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PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.
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Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso , Humanos , Hígado , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA. METHODS: A total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA). RESULTS: Significant differences were observed in the survival rates of patients with Deauville scores of 1-3 and 4-5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1-3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4-5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%). CONCLUSION: PCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata. KEY POINTS: We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Infecciones por Virus de Epstein-Barr/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/patología , Estudios de Cohortes , ADN Viral , PronósticoRESUMEN
There is an increasing demand for multiplexing of quantum key distribution with optical communications in single fiber in consideration of high costs and practical applications in the metropolitan optical network. Here, we realize the integration of quantum key distribution and an optical transport network of 80 Gbps classical data at 15 dBm launch power over 50 km of the widely used standard (G.652 Recommendation of the International Telecom Union Telecom Standardization Sector) telecom fiber. A secure key rate of 11 Kbps over 20 km is obtained. By tolerating a high classical optical power up to 18 dBm of 160 Gbps classical data on single-mode fiber, our result shows the potential and tolerance of quantum key distribution being used in future large capacity transmission systems, such as metropolitan area networks and data centers. The quantum key distribution system is stable, practical, and insensitive to the polarization disturbance of channels by using a phase coding system based on a Faraday-Michelson interferometer. We also discuss the fundamental limit for quantum key distribution performance in the multiplexing environment.
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To date, various quantum random number schemes have been demonstrated. However, the cost, size, and final random bit generation rate usually limits their wide application on-shelf. To overcome these limitations, we propose and demonstrate a compact, simple, and low-cost quantum random number generation based on a linear optocoupler. Its integrated structure consists mainly of a light emitting diode and a photodetector. Random bits are generated by directly measuring the intensity noise of the output light, which originates from the random recombination between holes of the p region and electrons of the n region in a light emitting diode. Moreover, our system is robust against fluctuation of the operating environment, and can be extended to a parallel structure, which will be of great significance for the practical and commercial application of quantum random number generation. After post-processing by the SHA-256 algorithm, a random number generation rate of 43 Mbps is obtained. Finally, the final random bit sequences have low autocorrelation coefficients with a standard deviation of 3.16×10-4 and pass the NIST-Statistical Test Suite test.
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PURPOSE: To investigate the effects of dose reduction on image quality and lesion detectability of oncological 18F-FDG total-body PET/CT in pediatric oncological patients and explore the minimum threshold of administered tracer activity. METHODS: A total of 33 pediatric patients (weight 8.5-58.5 kg; age 0.8-17.6 years) underwent total-body PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Low-dose images (0.12-1.85 MBq/kg) were simulated by truncating the list-mode PET data to reducing count density. Subjective image quality was rated on a 5-point scale. Semi-quantitative uptake metrics for low-dose images were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions and were compared with full-dose images. The micro-lesion detectability was compared among the dose-dependent PET images. RESULTS: Our analysis shows that sufficient subjective image quality and lesion conspicuity could be maintained down to 1/30th (0.12 MBq/kg) of the administered dose of 18F-FDG, where good image quality scores were given to 1/2- and 1/10- dose groups. The image noise was significantly more deranged than the overall quality and lesion conspicuity in 1/30- to 1/10-dose groups (all p < 0.05). With reduced doses, quantitative analysis of ROIs showed that SUVmax and SD in the liver increased gradually (p < 0.05), but SUVmax in the lesions and lesion-to-background ratio (LBR) showed no significant deviation down to 1/30-dose. One hundred percent of the 18F-FDG-avid micro-lesions identified in full-dose images were localized down to 1/15-dose images, while 97% of the lesion were localized in 1/30-dose images. CONCLUSION: The total-body PET/CT might significantly decrease the administered dose upon maintaining the image quality and diagnostic performance of micro-lesions in pediatric patients. Data suggests that using total-body PET/CT, optimal image quality could be achieved with an administered dose-reduction down to 1/10-dose (0.37 MBq/kg).
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Fluorodesoxiglucosa F18 , Neoplasias , Adolescente , Niño , Preescolar , Humanos , Lactante , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the degree of gastric, enteric, colonic, and rectal filling in multidetector computed tomography (MDCT) whole gastroenterography. METHODS: In this prospective study involving 124 patients, 78 and 46 patients underwent MDCT whole gastroenterography using positive and neutral oral contrast agents, respectively. The degree of filling of the stomach, small and large bowel, was qualitatively analyzed by experienced radiologists using a 3-point scoring system. RESULTS: The majority of patients received a score of ≥2 for small intestine filling using both positive and neutral contrast agents (90.5% and 78.2%, respectively), and <9% of the patients had a score of 0. The highest score for the degree of filling in the small intestine was observed in the ileum, followed by the duodenum and jejunum. There was a significant difference in the degree of filling achieved with positive and neutral contrast agents in the duodenum (P = .013) and jejunum (P = .047). More than 74% of cases had an optimal filling of the stomach, whereas >80% of the cases had an optimal filling of the colorectal segments. Only ≤5.1% had a score of 0 for the analyzed segments of the colorectum. Positive and neutral contrast agents were associated with similar degree of filling in the stomach and colon segments without a significant difference in the extent of contrast agent filling (P > .05). CONCLUSIONS: Multidetector computed tomography whole gastroenterography was found to be a simple, safe, noninvasive, painless, and effective modality for the diagnosis of stomach and bowel complications in clinical settings.
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Neoplasias del Colon/diagnóstico por imagen , Medios de Contraste , Tracto Gastrointestinal/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Colon/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Femenino , Humanos , Intestino Delgado/diagnóstico por imagen , Masculino , Manitol/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Dosis de Radiación , Recto/diagnóstico por imagen , Estómago/diagnóstico por imagen , Ácidos Triyodobenzoicos/administración & dosificaciónRESUMEN
We investigate quantum random number generation based on backward spontaneous Raman scattering in standard single-mode fiber, where the randomness of photon wavelength superposition and arrival time is simultaneously utilized. The experiment uses four avalanche photodiodes working in gated Geiger mode to detect backward Raman scattering photons from four different wavelength channels and a time-to-digital converter placed behind the detectors to record their arrival time. Both information of the wavelength and arrival time interval of photons from different channels are applied to generate random bits. Due to the independence of these two entropy sources, the random number resource of the present system is fully utilized. Five-bit raw data can be obtained for every effective click, which contains 2.87-bit min-entropy. To obtain the optimal generation rate of random bits, appropriate pump power and fiber length are adopted. The post-processing method by the SHA-256 hashing algorithm is used to remove the bias of the raw data, after which the final random bit sequences pass the NIST statistical test.
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Cornelia de Lange syndrome (CdLS) is a rare neurodevelopmental syndrome for which mutations in five causative genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex, account for ~70% of cases. Herein we report on four female Subjects who were found to carry novel intragenic deletions in HDAC8. In one case, the deletion was found in mosaic state and it was determined to be present in ~38% of blood lymphocytes and in nearly all cells of a buccal sample. All deletions, for which parental blood samples were available, were shown to have arisen de novo. X-chromosome inactivation studies demonstrated marked skewing, suggesting strong selection against the mutated HDAC8 allele. Based on an investigation of the deletion breakpoints, we hypothesize that microhomology-mediated replicative mechanisms may be implicated in the formation of some of these rearrangements. This study broadens the mutational spectrum of HDAC8, provides the first description of a causative HDAC8 somatic mutation and increases the knowledge on possible mutational mechanisms underlying copy number variations in HDAC8. Moreover our findings highlight the clinical utility of considering copy number analysis in HDAC8 as well as the analysis on DNA from more than one tissue as an indispensable part of the routine molecular diagnosis of individuals with CdLS or CdLS-overlapping features.
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Síndrome de Cornelia de Lange/diagnóstico , Síndrome de Cornelia de Lange/genética , Estudios de Asociación Genética , Histona Desacetilasas/genética , Fenotipo , Proteínas Represoras/genética , Eliminación de Secuencia , Secuencia de Bases , Niño , Preescolar , Puntos de Rotura del Cromosoma , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Exones , Facies , Femenino , Duplicación de Gen , Humanos , Análisis de Secuencia de ADN , Inactivación del Cromosoma XRESUMEN
Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.
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Pueblo Asiatico/genética , Catepsina K/genética , Cálculos Renales/etiología , Picnodisostosis/complicaciones , Picnodisostosis/genética , Adulto , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Mutación Missense , LinajeRESUMEN
INTRODUCTION: Fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) is a powerful tool for monitoring the response of diffuse large B-cell lymphoma (DLBCL) to therapy, but the criteria to interpret PET/CT results remain under debate. We investigated the value of post-treatment PET/CT in predicting the prognosis of DLBCL patients when interpreted according to qualitative visual trichotomous assessment (QVTA) criteria compared with the Deauville criteria. METHODS: In this retrospective study, final PET/CT scans of DLBCL patients treated with rituximab-based regimens between October 2005 and November 2010 were interpreted using the Deauville and QVTA criteria. Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test. RESULTS: A total of 253 patients were enrolled. The interpretation according to the Deauville criteria revealed that 181 patients had negative PET/CT scan results and 72 had positive results. The 3 year overall survival (OS) rate was significantly higher in patients with negative scan results than in those with positive results (91.6% vs. 57.5%, P<0.001). The 72 patients with positive scan results according to the Deauville criteria were divided into two groups by the interpretation according to the QVTA criteria: 29 had indeterminate results, and 43 had positive results. The 3 year OS rate was significantly higher in patients with indeterminate scan results than in those with positive results (91.2% vs. 33.5%, P<0.001) but was similar between patients with negative and indeterminate scan results (91.6% vs. 91.2%, P=0.921). CONCLUSIONS: Compared with the Deauville criteria, using the QVTA criteria for interpreting post-treatment PET/CT scans of DLBCL patients is likely to reduce the number of false positive results. The QVTA criteria are feasible for therapeutic outcome evaluation and can be used to guide risk-adapted therapy.
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Linfoma de Células B , Tomografía de Emisión de Positrones , Pronóstico , Anticuerpos Monoclonales de Origen Murino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso , Métodos , Imagen Multimodal , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overall survival rate (93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.
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Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Persona de Mediana Edad , Imagen Multimodal , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a critical pathological factor and the degree of MVI influences treatment decisions and patient prognosis. The present study aimed to predict the MVI classification based on preoperative MRI features and clinical parameters. The present retrospective cohort study included 150 patients (training cohort, n=108; validation cohort, n=42) with pathologically confirmed HCC. Clinical and imaging characteristics data were collected from Shengli Oilfield Central Hospital (Dongying, China). Univariate and multivariate logistic regression analyses were conducted to assess the association of clinical variables and MRI parameters with MVI (grade M1 and M2) and the M2 classification. Nomograms were developed based on the predictive factors of MVI and the M2 classification. The discrimination capability, calibration and clinical usefulness of the nomograms were evaluated. Multivariate analysis revealed an association between the Lens culinaris agglutinin-reactive fraction of α-fetoprotein, protein induced by vitamin K absence-II and tumor margin and MVI-positive status, while peritumoral enhancement and tumor size were demonstrated to be marginal predictors, but were also included in the nomogram. However, among MVI-positive patients, only peritumoral hypointensity and tumor size were demonstrated to be risk factors for the M2 classification. The nomograms, incorporating these variables, exhibited a strong ability to discriminate between MVI-positive and MVI-negative patients with HCC in both the training and validation cohort [area under the curve (AUC), 0.877 and 0.914, respectively] and good performance in predicting the M2 classification in the training and validation cohorts (AUC, 0.720 and 0.782, respectively). Nomograms incorporating clinical parameters and preoperative MRI features demonstrated promising potential as straightforward and effective tools for predicting MVI and the M2 classification in patients with HCC. Such predictive tools could aid in the judicious selection of optimal clinical treatments.
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The metabolic activities of microorganisms play a crucial role in the quality development of fermented sausage. This study investigated the effect of inoculation with different combinations of starter cultures (Lactiplantibacillus plantarum YR07, Latilactobacillus sakei L.48, Staphylococcus xylosus S.14, and Mammaliicoccus sciuri S.18) on the quality of sausages. Inoculation with mixed starter cultures promoted protein degradation to generate amino acids and the conversion to volatile compounds, which enhanced the flavor development in fermented sausages. The bacterial community analyses demonstrated that the inoculation of mixed starter cultures could inhibit the growth of spoilage and pathogenic bacteria, thereby reducing the total content of biogenic amines. The correlation analysis between the core bacteria and characteristic volatile compounds revealed that fermented sausages inoculated with Lactobacillus and coagulase negative staphylococci exhibited significant positive correlations with the majority of key characteristic volatile compounds. In four treatments, inoculation with L. plantarum YR07 and M. sciuri S.18 greatly promoted the formation of characteristic volatile compounds (3-hydroxy-2-butanone, hexanal, and 1- octen-3ol). Therefore, the combined inoculation of L. plantarum YR07 and M. sciuri S.18 is promising to enhance fermented sausage's flavor profile and safety.
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Lactobacillus plantarum , Microbiota , Microbiología de Alimentos , Fermentación , Lactobacillus/metabolismoRESUMEN
PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.
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Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.
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Colitis Ulcerosa , Colitis , Humanos , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Células Th17/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Células Epiteliales/metabolismo , Tretinoina/metabolismo , Tretinoina/farmacología , Tretinoina/uso terapéuticoRESUMEN
AIM: To evaluate the protective effects of strontium fructose 1,6-diphosphate (FDP-Sr), a novel strontium salt that combined fructose 1,6-diphosphate (FDP) with strontium, on bone in an ovariectomy-induced model of bone loss. METHODS: Eighty female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Three months later, the rats were assigned to six groups (10 for each): sham-operated, OVX control, OVX+FDP-Sr (110, 220, or 440 mg/kg), or OVX+strontium ranelate (SR, 180 mg/kg). Drugs were administered orally for 3 months. When the treatment was terminated, the following parameters were assessed: bone mineral density (BMD), the biomechanical properties of the femur and lumbar vertebrae, trabecular histomorphology, serum phosphorus, calcium, bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRACP5b), N-telopeptide of type I collagen (NTx) and a series of markers for oxidative stress. Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) levels in serum were measured using ELISA and their gene expression levels in the bone were measured using R-T PCR. RESULTS: Treatment with FDP-Sr (220 or 440 mg/kg) or SR (180 mg/kg) significantly increased the BMD and improved the bone microarchitecture and bone strength in OVX rats. The treatments also decreased in the levels of H(2)O(2) and MDA, restored the CAT level in serum and bone marrow, increased the serum B-ALP and decreased NTx and TRACP 5b in OVX rats. Treatment with FDP-Sr decreased the RANKL level, and increased the OPG level in serum in a dose-dependent manner. It also significantly down-regulated the RANKL expression and up-regulated OPG expression in bone marrow. CONCLUSION: FDP-Sr may be an effectve treatment for postmenopausal osteoporosis that acts, in part, via a decrease in osteoclastogenesis through the OPG\RANKL\RANK pathway.
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Fructosadifosfatos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Osteoporosis Posmenopáusica/prevención & control , Animales , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/patología , Femenino , Fructosadifosfatos/farmacología , Humanos , Factores Inmunológicos/farmacología , Factor I del Crecimiento Similar a la Insulina/análisis , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/patología , Osteoprotegerina/sangre , Estrés Oxidativo/efectos de los fármacos , Ligando RANK/sangre , Ratas , Ratas Sprague-Dawley , Receptor Activador del Factor Nuclear kappa-B/sangre , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the association between vitamin D deficiency and risk of gestational diabetes mellitus (GDM) in pregnant Chinese women. METHODS: A nested case-control study was conducted. Clinical and biochemical data were analyzed for 200 subjects with GDM and 200 subjects with normal glucose tolerance (NGT). RESULTS: The median (interquartile range) serum 25-hydroxyvitamin D (25OHD) levels were 22.39 (17.67, 29.38) and 25.86 (19.09, 34.88) nmol/L in the GDM and NGT groups, respectively. Rates of 25OHD deficiency or insufficiency were significantly higher in the GDM group than in the NGT group. Subjects with 25OHD levels <25 nmol/L had a 1.8-fold higher risk of GDM compared with subjects with higher vitamin D levels. In the GDM group, serum 25OHD was independently associated with HbA1c and insulin resistance after adjusting for confounding factors. In the NGT group, serum 25OHD was independently associated with fasting plasma glucose and systolic blood pressure after adjusting for maternal age and other confounding factors. CONCLUSION: 25OHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM.
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Diabetes Gestacional/epidemiología , Deficiencia de Vitamina D/epidemiología , Adulto , Pueblo Asiatico , Diabetes Gestacional/sangre , Femenino , Humanos , Embarazo , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
OBJECTIVE: To explore the feasibility, short-term efficacies and complications of computed tomography (CT)-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer. METHODS: From October 2009 to November 2010, a total of 25 lesions for 12 patients were diagnosed as recurrent ovarian cancer by positron emission tomography/computed tomography (PET/CT). Among 25 lesions, 21 underwent ¹²5I seed implantation. And 4 lesions of liver and spleen in one patient were treated with microwave ablation. Nine patients underwent 2 - 6 cycles of chemotherapy after seeding. There were 11 lesions with diameter > 2 cm and 10 ≤ 2 cm. According to the area of physiologic 18FDG uptake in lesions, the treatment plans were formulated by computerized treatment planning system (TPS) and Memorial Sloan-Ketterin nomograph. The matched peripheral dose (MPD) was 145 Gy in target mass. A median of 20.5 seeds per patient (range: 9 - 45) were implanted. The efficacies were evaluated by CT and 18F-FDG PET/CT findings. RESULTS: One patient died of renal failure while the other patients survived during a median follow-up of 15 mouths (range: 9 - 19). Ten lesions showed complete remission, 6 partial remission and 5 progressive disease. The effective rate was 76.2% (16/21). Compared with those > 2 cm, the lesions ≤ 2 cm in diameter had a better local control rate by Fisher's exact test (P = 0.035). The hepatic and renal lesions treated by microwave ablation showed inactivation on PET/CT. Only one patient suffered from sciatic nerve injury caused by punctuation and numbness and pain of right lower extremity were persistent. There was no onset of the complications of radiation injury, such as intestinal fistula and proctitis. CONCLUSION: The CT-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer yields excellent short-term efficacies with fewer complications. The combined modality of ¹²5I interstitial implant and chemotherapy may further improve the patient outcomes.
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Braquiterapia/métodos , Radioisótopos de Yodo/administración & dosificación , Neoplasias Glandulares y Epiteliales/radioterapia , Neoplasias Ováricas/radioterapia , Adulto , Anciano , Carcinoma Epitelial de Ovario , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.
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Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Lactobacillus johnsonii , Receptor Toll-Like 1 , Animales , Ratones , Antiinflamatorios , Colitis/genética , Colitis/microbiología , Colitis/terapia , Colitis Ulcerosa/genética , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/terapia , Sulfato de Dextran/toxicidad , Interleucina-10/genética , Macrófagos , ARN Ribosómico 16S , Receptor Toll-Like 1/genética , Receptor Toll-Like 1/metabolismoRESUMEN
AIM: To explore the alteration of endogenous metabolites and identify potential biomarkers using metabolomic profiling with gas chromatography coupled a time-of-flight mass analyzer (GC/TOF-MS) in a rat model of estrogen-deficiency-induced obesity. METHODS: Twelve female Sprague-Dawley rats six month of age were either sham-operated or ovariectomized (OVX). Rat blood was collected, and serum was analyzed for biomarkers using standard colorimetric methods with commercial assay kits and a metabolomic approach with GC/TOF-MS. The data were analyzed using multivariate statistical techniques. RESULTS: A high body weight and body mass index inversely correlated with serum estradiol (E2) in the OVX rats compared to the sham rats. Estrogen deficiency also significantly increased serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Utilizing GC/TOF-MS-based metabolomic analysis and the partial least-squares discriminant analysis, the OVX samples were discriminated from the shams. Elevated levels of cholesterol, glycerol, glucose, arachidonic acid, glutamic acid, glycine, and cystine and reduced alanine levels were observed. Serum glucose metabolism, energy metabolism, lipid metabolism, and amino acid metabolism were involved in estrogen-deficiency-induced obesity in OVX rats. CONCLUSION: The series of potential biomarkers identified in the present study provided fingerprints of rat metabolomic changes during obesity and an overview of multiple metabolic pathways during the progression of obesity involving glucose metabolism, lipid metabolism, and amino acid metabolism.