical therapy.
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BACKGROUND: Esophageal cancer (EC), as a serious threat to human life and health, is one of the most common cancers around the world. Many studies have suggested that many microRNAs are involved in tumorigenesis and progression. METHODS: To search for a novel and promising predictive therapeutic target or biomarker to achieve the goal of the early diagnosis and treatment of EC, we used the EC cell lines Eca-109 and KYSE-150 and normal human esophageal epithelial cells (HEECs) to investigate the effect of ABI3BP on EC. RESULTS: We found that ABI family member 3 binding protein (ABI3BP) was downregulated in EC and suppressed the proliferation, activity, migration, and invasion of EC cells. ABI3BP was downregulated by miR-183, which plays the role of an oncogene. CONCLUSION: ABI3BP and miR-183 can be considered potential biomarkers for the diagnosis of patients with EC and can be effective targets for antitumor therapy.
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Proteínas de Transporte/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , MicroRNAs/metabolismo , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , MicroRNAs/genética , Cicatrização/genética , Cicatrização/fisiologiaRESUMO
Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H2)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H2-therapy, respectively. Patients underwent H2 inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Hidrogênio/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Hidrogênio/administração & dosagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Although it is becoming increasingly apparent that histone methyltransferases and histone demethylases play crucial roles in the cellular response to hypoxia, the impact of hypoxic environments on global patterns of histone methylation is not well demonstrated. In this study, we try to detect the global levels of histone lysine methylation in HCC cases and analyze the correlation between these modifications and the activation of hypoxia-inducible factor 1α (HIF-1α). Immunohistochemistry was used to detect the global levels of histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 9 trimethylation (H3K9me3), histone H3 lysine 27 trimethylation (H3K27me3) and the nuclear expression of HIF-1α in tissue arrays from 111 paraffin-embedded HCC samples. Our analyses revealed that the global levels of H3K9me2, H3K9me3 and the nuclear expression of HIF-1α were distinctly higher in HCC tissues than in peritumoral tissues. Both H3K9me2 and H3K9me3 were positively correlated with the degree of tumor differentiation and the patients' prognosis. Analysis based on the Pearson's correlation coefficient indicated a positive correlation between H3K9me2 and the nuclear expression of HIF-1α, and meanwhile, a significant correlation between the expression of H3K9me2 and H3K9me3 was also found. In addition, the combination of H3K9me2, H3K9me3 and HIF-1α, rather than one single histone modification or molecular maker, is a better prognostic maker for HCC patients. These findings provide new insights on the complex networks underlying cellular and genomic regulation in response to hypoxia and may provide novel targets for future therapies.