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Erythro-myeloid progenitors of the yolk sac that originates during early embryo development has been suggested to generate tissue-resident macrophage, mast cell, and even endothelial cell populations from fetal to adult stages. However, the heterogeneity of erythro-myeloid progenitors (EMPs) is not well characterized. Here, we adapt single-cell RNA sequencing to dissect the heterogeneity of EMPs and establish several fate-mapping tools for each EMP subset to trace the contributions of different EMP subsets. We identify two primitive and one definitive EMP subsets from the yolk sac. In addition, we find that primitive EMPs are decoupled from definitive EMPs. Furthermore, we confirm that primitive and definitive EMPs give rise to microglia and other tissue-resident macrophages, respectively. In contrast, only Kit+ Csf1r- primitive EMPs generate endothelial cells transiently during early embryo development. Overall, our results delineate the contribution of yolk sac EMPs more clearly based on the single-cell RNA sequencing (scRNA-seq)-guided fate-mapping toolkit.
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Células Endoteliales , Saco Vitelino , Microglía , Células Progenitoras Mieloides , Análisis de Secuencia de ARN , Linaje de la Célula , Hematopoyesis/genéticaRESUMEN
Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.
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ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.
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Trasplante de Hígado , Adulto , Humanos , Niño , Complicaciones Posoperatorias , EsplenectomíaRESUMEN
Objective: To explore the outcome of the pediatric-to-adult liver transplantation, including postoperative complications and relevant factors which affecting graft survival. Methods: Data of 55 patients undergoing pediatric-to-adult liver transplantation at the First Affiliated Hospital of Zhejiang University between January 2015 and August 2021 were retrospectively analyzed. The donors consisted of 34 males and 21 females, and the age was (11.8±4.7) years (range: 1 to 17 years). Among the cases,17 cases (30.9%) were donation of brain death,32 cases (58.2%) were donation of cardiac death, and 6 cases (10.9%) were donation after brain death plus cardiac death. The recipients consisted of 32 males and 23 females, and the age was (51.6±10.1) years (range: 27 to 70 years). Among the recipients,10 cases (18.2%) were ABO-incompatible liver transplantation.The influencing factors of early graft survival were analyzed by Student t test,Mann-Whitney U test or χ2 test,respectively.Survival curve was drawn by Kaplan-Meier method.Logistic multivariate analysis was used to analyze the independent relevant factors of early postoperative graft loss. Results: Up to October 31,2021,the follow-up time (M(IQR)) was 36.0(43.1)months(range:5.9 to 81.7 months).There were 13 cases with graft loss (two of them underwent re-transplantation due to acute liver failure).The monofactor analysis indicated that cold ischemia time and donor-recipient blood group matching were the relevant factors affecting the early graft survival rate(both P<0.05).Logistic multivariate analysis showed that cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors(both P<0.05).Postoperative hepatic artery thrombosis occurred in 3 cases(5.5%), portal vein thrombosis diagnosed in 4 cases(7.3%), portal vein stenosis occurred in 2 cases(3.6%),biliary complications diagnosed in 7 cases(12.7%), and small liver syndrome was found in 8 cases(14.5%). Conclusions: Adult liver transplantation with pediatric donor liver is an effective method to treat end-stage liver disease.Cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors for the early graft survival.
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Antígenos de Grupos Sanguíneos , Trasplante de Hígado , Trombosis de la Vena , Adolescente , Adulto , Anciano , Muerte Encefálica , Niño , Preescolar , Muerte , Femenino , Hemorragia Gastrointestinal , Humanos , Lactante , Trasplante de Hígado/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.
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Objective: To determine the 2-year visual prognosis in Chinese type 2 diabetic patients with mild visual impairment and identify the predictors factors. Method: This was a 2-year population-based cohort study. The study population consisted of 650 type 2 diabetic patients with bilateral mild visual impairment in 2014 who were followed up in 2016. The demographic information, systemic and ophthalmological examination results for each participant was collected. Mild visual impairment was defined as best-corrected visual acuity (BCVA)<20/25 to ≥20/63, moderate and severe visual impairment was defined as BCVA<20/63 to ≥20/400, blindness was defined as BCVA<20/400 following the International Council of Ophthalmology (ICO) 2002 definition. The two-year visual prognosis was divided into three groups: visual impairment regression, progression, and stable. Using chi-square test or independent t-test, the predictor factors of visual prognosis and the leading causes of visual impairment were studied. Results: 605 patients completed the follow-up in 2016. Among them, 477 were still bilateral mild visual impairment, accounting for 78.8% (477/605). The level of unilateral or bilateral visual impairment regressed in 8.1% (49/605), while progressed in 13.1% (79/605). Young age (t=2.7, P<0.05), short duration of diabetes (t=2.5, P<0.05), low blood glycemic hemoglobin (t=2.5, P<0.05) and total cholesterol (t=2.8, P<0.05) were associated with regression of visual impairment. Low levels of education (t=5.2, P<0.05), high blood glycemic hemoglobin (t=2.4, P<0.05) and total cholesterol (t=2.4, P<0.05)were associated with progression of visual impairment. Cataracts and diabetic retinopathy were the first and second cause of mild, moderate severe visual impairment or blindness. Conclusions: The percentage of 2-year visual acuity decline is relatively high in type 2 diabetic patients with mild visual impairment. We should strengthen blood glucose and cholesterol control to reduce the progress of visual impairment.(Chin J Ophthalmol, 2021, 57: 766-771).
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Seguimiento , Humanos , Prevalencia , Trastornos de la VisiónRESUMEN
OBJECTIVE: To investigate how nuclear factor-E2-related factor 2 (Nrf2) involved in the protective effect of isoflurane (Iso) preconditioning in oxygen glucose deprivation (OGD)-induced cortical neuron injury. METHODS: Primary mouse cortical neurons were divided into Control, ML385 (an Nrf2 inhibitor), Iso, Iso + ML385, OGD, ML385 + OGD, Iso + OGD, and Iso + ML385 + OGD groups. Lactate dehydrogenase activity (LDH) release and oxidative stress indexes were quantified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability, Annexin V-FITC/propidium iodide (PI) staining to measure cell apoptosis, dichloro-dihydro-fluorescein diacetate (DCFH-DA) method to test reactive oxygen species (ROS), and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting to evaluate genes and protein expression. RESULTS: Iso preconditioning reduced LDH release and inhibited cell cytotoxicity in OGD-induced cortical neurons, which was abolished by ML385. Iso preconditioning increased the Nrf2 nuclear translocation in cortical neurons. Meanwhile, Iso decreased the OGD-induced apoptosis with the down-regulations of Bax and Caspase-3 and the up-regulation of Bcl-2, which was reversed by ML385. OGD enhanced the level of ROS and malondialdehyde (MDA) in cortical neurons, but reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were aggravated in ML385 + OGD group and mitigated in Iso + OGD group. No observable difference was found between OGD group and Iso + ML385 + OGD group regarding apoptosis-related proteins and oxidative stress-related indexes. CONCLUSION: Iso preconditioning up-regulated Nrf2 level to play its protective role in OGD-induced mouse cortical neuron injury.
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Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Glucosa/deficiencia , Hipoxia/tratamiento farmacológico , Isoflurano/farmacología , Factor 2 Relacionado con NF-E2/farmacología , Neuronas/efectos de los fármacos , Anestésicos por Inhalación/metabolismo , Anestésicos por Inhalación/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Humanos , Hipoxia/fisiopatología , Isoflurano/metabolismo , Redes y Vías Metabólicas , Ratones , Modelos Animales , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos NeuroprotectoresRESUMEN
The low surgical resection rate and high postoperative recurrence rate of hepatocellular carcinoma(HCC) are urgent clinical problems to be solved. Therefore, it is important to develop effective perioperative treatment. In recent years, a growing number of studies have shown that systemic therapy is expected to break through the limitations of traditional local treatment and play an important role in preoperative treatment. For example, some novel targeted agents and immunocheckpoint inhibitors have shown excellent potential as neoadjuvant treatment for HCC. Meanwhile, researchers have explored the application of systemic therapy as adjuvant therapy, but due to different criteria for patient selection, no consensus is reached on its efficacy. By far, there is no standard procedure for the application of systemic therapy in HCC perioperative period, little is known about the efficacy and safety of targeted drugs and immunotherapy. This article discusses the feasibility of systemic therapy as neoadjuvant and adjuvant treatment of HCC, as well as its adverse events, with an aim to provide new horizons of HCC systemic therapy in the perioperative period.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Neoadyuvante , Atención Perioperativa , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/terapia , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Terapia Combinada/tendencias , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/tendencias , Atención Perioperativa/tendenciasRESUMEN
Neoadjuvant therapy has been proved beneficial in patients with non-metastatic pancreatic cancer and it has received unprecedented attention in past years. However, the clinical value of neoadjuvant therapy in resectable pancreatic cancer patients remains controversial.Although the NCCN guideline has recommended that resectable pancreatic cancer patients with high-risk factors should be given preoperative neoadjuvant therapy, there is no consensus on specific criteria, treatment options, treatment duration and timing of surgery.More high-level evidences are strongly required.Recently, the development of new technologies such as liquid biopsy and radiomics analysis for pancreatic cancer will also help to address some clinical problems.This article reviewed the developments and controversies in neoadjuvant therapy for resectable pancreatic cancer.
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Terapia Neoadyuvante/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , HumanosRESUMEN
Pancreatic cancer is a fatal disease with low resectability, high recurrence rate and despairing prognosis.Neoadjuvant therapy has been proven to improve resectability, especially R0 resection rate, and extend overall survival.It has become the hotspot in the field of pancreatic cancer in the last decade.However, the concomitant adverse effects on surgery and postoperative complication also draw wide attention.In this reivew, the indication and the effects of neoadjuvant therapy on pancreas and body composition according the latest studies are summarized.Futhermore, the effects of neoadjuvant therapy on postoperative complication from multiple aspects are discussed.
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Terapia Neoadyuvante , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias , PronósticoRESUMEN
Objective: To study the clinicopathologic features of intraductal papillary neoplasm of the bile duct(IPNB) and to analyze the diagnostic and therapeutic patterns. Methods: The data of 46 patients with IPNB undergoing surgery in Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to November 2017 were retrospectively analyzed.There were 23 males and 23 females with age of (64±8)years.Patients were followed up by clinics and telephone inquiry.Categorical data were compared with χ(2) test or Fisher's exact test. Results: Abdominal pain(in 31 patients), fever (in 15 patients) and jaundice (in 11 patients) were the most common symptoms.Twenty-five patients were accompanied with cholangiolithiasis and 25 were accompanied with liver atrophy.Preoperative laboratory examination was mainly manifested as the abnormal liver function caused by biliary obstruction.Typical imaging findings included bile duct dilation (in 45 patients) and mass within bile duct (in 22 patients). All the patients were diagnosed as IPNB histopathologically.Among them, high-grade intraepithelial neoplasia and related adenocarcinoma were more common in mucus-hypersecretion IPNB ((13/15 vs. 51.6%(16/31))(χ(2)=5.331, P=0.021). Hepatectomy was performed in 25 patients, hepatectomy combined with biliary resection and reconstruction in 12 cases, biliary resection and reconstruction in 3 cases, pancreatoduodenectomy in 3 cases, hepatopancreaticoduodenectomy in 1 case, liver transplantation in 1 case and radiofrequency ablation in 1 case.Forty-one patients were followed up with a median of 30 (12, 41) months.Seven patients suffered recurrence and 6 died. Conclusion: IPNB is a rare disease with limited knowledge currently.Images are the main diagnositc means and surgery is the first choice.
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Neoplasias de los Conductos Biliares , Anciano , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios RetrospectivosRESUMEN
Objective: To investigate the prevalence, subtypes and risk factors of cataract in type 2 diabetic individuals. Methods: Geographically defined cluster sampling method was used in this population-based, cross-sectional study. There were 7 756 type 2 diabetes individuals in Xinjing Town with a residential population of 88 864. The type 2 diabetic individuals were randomly selected from 20 basic sample units in Xinjing Town of Changning District from April to June 2016. All participants received visual acuity measurement and eye examination. The standard of lens opacity assessment was according to the Lens Opacities Classification Systemâ ¡(LOCSâ ¡). The prevalence of cataract in diabetic individuals was calculated with LOCS≥2. Multivariate Logistic regression analysis was used to explore the relevant factors of cataract in type 2 diabetic individuals. Results: A total of 1 719 type 2 diabetic individuals were included in the analysis. There were 682 men (39.67%) and 1 037 women (60.33%) in this population. There were 434 cataract individuals and the prevalence of cataract was 25.25%. There were 269 cases of nuclear type (15.7%), 38 cases of cortical type (2.2%), 2 cases of posterior subcapsular type (0.12%) and 42 cases of mixed type (2.4%) in the 1 719 individuals. Multivariate Logistic regression analysis showed that age (P<0.001), duration of diabetes (P<0.001), education (P=0.005), fasting blood glucose (P(6.1-7.7mmol/L)=0.025, P(7.8-24.3mmol/L)=0.022, compared with 3.6-6.0 mmol/L of fasting blood glucose), and ocular axial length (P<0.001) were associated with cataract. Conclusion: Cataract is a common ophthalmic disease in adults with type 2 diabetes in Xinjing Town. Regular screening of diabetes in the high risk population and intensive control of both glucose and blood pressure in diabetic patients are recommended to prevent and delay the development of cataract. (Chin J Ophthalmol, 2017, 53: 489-494).
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Catarata , Diabetes Mellitus Tipo 2 , Adulto , Catarata/epidemiología , Catarata/etiología , China/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Prevalencia , Factores de RiesgoRESUMEN
Pancreatic cancer is mainly diagnosed at an advanced stage when adjacent vessel invasion is present; however, radical resection is potentially curative for selected patients with adjacent vessel invasion. Therefore, accurately judging the resectability of patients with adjacent vessel invasion represents a crucially important step in diagnosis and treatment. Currently, decisions regarding resectability are based on imaging studies, commonly contrast computed tomography (CT). Several radiological classifications have been published for vascular infiltration in pancreatic cancer. However, radiologists always formulate these CT grading systems according to their own experience, resulting in different judgment methods and parameters. And it is controversial in evaluating performance and clinical application. Besides, the conventional CT grading systems mainly focus on the evaluation of vessel invasion so as to less on the outcome of patient evaluation. In this review, we summarize the mainstream CT grading systems for vascular invasion in pancreatic cancer, with the aim of improving the clinical value of CT grading systems for predicting resectability and survival.
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Neovascularización Patológica/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/normas , Humanos , Clasificación del Tumor , Neovascularización Patológica/clasificación , Neovascularización Patológica/patología , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/patologíaRESUMEN
The morbidity of pancreatic ductal adenocarcinoma (PDAC) has been increasing over years, while the treatment efficacy and prognosis of PDAC remain far from satisfying. The newly-ermerged tumor immunotherapy has not only made lots of breakthroughs in various malignancies, but also brought an opportunity to the treatment of pancreatic cancer.PDAC immunotherapies, mainly including vaccine therapy, adoptive T cell thanfer therapy, checkpoint blockade therapy, have achieved a certain effect, however, the clinical outcomes have not been satisfactory. Therefore, the combination of immunotherapies based on different theoretical views is important and is likely to be the trend in the future. Carcinoma associated fibroblast (CAF) is the most common cell in pancreatic cancer stromal component. It will be helpful to develop more potential therapeutic targets by further exploring CAF and the mechanism of fibrosis mediated immunosuppression.
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Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Inmunoterapia , Neoplasias Pancreáticas/terapia , Humanos , Neoplasias PancreáticasRESUMEN
Objective: To investigate the prevalence, underlying causes and risk factors of moderate or severe visual impairment and blindness in a population with type 2 diabetes in Xinjing Town, Shanghai, China. Methods: A cross-sectional survey among local Han adult residents, who were previously diagnosed as type 2 diabetes, was conducted between October 2014 and January 2015. The survey was preceded by a pilot study; operational methods were refined and quality assurance evaluation was carried out. The best corrected visual acuity was recorded and classified following the modified World Health Organization grading system. Assigned ophthalmic doctors assured the leading causes of every blind or visually impaired eye. Binary logistic regression analysis was used to determine the related factors of blindness and moderate or severe visual impairment. Results: A total of 2 216 type 2 diabetic residents were enrolled, and 166 eyes (3.7%, 166/4 432) were blind. Cataract was the leading cause of blindness (39.8%); macular degeneration (18.0%) and eyeball atrophy (11.4%) were the second and third leading causes of blindness, respectively. Moderate or severe visual impairment was found in 376 eyes (8.5%, 376/4 432), and the most frequent cause was cataract (65.7%), followed by diabetic retinopathy (9.8%) and macular degeneration (9.4% ). Older age, female gender, earlier onset diabetes and a lower spherical equivalent in the better eye were associated with best corrected visual acuity<20/63 in the better eye. Conclusion: The prevalences of moderate or severe visual impairment and blindness in our population with type 2 diabetes were high. (Chin J Ophthalmol, 2016, 52: 825-830).
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Ceguera/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Baja Visión/epidemiología , Adulto , Anciano , Ceguera/etiología , Catarata/complicaciones , China/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Retinopatía Diabética/complicaciones , Femenino , Humanos , Modelos Logísticos , Degeneración Macular/complicaciones , Masculino , Persona de Mediana Edad , Atrofia Óptica/complicaciones , Proyectos Piloto , Prevalencia , Factores de Riesgo , Factores Sexuales , Baja Visión/etiología , Agudeza VisualRESUMEN
OBJECTIVE: This study aimed to explore the predictive value of the apparent diffusion coefficient (ADC) of diffusion weighted imaging (DWI) in evaluating the therapeutic effects of synchronic chemoradiotherapy of cervical squamous cell carcinoma by using the functional imaging of 1.5T MR. MATERIALS AND METHODS: Fifty patients with cervical squamous cell carcinoma receiving synchronic chemoradiotherapy in the present hospital from October 2010 to February 2014 were enrolled in this study. MRI examination was performed on each patient before and after chemoradiotherapy. Eleven patients received an additional MRI examination when the in vitro cumulative radiation dose reached 36 Gy. The mean tumor ADC values of DWI sequence were measured before, under, and after chemoradiotherapy. At the end of the treatment, patients were divided into complete remission (CR) and partial remission (PR) groups on the basis of the residual tumors. Then the tumor ADC values and their changes before and after the treatment were analyzed using independent sample t-test. RESULTS: At the end of the treatment, 32 patients achieved CR and 18 patients achieved PR. The tumor ADC values increased gradually with the treatment, showing significant difference between before, under, and after the treatment (p < 0.01). The mean tumor ADC values were remarkably higher in CR group than in PR group (p < 0.001). CONCLUSION: The ADC values of MR functional imaging DWI can reflect the hydrone diffusion movement of tumor after the treatment, so that it is able to identify CR and PR in the patients, providing a new way and method for evaluating the therapeutic effects of cervical squamous cell carcinoma.
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Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Imagen de Difusión por Resonancia Magnética , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patologíaRESUMEN
UNLABELLED: In this study, we comprehensively investigated the effect of dietary protein sources on the gut microbiome of weaned piglets with diets comprising different protein source using High-throughput 16SrRNA gene-based Illumina Miseq. A total of 48 healthy weaned piglets were allocated randomly to four treatments with 12 piglets in each group. The weaned piglets were fed with diets containing soybean meal (SBM), cottonseed meal (CSM), SBM and CSM (SC) or fish meal (FM). The intestinal content samples were taken from five segments of the small intestine. DNA was extracted from the samples and the V3-V4 regions of the 16SrRNA gene were amplified. The microbiota of the contents of the small intestine were very complex, including more than 4000 operational taxonomic units belonging to 32 different phyla. Four bacterial populations (i.e. Firmicutes, Proteobacteria, Bacteroidetes and Acidobacteria) were the most abundant bacterial groups. The genera Lactobacillus and Clostridium were found in slightly higher proportions in the groups with added CSM compared to the other groups. The proportion of reads assigned to the genus Escherichia/Shigella was much higher in the FM group. In conclusion, dietary protein source had significant effects on the small microbiome of weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: Dietary protein source have the potential to affect the small intestine microbiome of weaned piglets that will have a large impact on its metabolic capabilities and intestinal health. In this study, we successfully identified the microbiomes in the contents of the small intestine in the weaned piglets that were fed different protein source diets using high-throughput sequencing. The finding provided an evidence for the option of the appropriate protein source in the actual production.
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Proteínas en la Dieta/metabolismo , Contenido Digestivo/microbiología , Microbioma Gastrointestinal , Glycine max/metabolismo , Intestino Delgado/microbiología , Porcinos/microbiología , Acidobacteria/aislamiento & purificación , Animales , Bacteroidetes/aislamiento & purificación , Aceite de Semillas de Algodón/metabolismo , Dieta , Firmicutes/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Intestino Delgado/metabolismo , Proteobacteria/aislamiento & purificación , ARN Ribosómico 16S/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide. Myocyte enhancer factor 2C (MEF2C) was traditionally regarded as a development-associated factor and was recently reported to be an oncogene candidate. We have previously reported overexpression of MEF2C in HCC; however, the roles of MEF2C in HCC remain to be clarified. In this study, HCC cell lines and a xenograft mouse model were used to determine the functions of MEF2C in vitro and in vivo, respectively. Specific plasmids and small interfering RNA were used to upregulate and downregulate MEF2C expression, respectively. Functional assays were performed to assess the influence of MEF2C on cell proliferation, and VEGF-induced vasculogenic mimicry, migration/invasion as well as angiogenesis. Co-immunoprecipitation was conducted to identify the interaction of MEF2C and ß-catenin. Human HCC tissue microarrays were used to investigate correlations among MEF2C, ß-catenin and involved biomarkers. MEF2C was found to mediate VEGF-induced vasculogenic mimicry, angiogenesis and migration/invasion, with involvement of the p38 MAPK and PKC signaling pathways. However, MEF2C itself inhibited tumor growth in vitro and in vivo. MEF2C was upregulated by and directly interacted with ß-catenin. The nuclear translocation of ß-catenin blocked by MEF2C was responsible for MEF2C-mediated growth inhibition. The nuclear translocation of MEF2C was associated with intracellular calcium signaling induced by ß-catenin. HCC microarrays showed correlations of nuclear MEF2C with the angiogenesis-associated biomarker, CD31, and cytosolic MEF2C with the proliferation-associated biomarker, Ki-67. MEF2C showed double-edged activities in HCC, namely mediating VEGF-induced malignancy enhancement while inhibiting cancer proliferation via blockade of Wnt/ß-catenin signaling. The overall effect of MEF2C in HCC progression regulation was dictated by its subcellular distribution. This should be determined prior to any MEF2C-associated intervention in HCC.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Factor A de Crecimiento Endotelial Vascular/fisiología , Vía de Señalización Wnt/fisiología , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular/genética , Progresión de la Enfermedad , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Factores de Transcripción MEF2/metabolismo , Factores de Transcripción MEF2/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Tisular , Células Tumorales Cultivadas , beta Catenina/metabolismoRESUMEN
Killer cell immunoglobulin-like receptor (KIR) and human leucocyte antigen (HLA) play crucial role in maintaining immune homoeostasis and controlling immune responses. To investigate the influence of KIR and HLA-C ligands on the risk of pulmonary tuberculosis (PTB), we studied 200 patients who were confirmed to have PTB and 200 healthy controls on the different frequencies of KIR and HLA-C ligands. Genotyping of these genes was conducted by sequence-specific primer polymerase chain reaction (SSP-PCR) method. Gene frequencies were compared between PTB group and the control group by χ(2) test, and P < 0.05 was regarded as statistically significant. As a result, the frequency of KIR genotype A/B was increased in PTB than controls but A/A was decreased. Moreover, striking differences were observed in the frequencies of HLA-Cw*08 between the two groups. Besides, the frequencies of '2DL2/3 with C1' in PTB were increased compared with control group. In addition, individuals with no KIR2DS3 and no Cw*08 were higher in controls than in PTB. KIR2DS1 was increased in PTB when HLA-C group 2 alleles were missing. In conclusion, KIR and HLA-C gene polymorphisms were related to susceptibility to PTB.