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OBJECTIVE: The aim of this study was to investigate the effect of recombinant human B-type natriuretic peptide (rhBNP) on improving ventricular function in patients with ST-elevation myocardial infarction (STEMI). PATIENTS AND METHODS: In this retrospective study, 96 patients with STEMI admitted to Cangzhou Central Hospital from June 2017 to June 2019 were recruited and randomized to either a control group or an experimental group, with 48 patients in each group. Patients in both groups were given conventional pharmacological therapy, and an emergency coronary intervention was performed within 12 hours. Patients in the experimental group received rhBNP intravenously postoperatively, whereas patients in the control group received an equal amount of 0.9% NaCl solution through an intravenous drip. Postoperative recovery indicators were compared between the two groups. RESULTS: Patients treated with rhBNP showed better postoperative respiratory frequency, heart rate, blood oxygen saturation, pleural effusion, acute left heart remodeling after surgery and central venous pressure at 1-3 days after surgery than those without (p<0.05). Early diastolic blood flow velocity/early diastolic motion velocity (E/Em) and wall-motion score indices (WMSI) of patients in the experimental group were markedly lower compared to the control group one week after surgery (p<0.05). Patients receiving rhBNP had better left ventricular ejection fraction (LVEF) and WMSI six months after surgery and higher left ventricular end diastolic volume (LVEDV) and LVEF one week after surgery than the controls (p<0.05). Administration of rhBNP for patients with STMI provided a higher treatment safety by significantly reducing the incidence of left ventricular remodeling and complication than conventional medication (p<0.05). CONCLUSIONS: Intervention with rhBNP in STEMI patients could effectively inhibit ventricular remodeling, alleviate symptoms, reduce adverse complications and improve ventricular function.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/cirugía , Péptido Natriurético Encefálico/uso terapéutico , Volumen Sistólico , Estudios Retrospectivos , Función Ventricular Izquierda , Función Ventricular , Remodelación VentricularRESUMEN
Objective: To explore the risk factors for mortality in pediatric acute respiratory distress syndrome (PARDS) requiring extracorporeal membrane oxygenation (ECMO) support. Methods: Clinical data of 109 patients with severe PARDS supported by ECMO, who were hospitalized in 6 ECMO centers in China from September 2012 to February 2020, were retrospectively analyzed. They were divided into survival group and death group according to the prognosis. Chi-square test and rank sum test were used to compare the variables between the two groups, including the demographic data, laboratory examination results, clinical data before and after ECMO, and other supportive treatment. Univariate and multivariate Logistic regression models were used to analyze the prognostic risk factors. Results: In these 109 cases, 54 died and 55 survived. Compared with the survival group, the death group had higher incidences of acute kidney injury (AKI) (48.1% (26/54) vs. 21.8% (12/55), χ²=8.318, P=0.004) and coagulation dysfunction (22.2% (12/54) vs. 7.3% (4/55), χ²=4.862, P=0.027), and higher rate of renal replacement therapy (48.1% (26/54) vs. 21.8% (12/55), χ²=9.694, P=0.008) during ECMO support. Logistic regression analysis showed that continuous renal replacement therapy (CRRT) and AKI were independent risk factors for death in patients with severe PARDS requiring ECMO support (HR=3.88,95%CI 1.04-14.52, HR=4.84,95%CI 1.21-19.46, both P<0.05). Conclusion: AKI and CRRT are independent risk factors for predicting mortality in patients with severe PARDS requiring ECMO support.
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Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Niño , China/epidemiología , Humanos , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The aim of this study was to determine whether endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa cells in patients with polycystic ovary syndrome (PCOS). A total of 116 patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles at the Binzhou Medical University Hospital IVF Center between September 2019 and January 2020 were enrolled in the study. Apoptosis of the granulosa cells in each patient was analyzed using flow cytometry, and progesterone and estrogen levels in the cell-culture fluid were measured by enzyme-linked immunosorbent assay. The expressions of X-box-binding protein 1 (XBP1(s)), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), B-cell CLL/lymphoma 2 protein (Bcl-2), and Bcl-2 associated X protein (Bax) at the gene or protein level were analyzed using quantitative real-time polymerase chain reaction and Western blotting, respectively. In patients with PCOS, body mass index and basal serum concentrations of luteinizing hormone, testosterone (T), and anti-Mullerian hormone significantly increased (P < 0.05). The number of oocytes retrieed and the rate of clinical pregnancy after the first frozen embryo transfer also significantly increased (P < 0.05). Although apoptosis rate in the granulosa cells significantly increased in patients with PCOS, progesterone (P) and estrogen (E2) levels in the cell-culture fluid significantly decreased (P < 0.05). The apoptosis of granulosa cells was also found to affect blastocyst formation. Furthermore, the messenger ribonucleic acid (mRNA) expressions of XBP1(s), ATF6, CHOP, and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). The protein expressions of CHOP and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). After treatment of the granulosa cells with tauroursodeoxycholic acid, apoptosis rate and mRNA or protein expressions of XBP1(s), CHOP, and Bax significantly decreased, while the expression of Bcl-2 and levels of progesterone and estrogen significantly increased (P < 0.05). We conclude that ER stress could induce the apoptosis of granulosa cells in patients with PCOS. Cell apoptosis may decrease the number of blastocysts formed.
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Síndrome del Ovario Poliquístico , Apoptosis , Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Femenino , Células de la Granulosa , Humanos , EmbarazoRESUMEN
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of miR-99b in mediating hepatocellular carcinoma invasion and migration, by C.-J. Liu, J.-H. Yang, F.-Z. Huang, J.-H. Yang, C.-P. Liu, X.-H. Mao, W.-M. Yi, X.-B. Shen, C. Peng, M.-F. Chen, B. Jiang, J.-S. Wu, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2273-2281-DOI: 10.26355/eurrev_201804_14815-PMID: 29762829" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14815.
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Objective: To explore the reference ranges and influential factors of disturbance coefficient (DC) in children without craniocerebral injury at different ages. Methods: Two hundred children without craniocerebral injury admitted to the Department of Orthopaedics in Children's Hospital of Chongqing Medical University from May 2018 to October 2019 were enrolled in this prospective study. The children were divided into four groups according to age, 0-1 year, >1-3 years, >3-5 years and >5-16 years, each of which included 50 children. Each child had DC measured twice with the non-invasive dynamic cerebral edema monitor, and the average value was used as the terminal DC value. Each measurement lasted 15 minutes, 12 hours apart. The difference of DC values among the four groups and between different genders were compared with ANOVA test and nonparametric test. And the Loess local weighted nonparametric regression analysis was used to explore the change of DC according to the increase of age, weight and head circumference (HC). Results: The reference values of DC for children of 0-1 year,>1-3 years, >3-5 years, and >5-16 years were 60±14, 92±18, 112±18, 135±18, respectively (F=175.690, P<0.01). There was no statistical significance in DC between male and female children either in the whole or in each separate age group (103 (81, 125) vs. 102 (68, 123) , Z=-0.739, P=0.460; 59 (52, 68) vs. 57 (53, 65) , Z=-0.243, P=0.808; 88 (81, 105) vs. 95 (70, 105) , Z=-0.776, P=0.437; 117 (99, 120) vs. 113 (101, 123) , Z=-0.170, P=0.865; 137 (123, 143) vs. 142 (123, 160) , Z=-1.279, P=0.201). When the child's age was younger than 5 years, weight was less than 18 kg or HC was less than 51 cm, the DC increased significantly with the increase of age, weight or HC. However, when the age, weight and HC were over the above values, the DC did not show obvious increase, but approaching to stable values of 135, 130, and 130, respectively. Conclusions: For children without craniocerebral injury, the reference values of DC are obviously different at different ages. DC is positively related to age, weight and HC, but not related to gender.
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Cefalometría , Adolescente , Niño , Preescolar , Traumatismos Craneocerebrales , Edema/diagnóstico , Femenino , Cabeza/anatomía & histología , Hospitalización , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
Objective: To explore the resistance mechanism and gene type of carbapenems-resistant Klebsiella pneumoniae (CRKP) in burn care unit. Methods: A total of 27 CRKP strains were primarily isolated from 22 patients [20 males, 2 females, aged (42±16) years] admitted to burn care unit of Institute of Burn Research of the First Affiliated Hospital of Army Medical University (the Third Military Medical University, hereinafter referred to as our department) from January to December 2017. After identification of bacteria, the months of detection and distribution of sample source were analyzed. Drug resistance tests of 15 antibiotics were conducted. Polymerase chain reaction was used to detect the drug resistant genes. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used to analyze the gene type of strains. Results: (1) During the whole year of 2017, CRKP strains were mostly detected in August (8 strains), September (6 strains), and October (5 strains), with no CRKP in January, March, June, November, and December. Five strains from bed units were detected in August (2 strains), September (1 strain), and October (2 strains). (2) Twenty-seven CRKP strains were derived from blood samples (40.7%, 11/27), wound exudate samples (18.5%, 5/27), deep vein catheter samples (11.1%, 3/27), sputum samples (7.4%, 2/27), urine samples (3.7%, 1/27), and bed unit samples (18.5%, 5/27). (3) The 27 CRKP strains were detected with drug-resistance rates of 100.0% to 7 antibiotics including cefoperazone/sulbactam, piperacillin/tazobactam, cefazolin, ceftriaxone, cefepime, ertapenem, and compound sulfamethoxazole, no drug-resistance to tigecycline, with drug-resistance rates higher than 81.0% to the rest 7 antibiotics. (4) Detection rates for resistance gene bla(CTX-M-10), bla(SHV), bla(TEM), bla(CTX-M-14), bla(ACT), and bla(KPC) were all above 92.5%. (5) According to PFGE, the 27 CRKP strains had 6 types (A, A(1), A(2), B, C, and D). Strains of type A were mainly detected in February, May, and September, with detection rate of 37.0% (10/27). Strains of type C were mainly detected in July, August, and October, with detection rate of 48.1% (13/27). Strains of types A(1), A(2), B, and D were scatteredly detected, with detection rate of 3.7% (1/27) respectively. According to MLST, the 27 CRKP strains had 6 STs. ST11 was the most frequent type, accounting for 74.1% (20/27), which was detected in August to October. The detection rate of ST395, ST2230, ST215, ST260, and STnew ranged from 3.7%(1/27) to 7.4%(2/27), and the strains were scatteredly detected. Conclusions: The main source of CRKP from burn care unit of our department was bloodstream. All the CRKP strains showed high drug-resistance rate and complicated resistance mechanism. There were small scale outbreaks caused by CRKP of type A, type C, and ST11, which should be paid more attention to in clinical treatment and infection control.
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Quemaduras/microbiología , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/efectos de los fármacos , Adulto , Antibacterianos/farmacología , Unidades de Quemados , Femenino , Humanos , Klebsiella pneumoniae/clasificación , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , beta-Lactamasas/genéticaRESUMEN
OBJECTIVE: This study aims to investigate effects of checkpoint kinase, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding protein 1 (53BP1) silencing on p53, checkpoint kinase 1 and 2 (CHK1 and CHK2), and CHK2-T68 expression. MATERIALS AND METHODS: Eca109 cells were divided into untransfected Eca109, Blank-vector, MDC1-RNAi transfection, and 53BP1-RNAi transfection group. Streptavidin-peroxidase (SP) immunohistochemical assay was used to examine CHK2-T68 expression. About 4 groups were used to establish esophageal carcinoma nude-mouse models, and assigned as Eca-109 control (or Eca-109 plus 15 Gy γ-rays irradiation, Eca-109+IR), Blank-vector (or Blank-vecor+IR), 53BP1-RNAi (or 53BP1-RNAi+IR), and MDC1-RNAi group (or MDC1-RNAi+IR group) by injecting. The expression of p53, CHK1, CHK2 were evaluated using SP immunohistochemical assay. RESULTS: 53BP1 and MDC1 down-regulation significantly inhibited expression of CHK2-T68 in Eca-109 cells compared to untreated group (p<0.05). There were significant differences for CHK2-T68 expressions in different time and groups (p<0.05). 53BP1 down-regulation significantly reduced p53 and enhanced CHK1 and CHK2 expression compared to that of Eca-109 control group (p<0.05) in Eca-109 cells. 53BP1 down-regulation significantly regulated CHK1, CHK2, and p53 in xenograft nude mice models exposed to γ-ray irradiation compared to that of untreated group (p<0.05). p53 was negatively correlated with CHK1 and CHK2 in xenograft nude mice models. CONCLUSIONS: 53BP1 regulated the cell cycle arrest by modulating p53, CHK1, and CHK2 expression in both Eca-109 cells and xenograft nude mice models.
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Puntos de Control del Ciclo Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Células Tumorales CultivadasRESUMEN
Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within-subject variability. Here, the bioequivalence of 2 formulations of sarpogrelate (100-mg tablets) was assessed by using the reference-scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. In this open and randomized 4-way replicate study, a single dose of sarpogrelate was administered followed by a 3-day washout period. The sarpogrelate concentration in blood samples was measured by liquid chromatography-tandem mass spectrometry within 6 hours (fasting) or 10 hours (fed) of drug administration, and the PK parameters were determined by a noncompartmental model. The bioequivalence of the 2 formulations under both conditions was assessed using the ratios of ln(peak concentration [Cmax ]) and ln(area under the concentration-time curve [AUC]) within the limits based on the RSABE method. The 90% CIs for the ratios of lnCmax , lnAUC0-t , and lnAUC0-∞ were 0.8531-1.1100, 0.9616-1.0737, and 0.9550-1.0684, respectively, under fasting conditions and 0.8918-1.1076, 0.9818-1.0694, and 0.9818-1.0686, respectively, under fed conditions, which were within the RSABE acceptance limits. Food intake decreased the systemic exposure and the Cmax of sarpogrelate by 0.9-fold and 0.5-fold, respectively.
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Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/farmacocinética , Ayuno/sangre , Succinatos/administración & dosificación , Succinatos/farmacocinética , Adulto , Disponibilidad Biológica , China , Estudios Cruzados , Composición de Medicamentos , Interacciones Alimento-Droga , Humanos , Masculino , Persona de Mediana Edad , Equivalencia Terapéutica , Adulto JovenRESUMEN
Three dimentional printing is a new rapid prototyping technology based on digital model files, which developed through a combination of multi-disciplines such as information technology, precision machinery and materials science. With rapid development in recent years, three dimentional printing technology has been widely used in the medical fields, stomatology especially. It gradually penetrates into various parts of stomatology, such as education, practice and innovation, making stomatology clinical medicine more and more efficient, accurate and minimally invasive. Combined with basic research and clinical cases, this article describes the application and developent prospects of three dimentional printing technology in stomatology.
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Medicina Oral , Impresión TridimensionalRESUMEN
The Editors-in-Chief are issuing an editorial expression of concern to alert readers that after publication of this article1 concerns have been raised with respect to the integrity of Figs 1c, 1e, 2b, 6b, and 7a. Chongqing Medical University is investigating these concerns and appropriate editorial action will be taken once the outcome of this investigation is known. The authors do not agree with this notice.
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OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults with a high rate of malignancy. The potent invasion and migration of HCC mainly impact the prognosis and recurrence of the disease. Our previous study found that miR-99b was highly expressed in HCC, and its expression was associated with vascular invasion. It was speculated that miR-99b may play a role in HCC invasion and migration, while the specific mechanism remains unclear. MATERIALS AND METHODS: qRT-PCR was applied to detect expressions of miR-99b and KAI1 genes in L02, HepG2, and MHCC97H cells. HepG2 cells were transfected with miR-99b inhibitor, miR-99b mimic, and NC. Flow cytometry was used to test cell cycle and apoptosis. Dual-luciferase reporter gene assay was adopted to validate the target gene of miR-99b. Wound healing assay was used to detect cell migration. Transwell assay was performed to detect cell invasion. Western blot was performed to detect KAI1, E-cadherin, and N-cadherin expressions. Immunofluorescence assay was adopted to test Vimentin expression. RESULTS: The level of miR-99b was reduced in L02 while up-regulated in MHCC97H. By contrast, the expression of KAI1 was increased in L02 but declined in MHCC97H. The transfection of miR-99b mimic inhibited HepG2 apoptosis and accelerated cell cycle. MiR-99b suppressed KAI gene expression through targeting its 3'-UTR. MiR-99b mimic or si-KAI1 transfection promoted cell invasion and migration, while their simultaneous action significantly enhanced cell invasion and migration. The overexpression of miR-99b or knockdown of KAI1 significantly weakened HepG2 cell adhesion, reduced E-cadherin expression, upregulated N-cadherin and Vimentin, and promoted cell epithelial-mesenchymal transition (EMT). CONCLUSIONS: MiR-99b contributes to promoting function in HCC migration and invasion through inhibiting KAI1 expression.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Proteína Kangai-1/genética , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Antígenos CD/biosíntesis , Apoptosis/genética , Cadherinas/biosíntesis , Ciclo Celular/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/genética , Transfección , Regulación hacia Arriba , Vimentina/biosíntesisRESUMEN
Objective: To assess the value of urine soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in early diagnosis and prognosis of sepsis associated acute kidney injury (AKI). Methods: This was a case-control study. A total of 62 patients with sepsis during November 2016 to June 2017 were collected, who were divided into non-AKI sepsis (n= 49) and AKI sepsis (n=13) groups according to the serum creatinine (SCr) or urine output, sepsis with shock (n=22) and sepsis without shock (n=40) groups according to the presence of shock, survival (n=47) and death (n=15) groups according to the mortality. Twenty healthy children were recruited in control group, whose urine sTREM-1 were used as reference value. Urine and blood specimens were detected on admission (within 12 h), at 24 h and 48 h after admission. Student's t-test and Mann-Whitney U test were used for statistical analysis. Results: On admission, the level of urine sTREM-1 were significantly higher in sepsis patients than in healthy controls (96.8 (71.3, 105.8) vs. 68.6 (60.6, 71.1)ng/L, Z=4.708, P<0.05). Comparing of sTREM-1 in different groups showed that the levels were higher in AKI sepsis patients than in the non-AKI ones ((106±5) vs. (86±18) ng/L, t=6.670, P<0.05), higher in the sepsis with shock group than in sepsis without shock group ((98±11) vs. (86± 20) ng/L, t=3.059, P<0.05), and also higher in death group than in survival group ((101±12) vs. (87±18) ng/L, t=3.615, P<0.05). The area under the receiver operating characteristic (AUROC) of urine sTREM-1 in predicting sepsis associated AKI was 0.814 (95%CI: 0.708-0.920), which was higher than that in predicting shock, increased serum creatinine, hyperlipidemia or hyperbilirubinemia (0.530, 0.425, 0.429 and 0.443, respectively). The optimal sTREM-1 cut-off point for predicting sepsis associated kidney injury was 96.5 ng/L, with specificity and sensitivity of 100% and 57.1%. The odds ratio(OR) of urine sTREM-1 was 0.879 with a significance of 0.005 after adjusting shock, prognosis, serum creatinine, lactate and total bilirubin level, indicating that the urine sTREM-1 was an independent risk factor of sepsis associated AKI. Conclusion: Urine sTREM-1 can be used as an early diagnostic biomarker for sepsis associated AKI, with advantage of noninvasiveness and convenience. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-DDD-17010743.
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Lesión Renal Aguda , Receptores Inmunológicos , Sepsis , Receptor Activador Expresado en Células Mieloides 1 , Lesión Renal Aguda/complicaciones , Biomarcadores , Estudios de Casos y Controles , Niño , Diagnóstico Precoz , Humanos , Glicoproteínas de Membrana , Estudios Prospectivos , Sepsis/diagnóstico , Sepsis/etiología , Sepsis/metabolismo , Receptor Activador Expresado en Células Mieloides 1/metabolismo , UrinálisisRESUMEN
Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls. Patients with higher levels of EGF were more likely to have neck lymph node metastasis (P=0.026), advanced stage cancer (P=0.04), and a worse survival status (P=0.0019). Multivariate analysis using the Cox proportional hazards model indicated that the EGF level was an independent predictor of poor survival (hazard ratio 1.99, P=0.018). Patients with higher preoperative serum EGF levels had significantly poorer cancer-specific survival by Kaplan-Meier analysis (P=0.032). This study indicates that a higher preoperative serum EGF level is associated with neck lymph node metastasis, more advanced stage, and poor survival. EGF should be considered as a potential prognostic biomarker and a therapeutic target for patients with oral cancer.
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Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Factor de Crecimiento Epidérmico/sangre , Neoplasias de la Boca/sangre , Neoplasias de la Boca/patología , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico por imagen , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico por imagen , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human immunodeficiency virus (HIV) coinfection. AIM: To evaluate the effectiveness and safety of generic VEL/SOF-based therapy for HCV infection in patients with or without HIV coinfection in Taiwan. METHODS: Sixty-nine HIV/HCV-coinfected and 159 HCV-monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti-viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12 ) were analysed. RESULTS: The SVR12 was achieved in 67 HIV/HCV-coinfected patients (97.1%; 95% CI: 90.0%-99.2%) and in 156 HCV-monoinfected patients (98.1%; 95% CI: 94.6%-99.4%) receiving VEL/SOF-based therapy, respectively. The SVR12 rates were comparable between HIV/HCV-coinfected and HCV-monoinfected patients, regardless of pre-specified baseline characteristics. One hundred twenty-two (53.5%) and seven (3.1%) patients had baseline resistance-associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV-coinfected and HCV-monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV-coinfected patients receiving anti-retroviral therapy containing tenofovir disoproxil fumarate (TDF). CONCLUSIONS: Generic VEL/SOF-based therapy is well-tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.
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Antivirales/administración & dosificación , Carbamatos/administración & dosificación , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Sofosbuvir/administración & dosificación , Adulto , Anciano , Antivirales/uso terapéutico , Coinfección , Combinación de Medicamentos , Femenino , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico , Respuesta Virológica Sostenida , Taiwán , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.
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Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Secuenciación del Exoma/métodos , Mieloma Múltiple/genética , Células Neoplásicas Circulantes , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Variaciones en el Número de Copia de ADN/genética , Progresión de la Enfermedad , Femenino , Humanos , Biopsia Líquida/métodos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Mutación/genética , Medicina de Precisión/métodosRESUMEN
Objective: To establish a three-dimensional (3D) finite element (FE) model of the whole cervical spinal cord (WSCS) and explore the biomechanical behaviors of cervical spinal cord injury related to different bone fragment impact velocities by FE analysis. Methods: A 3D FE model of WCSC was established based on the morphologic data of each segment of the human cervical cord. The reconstruction structures, which included the dura mater, the cerebrospinal fluid, the gray and white matter in the C(2) to C(7) cervical vertebrae, were validated.On the validated WCSC model, three kinds of pellets with same mass (7 g) but different impact areas (314, 157 and 78.5 mm(2)) were created to represent the bone fragments.These were positioned in the middle of the spinal cord to impact at various initial velocities.The maximum of von Mises stress and the reduction of the cross-sectional area (CSA) of the spinal cord were measured from each impact. Results: The compression of WCSC (percentage) and the time to reach maximum compression were similar with the results reported in literatures, indicating the validity of the model.Regardless of the impact areas of the pellet, the maximum of von Mises stress and the reduction of CSA of the spinal cord increased with the increased velocity.The maximum of von Mises stress was 5.0-7.0 kPa at a pellet velocity of 1.5 m/s, and the reduction of CSA was 9.3%-12.3%.At a velocity of 3.5 m/s, the maximum of von Mises stress was 42-54 kPa and the reduction of CSA was over 30%.The stress of the spinal cord significantly increased when pellet velocity exceeded 3.5 m/s, and the fastest increase was recorded at 4.5 m/s.The von Mises stress of the spinal cord ranged between 240 and 320 kPa at a velocity of 6.0 m/s, and CSA decreased by more than 50%. Conclusion: The 3D FE model of WSCS could provide more insights on the biomechanical mechanisms of spinal cord injury through various bone fragment impacts in burst fracture.When the impact velocity of the bone fragment exceeds 3.5 m/s, the maximum stress significantly increases and the reduction of CSA of the spinal cord is over 30%, and this could possibly lead to the contusion injury of the spinal cord.
Asunto(s)
Traumatismos de la Médula Espinal , Fenómenos Biomecánicos , Médula Cervical , Vértebras Cervicales , Análisis de Elementos Finitos , Humanos , Médula Espinal , Estrés MecánicoRESUMEN
BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.