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BACKGROUND: The aim of this study was to assess the survival outcomes of cisplatin-paclitaxel chemotherapy plus bevacizumab (CPB) versus cisplatin-paclitaxel chemotherapy alone (CPA) in postmenopausal women with previously untreated advanced cervical cancer (CC). METHODS: Consecutive postmenopausal women who experienced CPB or CPA were identified retrospectively from our medical centre during 2015-2019. Follow-up visits occurred 1 and 3 months after starting CPB or CPA. Afterwards, this assessment was conducted every 3 months for 1 year and then yearly thereafter. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were the frequency and severity of adverse events (AEs). RESULTS: Two hundred forty-six postmenopausal women were included (CPB, n = 124; CPA, n = 122). The median follow-up for the entire cohort was 24 months (range, 2-32). At the final follow-up, a significant difference was detected in terms of median OS (16.4 months [95% CI, 15.3-17.1] for CPB vs. 12.3 months [95% CI, 10.2-13.5] for CPA; hazard ratio (HR) 0.69, 95% CI, 0.49-0.99; p = 0.001), and the median PFS was longer in the CPB group than in the CPA group (9.2 months [95% CI, 8.3-10.7] vs. 7.9 months (95% CI, 6.1-8.6) (HR 0.62, 95% CI, 0.47-0.82; p < 0.001). There were significant differences in the number of AEs between the groups (hypertension grade ≥ 2 [p < 0.001], neutropenia grade ≥ 4 [p < 0.001], and thrombosis/embolism grade ≥ 3 [p = 0.030]). CONCLUSIONS: Among postmenopausal women with previously untreated advanced CC, those who received CPB experienced superior survival benefits compared to those who received CPA. The safety profile for CPB was controllable despite the long duration of CPB use.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Posmenopausia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Diagnosing pulmonary thromboembolism (PTE) remains challenging due to the lack of specific clinical symptoms and biomarkers. Circulating microRNAs (miRNAs) have proved to be potential biomarkers for numerous cardiovascular diseases. The aims of this study were to quantitatively analyze the expression of plasma miRNA-190 and miRNA-197 in patients with PTE and to evaluate the diagnostic value for PTE. METHODS: Thirty patients diagnosed with PTE by computed tomographic pulmonary angiography at the emergency department were enrolled in this study, and plasma was collected immediately. For comparison, myocardial infarction (MI, n = 45) and healthy participants (NC, n = 45) were recruited as the control groups. Quantitative reverse transcription PCR (qRT-PCR) was conducted to reveal the relative expression levels of miRNA-190 and miRNA-197 in each group. The plasma concentrations of D-dimer were measured by immunoturbidimetric assay. The diagnostic value was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). RESULTS: The relative expression levels of miRNA-190 and miRNA-197 in the PTE group were both significantly higher than in the MI group (t = 3.602 t = 4.791, P < .05, respectively) and the healthy control group (t = 5.814, t = 5.886, P < .05, respectively). As diagnostic indicator, the sensitivity and specificity of miRNA-190 were 75.56% and 80%, respectively, with an AUC of 0.7844 (95%CI: 0.6858-0.8831, P < .001). The sensitivity and specificity of miRNA-197 were 73.33% and 86.67%, respectively, with an AUC value of 0.7931 (95%CI: 0.6870-0.8991, P < .001). Combining miRNA-190 and miRNA-197 with D-dimer levels significantly increased the diagnostic power, improving the AUC to 0.9536 (95% CI: 0.9083-0.9989, P < .001). CONCLUSIONS: The relative expression levels of miRNA-190 and miRNA-197 in PTE patients were significantly higher than in the MI and healthy control groups, indicating that (a) both may be involved in the pathophysiological process of PTE and (b) both may serve as potential noninvasive diagnostic markers for PTE. The combination of miRNA-190, miRNA-197, and D-dimer levels showed better sensitivity and specificity, which is more conducive to the diagnosis of PTE.
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MicroARNs/sangre , Embolia Pulmonar/diagnóstico , Adulto , Biomarcadores , China , Estudios de Cohortes , Angiografía por Tomografía Computarizada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/epidemiología , Sensibilidad y EspecificidadRESUMEN
A new lead oxyborate, Pb4B6O13, has been successfully synthesized by introducing stereochemically active Pb2+ cations and distorted OPb4 tetrahedra into asymmetric borates. Pb4B6O13 exhibits an unprecedented two-dimensional ∞(B6O12)6- layer structure with a large second harmonic generation (SHG) response that is 3 times that of KH2PO4. In addition, theoretical work, including dipole moment calculations, electronic structure, and SHG coefficients combined with SHG density analysis, is reported. The results suggest that the enhanced SHG of Pb4B6O13 is attributed to the synergy effect of three functional units.
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RATIONALE: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. PATIENT CONCERNS: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. DIAGNOSIS: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. INTERVENTIONS: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. OUTCOMES: Currently, the patient demonstrates a stable disease by clinical evaluation. LESSONS: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.
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Adenolinfoma , Linfoma de Células del Manto , Neoplasias de la Parótida , Humanos , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/complicaciones , Linfoma de Células del Manto/diagnóstico , Femenino , Anciano , Adenolinfoma/patología , Adenolinfoma/complicaciones , Adenolinfoma/cirugía , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/complicaciones , Glándula Parótida/patología , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/cirugíaRESUMEN
Two new molybdenum(VI) phosphates, RbMoO(2)PO(4) and Rb(4)Mo(5)P(2)O(22), have been synthesized by standard solid-state reactions, and their structures were determined by single-crystal X-ray diffraction. The former is centrosymmetric, whereas the latter is noncentrosymmetric and chiral. Their crystal structures both consist of corner- and edge-shared MoO(6) octahedra, PO(4) tetrahedra, and RbO(n) (n = 8 or 10) polyhedra and exhibit three- and one-dimensional structures, respectively. Powder second-harmonic generation (SHG) measurements revealed an SHG efficiency of approximately 1.4 × KH(2)PO(4) (KDP) for Rb(4)Mo(5)P(2)O(22). Thermal analysis, infrared and UV-vis-NIR diffuse reflectance spectroscopy, and electronic band structure calculations were also performed on the reported materials. Crystal data are the following: RbMoO(2)PO(4), orthorhombic, space group Fddd (No. 70), a = 11.012(5) Å, b = 12.403(5) Å, c = 15.839(7) Å, V = 2163.3(16) Å(3), and Z = 16; Rb(4)Mo(5)P(2)O(22), orthorhombic, space group C222(1) (No. 20), a = 6.5300(5) Å, b = 19.7834(18) Å, c = 17.3451(15) Å, V = 2240.7(3) Å(3), and Z = 4.
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Molibdeno/química , Fosfatos/química , Teoría Cuántica , Rubidio/química , Cristalografía por Rayos X , Modelos MolecularesRESUMEN
The structures of two new lead-containing oxyborate bromines, Pb2(O4Pb8)(BO3)3Br3 (1) and Pb2(O8Pb12)(BO3)2Br6 (2), are determined by single-crystal X-ray diffraction for the first time. Both of them crystallize in the space group C2/c of the monoclinic crystal system. Although the two compounds have the same type of fundmental building units (FBUs), the OPb4 anion-centered tetrahedra and BO3 triangles, they exhibit different connection modes. Compound 1 consists of single ∞(1)[OPb2] chains, while compound 2 possesses ∞(1)[O2Pb3] ribbons. Interestingly, large Br atoms profoundly influence the conformation of polyions based on the OPb4 anion-centered tetrahedra, resulting in single ∞(1)[OPb2] chains linked up by finite zweier chains with four OPb4 tetrahedra via the opposite edges in compound 1 and ∞(1)[O2Pb3] ribbons with sequential condensation of OPb2 chains in compound 2. A detailed description of the effect of large Br atoms on the conformation of polyions is discussed. IR spectroscopy, UV-vis-NIR diffuse reflectance spectroscopy, and thermal analysis are also performed on the reported materials.
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Purpose: To study and compare the pharmacokinetic characteristics of enteric-coated sustained-release (EcSr) aspirin tablets with enteric-coated (Ec) aspirin tablets (Bayer S.p.A) in healthy Chinese participants. Patients and Methods: In this open, randomized, single-dose, three-way, crossover study, 18 healthy participants randomly received 100 mg EcSr tablets pre-prandially (a.c.), EcSr tablets post-prandially (p.c.), or Ec tablets a.c. in each period. The concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma were determined by the LC-MS/MS method, and the pharmacokinetic parameters were calculated using WinNonlin (version 8.1). Results: The essential PK parameters under the three treatment conditions (ie Ec a.c., EcSr a.c. and EcSr p.c.) were as follows: Cmax, ASA: 758.38±455.34, 222.77±98.04 and 194.54±61.19 ng, Tmax, ASA: 6.75(2,16), 4.5(2,11) and 8.25(5,11) h, T1/2, ASA: 0.43±0.08, 1.44±0.59 and 4.32±10.04 h, AUC0-t, ASA: 1008.88±452.27, 918.04±238.40 and 845.55±183.25 h·ng/mL; Cmax, SA: 6409.38±2098.52, 2863.53±679.73 and 2913.75±853.27ng/mL, Tmax, SA: 7.25(2,24), 10(3.5-14) and 10(7,14) h, T1/2, SA: 2.21±0.46, 2.69±0.72 and 3.51±2.06h, AUC0-t, SA: 29,131.41±9376.23, 27,243.97±7465.16, 27,240.25±7444.67 h·ng/mL. When taking EcSr aspirin tablets, the 90% confidence intervals of the geometric mean ratios (pre-prandial/post-prandial) of AUC0-t, ASA and AUC0-∞, ASA, Cmax, SA, AUC0-t, SA and AUC0-∞, SA were within the range of 80.00%-125.00%. Conclusion: EcSr aspirin tablets showed less inter-individual variation in release and absorption than Ec aspirin tablets, which was well reflected by comparing essential PK parameters. Furthermore, meals had no significant effect on the pharmacokinetics of EcSr aspirin tablets.
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Aspirina , Preparaciones de Acción Retardada , Pueblos del Este de Asia , Humanos , Aspirina/farmacocinética , Cromatografía Liquida , Estudios Cruzados , Preparaciones de Acción Retardada/farmacocinética , Voluntarios Sanos , Ácido Salicílico , Espectrometría de Masas en Tándem , Comprimidos Recubiertos/farmacocinéticaRESUMEN
Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.
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Neoplasias Encefálicas , Glioma , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , PronósticoRESUMEN
OBJECTIVES: Hyperglycemia that develops during pregnancy is a diagnostic criterion of gestational diabetes mellitus (GDM). Current studies have shown that the expression of miRNA-181d is significantly enhanced in the glomeruli of type 2 diabetic. However, the relationship between miR-181d and GDM has never been reported before. MATERIAL AND METHODS: The serum samples were collected from patients with GDM and subjected to qRT-PCR to verify the potential altered the miR-181d expression. In an in vitro GDM model, the miR-181d expression was induced by high glucose treatment, a miR-181d inhibitor was transfected into INS-1 cells to reduce miR-181d expression. Then, the level of insulin mRNA, cell viability, and content of total insulin were analyzed through ELISA, CCK-8 assay, and qRT-PCR assay. The relative apoptosis rates were detected by Annexin-V/PI assays. Finally, the shIRS2 transfection was performed to test whether in pancreatic ß cells, IRS2 had similar insulin-enhancing functions as the miR-181d inhibitor. RESULTS: MiR-181d expression level was positively correlated with fasting blood glucose levels and the inhibition of miR-181d reduced insulin resistance, enhanced cells viability and suppressed high-glucose-induced apoptosis. In addition, the suppression of miR-181d improved the functions of INS-1 cells by targeting IRS2. CONCLUSIONS: In summary, this study indicated that miR-181d modulated the process of insulin signaling and cell viability and apoptosis in pancreatic ß cells by targeting IRS-2, suggesting that miR-181d inhibition is a potential target for GDM therapy.
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Diabetes Gestacional , Resistencia a la Insulina , Células Secretoras de Insulina , MicroARNs , Diabetes Gestacional/fisiopatología , Femenino , Humanos , Insulina , Proteínas Sustrato del Receptor de Insulina/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , MicroARNs/genética , EmbarazoRESUMEN
Chronic obstructive pulmonary disease (COPD) is a long-term lung disease characterized by irreversible lung damage resulting in airflow limitation, abnormal permanent air-space enlargement, and emphysema. Cigarette smoking is the major cause of COPD with 15% to 30% of smokers developing either disease. About 50% to 80% of patients with lung cancer have preexisting COPD and smokers who have COPD are at an increased risk for developing lung cancer. Therefore, COPD is considered an independent risk for lung cancer, even after adjusting for smoking. A crucial early event in carcinogenesis is the induction of the genomic instability through alterations in the mitotic spindle apparatus. To date, the underlying mechanism by which COPD contributes to lung cancer risk is unclear. We hypothesized that tobacco smoke carcinogens induce mitotic spindle apparatus abnormalities and alter expression of crucial genes leading to increased genomic instability and ultimately tumorigenesis. To test our hypothesis, we assessed the genotoxic effects of a potent tobacco-smoke carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)] on bronchial epithelial cells from patients with COPD and normal bronchial epithelial cells and identified genes associated with mitotic spindle defects and chromosome missegregation that also overlap with lung cancer. Our results indicate that exposure to NNK leads to a significantly altered spindle orientation, centrosome amplification, and chromosome misalignment in COPD cells as compared with normal epithelial cells. In addition, we identified several genes (such as AURKA, AURKB, and MAD2L2) that were upregulated and overlap with lung cancer suggesting a potential common pathway in the transition from COPD to lung cancer.
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Células Epiteliales/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Mitosis , Nitrosaminas/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/patología , Huso Acromático/patología , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinógenos/toxicidad , Daño del ADN , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Proteína Forkhead Box M1/metabolismo , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/metabolismo , Proteínas Mad2/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Huso Acromático/efectos de los fármacosRESUMEN
The current study tested expression and potential function of circular RNA ecto-5'-nucleotidase (circNT5E) in human non-small cell lung cancer (NSCLC). We show that circNT5E levels are significantly elevated in human NSCLC tissues and cells, correlating with downregulation of its potential targets, miR-134, miR-422a and miR-338. In A549 and primary NSCLC cells, circNT5E shRNA inhibited cancer cell growth, proliferation and migration, whiling inducing apoptosis activation. Conversely, ectopic circNT5E overexpression promoted A549 cell progression in vitro. miR-134 is the primary target of circNT5E in lung cancer cells. RNA-Pull down assay in A549 cells confirmed the direct association between biotinylated-miR-134 and circNT6E. miR-134 levels were significantly increased in circNT5E-silenced A549 cells, but reduced with circNT5E overexpression. Forced overexpression of miR-134 mimicked circNT5E shRNA-induced actions, inhibiting NSCLC cell growth and proliferation. In contrast, miR-134 inhibition largely attenuated circNT5E shRNA-induced anti-NSCLC cell activity. Importantly, circNT5E shRNA was ineffective in miR-134-overexpressed A549 cells. Collectively, circNT5E promotes human NSCLC cell progression possibly by sponging miR-134.
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5'-Nucleotidasa/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , ARN Circular , 5'-Nucleotidasa/genética , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , MicroARNs/genética , Persona de Mediana EdadRESUMEN
Bromodomain-containing protein 4 (BRD4) overexpression in non-small cell lung cancer (NSCLC) promotes cancer progression. Here, we show that miR-4651 selectively targets and negatively regulates BRD4 in A549 and primary human NSCLC cells. RNA pull-down experiments confirmed that miR-4651 directly binds to BRD4 mRNA. Further, ectopic overexpression of miR-4651 in A549 cells and primary NSCLC cells decreased BRD4 3'-UTR luciferase reporter activity and its expression, whereas miR-4651 inhibition elevated both. Functional studies demonstrated that NSCLC cell growth, proliferation, and migration were suppressed with ectopic miR-4651 overexpression but enhanced with miR-4651 inhibition. BRD4 re-expression using a 3'-UTR mutant BRD4 reversed A549 cell inhibition induced by miR-4651 overexpression. Further, miR-4651 overexpression or inhibition failed to alter the functions of BRD4-KO A549 cells. In vivo, miR-4651-overexpressing A549 xenografts grew slowly than control A549 xenografts in severe combined immunodeficient mice. Finally, miR-4651 was downregulated in human NSCLC tissues, correlating with BRD4 elevation. Together, miR-4651 targets BRD4 to inhibit NSCLC cell growth in vitro and in vivo.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Ciclo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , MicroARNs/genética , Factores de Transcripción/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Pronóstico , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Two new metal borate-phosphates, Pb4O(BO3)(PO4) (1) and Bi4O3(BO3)(PO4) (2), have been successfully designed and synthesized. The structures of the title compounds were determined by single-crystal X-ray diffraction. The title compounds have similar crystal structures consisting of oxygen-centered (OPb4) or (OBi4) tetrahedra as well as isolated BO3 and PO4 groups. Structural comparison and the Madelung energy calculation indicate that the title compounds also exhibit a strong correlation with the known metal borates and phosphates. In addition, a strategy of BO3-PO4 substitution is proposed for designing new borate-phosphates. Thermal analyses, IR spectroscopy and UV-vis-NIR diffuse reflectance spectroscopy have also been performed.