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OBJECTIVE: To observe the clinical efficacy of medical education combined with extended care in patients with bronchial asthma and its effect on adherence to inhaled glucocorticoids. METHODS: Ninety-eight patients with bronchial asthma were divided into the control group and the experimental group, n = 49, by utilizing the random number table method. The control group was given routine education and care as well as routine out-of-hospital instructions, and the experimental group was given medical education and extended care based on the control group. Asthma disease knowledge mastery, asthma control, quality of life, medication adherence and lung function were compared between both groups, and the number of asthma attacks and re-hospitalizations were recorded. RESULTS: The experimental group performed higher scores of health knowledge, asthma control test and quality of life, rate of complete adherence, forced expiratory volume in one second (FEV1), peak expiratory flow rate, and FEV1/forced vital capacity. The number of asthma attacks and the times of re-hospitalizations were lower in the experimental group (all p < 0.05). CONCLUSION: Medical education combined with extended care can improve bronchial asthma patients' mastery of asthma disease knowledge, effectively control patients' conditions, enhance patients' quality of life and lung function, increase patients' adherence to inhaled glucocorticoids, and reduce the recurrence of bronchial asthma patients.
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Eutrophic shallow lakes are hotspots of carbon (C) and nitrogen (N) accumulation and transformation, and are increasingly recognized as important sources of greenhouse gases (GHGs: CO2, CH4 and N2O). Lacustrine groundwater discharge (LGD) is a crucial component of the water budget and terrestrial material delivery for lakes, but its interplays with intrinsic CN biogeochemical processes remain less tackled. In this study, C and N ingredients and multiple stable isotopes (δ2H, δ18O, δ13C, and δ15N) were measured seasonally in groundwater, river water and lake water of a large eutrophic shallow lake in eastern China. The results revealed that groundwater is enriched with various forms of C and N that have similar sources and pathways as surface water in the lake and rivers. The isotope balance model also indicated that LGD derived C and N contribute significantly to lake inventories in addition to river runoff. These allochthonous C and N provide extra substrates for related biogeochemical processes, such as algae proliferation, organic matter degradation, methanogenesis and denitrification. Simultaneously, the excess oxygen consumption leads to depletion and hypoxia in the lake, further facilitating the processes of methanogenesis and denitrification. LGD functions not only as an external source of C and N that directly increases GHG saturations, but also as a mediator of internal CN pathways, which significantly affect hypoxia formation, GHG productions and emissions in the eutrophic lake. This study highlights the unrevealed potential regulation of LGD on biogeochemical processes in the eutrophic lake, and underscores the need for its consideration in environmental and ecological studies of lakes both regionally and globally.
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Placental hypoxia is hazardous to maternal health as well as fetal growth and development. Preeclampsia and intrauterine growth restriction are common pregnancy problems, and one of the causes is placental hypoxia. Placental hypoxia is linked to a number of pregnancy illnessesv. To investigate their potential function in anoxic circumstances, we mimicked the anoxic environment of HTR-8/Svneo cells and performed lncRNA and circRNA studies on anoxic HTR-8/Svneo cells using high-throughput RNA sequencing. The miRNA target genes were predicted by integrating the aberrant expression of miRNAs in the placenta of preeclampsia and intrauterine growth restriction, and a ceRNA network map was developed to conduct a complete transcriptomic and bioinformatics investigation of circRNAs and lncRNAs. The signaling pathways in which the genes were primarily engaged were predicted using GO and KEGG analyses. To propose a novel explanation for trophoblastic organism failure caused by lncRNAs and circRNAs in an anoxic environment.
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Redes Reguladoras de Genes , RNA Circular , RNA Longo não Codificante , Humanos , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , Linhagem Celular , RNA-Seq , Hipóxia Celular/genética , Gravidez , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Placenta/metabolismo , Trofoblastos/metabolismo , Trofoblastos/citologia , Biologia Computacional/métodos , Perfilação da Expressão GênicaRESUMO
Potential role and associated mechanisms of Annexin A8 (ANXA8), a member of the Annexins family, in cervical squamous cell carcinoma (CESC) are still unclear, despite being upregulated in various malignant tumors. Here, we observed a notably elevated expression of ANXA8 in CESC cells. The inhibition of ANXA8 amplified the susceptibility of CESC cells to Erastin and sorafenib-induced ferroptosis, whereas it exerted minimal influence on DPI7 and DPI10-induced ferroptosis. The results from the Fe2+ concentration assay showed no significant correlation between ANXA8 gene knockdown and intracellular Fe2+ concentration induced by ferroptosis inducers. Western blot analysis demonstrated that the knockdown of ANXA8 did not alter ACSL4 and LPCAT levels under ferroptosis-inducing conditions, but it did result in a reduction in intracellular GSH levels induced by the ferroptosis inducer. Subsequently, we identified TFAP2A as an upstream transcription factor of ANXA8, which plays a role in regulating cell ferroptosis. The knockdown of TFAP2A significantly elevated MDA levels and depressed GSH levels in the presence of a ferroptosis inducer, thereby inhibiting cell ferroptosis. However, this inhibitory effect could be reversed by ANXA8 overexpression. Therefore, our research suggests that the TFAP2A/ANXA8 axis exerts regulatory control over ferroptosis in CESC cells by mediating GSH synthesis in System Xc.
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We reported a 51-year-old male electric welder with stage I pneumoconiosis, who had no significant cough, sputum, fever, chest pain, or other discomfort. However, regular physical examination at our hospital revealed bilateral pulmonary nodules with cavity formation. Blood routine, liver or kidney function, and infection-related biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT), were normal. Sputum and alveolar lavage fluid (BALF) acid-fast bacilli (AFB) smears, BALF Mycobacterium tuberculosis (TB) PCR, and T-SPOT.TB were negative. The nucleic acid sequence of Mycobacterium europaeum was detected by BALF metagenomic next-generation sequencing (mNGS), which was confirmed by the subsequent positive culture for NTM. Considering stable conditions, no significant discomfort, and no significant changes in the lung lesion, the patient was diagnosed with inactive nontuberculous mycobacterial pulmonary disease (NTM-PD).
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OBJECTIVE: To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients. METHODS: Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs. RESULTS: Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower. CONCLUSION: Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.
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Carcinoma , Neoplasias de Cabeça e Pescoço , Segunda Neoplasia Primária , Neoplasias das Glândulas Salivares , Humanos , Estudos Retrospectivos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Glândulas Salivares/patologia , Programa de SEERRESUMO
Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. Methylation of some genes plays a crucial role in the tendency to malignancy as well as poor prognosis of thyroid cancer, suggesting that methylation features can serve as complementary markers for molecular diagnosis. In this study, we aimed to develop and validate a diagnostic model for PTC based on DNA methylation markers. A total of 142 thyroid nodule tissue samples containing 84 cases of PTC and 58 cases of thyroid adenoma (TA) were collected for reduced representation bisulfite sequencing (RRBS) and subsequent analysis. The diagnostic model was constructed by the logistic regression (LR) method followed by 5-cross validation and based on 94 tissue methylation haplotype block (MHB) markers. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.974 (95% CI, 0.964-0.981) on 108 training samples and 0.917 (95% CI, 0.864-0.973) on 27 independent testing samples. The diagnostic model scores showed significantly high in males (P = 0.0016), age ≤ 45 years (P = 0.026), high body mass index (BMI) (P = 0.040), lymph node metastasis (P = 0.00052) and larger nodules (P = 0.0017) in the PTC group, and the risk score of this diagnostic model showed significantly high in recurrent PTC group (P = 0.0005). These results suggest that the diagnostic model can be expected to be a powerful tool for PTC diagnosis and there are more potential clinical applications of methylation markers to be excavated.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Masculino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/genética , Metilação de DNA/genética , Haplótipos , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Recidiva Local de Neoplasia/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
Thyroid cancer is the most common type of endocrine system cancer. The pre-cancer and early stages are usually benign or slowly growing, and do not need invasive treatments. This study investigated the challenging classification task of four classes of samples, i.e., normal controls (N), thyroid adenomas (TA), papillary thyroid cancers (PTC) and metastasized papillary thyroid cancers (MPTC). We proposed a multi-view progression diagnosis framework ThyroidBloodTest to integrate the two views of RNAseq platelet transcriptomes (View-T) and blood routine (View-B) features. Platelet transcriptome represented the molecular-level information, while the blood routine features were easy to obtain in the clinical practice. Eleven feature selection algorithms and seven classifiers were evaluated for both views. The experimental data suggested the importance of choosing appropriate data analysis algorithms and feature engineering techniques like principal component analysis (PCA). The best ThyroidBloodTest model achieved Acc = 0.8750 for the four-class classification of the N/TA/PTC/MPTC samples based on the integrated feature space of View-T and View-B. The cellular localization cytosol and three post-translational modification types acetylation/phosphorylation/ubiquitination were observed to be enriched in the proteins encoded by the View-T biomarkers. The numbers of different immune cells also contributed positively to the progression diagnosis of thyroid cancer. The proposed multi-view prediction model demonstrated the necessity of integrating both platelet transcriptomes and blood routine tests for the progression diagnosis of thyroid cancer.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/genética , Transcriptoma/genética , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genéticaRESUMO
Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14+ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.
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Psoríase , Receptores de Antígenos de Linfócitos T gama-delta , Humanos , Butirofilinas/metabolismo , Regulação para Cima , Fator de Necrose Tumoral alfa , Antígenos , Antígenos CD , Ativação Linfocitária , Linfócitos TRESUMO
In order to investigate the therapeutic evaluation of percutaneous kyphoplasty (PKP) for the treatment of osteoporotic thoracolumbar compression fractures by three-dimensional (3D) reconstruction of computed tomography (CT) based on the deep learning V-Net network, the traditional V-Net was optimized first and a new and improved V-Net was proposed. The introduced U-Net, V-Net, and convolutional neural network (CNN) were compared in this study. Then, 106 patients with osteoporotic thoracolumbar compression fractures were enrolled, and 128 centrums were divided into the test group with 53 cases of PKP and the control group with 53 cases of percutaneous vertebroplasty (PVP) according to different surgical protocols. All patients underwent CT scan based on the improved V-Net, and data of centrum measurement indicators, pain score, and therapeutic evaluation results of the modified Macnab were collected. The Dice coefficient of the improved V-Net was observably higher than that of U-Net, V-Net, and CNN, while the Hausdorff distance was lower than that of U-Net, V-Net, and CNN (P < 0.05). The anterior height, central height, and posterior height of the centrum were significantly higher than those in the control group after operation (3, 5, and 7 days), while the Cobb angle of vertebral kyphosis was significantly lower than that in the control group (P < 0.05). The score of visual analog scale (VAS) and analgesic use score of patients in the test group were markedly lower than those in the control group (3, 5, and 7 days after operation), P < 0.05. Besides, the excellent and good rate of the test group was remarkably higher than that of the control group, P < 0.05. Hence, the improved V-Net had better quality of segmentation and reconstruction than the traditional deep learning network. Compared with PVP, PKP was helpful in restoring the height of the centrum in patients with osteoporotic thoracolumbar compression fractures and correct kyphosis, with better analgesic effect safety.
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Aprendizado Profundo , Fraturas por Compressão , Cifoplastia , Cifose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Imageamento Tridimensional , Cifoplastia/métodos , Cifose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vertebroplastia/métodosRESUMO
Psoriasis is a chronic, immune-mediated inflammatory disease which pathogenesis is closely linked to γδ T cells. Recently, a critical role for butyrophilin 3A1 (BTN3A1) in mediating the activation of Vγ9Vδ2 T cells, which are reported to redistribute from blood to the perturbed skin lesions in psoriasis, has been proposed. Additional molecular partners, including RhoB and periplakin, have also been speculated to interact with BTN3A1 in modulating Vγ9Vδ2 T-cell activation. Immunohistochemical staining was performed to examine the expressions of BTN3A1, RhoB, and the plakin family members, including periplakin, epiplakin, and envoplakin in the psoriasis vulgaris lesions as compared with the normal control. The expressions of BTN3A1 and RhoB were found significantly upregulated in the psoriatic lesions. Besides, a downregulation of periplakin and an upregulation of epiplakin were noticed in the psoriasis vulgaris lesions. Our data suggest that BTN3A1 and RhoB might participate in the pathogenesis of psoriasis through Vγ9Vδ2 T-cell responses. In addition, a potential involvement of the plakin protein family, especially periplakin and epiplakin, in psoriasis pathology was proposed.
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Psoríase , Receptores de Antígenos de Linfócitos T gama-delta , Antígenos CD/metabolismo , Butirofilinas/química , Butirofilinas/metabolismo , Humanos , Plaquinas , Receptores de Antígenos de Linfócitos T gama-delta/metabolismoRESUMO
OBJECTIVE: To assess the capacity of support vector machine (SVM) algorithms that are developed based on platelet RNA-seq data in identifying thyroid neoplasm patients and differentiating patients with thyroid adenomas, papillary thyroid cancer and metastasized papillary thyroid cancer. METHODS: Platelets were collected and isolated from 109 patients and 63 healthy controls. RNA-seq was performed to find transcripts with differential levels. Genes corresponding to these altered transcripts were identified using R packages. All samples were subsampled into a training set and a validation set. Two SVM algorithms were developed and trained with the training set, using the genes with differential transcript levels (GDTLs) as classifiers, and validated with the validation set. GO and KEGG pathway enrichment analysis were performed using the R package clusterProfiler. RESULTS: We detected 765 GDTLs (442 up-regulated and 323 down-regulated) in platelets of patients and healthy controls. The algorithm identifying thyroid neoplasm patients achieved an accuracy of 97%, with an AUC (area under curve) of 0.998. The other algorithm differentiating patients with multiclass thyroid neoplasms had an average accuracy of 80.5%. GO analysis showed that GDTLs were strongly involved in biological processes such as neutrophil degranulation, neutrophil activation, autophagy and regulation of multi-organism process. KEGG pathway enrichment analysis revealed that GDTLs were mainly enriched in NOD-like receptor signaling pathway and pathways in endocytosis, osteoclast differentiation, human cytomegalovirus infection and tuberculosis. CONCLUSION: Our results indicated that the combination of SVM algorithms and platelet RNA-seq data allowed for thyroid neoplasm diagnostics and multiclass thyroid neoplasm classification.
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Máquina de Vetores de Suporte , Neoplasias da Glândula Tireoide , Algoritmos , Plaquetas , Humanos , RNA-Seq , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Frailty is linked to perioperative morbidity and mortality. We evaluated the impact of preoperative frailty on inpatient outcomes of patients undergoing surgery for thyroid malignancy. METHODS: This population-based, retrospective observational study extracted data of hospitalized patients who were 18 years and older with a primary diagnosis of thyroid cancer undergoing thyroidectomy from the US Nationwide Inpatient Sample (NIS) database (2005-2014). Participants were stratified into frail and non-frail using the Johns Hopkins (ACG) frailty-defining diagnosis indicator. Study endpoints were in-hospital mortality, incidence of surgical and medical complications and prolonged length of stay. Univariate and multivariate analysis were performed to determine associations between the endpoints and frailty. RESULTS: Data of 38,202 patients were included. After adjusting for possible confounders, frailty remained significantly associated with higher odds of in-hospital mortality (OR: 3.839, 95% CI: 1.738-8.480), prolonged length of stay (OR: 5.420, 95% CI: 3.799-7.733), surgical complications (OR: 3.144, 95% CI: 2.443-4.045) and medical complications (OR: 6.734, 95% CI: 5.099-8.893) compared with non-frailty. In patients > age 65 years, adjusted odds ratio for frailty was 4.099 (95% CI: 1.736-9.679) for in-hospital mortality, 6.164 (95% CI: 3.514-10.812) for prolonged length of stay, 3.736 (95% CI: 2.620-5.328) for surgical complications, and 5.970, 95% CI: 4.088-8.720 for medical complications, all with significance. CONCLUSION: Frailty is associated with increased risk for adverse inpatient outcomes, including prolonged hospital stay, surgical and medical complications and mortality independent of age and comorbidities in thyroid cancer patients undergoing surgery. Study findings may provide valuable information for preoperative risk stratification.
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Fragilidade/complicações , Mortalidade Hospitalar , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/complicações , Resultado do TratamentoRESUMO
Psoriasis-2 (PSORS2) is caused by the heterozygous mutation of the caspase recruitment domain 14 (CARD14) gene on chromosome 17q25. To evaluate the contribution of CARD14 variants in psoriasis of the Chinese Han population, we performed deep sequencing of the CARD14 gene in 372 Chinese Han patients with psoriasis. The exonic nucleotide variants were confirmed by Sanger sequencing in the affected individuals and 1114 controls. In 27 patients with psoriasis, we identified 15 variations, including three novel variants: c.381C[G (p.Cys127Trp), c.712A[G (p.Met238Val) and c.2260_2261delinsGG (p.Gln754Gly). These findings could enrich and update the Human Gene Mutation Database of CARD14 variants for psoriasis.
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Povo Asiático/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Mutação , Psoríase/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Psoríase/epidemiologia , Psoríase/patologiaRESUMO
Previous studies have reported a higher incidence of depression and anxiety in psoriasis patients compared to the general population, which has important implications for assessment and treatment. In this study, we determined the frequency of depression and anxiety in Chinese patients with psoriasis and its relationship with disease severity and other demographic variables. The study included 208 Chinese patients with psoriasis vulgaris. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) were used to screen for depression and anxiety. The Psoriasis Area and Severity Index (PASI) was used to assess the severity of psoriasis. Of the 208 patients included in the study, 29 patients (13.9%) were positive for moderate-to-severe depression (PHQ-9 ≥ 10) and 22 patients (10.6%) were positive for anxiety (GAD-7 ≥ 10) symptoms. Both positive stress reactors who perceived stress as an exacerbating factor of psoriasis and moderate-to-severe psoriasis were found to be positive predictors for the presence of moderate-to-severe depression or anxiety symptoms while longer duration and late onset age played a protective role. In the sample of Chinese patients with psoriasis there was a clinically significant prevalence of depression and anxiety. Our study suggests that Chinese psoriasis patients should be screened for psychiatric comorbidities.
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Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Psoríase/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , China/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments. DESIGN: Literature review, pooling analysis and correlation analysis. DATA SOURCES: PubMed, from 1 January 2010 to 30 June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments. RESULTS: Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29). CONCLUSIONS: No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
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Viés , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estatística como Assunto , Resultado do Tratamento , HumanosRESUMO
BACKGROUND: The expression and function of androgen receptors (AR) and estrogen receptor alpha (ER-É) in laryngeal squamous cell carcinoma (LSCC) have remained controversial for decades. Prolactin receptor (PRLR) is a sex-related hormone, that has been rarely documented in terms of expression or function compared with data on other hormone receptors in laryngeal carcinoma. METHODS: This study reports on immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis of tumour tissue and adjacent normal tissue in 96 patients with LSCC (82 males and 14 females). The expression levels of the receptors were related to clinicopathologic parameters and survival data. RESULTS: At both protein and mRNA levels, the expression level of AR, ER-É, and PRLR was much higher in LSCC than in adjacent normal tissues (p < .05). Among them, higher PRLR expression in tumour tissues tended to have a significantly poorer survival rate (p = .03) for patients with LSCC. Furthermore, higher expression of ER-É in tumours was correlated with higher expression level of PRLR (r = .823, p = .03). CONCLUSION: The findings of this study indicate that the sex-related hormone receptors play an important role in the development of LSCC. The PRLR represents a novel prognosticator, because of its negative effect on survival and its interaction with ER-É.
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Carcinoma de Células Escamosas/metabolismo , Receptor alfa de Estrogênio/metabolismo , Neoplasias Laríngeas/metabolismo , Receptores Androgênicos/metabolismo , Receptores da Prolactina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Receptores Androgênicos/genética , Receptores da Prolactina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
BACKGROUND: In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. METHODS: Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. RESULTS: A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), P<0.01, I2=11%; exp-DCR: OR=0.90 (0.81-1.01), P=0.07, I2=42%] and control arms [con-ORR: OR=0.79 (0.72-0.85), P<0.01, I2=17%; con-DCR: OR=0.94 (0.86-1.02), P=0.14, I2=12%]. No sign of evaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I2=0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I2=0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). CONCLUSIONS: Blind independent central review remained irreplaceable to monitor local assessment, but its complete-case implementation may be unnecessary.
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The present study reports a rare case of a renal clear cell carcinoma with thyroid and parotid metastases. A 56-year-old female, with a painless, right preauricular mass present for 6 months was referred to Renji Hospital (Shanghai, China). Physical examination revealed a mass of 3×3 cm, which was smooth, firm, immobile and non-tender. There was no accompanying facial weakness. Parotid ultrasonography revealed a hypoechoic mass within the right parotid gland, which was potentially a parotid mixed tumor. In July 2011, the patient underwent a superficial parotidectomy with preservation of the facial nerve. Pathology confirmed as right parotid clear cell carcinoma (metastasis). The patient's relevant medical history included a right radical nephrectomy for renal clear cell carcinoma (clinical stage III) in 2004. Additionally, in 2009, the patient underwent a resection of thyroid metastatic renal cell carcinoma. To the best of our knowledge, no similar case has previously been reported in English-language literature. The present study discusses a case report, and investigates the clinical features and treatment strategy.