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BACKGROUND: There is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors. METHODS: Clinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively. RESULTS: There were 263 (21.8%) cases of EH combined with CAD in the training group. Multivariate logistic regression showed that FMD, age, duration of EH, waist circumference, and diabetes mellitus were independent influencing factors for CAD in EH patients. Smoking which was close to statistical significance (P = 0.062) was also included in the regression model to increase the accuracy. Ultimately, the nomogram for predicting CAD in EH patients was constructed according to above predictors after proper transformation. The AUC values of the training group and the validation group were 0.799 (95%CI 0.770-0.829) and 0.836 (95%CI 0.787-0.886), respectively. Calibration curve and Hosmer-Lemeshow test showed that the model had good calibration (training group: χ2 = 0.55, P = 0.759; validation group: χ2 = 1.62, P = 0.446). The decision curve also verified the clinical applicability of the nomogram. CONCLUSION: The nomogram based on FMD and traditional risk factors (age, duration of EH disease, smoking, waist circumference and diabetes mellitus) can predict CAD high-risk group among patients with EH.
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Enfermedad de la Arteria Coronaria , Hipertensión , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Modelos Estadísticos , Nomogramas , Estudios Retrospectivos , Pronóstico , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión Esencial , Factores de RiesgoRESUMEN
BACKGROUND: Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery. METHODS: In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored. RESULTS: The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3-16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes. CONCLUSION: Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).
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Hipotensión , Oxitócicos , Inercia Uterina , Embarazo , Femenino , Recién Nacido , Humanos , Oxitocina , Fenilefrina , Estudios Prospectivos , Hipotensión/etiología , Hipotensión/prevención & control , Método Doble Ciego , Infusiones IntravenosasRESUMEN
In this work, the multilevel resistive random access memories (RRAMs) have been achieved by using the structure of Pt/MoO3/Hf/MoO3/Pt with four stable resistance states. The devices show good retention property of each state (>104s) and large memory window (>104). The simulation and experimental study reveal that the resistive switching mechanism is ascribed to combination of the conductive filament in the stack of MoO3/Hf next to the top electrode and redox reaction at the interface of Hf/MoO3next to bottom electrode. The fitting results of current-voltage characteristics under low sweep voltage indicate that the conduction of HRSs is dominated by the Poole-Frenkel emission and that of LRS is governed by the Ohmic conduction. Based on the RRAM, the tunable high-pass filter (HPF) with configurable filtering characteristics has been realized. The gain-frequency characteristics of the programmable HPF show that the filter has high resolution and wide programming range, demonstrating the viability of the multilevel RRAMs for future spiking neural network and shrinking the programmable filters with low power consumption.
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Liposarcoma(LPS) is the most common type of soft tissue sarcoma accounting for 20 % of all adult sarcomas. However, the molecular pathogenesis of this malignancy is still poorly understood. Here, we showed that GPS2 expression was downregulated in LPS and correlated with the prognosis of this disease. In vitro study showed that knockdown of GPS2 resulted in enhanced proliferation and migration of LPS cell line SW872, without significant influence of cell death. Conclusively, our results suggest that GPS2 may act as a tumor suppressor in LPS and serve as a potential prognosis marker for this disease.
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Péptidos y Proteínas de Señalización Intracelular/metabolismo , Liposarcoma/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adipogénesis , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Biomarcadores , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Femenino , Estudios de Seguimiento , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Liposarcoma/genética , Liposarcoma/mortalidad , Liposarcoma/patología , Masculino , Persona de Mediana Edad , Pronóstico , Transducción de Señal , Proteínas Supresoras de Tumor/genéticaRESUMEN
The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.
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Carcinoma/radioterapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Encéfalo/patología , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/secundario , Estudios de Casos y Controles , Femenino , Humanos , Hipotiroidismo , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Puntaje de Propensión , Traumatismos por Radiación/patología , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/mortalidad , Estudios Retrospectivos , Factores Sexuales , Tasa de SupervivenciaRESUMEN
The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.
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Carcinoma de Células Escamosas , Quimioradioterapia , Neoplasias Esofágicas , Esófago , Radioterapia de Intensidad Modulada , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Esófago/diagnóstico por imagen , Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Planificación de Atención al Paciente , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Melatonin, a well-known antioxidant, has been shown to possess anti-invasive properties for glioma. However, little is known about the effect of melatonin on glioma cell migration and invasion under hypoxia, which is a crucial microenvironment for tumor progress. In addition, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration and invasion. Therefore, we investigated the possible role of these kinases and its related signaling in the regulation of human U251 glioma cells behavior by melatonin under hypoxia. METHODS: The abilities of migration and invasion of U251 glioma cells were determined by wound healing and transwell assay in vitro. The intracellular production of reactive oxygen species (ROS) was measured by using the fluorescent probe 6-carboxy-2', 7'-dichorodihydrofluorescein diacetate (DCFH-DA). Immunofluorescence experiments and western blotting analysis were used to detect the expression level of protein. Small interfering RNAs (siRNA) was used to silence specific gene expression. RESULTS: The pharmacologic concentration (1 mM) of melatonin significantly inhibited the migration and invasion of human U251 glioma cells under hypoxia. The inhibitory effect of melatonin was accompanied with the reduced phosphorylation of FAK and Pyk2, and decreased expression of alpha v beta 3 (αvß3) integrin. Additionally, inhibition of αvß3 integrin by siRNA reduced the phosphorylation of FAK/Pyk2 and demonstrated the similar anti-tumor effects as melatonin, suggesting the involvement of αvß3 integrin- FAK/Pyk2 pathway in the anti-migratory and anti-invasive effect of melatonin. It was also found that melatonin treatment decreased the ROS levels in U251 glioma cells cultured under hypoxia. ROS inhibitor apocynin not only inhibited αvß3 integrin expression and the phosphorylation levels of FAK and Pyk2, but also suppressed the migratory and invasive capacity of U251 glioma cells under hypoxia. CONCLUSIONS: These results suggest that melatonin exerts anti-migratory and anti-invasive effects on glioma cells in response to hypoxia via ROS-αvß3 integrin-FAK/Pyk2 signaling pathways. This provides evidence that melatonin may be a potential therapeutic molecule targeting the hypoxic microenvironment of glioma.
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Movimiento Celular/efectos de los fármacos , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 2 de Adhesión Focal/metabolismo , Glioma/patología , Integrina alfaVbeta3/metabolismo , Melatonina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Línea Celular Tumoral , Silenciador del Gen/efectos de los fármacos , Glioma/metabolismo , Humanos , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , ARN Interferente Pequeño/metabolismoRESUMEN
This study is designed to explore the possible effects of Hemerocallis citrina baroni flavonids (HCBF) on liver fibrosis induced by CCl4 in rats. The liver fibrosis model was induced by CCl4, and HCBF were administered by gastric perfusion at 25 and 50 mg x kg(-1) qd for 50 days, while the contents of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), superoxide dismutase (SOD), maleic dialdehyde (MDA) and transforming growth factor-ß1 (TGF-ß1) were measured and the contents of PINP were measured in liver tissue, and the expression of TGF-ß1 were observed by immunohistochemisty and Western blot. The pathological changes of liver tissue were examined by HE. The results showed that HCBF (25, 50 mg x kg(-1)) improved the liver function significantly through reducing the level of ALT, AST, GGT and ALP (P < 0.05 or P < 0.01), and increasing the content of SOD (P < 0.01), while reducing the content of MDA (P < 0.05 or P < 0.01), the expression of TGF-ß1 (P < 0.05) and the content of PINP (P < 0.05). The results suggest that HCBF (25, 50 mg x kg(-1)) may inhibit the liver injury induced by CCl4 by decreasing the oxidative stress.
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Flavonoides/farmacología , Hemerocallis/química , Cirrosis Hepática/tratamiento farmacológico , Extractos Vegetales/farmacología , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Tetracloruro de Carbono , Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/inducido químicamente , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Superóxido Dismutasa/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , gamma-Glutamiltransferasa/metabolismoRESUMEN
Male genital lichen sclerosus (MGLSc) is a chronically relapsing disease characterized by a long course, gradual aggravation, and a tendency towards malignancy. Once called balanitis xerotica obliterans, MGLSc has a distinct predilection for the prepuce and glans, involving the urethra when aggravating, forming scarring tissues, and causing urethral stricture, which may seriously affect the patients'quality of life with such symptoms as urinary stream narrowing, dysuria, and painful penile erection. The etiology and pathogenesis of MGLSc have not yet been adequately explained though it is generally thought to be associated with autoimmune mechanism, genetic factors, infections, local trauma, and chronic urinary irritation. MGLSc can be fairly easily diagnosed according to its clinical manifestations and histopathological results, but can be hardly cured. Early diagnosis and prompt treatment are the most important approaches, which may relieve its symptoms, check its progression, and prevent its long-term sequelae. Ultrapotent topical corticosteroids are the choice for the treatment of MGLSc. For those who fail to respond to expectant medication or have dysuria due to urethral stricture and painful erection, rational surgery may be resorted to, with importance attached to long-term follow-up. This article presents an update of the diagnosis and treatment of MGLSc and MGLSc-induced urethral stricture.
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Enfermedades de los Genitales Masculinos , Liquen Escleroso y Atrófico , Enfermedades de los Genitales Masculinos/diagnóstico , Enfermedades de los Genitales Masculinos/etiología , Enfermedades de los Genitales Masculinos/terapia , Humanos , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/terapia , Masculino , Estrechez Uretral/etiologíaRESUMEN
Purpose: This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia. Patients and Methods: Sixty female patients aged 65-80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 µg/kg), while Group R received remimazolam alone. Dosing adjustments (±2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. Results: The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845-5.859) and 8.184 mg (95% CI, 6.636-13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533-8.068) and 11.298 mg (95% CI, 9.101-19.617), respectively. Conclusion: This study provides compelling evidence that the administration of 1 µg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 µg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.
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Benzodiazepinas , Relación Dosis-Respuesta a Droga , Fentanilo , Hipnóticos y Sedantes , Humanos , Femenino , Anciano , Fentanilo/administración & dosificación , Anciano de 80 o más Años , Hipnóticos y Sedantes/administración & dosificación , Benzodiazepinas/administración & dosificación , Anestesia GeneralRESUMEN
Background: Previous studies have explored the median effective concentration (EC50) of ropivacaine for labor epidural analgesia in parturients with obesity. However, the clinical relevance of the 90% effective concentration (EC90) remains unclear. This study aimed to determine and compare the dose-response curve of epidural ropivacaine for labor analgesia between parturients with and without obesity. Methods: Parturients were divided into two groups based on body mass index (BMI): group N, consisting of parturients with BMI <30 kg/m2, and group O, consisting of parturients with BMI >30 kg/m2. Within each group, the patients were randomized to receive one of five concentrations (0.0375%, 0.075%, 0.1125%, 0.15%, or 0.1875%) of epidural ropivacaine for labor analgesia. Analgesia was induced with a loading dose of 15 mL of the assigned concentration. Visual analogue scale (VAS) scores were recorded at baseline and 30 min post-dose to calculate the response (%) using the formula [(baseline VAS pain score-VAS pain score at 30 min)/baseline VAS pain score] ×100%. The EC50 and EC90 values were determined via nonlinear regression analysis. Results: The EC50 and EC90 values of ropivacaine were 0.061% (95% confidence interval [CI], 0.056%-0.066%) and 0.177% (95% CI, 0.152%-0.206%) in group N and 0.056% (95% CI, 0.051%-0.061%) and 0.161% (95% CI, 0.138%-0.187%) in group O, respectively. No significant differences were observed in the EC50 and EC90 values between the two groups (p-values = 0.121 and 0.351, respectively. Conclusion: In conclusion, within the parameters of this study, our findings suggest that obesity, characterized by a mean BMI value of 30.9, does not significantly influence the EC50 and EC90 values of epidural ropivacaine for labor analgesia. Further investigations are warranted to elucidate the dose-response relationship between ropivacaine and obesity with higher BMI values. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=190747, Identifier ChiCTR2300073273.
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BACKGROUND: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. METHODS: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. RESULTS: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. CONCLUSION: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD.
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Adenocarcinoma , Factor de Especificidad de Desdoblamiento y Poliadenilación , NADH Deshidrogenasa , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Proliferación Celular , NADH Deshidrogenasa/genética , Neoplasias Pancreáticas/genética , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Factor de Especificidad de Desdoblamiento y Poliadenilación/genéticaRESUMEN
Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.
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FOXJ1 is a member of the forkhead box (FOX) family of transcription factors. Recent studies suggested that FOXJ1 may function as a tumor suppressor gene in breast cancer. To investigate the potential roles of FOXJ1 in hepatocellular carcinoma (HCC), expression of FOXJ1 was first examined in eight paired frozen HCC and adjacent noncancerous liver tissues by Western blot, and we found that FOXJ1 was upregulated in HCC specimens. In addition, immunohistochemistry was performed to confirm our results in 108 HCC samples. Moreover, we also evaluated its relation with clinicopathological variables and the prognostic significance. The data showed that high expression of FOXJ1 was associated with histological grade (P < 0.001), and FOXJ1 was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that FOXJ1 expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that tumor grade (P < 0.0001), metastasis (P = 0.0451), tumor size (P = 0.0459), FOXJ1 (P = 0.0011), and Ki-67 (P = 0.0006) were independent prognostic markers for HCC. Furthermore, we noted that there existed the change of the level of FOXJ1 subcellular localization during cell-cycle transition in HepG2 cells by immunofluorescence and cell fractionation. Besides, we employed FOXJ1 overexpression/knockdown approaches to investigate the effects of FOXJ1 on HCC cell proliferation and cell-cycle distribution and found that overexpression of FOXJ1 can promote tumor cell proliferation and cell-cycle transition. Our results suggested that FOXJ1 was overexpressed in HCCs and associated with histological grade and poor prognosis. Overexpression of FOXJ1 was also involved in tumor cell proliferation and cell-cycle progression in HCC cell lines.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Factores de Transcripción Forkhead/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Factores de Transcripción Forkhead/genética , Expresión Génica , Humanos , Inmunohistoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
OBJECTIVE: To evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer. METHODS: We treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS). RESULTS: All the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases. CONCLUSION: Transrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.
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Braquiterapia , Hormonas/uso terapéutico , Radioisótopos de Yodo/administración & dosificación , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/terapia , Anciano , Terapia Combinada , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Resultado del TratamientoRESUMEN
Pancreatic ductal adenocarcinoma is a highly malignant cancer with poor prognosis, for which effective therapeutic strategies are urgently needed. The dual-specificity phosphatase PTPMT1 is localized in mitochondria and highly expressed in various cancers. Here, we investigated the function of PTPMT1 in pancreatic ductal adenocarcinoma. We inhibited its expression in pancreatic cancer cell lines using siRNAs or the specific PTPMT1 inhibitor alexidine dihydrochloride and observed that PTPMT1 silencing in pancreatic cancer cell lines drastically reduced cell viability, caused mitochondrial damage, and impaired mitochondrial function. Co-immunoprecipitation analysis demonstrated that PTPMT1 could interact with SLC25A6 and NDUFS2, indicating that it may modulate mitochondrial function via the SLC25A6-NDUFS2 axis. Collecively, our data highlight PTPMT1 as an important factor in pancreatic ductal adenocarcinoma and a potential therapeutic target.
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Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.
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AIM: To investigate the role of delta-like ligand 4 (DLL4) in the angiogenesis of high-grade malignant glioma. MATERIALS AND METHODS: DLL4 expression and microvessel density (MVD) were detected by immunohistochemistry in 51 human high-grade malignant glioma tissue samples. The vessel maturation index (VMI) was calculated as the percentage of a-smooth muscle actin (a-SMA)-positive vessels in relation to the amount of CD31-positive vessels. Double fluorescent immunostaining for CD31 and EphrinB2 or EphB4 was performed to identify the arterial (EphrinB2) or venous (EphB4) origins of glioma microvessels. RESULTS: Strong immunostaining of DLL4 and a positive correlation of DLL4 with the MVD were observed in high-grade malignant gliomas. The VMI of the DLL4-positive group was significantly higher than that of the DLL4-negative group. However, no significant association was found between DLL4 and EphrinB2 or EphB4 in high-grade gliomas. CONCLUSION: DLL4 may be an important regulator for vessel proliferation and maturation in human high-grade malignant gliomas.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Endotelio Vascular/metabolismo , Glioma/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neovascularización Patológica/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Adulto , Neoplasias Encefálicas/patología , Proteínas de Unión al Calcio , Proliferación Celular , Endotelio Vascular/patología , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Estadística como AsuntoRESUMEN
OBJECTIVE: To investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor ß1-connective tissue growth factor (TGFß1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis. METHODS: A rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFß1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody. RESULTS: The model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFß1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis. CONCLUSION: FTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFß1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.
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Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Glomerulonefritis Membranoproliferativa/patología , Glicoles de Propileno/farmacología , Transducción de Señal/efectos de los fármacos , Esfingosina/análogos & derivados , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Proliferación Celular , Factor de Crecimiento del Tejido Conjuntivo/genética , Regulación hacia Abajo , Proteínas de la Matriz Extracelular/metabolismo , Clorhidrato de Fingolimod , Expresión Génica , Mesangio Glomerular/metabolismo , Mesangio Glomerular/patología , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/metabolismo , Inmunosupresores/farmacología , Isoanticuerpos/inmunología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Proteinuria/orina , Ratas , Ratas Wistar , Esfingosina/farmacología , Antígenos Thy-1/inmunología , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
The unmixing algorithms of mixed snow pixels and the fractional snow cover products are an important research direc- tion for snow remote sensing. In the present study, we first designed the mixed snow pixels of different snow fraction/proportion in Northern Xinjiang, China as ground truth. Then, a SVC HR-1024 ground-based spectral radiometer was used for measuring the spectral property of this designed pixel for different snow fractions and different underlying surfaces. Finally, using the measured spectral data, the four mixed-pixel decomposition models were validated and evaluated for their performance in terms of accuracy and computational efficiency. The results showed that the reflectivity does not decline linearly with the reduction of snow ratio in the pixel, and that the unmixing accuracy inversely depends on the scales of the observation. Further, the comparison of the above mentioned unmixing algotihms showed that the linear regression method has the worst accuracy, especially when the snow proportion is less than 50%; the accuracy of sparse regression algorithm and non-negative matrix factorization were slightly higher than the full constrained linear mixed-pixel decomposition; however, full constrained linear mixed-pixel decomposition method had higher computational efficiency than the other two methods; the sparse regression algorithm has lowest computational efficiency. With unmixing remote sensing images, due to the large data volumes, we must consider the algorithms' computational efficiency. This study would promote quantitative researches on snow mixed pixel decomposition, and provide a theoretical basis for accurately extracting the snow coverage of interest area using remote sensing images.