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Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.
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Estudios Cruzados , Medicamentos Genéricos , Estradiol , Posmenopausia , Comprimidos , Equivalencia Terapéutica , Femenino , Humanos , Persona de Mediana Edad , Administración Oral , Pueblo Asiatico , China , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/efectos adversos , Pueblos del Este de Asia , Estradiol/farmacocinética , Estradiol/administración & dosificación , Estradiol/sangre , Estradiol/análogos & derivados , Voluntarios SanosRESUMEN
Kidney renal clear cell carcinoma (KIRC) pathogenesis intricately involves immune system dynamics, particularly the role of T cells within the tumour microenvironment. Through a multifaceted approach encompassing single-cell RNA sequencing, spatial transcriptome analysis and bulk transcriptome profiling, we systematically explored the contribution of infiltrating T cells to KIRC heterogeneity. Employing high-density weighted gene co-expression network analysis (hdWGCNA), module scoring and machine learning, we identified a distinct signature of infiltrating T cell-associated genes (ITSGs). Spatial transcriptomic data were analysed using robust cell type decomposition (RCTD) to uncover spatial interactions. Further analyses included enrichment assessments, immune infiltration evaluations and drug susceptibility predictions. Experimental validation involved PCR experiments, CCK-8 assays, plate cloning assays, wound-healing assays and Transwell assays. Six subpopulations of infiltrating and proliferating T cells were identified in KIRC, with notable dynamics observed in mid- to late-stage disease progression. Spatial analysis revealed significant correlations between T cells and epithelial cells across varying distances within the tumour microenvironment. The ITSG-based prognostic model demonstrated robust predictive capabilities, implicating these genes in immune modulation and metabolic pathways and offering prognostic insights into drug sensitivity for 12 KIRC treatment agents. Experimental validation underscored the functional relevance of PPIB in KIRC cell proliferation, invasion and migration. Our study comprehensively characterizes infiltrating T-cell heterogeneity in KIRC using single-cell RNA sequencing and spatial transcriptome data. The stable prognostic model based on ITSGs unveils infiltrating T cells' prognostic potential, shedding light on the immune microenvironment and offering avenues for personalized treatment and immunotherapy.
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Carcinoma de Células Renales , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Análisis de la Célula Individual , Linfocitos T , Transcriptoma , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Linfocitos T/metabolismo , Linfocitos T/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Pronóstico , Línea Celular Tumoral , Redes Reguladoras de Genes , Proliferación Celular/genéticaRESUMEN
PURPOSE: The TROG 13.01 (SAFRON II) trial was a phase 2 multicenter trial comparing single-fraction (SF) and multifraction (MF) stereotactic body radiation therapy. Patients with 1 to 3 peripheral pulmonary oligometastases were randomized 1:1 between 28 Gy in 1 fraction and 48 Gy in 4 fractions. There were no differences between arms in efficacy or toxicity. We performed an analysis to assess changes in pulmonary function tests (PFTs) between arms over time and assessed the effect of the number and total volume of targets on PFT change over time. METHODS AND MATERIALS: A linear mixed model was used to describe the PFTs by treatment arm over time. The effect of number and volume of targets on PFTs at 6 and 12 months was assessed by a simple linear model. RESULTS: Ninety patients were randomized; 87 were treated for 133 pulmonary oligometastases. Forty-four were randomized to the SF arm and 43 to the MF arm. There were no differences in absolute or relative PFT measures of forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), or forced vital capacity (FVC) between the 2 arms. At 12 months, there was a reduction in absolute DLCO from baseline (-1.7 mL/min/mm Hg [95% CI, -2.5 to -1.0]), relative DLCO (-5.5% [95% CI, -8.4% to -2.6%]), absolute FEV1 (-0.17 L [95% CI, -0.23 to -0.11]), and absolute FVC (-0.20 L [95% CI, -0.27 to -0.13]). In patients with multiple pulmonary targets, increase in target number (per lesion) was associated with a reduction in the absolute FEV1 at 6 months of -0.10 L (95% CI, -0.18 to -0.03; P = .007), FEV1 at 12 months of -0.10 L (95% CI, -0.20 to -0.01; P = .04), FVC at 6 months of -0.11 L (95% CI, -0.20 to -0.03; P = .014), and FVC at 24 months of -0.13 L (95% CI, -0.25 to -0.01; P = .036). Reduction in FEV1 was also seen per 10-mL increase in PTV at 12 months (-0.03 L [95% CI, -0.06 to -0.00], P = .036). The number of targets and PTV were not associated with DLCO. CONCLUSIONS: Treating multiple targets resulted in increased loss of FEV1 and FVC but not DLCO. There were no significant differences in PFT decline between SF and MF stereotactic body radiation therapy.
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Enfermedades Pulmonares , Pulmón , Humanos , Volumen Espiratorio Forzado , Capacidad Vital , Pruebas de Función RespiratoriaRESUMEN
AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no signiï¬cant differences in the primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period. CONCLUSION: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.
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Metilprednisolona , Equivalencia Terapéutica , Humanos , Área Bajo la Curva , Estudios Cruzados , Pueblos del Este de Asia , Ayuno , Voluntarios Sanos , Comprimidos , Metilprednisolona/farmacocinéticaRESUMEN
BACKGROUND: Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. OBJECTIVES: This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients. DATA SOURCES: Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022. STUDY ELIGIBILITY CRITERIA: We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines. PARTICIPANTS: SOT recipients who received COVID-19 vaccines. ASSESSMENT OF RISK OF BIAS: We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used. METHODS: We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls. RESULTS: A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%). CONCLUSIONS: A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.
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COVID-19 , Trasplante de Órganos , Vacunas , Humanos , Vacunas contra la COVID-19 , Receptores de Trasplantes , COVID-19/prevención & controlRESUMEN
Introduction: China has the largest population of diabetic patients (about 116 million) in the world. As a novel model of the fat index for Chinese people, the Chinese visceral adiposity index (CVAI) was considered a reliable indicator to assess the dysfunction of visceral fat. This study aimed to explore the dose-response relationship between CVAI and type 2 diabetes mellitus (T2DM) in the Chinese population, considering CVAI as a continuous/categorical variable. Method: Baseline and follow-up data were collected from waves 2011 and 2015, respectively, of the China Health and Retirement Longitudinal Study (CHARLS). Multivariate logistic regression models were used to explore the relationship between CVAI and T2DM. We built three models to adjust the possible effect of 10 factors (age, gender, education level, location, marital status, smoking status, drinking status, sleep time, systolic blood pressure (SBP), and diastolic blood pressure (DBP)) on the outcome. The restricted cubic splines were used to examine possible non-linear associations and visualize the dose-response relationship between CVAI and T2DM. Results: A total of 5,014 participants were included, with 602 (12.00%) T2DM patients. The last CVAI quartile group (Q4) presented the highest risk of T2DM (OR, 2.17, 95% CI, 1.67-2.83), after adjusting for all covariates. There was a non-linear (U-shaped) relationship between the CVAI and the risk of T2DM (p for non-linear <0.001) in the restricted cubic spline regression model. CVAI was a risk factor of T2DM when it exceeded 92.49; every interquartile range (IQR) increment in the CVAI was associated with a 57% higher risk of developing T2DM (OR = 1.57, 95% CI = 1.36-1.83) after adjusting for potential confounders. The area under the receiver operating characteristic curve (AUC) (95% confidence interval) for CVAI was 0.623, and the optimal cutoff point was 111.2. There was a significant interaction between CVAI and gender by stratified analysis. Conclusion: CVAI was closely associated with the risk of T2DM and might possibly be a potential marker in predicting T2DM development. The outcome suggested that it might be better to maintain CVAI within an appropriate range.
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Diabetes Mellitus Tipo 2 , Persona de Mediana Edad , Anciano , Humanos , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/complicaciones , Adiposidad , Estudios Longitudinales , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , China/epidemiologíaRESUMEN
OBJECTIVE: The aim of this study was to find differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs and related signaling pathways, contributing to understanding the molecular mechanism of acute recurrent pancreatitis (ARP). METHODS: First, peripheral whole blood samples from five acute pancreatitis (AP) patients, five ARP patients and five healthy individuals ( N ) were collected for RNA sequencing. Second, differentially/specifically expressed lncRNAs, miRNAs and mRNAs were identified in AP vs. N , ARP vs. N and ARP. Third, the ceRNA (lncRNA-miRNA-mRNA) networks of common/specifical lncRNAs, miRNAs and mRNAs were constructed in AP vs. N , ARP vs. N and ARP. Finally, functional analysis of common mRNAs in AP vs. N and ARP vs. N was performed. RESULTS: A total of 315 common lncRNAs, 12 common miRNAs and 909 common mRNAs were identified between AP and ARP. Ninety-four specifically expressed lncRNAs, one specifically expressed miRNAs and 286 specifically expressed mRNAs were found in ARP. Some interaction pairs were identified in AP and ARP, such as LUCAT1/NEAT1-hsa-miR-16-2-3p-HK2, CHRM3-AS2-hsa-miR-122-5p/hsa-miR-145-3p-DBH/CACNA1C, CHRM3-AS2-hsa-miR-200a-3p-PDGFD, RBM26-AS1-hsa-miR-200b-3p-FHIT and LINC00891/KTN1-AS1-hsa-miR-143-3p-tyrosine kinase (TXK). ASAP1-IT2/DGCR9-hsa-miR-342-5p-ABCC5/MAP2K6 was the only one specific interaction pair identified in ARP. Four significantly enriched signaling pathways were identified in AP vs. N and ARP vs. N , including amino sugar and nucleotide sugar metabolism (involved NPL and HK2), MAPK signaling pathway (involved CACNA1C and PDGFD), metabolic pathways (involved DBH and FHIT) and leukocyte transendothelial migration (involved TXK). CONCLUSION: The identified altered lncRNAs, miRNAs, mRNAs and related signaling pathways may be involved in the AP development and recurrence.
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MicroARNs , Pancreatitis , ARN Largo no Codificante , Enfermedad Aguda , Redes Reguladoras de Genes , Humanos , Proteínas de la Membrana/genética , MicroARNs/genética , MicroARNs/metabolismo , Pancreatitis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , Receptor Muscarínico M3/genéticaRESUMEN
BACKGROUND: D2 lymph node dissection for advanced gastric cancer is advocated, and station 8p lymph node should be considered in selected patients, which is, however, technically difficult. AIM: To introduce a new and easy-to-perform procedure for dissection of the lymph nodes superior to the pancreas. METHODS: A series of patients who underwent laparoscopic gastrectomy for gastric cancer were retrospectively included with utilization of a new procedure for superior pancreatic lymphadenectomy (LND) with portal vein priority via the posterior common hepatic artery approach (SPLD-PPPH) based on a newly defined portal triangle. The surgical outcome of the patients, as well as the efficacy and safety of SPLD-PPPH are reported. RESULTS: A total of 51 patients were included with most of them being male (n = 34, 66.7%). According to the 8th edition of AJCC TNM staging, there were four (7.8%) patients in stage I, 13 (25.5%) in stage II, 33 (64.7%) in stage III and one (2.0%) in stage IV. The average duration for LND was about 1 h (67.7 ± 6.9 min). After surgery, four patients developed morbidities, but all were treated successfully with no perioperative mortality. Among the 51 patients included, the percentage of patients who had lymph node metastasis at station 8p was 9.8%. Of note, with a total of 14 lymph nodes harvested at station 8p, the incidence of nodal metastasis was 14.3%. CONCLUSION: About one in 10 patients with advanced gastric cancer had nodal metastasis at station 8p. The new approach of SPLD-PPPH is safe and effective for D2+ LND during laparoscopic radical gastrectomy.
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Epidemiological studies have indicated that natural disasters have important impacts on ischemic stroke. This study determined the associations between natural disasters and the incidence and prevalence of ischemic stroke at the global level. A 28-year ecological trend study was performed to estimate worldwide changes in the incidence and prevalence of ischemic stroke and their associations with natural disasters by analyzing data from 193 countries. Quantum geographic information system-based visualization and multivariable linear regression were used. Changes in the incidence and prevalence of ischemic stroke, as well as disaster occurrence, varied among the different regions over the past 28 years (p < 0.001). Multiple linear regression revealed an independent and positive association between disaster occurrence and the incidence of ischemic stroke in males, females and both sexes combined (standardized coefficients = 0.515, 0.470 and 0.483, p < 0.001); similar associations were found for the prevalence of ischemic stroke (standardized coefficients = 0.471, 0.417 and 0.438, p < 0.001). The incidence and prevalence of ischemic stroke changed significantly at the global level and were independently associated with natural disasters. Both males and females show common but different vulnerabilities to natural disasters. This evidence supports policy making and resource allocation for disaster response and disease burden reduction.
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Salud Global/tendencias , Accidente Cerebrovascular Isquémico/epidemiología , Desastres Naturales , Femenino , Humanos , Incidencia , Accidente Cerebrovascular Isquémico/diagnóstico , Masculino , Prevalencia , Medición de Riesgo , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de TiempoRESUMEN
OBJECTIVE: This study was conducted to assess the pharmacokinetic and safety profiles between a new oral formulation of terazosin hydrochloride capsule compared with the brand-name drug. MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-period crossover study under fasting or fed conditions was conducted in healthy Chinese subjects. 24 individuals were selected, respectively. Each subject was randomized at the beginning to receive a 2-mg capsule of the test or the reference terazosin during the first period and then received the alternate formulation during the second period following a 1-week washout period. Blood samples were collected at pre-dose and up to 60 hours after administration. Plasma terazosin was quantified by a validated LC-MS/MS method. RESULTS: 48 healthy subjects were enrolled, and 47 completed the study. Cmax, AUC0-t, and AUC0-∞ were similar and the 90% CIs for the geometric mean ratios of these parameters between the two groups were all bounded within the predefined bioequivalence criterion of 80 - 125% under both fasting and fed conditions. Throughout the study period, a total of 30 treatment-emergent adverse events (TEAEs) were reported under fasting condition. 35 TEAEs were observed under fed conditions. No serious adverse event was observed. CONCLUSION: The test and reference formulations of terazosin were bioequivalent and well tolerated under both fasting and fed conditions.
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Ayuno , Espectrometría de Masas en Tándem , Área Bajo la Curva , China , Cromatografía Liquida , Estudios Cruzados , Voluntarios Sanos , Humanos , Prazosina/análogos & derivados , Comprimidos , Equivalencia TerapéuticaRESUMEN
BACKGROUND: Natural disasters are believed to be associated with cardiovascular disease. This study aimed to explore the changes in mortality due to ischemic heart disease (IHD) and their associations with natural disasters at the global level. METHODS: Country-specific data on the impact of natural disasters, rates of mortality due to IHD and years of life lost (YLL) and socioeconomic variables were obtained for 193 countries for the period from 1990 to 2017. An ecological trend study was conducted to estimate the changes in the IHD mortality and YLL rates and their associations with natural disasters (occurrence, casualties and total damage). Correlation analyses and multivariate linear regression were used. RESULTS: Significant changes were found in the IHD mortality and YLL rates and the occurrence of disasters between the two equal periods (1990 to 2003 and 2004 to 2017) (p<0.001). The bivariate Pearson correlation test revealed that the trend in the occurrence of natural disasters was positively correlated with trends in the IHD mortality and YLL rates among females and all individuals (p<0.05) and was marginally correlated among males. Multiple linear regression revealed an independent association between the occurrence of natural disasters and the IHD mortality rate among males, females and all individuals (standardized coefficients = 0.163, 0.357 and 0.241, p<0.05), and similar associations were found for the YLL rate (standardized coefficients = 0.194, 0.233 and 0.189, p<0.05). CONCLUSIONS: Our study demonstrated significant changes in the IHD mortality and YLL rates at the global level and their independent associations with natural disasters. Both males and females were vulnerable to natural disasters. These results provide evidence that can be used to support policy making and resource allocation when responding to disasters and developing strategies to reduce the burden of IHD.
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Isquemia Miocárdica/mortalidad , Ecología , Femenino , Humanos , Masculino , Desastres Naturales/mortalidad , Factores de RiesgoRESUMEN
Background: Pancreatic cancer (PC) is a malignant tumor with hidden incidence, high degree of malignancy, rapid disease progression, and poor prognosis. Eukaryotic translation initiation factor 3 subunit B (EIF3B) is necessary for tumor growth, which is an alternative therapeutic target for many cancers. However, little is known about the relationship between EIF3B and PC. Methods: The expression of EIF3B in PC was detected by immunohistochemistry. EIF3B knockdown cell models were constructed by lentivirus infection. The MTT assay, the wound-healing assay, the transwell assay, the flow cytometry, and the Human Apoptosis Antibody Array was used to detect the effects of EIF3B knockdown on cell proliferation, cell migration, cell apoptosis, and cell cycle in vitro. Also, the effects of EIF3B knockdown on the tumor growth of PC were determined in vivo. Results: This study showed that the expression level of EIF3B was significantly up-regulated in PC tumor tissues and associated with pathological grade. In vitro, EIF3B knockdown inhibited the PC cell proliferation and migration, and the apoptosis levels were obviously promoted by regulating apoptosis-related proteins including Bcl-2, HSP27, HSP60, Survivin, sTNF-R2, TNF-α, TNF-ß, TRAILR-3, TRAILR-4, and XIAP. Furthermore, the tumor growth of PC was inhibited after the knockdown of EIF3B in vivo. Conclusion: EIF3B was up-regulated in PC and was a promoter in the development and progression of PC, which could be considered as a therapeutic target for the treatment of PC.
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BACKGROUND: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. METHODS: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. RESULTS: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P < 0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046). CONCLUSIONS: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.
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COVID-19/fisiopatología , Adulto , Anciano , COVID-19/diagnóstico , Preescolar , China , Comorbilidad , Tos , Brotes de Enfermedades , Femenino , Fiebre , Hospitalización , Humanos , Lactante , Pulmón/diagnóstico por imagen , Linfopenia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND Acute pancreatitis (AP) is generally a self-limiting inflammatory disease, but is associated with a high mortality rate when severe. The present study aimed to investigate the effects of rhein and honokiol on AP. MATERIAL AND METHODS Thirty mice were randomly divided into 5 groups (n=6 per group): blank control, AP model, AP+rhein, AP+honokiol, and AP+rhein+honokiol. The AP model was prepared by intraperitoneal injection of cerulein and lipopolysaccharide (LPS). We observed the pathological changes of the pancreas by hematoxylin and eosin (H&E) staining. A mouse amylase kit was utilized to detect the level of amylase content in serum. Gas chromatography mass spectrometer analysis was performed to detect the differences in metabolites among the blank control, AP model, and AP+rhein+honokiol groups. RESULTS The serum amylase level was significantly higher in the AP model, which suggested that the AP model was constructed successfully. The AP+rhein+honokiol group had significantly reduced interstitial edema, inflammatory cell infiltration, hemorrhage, and necrosis. In addition, the rhein and honokiol treatment influenced some of the metabolic pathways in AP, including riboflavin metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and the pentose and glucuronate interconversions pathway. CONCLUSIONS This study showed that the combination of rhein and honokiol ameliorated pathological changes in the pancreas of mice with AP.
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Amilasas/sangre , Antraquinonas , Compuestos de Bifenilo , Inhibidores Enzimáticos , Lignanos , Páncreas , Pancreatitis/tratamiento farmacológico , Animales , Antraquinonas/administración & dosificación , Antraquinonas/farmacología , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/farmacología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Lignanos/administración & dosificación , Lignanos/farmacología , Masculino , Metaboloma , Ratones , Ratones Endogámicos C57BL , Páncreas/metabolismo , Páncreas/patologíaRESUMEN
RATIONALE: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The initial epidemiological investigations showed that COVID-19 occurred more likely in adults, with patients younger than 10 years old accounting for less than 1% of the total number of confirmed cases, and infant infections were more rare. In our case, we present an infant who was only 35 days old when he was tested positive for COVID-19. PATIENT CONCERNS: In this report, a 35 day-old male infant with atypical symptoms had close contact with 2 confirmed patients of COVID-19 who were his grandmother and mother. DIAGNOSIS: The patient was diagnosed as COVID-19 after his oropharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcription-polymerase chain reaction assay. INTERVENTIONS: The therapeutic schedule included aerosol inhalation of recombinant human interferon α-2b and supportive therapy. OUTCOMES: Two consecutive (1 day apart) oropharyngeal swabs tested negative for severe acute respiratory syndrome coronavirus 2; then, the patient was discharged on February 27, 2020. LESSONS: Strengthening infants' virus screening in families with infected kins is important for early diagnosis, isolation, and treatment when symptoms are atypical. The infectivity of infants with mild or asymptomatic COVID-19 should not be ignored because this may be a source of transmission in the community.
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Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Orofaringe/virología , Neumonía Viral/diagnóstico , Administración por Inhalación , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Transmisión de Enfermedad Infecciosa/prevención & control , Humanos , Lactante , Interferón alfa-2/administración & dosificación , Interferón alfa-2/uso terapéutico , Masculino , Pandemias , Aislamiento de Pacientes/métodos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/transmisión , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/normas , SARS-CoV-2 , Manejo de Especímenes/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) develop brain metastases in 25-50% of cases during the course of their disease. Data on the incidence of metastases occurring in the hippocampus/perihippocampal zones are limited. This is important when considering hippocampal-sparing brain radiation (HS-BR), a method that could potentially reduce the neurocognitive impact of such treatment. The aim of this study was to assess the incidence of hippocampal/perihippocampal metastases in a cohort of patients with advanced NSCLC treated at our institution. METHODS: This retrospective cohort study included NSCLC patients discussed at our institutional lung cancer multidisciplinary meeting between 2000 and 2016. MRI and contrast-enhanced CT (ceCT) brain images were reviewed to assess the incidence of hippocampal/perihippocampal metastases including metastases within the hippocampal subgranular zone and a 5 mm margin (hippocampal avoidance region) defined as per the RTOG 0933 study. RESULTS: Of 2146 patients reviewed, 357 (16.6%) had brain metastases. A total of 335 patients had available MRI/ceCT brain images for review. Thirty (9%) patients had brain metastases in the hippocampal avoidance region, 8 (2.4%) with hippocampal metastases and 22 (6.6%) with perihippocampal metastases. Univariate analyses did not show an association between developing metastases in the hippocampal avoidance region and age (P = 0.75), gender (P = 0.91) and tumour type (P = 0.298). CONCLUSION: The incidence of metastases in the hippocampal avoidance region in our large cohort of patients was 9%. With low rates of metastases in this region, HS-BR can be considered a feasible option in the management of patients with advanced NSCLC.
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Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Hipocampo/patología , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico por imagen , Estudios de Cohortes , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Incidencia , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective: Pharmacokinetic (PK) similarity between biosimilar candidate LRG201902 and European Union-sourced liraglutide reference product (Victoza®) was evaluated. Safety and immunogenicity were also assessed. Methods: This single-dose, randomized, open-label, 2-period crossover study (CTR20192342) was conducted in thirty-eight healthy adult male subjects. Volunteers were randomized 1:1 at the beginning to receive a single 0.6 mg dose of Victoza® or LRG201902 by subcutaneous injection during the first period. Following 8 days washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 72 h after administration. The primary pharmacokinetic endpoints were AUC0-t, AUC0-∞, and Cmax. Pharmacokinetic similarity was achieved if 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0-t, AUC0-∞, and Cmax were within the range of 80-125%. Other pharmacokinetic parameters including Tmax, t½, and λz were also measured. Safety profile and immunogenicity data were collected from each subject. Results: Cmax, AUC0-t, and AUC0-∞ were similar between the two groups. GMRs of Cmax, AUC0-t, and AUC0-∞ were 113.50%, 107.21%, and 106.97% between LRG201902 and Victoza® respectively. The 90% CIs for the GMRs of Cmax, AUC0-t, and AUC0-∞ were all within the PK equivalence criteria. Mean serum concentration-time profiles, secondary pharmacokinetic parameters (Tmax, t½, and λz) were comparable between groups. Treatment-related adverse events were reported by 27.8% and 23.7% subjects in the LRG201902 and Victoza® arms, respectively. All post-dose samples were detected negative for anti-drug antibodies. Conclusion: This study demonstrates pharmacokinetic similarity of LRG201902 to Victoza® in healthy subjects. The safety and immunogenicity profiles were similar for the two products.
RESUMEN
BACKGROUND: In pancreatic cancer, acute pancreatitis (AP) is a serious morbidity, but its negative effect on long-term outcomes remains to be elucidated. AIM: To investigate the effects of AP on the tumor recurrence pattern of pancreatic ductal adenocarcinoma (PDAC) and tumor-specific survival. METHODS: The medical records of 219 patients with curative pancreatectomy for pancreatic cancer at the Pancreatic Surgery Center of West China Hospital from July 2012 to December 2016 were analyzed retrospectively. The severity of acute pancreatitis was classified according to the Atlanta classification of AP. The patient demographics and tumor characteristics were assessed. Early recurrence was defined as a relapse within 12 mo after surgery. Overall and disease-free survival and recurrence patterns were analyzed. Mild acute pancreatitis was excluded because its negative effects can be negligible. RESULTS: Early recurrence in AP group was significantly higher than in non-AP group (71.4% vs 41.2%; P = 0.009). Multivariate analysis of postoperative early recurrence showed that moderate or severe AP was an independent risk factor for an early recurrence [odds ratio (OR): 4.13; 95% confidence interval (CI): 1.41-12.10; P = 0.01]. The median time to recurrence was shorter in patients with AP than in those without (8.4 vs 12.8 mo; P = 0.003). Multivariate analysis identified AP as an independent prognostic factor for overall survival [relative risk (RR): 2.35; 95%CI: 1.45-3.83] and disease-free survival (RR: 2.24; 95%CI: 1.31-3.85) in patients with PDAC. CONCLUSION: Patients with moderate or severe acute pancreatitis developed recurrences earlier than those without. Moderate or severe AP is associated with shorter overall and disease-free survival of patients with PDAC.
Asunto(s)
Carcinoma Ductal Pancreático/cirugía , Recurrencia Local de Neoplasia/epidemiología , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Pancreatitis/epidemiología , Adulto , Anciano , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/mortalidad , China , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/mortalidad , Pancreatitis/diagnóstico , Pancreatitis/etiología , Pancreatitis/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: In the study, we aimed to find key long noncoding RNAs (lncRNAs) significantly associated with the diagnosis of colon adenocarcinoma (COAD) and lncRNA signatures to provide survival risk prognosis for patients with COAD. METHODS: The lncRNA and messenger RNA (mRNA) expression profiles and clinical information of patients with COAD were obtained from the Cancer Genome Atlas database. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between COAD and normal tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for COAD were identified by using feature selection procedure and classification model. Functional enrichment analysis revealed the possible roles of mRNAs coexpressed with lncRNAs in some cancer-related biological processes and pathways. Receiver operating characteristic curve of these lncRNA biomarkers were obtained by using 10-fold cross-validation. Univariate and multivariate Cox regression analysis for these DElncRNAs were performed to obtain the lncRNAs related to overall survival time. The expression levels of selected DElncRNAs were validated by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 169 DElncRNAs (60 downregulated and 109 upregulated) and 1236 DEmRNAs (708 downregulated and 528 upregulated) between COAD and normal tissues were identified. Eight lncRNAs of XXbac-B476C20.9, PP7080, CDKN2B-AS1, LINC00092, CA3-AS1, HAND2-AS1, CTD-2269F5.1, and LINC01082 were selected as optimal diagnostic lncRNA biomarkers for COAD. The expression of eight optimal diagnostic lncRNA biomarkers in qRT-PCR validation was consistent with our integrated analysis. Among them, XXbac-B476C20.9 was not only one of the eight optimal diagnostic lncRNA biomarkers, but also related to the prognosis of COAD. CONCLUSION: Our study demonstrated the promising potential of XXbac-B476C20.9 as an independent biomarker for diagnosis and prognosis of patients with COAD.
Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Neoplasias del Colon/genética , ARN Largo no Codificante/genética , Adenocarcinoma/patología , Anciano , Neoplasias del Colon/patología , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Humanos , Masculino , MicroARNs/genética , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genéticaRESUMEN
PURPOSE: The aim of this study is to review our initial experience of Double contrast-enhanced ultrasonography (DCEUS) in the preoperative detection of pancreatic tail occult tumors. METHODS: Thirty-five patients were recruited to undergo DCEUS of the pancreas suspected by occult lesions of pancreatic with MRI or clinical evidence. The radiologists assessed the images (conventional US, DCEUS, and MRI) for enhancement phases, tumor presence, location, enhancement characteristics, and tumor conspicuity. The differences in the onset times of the phases between DCEUS and MRI were noted. Tumor conspicuity was graded on a four-point scale for conspicuity comparison among three imaging modalities. RESULTS: Pancreatic tail tumors were missed on conventional transabdominal US in 11 of 35 patients. DCEUS revealed 12 lesions of 35 patients. Pancreatic tail tumors were identified on MRI in 10 of 35 patients. The sensitivity and specificity of DCEUS for depicting occult lesions of ≤ 2.2 cm were 92% and 95%, respectively. In contrast, the sensitivity and specificity of conventional US were 67% and 66%, respectively. The sensitivity and specificity of MRI were 91% and 88%, respectively. The conspicuity ratings of the three phases did not significantly differ between the DCEUS and MRI groups (P > 0.05). The DCEUS phases started much earlier than the corresponding MRI phases. CONCLUSION: DCEUS is a promising technique in the detection of occult pancreatic tail tumors and is possibly superior to dynamic enhanced MRI in the case of some peripheral lesions.