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Objective: To explore the value of predicting shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) based on whole brain CT perfusion(CTP) and clinical data within 24 hours at admission. Methods: The clinical and imaging data of aSAH patients who received interventional embolization in our hospital were retrospectively collected from March 2018 to August 2022. All patients underwent one-stop whole brain CT examination within 24 hours after symptom onset, and the qualitative and quantitative CTP parameters were obtained after post-processing. Follow-up was conducted once every 2 months by consulting electronic medical records or by telephone for 6 months. According to whether SDHC occurred or not, the patients were divided into SDHC group and non-SDHC group. The differences between the two groups were compared. Logistic regression model was used to analyze and determine the predictive factors of SDHC, and the SDHC predictive model was established. The effectiveness of the predictive model was evaluated by drawing the receiver operating characteristic (ROC) curve of the subjects. Results: A total of 414 patients were included, including 132 males and 282 females, aged (59±11) years. 17.6%(73/414) patients had SDHC. There were significant differences in the occurrence of acute hydrocephalus, the World Neurosurgical League Scale (WFNS), the Hunt-Hess scale, the modified Fisher score (mFS), and the qualitative and quantitative parameters of CTP between the two groups (both P<0.001). Multivariate logistic regression analysis showed that acute hydrocephalus (OR=8.621, 95%CI: 4.237-17.542),old age (OR=1.107, 95%CI: 1.068-1.148), high mFS and high Hunt-Hess classification (OR=3.740, 95%CI: 1.352-10.342) were the risk factors of SDHC in aSAH patients, and high mean cerebral blood flow (mCBF) (OR=0.931, 95%CI: 0.885-0.980) was a protective factor of SDHC.The area under ROC curve (AUC) of the prediction model constructed by these five variables was 0.923(95%CI: 0.89-0.95), with 84.5% sensitivity and 87.7% specificity. Conclusion: The mCBF and acute hydrocephalus, age, mFS and Hunt-Hess classification within 24 hours at admission can be used to predict SDHC for aSAH patients.
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Hidrocefalia , Hemorragia Subaracnoidea , Masculino , Femenino , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/cirugía , Estudios Retrospectivos , Encéfalo , Perfusión/efectos adversosRESUMEN
Objective: To explore the safety and myocardial protection efficacy of del Nido cardioplegia in adult cardiac and major vascular surgery with long aortic cross-clamp (ACC) time. Methods: A total of 2 536 patients who underwent adult cardiac and major vascular surgery with ACC time>90 min at Beijing Anzhen Hospital from March 2018 to March 2023 were collected. The patients were divided into two groups according to the type of cardioplegia solution: the del Nido cardioplegia solution group (DC group) and the cold blood cardioplegia solution group (BC group). Preoperative baseline data of the patients (age, gender, comorbidities, ejection fraction, etc) were adjusted using propensity score matching (PSM). Cardiopulmonary bypass (CPB) time, ACC time, total amount of cardioplegia solution, in-hospital mortality rate, length of intensive care unit (ICU) stay, mechanical ventilation time, postoperative complications, left ventricular ejection fraction, and troponin levels were compared between the two groups. Results: After PSM, a total of 306 patients were included, including 223 males and 83 females, with a mean age of (52.0±12.3) years. There were 153 cases in the DC group and 153 cases in the BC group. Compared with the DC group, the cross-clamp time was longer [109(100, 150) min vs 102(91, 133) min, P<0.001], the rate of return to spontaneous rhythm was lower [51.6% (79/153) vs 86.9%(133/153), P<0.001], and intraoperative peak glucose was higher [12.6 (6.5, 15.9) mmol/L vs 10.1 (8.5, 12.4) mmol/L, P=0.005] in the BC group. In addition, perioperative mortality [4.6% (7/153) vs 3.3% (5/153), P=0.132], stroke[3.9% (6/153) vs 3.3% (5/153), P=0.759], renal insufficiency [3.3% (5/153) vs 6.5% (10/153), P=0.186], atrial fibrillation [4.6% (7/153) vs 2.6% (4/153), P=0.652] and low cardiac output syndrome [3.9% (6/153) vs 4.6% (7/153), P=0.716] did not differ between the two groups. Compared with BC group, DC group had lower level of high sensitivity troponin (hsTnI) [1.2 (0.8, 1.8) µg/L vs 1.3 (0.9, 2.3) µg/L, P=0.030] and creatine kinase isoenzyme (CK-MB) [31.0 (20.0, 48.9) µg/L vs 37.0 (24.0, 58.9) µg/L, P=0.011] at 24 h postoperatively, and shorter length of ICU stay [35.6 (19.8, 60.5) h vs 42.6 (21.9, 83.6) h, P=0.015] and mechanical ventilation time [20.5 (15.5, 41.0) h vs 31.5 (17.1, 56.0) h, P=0.012]. Subgroup analysis showed that in the 120-180 minute subgroup, patients in the DC group had a shorter cross-clamp time [132 (124, 135) min vs 136 (124, 138) min, P<0.001], while levels of hsTnI [1.6 (1.1, 2.0) µg/L vs 1.4 (1.0, 2.6) µg/L, P=0.030] and CK-MB [38.8 (23.5, 55.5) µg/L vs 37.0 (24.5, 62.3) µg/L, P=0.011] were higher than those in the BC group. Conclusions: In adult cardiac and major vascular surgery with ACC times>90 min, comparable myocardial protection is observed with the use of DC compared with BC. Additional advantages in glycemic control, return to spontaneous rhythm, and improved surgical procedures make DN an attractive alternative for myocardial protection in adult cardiac surgery.
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Paro Cardíaco Inducido , Función Ventricular Izquierda , Masculino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Volumen Sistólico , Paro Cardíaco Inducido/métodos , Soluciones Cardiopléjicas , Troponina , Procedimientos Quirúrgicos Vasculares , Estudios RetrospectivosRESUMEN
The early diagnosis of lung cancer has become the focus of clinical attention, with the incidence and mortality of lung cancer increasing. Aberrant DNA methylation occurs in the primary stage of lung cancer, then the methylation degree can be changed dynamically due to the progress and the treatment of lung cancer. To date, a growing number of studies have reported that special gene methylation exploits in the clinical diagnosis, curative effect monitoring, and prognosis evaluation of lung cancer. Meanwhile, clinical trials about DNA methyltransferase inhibitors for lung cancer therapy are also underway. It is worth looking forward that detecting aberrant DNA methylation helps diagnose and treat lung cancer.
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Metilación de ADN , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , PulmónRESUMEN
Objective: To explore the value of radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (MRI) in differentiation fat-poor angiomyolipoma (fp-AML) from alpha-fetoprotein-negative hepatocellular carcinoma (n-HCC) in the background of non-cirrhotic liver. Methods: The complete data of 121 patients from Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University and Sun Yat-sen University Cancer Center with hepatic fp-AML and n-HCC confirmed by pathology from October 2010 to July 2020 were retrospectively analyzed. Among them, 75 were males and 46 were females, aged from 23 to 80 (55±12) years. A total of 93 patients from Zhongshan Hospital Affiliated to Fudan University were divided into the training cohort (n=75) and internal test cohort (n=18) according to entry time, and the patients of other 2 hospitals were divided into external test cohort (n=28). The radiomics features were extracted from the preoperative triple-phase contrast-enhanced images. The feature selection algorithm based on Joint Mutual Information Maximisation (JMIM) was used to extract the optimal feature subset, and support vector machine (SVM) was used to build the radiomics model. The diagnostic performance of radiomics model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with that of two radiologists. Results: In the internal cohort, the area under the curve (AUC) for the differential diagnosis between fp-AML and n-HCC of the radiomics model was 0.819 (with an accuracy of 72.2%), outperforming than radiologist 1 with 10 years of diagnostic experience (AUC=0.542, P=0.029) and radiologist 2 with 2 years of diagnostic experience (AUC=0.375, P=0.004). In the external cohort, the AUC of the radiomics model was 0.772 (with and accuracy of 71.4%), which was comparable to that of radiologist 1 (AUC=0.661, P=0.442) and better than that of radiologist 2 (AUC=0.400, P=0.008). Conclusion: The radiomics model based on dynamic contrast-enhanced MRI is of high accuracy for preoperatively differentiating hepatic fp-AML from n-HCC in the noncirrhotic liver.
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Angiomiolipoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Anciano , Anciano de 80 o más Años , Angiomiolipoma/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , alfa-FetoproteínasRESUMEN
Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.
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Proteína BRCA1 , Proteína BRCA2 , Neoplasias de la Mama , Reparación del ADN por Recombinación , Neoplasias de la Mama Triple Negativas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Mutación , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
OBJECTIVE: Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation. METHODS: The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed. RESULTS: This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy. CONCLUSION: The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.
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Acidosis Láctica , Accidente Cerebrovascular , Adulto , Niño , ADN Mitocondrial/genética , Humanos , Masculino , Encefalomiopatías Mitocondriales , Mutación , Adulto JovenRESUMEN
BACKGROUND: The extensive involvement of microRNAs (miRNAs) in the pathogenesis of psoriasis is well documented. However, little is known about the contribution of specific miRNAs to the prevalence of this disease. OBJECTIVES: To explore the role of miR-145-5p in psoriasis. METHODS: miRNA microarray analysis was performed in four patients with psoriasis and four controls. Quantitative reverse-transcriptase polymerase chain reaction and fluorescence in situ hybridization were used to identify the dysregulated miRNAs. Luciferase assays were performed to determine whether miR-145-5p targets mixed-lineage kinase (MLK)3. CCK-8 assay and Magnetic Luminex Assay were performed to measure cell proliferation and chemokine secretion. Western blot analysis was used to investigate the protein levels of MLK3 and its downstream effectors. Mouse models of psoriasis were established for in vivo experiments. RESULTS: miR-145-5p was downregulated in psoriatic lesional skin. Luciferase assays showed that MLK3 is a direct target of miR-145-5p. Overexpression of miR-145-5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR-145-5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR-145-5p inhibitor-induced promotion of cell proliferation and chemokine expression. miR-145-5p regulates nuclear factor-κB and signal transducer and activator of transcription 3 by targeting MLK3. Delivery of agomiR-145-5p into the skin decreased epidermal hyperplasia and ameliorated psoriasis-like dermatitis. Delivery of antagomiR-145-5p led to the opposite effects. CONCLUSIONS: Our findings indicate that miR-145-5p negatively regulates proliferation and chemokine secretion of NHEKs by targeting MLK3, and downregulation of miR-145-5p contributes to skin inflammation in psoriasis lesions.
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Queratinocitos/patología , Quinasas Quinasa Quinasa PAM/genética , MicroARNs/metabolismo , Psoriasis/genética , Piel/inmunología , Adulto , Animales , Antagomirs/farmacología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Imiquimod/inmunología , Queratinocitos/inmunología , Masculino , Ratones , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , Análisis de Secuencia por Matrices de Oligonucleótidos , Cultivo Primario de Células , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Piel/citología , Piel/patología , Adulto Joven , Proteina Quinasa Quinasa Quinasa 11 Activada por MitógenoRESUMEN
Objective: To compare eradication rates and compliance of patients with Helicobacter pylori(H. pylori)infection based on clarithromycin sensitivity. Methods: From July 2015 to January 2018,patients with H. pylori infection in Peking university people's hospital were randomly assignedto a 14-day treatment with clarithromycin quadruple therapy versus tailored quadruple therapy for a prospective study. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity. In the control group, all patients were given proton pump inhibitors (PPI), amoxicillin, clarithomycin and bismuth. Eradication status was assessed 4 weeks after treatment withurea breath test. Results: The H.pylori eradication rate were higher in the tailor therapy group than that in the control group in intention-to-treat[77.8% vs 65.3%,(P=0.001)] and per,protocol analyses [86.4% vs 70.2%,(P<0.001)], the differences between the two groups were statistically significant.The incidence of compliance between the two groups were also comparable. Conclusions: The tailored therapy basedon clarithromycinsensitivity has a better eradication efficacy and a higher eradication ratesin the patients with H. pylori infection.
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Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Estudios Prospectivos , Inhibidores de la Bomba de Protones , Resultado del TratamientoRESUMEN
A simple and fast analysis method to sort large data sets into groups with shared distinguishing characteristics is described and applied to single molecular break junction conductance versus electrode displacement data. The method, based on principal component analysis, successfully sorts data sets based on the projection of the data onto the first or second principal component of the correlation matrix without the need to assert any specific hypothesis about the expected features within the data. This is an improvement on the current correlation matrix analysis approach because it sorts data automatically, making it more objective and less time consuming, and our method is applicable to a wide range of multivariate data sets. Here the method is demonstrated on two systems. First, it is demonstrated on mixtures of two molecules with identical anchor groups and similar lengths, but either a π (high conductance) or a σ (low conductance) bridge. The mixed data are automatically sorted into two groups containing one molecule or the other. Second, it is demonstrated on break junction data measured with the π bridged molecule alone. Again, the method distinguishes between two groups. These groups are tentatively assigned to different geometries of the molecule in the junction.
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Although a variety of factors underlying diapause have been identified in arthropods and other organisms, the molecular mechanisms regulating diapause are still largely unknown. Here, to better understand this process, we examined diapause-associated genes in the two-spotted spider mite, Tetranychus urticae, by comparing the transcriptomes and proteomes of early diapausing and reproductive adult females. Amongst genes underlying diapause revealed by the transcriptomic and proteomic data sets, we described the noticeable change in Ca2+ -associated genes, including 65 Ca2+ -binding protein genes and 23 Ca2+ transporter genes, indicating that Ca2+ signalling has a substantial role in diapause regulation. Other interesting changes in diapause included up-regulation of (1) glutamate receptors that may be involved in synaptic plasticity changes, (2) genes involved in cytoskeletal reorganization including genes encoding each of the components of thick and thin filaments, tubulin and members of integrin signalling and (3) genes involved in anaerobic energy metabolism, which reflects a shift to anaerobic energy metabolism in early diapausing mites.
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Diapausa de Insecto , Proteoma , Tetranychidae/fisiología , Transcriptoma , Anaerobiosis , Animales , Señalización del Calcio , Citoesqueleto/metabolismo , Femenino , Perfilación de la Expresión Génica , Neurotransmisores/metabolismo , Reproducción , Análisis de Secuencia de ARNRESUMEN
Objective: To explore the computed tomography(CT) features of inflammatory myofibroblastic tumor(IMT) in different pathological types, and improve the diagnostic level of this disease. Methods: The CT features of 29 cases pathologically confirmed IMTs were retrospectively reviewed along with a literature review to analyze the CT features and pathological correlations, and three kinds of pathological classification of IMT in patients with gender , shape, boundary and location were respectively analyzed by Chi-Square test. Results: The age ranges from 2 to 78 years.There were 7 cases of mucinous blood vessel type and 13 cases of spindle cell type and 9 cases of fiber type.Immunohistochemically, Vimentin (22/29) and SMA (28/29) were positive in all the cases, ALK (4/29) and CD-67(6/29) were partly positive expression, other markers such as S-100 were negative expression.The Chi-Square test showed that there were statistically differences in the gender of the patients. Conclusion: The CT and clinical features differ according to pathological types of IMT. Its final diagnosis still needs to be combined with pathology and immunohistochemistry result. In all, CT has a role in assessing the extension of IMT and especially about the relationship with adjacent organs which can effectively direct the establishment of clinical treating scheme.
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Granuloma de Células Plasmáticas , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Vimentina , Adulto JovenRESUMEN
Objective: To retrospectively investigate the clinical characteristics, risk factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV infection, hospitalized from March 2011 to June 2014 in Peking University People's Hospital, were analyzed.Clinical characteristics were summarized and compared in CMV positive and negative groups, to investigate the risk factors for CMV infection.Statistical analyses were conducted with SPSS 20.0 software. Results: A total of 62 rheumatic patients were found to have CMV infection, with 48 regarded as CMV viremia, 7 diagnosed as CMV pneumonia, while the remaining 7 suffered both CMV viremia and pneumonia.Eleven of 62 patients (17.7%) had a fatal outcome.Systemic lupus erythematosus (SLE) was the most commonly underlying disease (41.9%), followed by Sjögren syndrome (16.1%) and systemic vasculitis (12.9%). Lymphopenia and the reduction of CD4+ T lymphocytes, corticosteroids, cyclophosphamide (CTX) or mycophenolate mofetil (MMF), combined use of more than 2 immunosuppressants and other severe underlying infections as risk factors for CMV infection in rheumatic patients.Meanwhile, the total dose of CTX wasn't different significantly between CMV positive and negative groups.Multivariate analysis revealed that large or pulsed dose of corticosteroids, combined use of immunosuppressants, and severe underlying infections remained independent risk factors for CMV infection. Conclusions: Lymphocytes, particularly the CD4+ T subsets, might play a vital role in the regulation and control of CMV infection.Other underlying infections, undergoing large dose corticosteroids therapy or combined use of immunosuppressants could be the risk factors for CMV infection in rheumatic patients.
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Infecciones por Citomegalovirus , Citomegalovirus , Enfermedades Reumáticas , Linfocitos T CD4-Positivos , Ciclofosfamida , Humanos , Inmunosupresores , Lupus Eritematoso Sistémico , Ácido Micofenólico , Neumonía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We report on the magnetotransport properties of chemical vapor deposition grown films of interconnected Bi2Te3 nanoplates. Similar to many other topological insulator (TI) materials, these granular Bi2Te3 films exhibit a linear magnetoresistance (LMR) effect which has received much recent attention. Studying samples with different degree of granularity, we find a universal correlation between the magnitude of the LMR and the average mobility (⟨µ⟩) of the films over nearly 2 orders of magnitude change of ⟨µ⟩. The granularity controlled LMR effect here is attributed to the mobility fluctuation induced classical LMR according to the Parish-Littlewood theory. These findings have implications to both the fundamental understanding and magnetoresistive device applications of TI and small bandgap semiconductor materials.
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This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI)=1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI=1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI=0.25-0.88) and 0.51 (95%CI=0.26- 0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR=0.47; 95%CI=0.22-0.82 and HR=0.52; 95%CI=0.31- 0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Polimorfismo Genético , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Platino (Metal)/administración & dosificación , Polimorfismo de Nucleótido Simple , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
Chrysanthemum (Chrysanthemum morifolium Ramat.) is a commercially important ornamental grown worldwide, and is also extensively used as an edible and medicinal plant. In the present work, viruses and viroids infecting chrysanthemum were investigated in China in 2012 and 2013. Typical viral symptoms were observed in field-grown chrysanthemum with leaf yellowing and mottled leaves in Wenjiang District, Sichuan Province, China. The incidence of these symptoms in the field was 12.3%. Chrysanthemum virus B (CVB), Tomato aspermy virus (TAV), Cucumber mosaic virus (CMV), Tobacoo mosaic virus (TMV), Chrysanthemum stunt viroid (CSVd), and Chrysanthemum chlorotic mottle viroid (CChMVd), which had previously been reported to infect chrysanthemum in China (2,3), were not detected by RT-PCR assay. Since these symptomatic chrysanthemum plants grew next to a tobacco field, viruses affecting tobacco were suspected as possible cause. Sixteen symptomatic leaves and 12 non-symptomatic leaves were collected and tested for Potato virus Y (PVY) presence using commercial PVY-specific DAS-ELISA kits (Catalog no. PSA20001, Agdia) Six samples were found positive for PVY. RT-PCR tests using specific primers for CP gene (CP-F 5'-ACTGTGATGAATGGGCTTATG-3'; CP-R 5'-GGCATATATGGTTCCTTTTTG-3') (4) amplified a single, expected 218-bp DNA fragment from chrysanthemum extracts from all six samples positive for PVY in ELISA. These six PCR fragments were sequenced and found 100% identical to each other. The sequence (GenBank Accession No. KJ174515) shared 99% identity with corresponding sequences of several PVY isolates (NC_001616, EF026076, HM590407, and JQ924288). The same six positive samples were subjected to a multiplex RT-PCR assay (1) to identify the PVY strain type, and all six PVY samples from Sichuan were found to belong to the PVYN-Wi strain. To our knowledge, this is the first report of the PVYN-Wi strain infecting chrysanthemum in Sichuan, China. References: (1) M. Chikh Ali et al. Plant Dis. 10:1370, 2013. (2) E. A. Nassar et al. Int. J. Virol. 8:14, 2012. (3) H. Yamamoto et al. J. Gen. Plant Pathol. 71:156, 2005. (4) J. Q. Zhang et al. J. Phytopathol. 161:92, 2013.
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Hepatocellular carcinoma suppressor 1 (HCCS1) was discovered as a novel tumor suppressor gene. We recently observed that adenovirus-mediated gene transfer of HCCS1 leads to cytotoxicity to human hepatocarcinoma cells. Here, we have demonstrated that adenovirus-mediated overexpression of HCCS1 induces apoptosis in hepatocarcinoma cells and have further characterized the apoptotic cascade. The results showed that lysosomal cathepsin D is released into the cytosol in response to HCCS1 overexpression and consequently triggers Bax insertion into the mitochondrial membrane, which leads to the release of cytochrome c. In addition, HCCS1 overexpression can induce an increase in intracellular free Ca(2+) concentration, which also results in cytochrome c release. The released cytochrome c activates downstream caspases, leading to the occurrence of the late stages of apoptosis. Moreover, we demonstrated that the disruption of HCCS1 in mice leads to embryonic lethality, accompanied by abnormal labyrinth architecture resulting from the excessive proliferation of trophoblast cells in the placenta. These results suggest that HCCS1 plays a role in apoptosis regulation and development.
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Apoptosis , Calcio/metabolismo , Catepsina D/metabolismo , Placenta/anomalías , Proteínas Supresoras de Tumor/fisiología , Animales , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Citocromos c/metabolismo , Femenino , Genes Letales , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/metabolismo , Lisosomas/enzimología , Ratones , Ratones Noqueados , Embarazo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas de Transporte Vesicular , Proteína X Asociada a bcl-2/metabolismoRESUMEN
We report on a field induced domain evolutionary procedure in the anisotropic Nd-Dy-Fe-Co-B/MgO/Fe multilayers by using first-order-reversal-curves and magnetic force microscopy. Different reversal behaviors and domain sizes are found in well coupled and decoupled multilayers by changing the thickness of the spacer layer. The competition between dipolar magnetostatic energy and Zeeman energy is evaluated by in-field observation throughout nucleation and annihilation processes. In addition, lithography-patterned arrays of soft Fe disks onto a continuous Nd-Dy-Fe-Co-B hard-magnetic layer are designed. By decreasing the applied field, it is found that magnetization orientations of the Fe disk and Nd-Dy-Fe-Co-B layer are aligned parallel. In the decoupled disk, although the out-of-plane magnetization orientations are observed, the orientation of the domains in the Fe disk is random. Furthermore, it is found that a stronger anisotropy of the Nd-Dy-Fe-Co-B layer decreases the interaction length. Our results provide a new understanding of anisotropic nanocomposite magnets with long-ranged magnetic interactions.
RESUMEN
Because an increase in flow rate accelerates intestinal transit, a reduction in the flow rate of formula delivery is recommended frequently for treatment of diarrhea that develops during enteral feeding. Because intestinal transit is slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit during enteral feeding may depend on a balance between the accelerating effect of flow and the inhibiting effect of the nutrient load. The addition of fiber to a formula may alter this balance. By delaying absorption of nutrients, fiber may extend the length of small intestine exposed to nutrients and thereby trigger more intense inhibitory feedback. To determine whether the addition of fiber favors nutrient-triggered inhibition over flow-driven acceleration, we studied intestinal transit after perfusion of a low-residue enteral formula compared with a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into the duodenum of dogs each with both a duodenal and midgut fistula. With the low-residue formula, intestinal transit accelerated when the flow rate increased from 50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however, intestinal transit was inhibited regardless of the flow rate. To determine whether the fiber-supplemented formula inhibited intestinal transit by displacing nutrients distally, we compared intestinal transit when the two formulas, delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal transit of the fiber-supplemented formula increased by 400%, eliminating the difference in intestinal transit speed between the two formulas. We concluded that the fiber-supplemented formula slowed intestinal transit by intensifying inhibitory feedback from the distal gut.
Asunto(s)
Fibras de la Dieta/farmacología , Fenómenos Fisiológicos del Sistema Digestivo , Nutrición Enteral/métodos , Tránsito Gastrointestinal/fisiología , Análisis de Varianza , Animales , Diarrea/etiología , Diarrea/fisiopatología , Fibras de la Dieta/administración & dosificación , Perros , Duodeno/efectos de los fármacos , Duodeno/fisiología , Nutrición Enteral/efectos adversos , Nutrición Enteral/normas , Retroalimentación , Alimentos Fortificados , Distribución Aleatoria , Pentetato de Tecnecio Tc 99mRESUMEN
Ileal perfusion of protein slows intestinal transit. Because optimal absorption of nutrients requires adequate time in contact with the mucosa, slowed intestinal transit may increase protein absorption by increasing the residence time of nutrients in the small intestine. Although protein supplements are routinely added to enteral feeding to correct protein malnutrition, little information is available on the effect of increasing the load of protein on intestinal transit and the efficiency of protein absorption. In six dogs equipped with duodenal and midintestinal fistulas, intestinal transit and the efficiency of protein absorption (percentage protein absorbed as estimated from the output of midintestinal fistula) were compared during intestinal perfusion with 0-, 50-, 100-, and 200-g/L solutions of a whey-based protein supplement. We found that intestinal transit slowed in a load-dependent fashion (P < 0.05); the amount of protein absorbed within the proximal one-half of the small intestine increased in a load-dependent fashion (P < 0.05) as intestinal transit slowed, and the percentage protein absorbed (reflecting the efficiency of protein absorption) was maintained at a high and nearly constant value of 66.5-72.5% across protein loads of 9-36 g. We conclude that enhanced protein absorption is associated with a load-dependent inhibition of intestinal transit.