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Objective: To investigate the effect and mechanism of SIRT7 in epithelial mesenchymal transformation (EMT) of pancreatic cancer cells. Methods: The pancreatic cancer cells were divided into siControl, siSIRT7, over-expression SIRT7, siSIRT7+siCOL4A1, and siSIRT7+siSLUG groups using siRNA or plasmid transfection. The proliferation, migration and invasion of pancreatic cancer cells were detected by EdU, wound healing assay and Transwell experiments, respectively. The expression of EMT and cancer stem cell (CSC) markers were detected by quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR) and western blot. RNA sequencing (RNA-seq) in SIRT7 knockdown PANC-1 cells was performed to explore the signaling pathways and target genes regulated by SIRT7. Then the target genes directly regulated by SIRT7 were identified with quantitative chromatin immunoprecipitation experiment (q-ChIP) and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR). The expressions of SIRT7 and target genes were detected by immunohistochemical (IHC) in pancreatic cancer tissues, and the correlation between SIRT7 and target gene expression was analyzed using TCGA dataset. The correlation between expression of SIRT7 or target genes and survival was analyzed on KM-plotter website. Finally, GeneMANIA, STRING and ENCORI were used to predict SIRT7-related proteins and miRNAs. Results: EdU assay showed that the cell proliferation rates in SIRT7-overexpressed PANC-1 [(19.33±0.35)%] and BxPC-3 cells [(17.00±1.89)%] were lower than those in the control group [(31.60±1.37)% and (24.33±0.78)%, respectively, Pï¼0.05]. The proliferation rates of SIRT7-knockdown PANC-1 [(23.94±1.00)% and (27.08±0.97)%] and BxPC-3 cells [(22.00±1.86)% and (25.96±1.61)%] were higher than those of the siControl group [(11.80±1.86)% and (13.42±1.39)%, respectively, Pï¼0.05]. In PANC-1 cells, the wound healing assay showed that the relative migration rate of SIRT7-overexpression cells [(76.67±2.74)%] was lower than that of control cells [(100.00±2.13)%, Pï¼0.05]; the relative migration rate of cells with SIRT7 knockdown [(134.22±4.08)% and (199.82±9.20)%, respectively] was higher than that of siControl group [(102.24±3.13)%, Pï¼0.05]. Compared with the control group, SIRT7 overexpression decreased the number of migrated BxPC-3 cells (45.66±1.69 vs 28.33±2.62, Pï¼0.05); while SIRT7 knockdown increased these numbers (65.66±2.86 and 82.00±2.94 versus 33.00±0.81, Pï¼0.01). Transwell experiment revealed that the number of invaded cells in SIRT7 overexpression groups (16.33±2.05 and 34.66±1.69) was lower than that control groups (54.33±4.64 and 58.66±5.90, Pï¼0.05); with SIRT7 knockdown, the numbers of invaded PANC-1 (63.66±2.49 and 69.33±3.29) and BxPC-3 cells (134.33±3.09 and 181.66±4.02) were higher than those in control groups (35.33±2.49 and 42.00±0.81, PË0.05). Also, SIRT7 knockdown decreased the expressions of epithelial markers and increased the expressions of mesenchymal and CSC markers. RNA-seq analysis showed that SIRT7 was involved in regulating a variety of cancer-related signaling pathways, including the pancreatic cancer pathway and the EMT pathway. Furthermore, SIRT7 could directly bind to the promoter regions of target genes, such as COL4A1 and SLUG. SIRT7 was negatively correlated with the expression and function of COL4A1 and SLUG in pancreatic cancer cells. The expressions of SIRT7, COL4A1, SLUG and SOX2 were verified in pancreatic cancer tissues by IHC. Finally, SIRT7 was predicted to be associated with many proteins and miRNAs based on GeneMANIA, STRING, and ENCORI online tools. Conclusions: SIRT7 can inhibit the EMT of pancreatic cancer cells through transcriptionally inhibiting the expression of target genes, such as COL4A1 and SLUG. Thus, SIRT7 may serve as a potential tumor suppressor gene in pancreatic cancer.
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Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Pancreáticas , Sirtuínas , Humanos , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , MicroRNAs/genética , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , RNA Interferente Pequeno/genética , Transdução de Sinais , Sirtuínas/metabolismo , Sirtuínas/genéticaRESUMO
Here, we reported the diagnosis and treatment of a case of HIV infected person complicated by an extremely rare infection with Mycobacterium celatum. Due to the similarity of homologous sequence regions between Mycobacterium celatum and Mycobacterium tuberculosis complex, the identification of conventional Mycobacterium species was incorrect, which was corrected after first-generation 16S rRNA sequencing. This report aimed to improve the clinical understanding of Mycobacterium celatum infection and the level of differential diagnosis between non-tuberculous mycobacterial disease and tuberculosis.
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Infecções por HIV , Infecções por Mycobacterium , Mycobacterium , Humanos , RNA Ribossômico 16S/genética , Mycobacterium/genética , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/microbiologia , Micobactérias não Tuberculosas/genética , Infecções por HIV/complicaçõesRESUMO
Bioaerosols in healthcare facilities are closely related to the health of medical staff and patients. Inhalation of microbial aerosol particles can lead to both infectious and non-infectious diseases. However, a systematic summary of bioaerosol types, sources, impact factors and health risk analysis is lacking.This article condutcted a literature review to understand the distribution characteristics, sources, influencing factors and health risks of bioaerosols in healthcare facilities, both domestically and internationally. The goal is to increase awareness of the distribution characteristics of bioaerosols in healthcare facilities and health risk of bioaerosols in medical institutions. This article also provides a reference for prevention and control of bioaerosols.
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Microbiologia do Ar , Humanos , Medição de Risco , Aerossóis/efeitos adversosRESUMO
BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.
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Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Infecção da Ferida Cirúrgica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Adulto JovemRESUMO
We investigated the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) on the proliferation, apoptosis, and alpha-actin-2 (ACTA2) expression of hepatic stellate cells (HSCs), and explored the possible mechanisms of hepatocyte growth factor (HGF). We established a co-culture system by culturing BMSCs on the upper layer and HSCs on the lower layer of a 6-well Transwell plate. Normal HSCs were cultured alone as a control. Cell apoptosis was determined by flow cytometry. We detected the expression of ACTA2 mRNA and ACTA2 protein in HSC using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. ACTA2 in HSCs was detected by fluorescent staining, and HGF in the co-culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The apoptotic rate of HSCs in the experiment group was 2.6 times that in the control group (P < 0.05). The expression levels of ACTA2 mRNA and ACTA2 protein were significantly inhibited in HSCs compared with the control group (P < 0.05). HGF concentration in the co-culture supernatant was 0.43 ± 0.47 mM in the experimental group, which was significantly higher than in the control group (0.16 ± 0.43 mM) (P < 0.05). The paracrine effect of BMSCs, which was caused by the suppression of ACTA2 and HGF expression, induced HSC apoptosis.
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Actinas/genética , Actinas/metabolismo , Células Estreladas do Fígado/citologia , Células-Tronco Mesenquimais/citologia , Comunicação Parácrina , Apoptose , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , HumanosRESUMO
Africa is host to diverse and locally adapted cattle breeds that are expected to survive the harsh and extreme tropical environments associated with diseases and parasite infections, heat stress and episodes of feed and water scarcity. Genomic copy number variations (CNVs) are considered to be primary role players in cattle breed formation and adaptation where isolation and genetic drift together with subsequent mutations have created an enormous diversity of local populations. CNVs are modifications in DNA structure comprising deletions, duplications and insertions that are >1 kb in size. Despite attracting much attention, the frequency and pattern of bovine CNV events, especially in African cattle breeds, are for the most part largely unknown. Characterization of genetic variation in the indigenous cattle of Africa will be a vital step toward dissecting the molecular mechanisms underlying phenotypic variation and local adaptation. This review therefore aims to describe the current knowledge regarding bovine CNVs and the implications and potentials they encompass for dissecting genetic adaptation and the genotypic skeleton of tropical African cattle populations.
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Adaptação Fisiológica/genética , Bovinos/genética , Variações do Número de Cópias de DNA , Clima Tropical , África , Animais , Cruzamento , FenótipoRESUMO
Tumor suppressor genes are the key targets of hypermethylation in breast cancer and may therefore lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified a correlation between RASSFIA gene methylation and breast cancer. To determine the relationship between RASSFIA methylation and breast cancer, we conducted a larger study. We took samples from 108 patients with breast cancer, 28 patients with benign breast tumors, and 33 subjects with normal breast tissues at the Second Affiliated Hospital of Nanjing Medical University at Wuxi between July 2013 and September 2015. We used the samples to investigate methylation levels of the RASSF1A gene for associations with breast cancer. Quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR were used to investigate the levels of RASSF1A mRNA expression and RASSF1A methylation, respectively. RASSFIA was not expressed in 22 of the 108 breast cancer tissue samples (20.37%), and there was no statistically significant difference (P > 0.05); however, RASSFIA expression was significantly lower than that in the normal breast tissue samples (P < 0.05). Moreover, the methylation rate of the RASSFIA gene promoter was significantly higher in the breast cancer tissues (64.81%) than in the normal breast tissues (18.18%) and benign breast tumors (17.86%) (P < 0.05). High methylation of the RASSF1A gene promoter was an important reason for its downregulation, and the gene played a critical regulated role in the incidence and development of breast cancer.
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The retracted article is: Ji Y, Jin HH, Wang MD, Cao WX, et al. (2016). Methylation of the RASSFIA promoter in breast cancer. Genet. Mol. Res. 15: gmr.15028261. There are significant parts of this article (particularly, in the discussion section) that are copied from "Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome", by Jia Xu, Priya B Shetty, Weiwei Feng, Carol Chenault, Robert C Bast Jr, Jean-Pierre J Issa, Susan G Hilsenbeck and Yinhua Yu, published in BMC Cancer 2012; 12: 243. DOI: 10.1186/1471-2407-12-243. The first paragraphs of both discussions are identical. This is concerning. The abstract and introduction sections have much of their text plagiarized. Overall, there is high plagiarism detected. The GMR editorial staff was alerted and after a thorough investigation, we have strong reason to believe that the peer review process was failure and, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract the article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.
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PURPOSE: To develop a CT-based model to classify pneumonitis etiology in patients with non-small cell lung cancer(NSCLC) after radiotherapy(RT) and Immune checkpoint inhibitors(ICIs). METHODS: We retrospectively identified 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + thoracic RT only, the training cohort, n = 100), and RT + ICIs (the test cohort, n = 30). Clinical and CT radiomics features were described and compared between different groups. We constructed a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier by CT radiomics to discern pneumonitis etiology. RESULTS: The patients in RT + ICIs group have more high grade (grade 3-4) pneumonitis compared to patients in ICIs only or RT only group (p < 0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RT-related pneumonitis(RP) and ICI-related pneumonitis(CIP), resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. The RF classifier showed favorable discrimination between RP and CIP with an area under the receiver operating curve (AUC) of 0.859 (95 %CI: 0.788-0.929) in the training cohort and 0.851 (95 % CI: 0.700-1) in the test cohort. The LDA classifier achieved an AUC of 0.881 (95 %CI: 0.815-0.947) in the training cohort and 0.842 (95 %CI: 0.686-0.997) in the test cohort. Our analysis revealed four principal CT-based features shared across both models:original_glrlm_LongRunLowGrayLevelEmphasis, wavelet-HLL_firstorder_Median, wavelet-LLL_ngtdm_Busynessï¼ and wavelet-LLL_glcm_JointAverage. CONCLUSION: CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after RT alone, ICIs alone or RT + ICIs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pneumonite por Radiação/complicações , Pneumonite por Radiação/tratamento farmacológico , Estudos Retrospectivos , Radiômica , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Pneumonia/tratamento farmacológicoRESUMO
The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.
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Estudo de Associação Genômica Ampla , Ossos do Metatarso , Animais , Estudo de Associação Genômica Ampla/veterinária , Galinhas/genética , Locos de Características Quantitativas , Fenótipo , Genômica , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In the clinical application of genomic data analysis and modeling, a number of factors contribute to the performance of disease classification and clinical outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling strategy and its clinical use. Although KNN is simple and clinically appealing, large performance variations were found among experienced data analysis teams in the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end points and controls from breast cancer, neuroblastoma and multiple myeloma, we systematically generated 463,320 KNN models by varying feature ranking method, number of features, distance metric, number of neighbors, vote weighting and decision threshold. We identified factors that contribute to the MAQC-II project performance variation, and validated a KNN data analysis protocol using a newly generated clinical data set with 478 neuroblastoma patients. We interpreted the biological and practical significance of the derived KNN models, and compared their performance with existing clinical factors.
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Modelos Estatísticos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Animais , Biomarcadores Tumorais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Intervalo Livre de Doença , Determinação de Ponto Final/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Estadiamento de Neoplasias , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Valor Preditivo dos Testes , Controle de Qualidade , Medição de Risco , Resultado do TratamentoRESUMO
Cognitive dysfunction, dementia and Alzheimer's disease (AD) are increasing as the population worldwide ages. Therapeutics for these conditions is an unmet need. This review focuses on the role of the positive GABA-A receptor modulating steroid allopregnanolone (APα), it's role in underlying mechanisms for impaired cognition and of AD, and to determine options for therapy of AD. On one hand, APα given intermittently promotes neurogenesis, decreases AD-related pathology and improves cognition. On the other, continuous exposure of APα impairs cognition and deteriorates AD pathology. The disparity between these two outcomes led our groups to analyze the mechanisms underlying the difference. We conclude that the effects of APα depend on administration pattern and that chronic slightly increased APα exposure is harmful to cognitive function and worsens AD pathology whereas single administrations with longer intervals improve cognition and decrease AD pathology. These collaborative assessments provide insights for the therapeutic development of APα and APα antagonists for AD and provide a model for cross laboratory collaborations aimed at generating translatable data for human clinical trials.
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The force produced by a single molecule of Escherichia coli RNA polymerase during transcription was measured optically. Polymerase immobilized on a surface was used to transcribe a DNA template attached to a polystyrene bead 0.5 micrometer in diameter. The bead position was measured by interferometry while a force opposing translocation of the polymerase along the DNA was applied with an optical trap. At saturating nucleoside triphosphate concentrations, polymerase molecules stalled reversibly at a mean applied force estimated to be 14 piconewtons. This force is substantially larger than those measured for the cytoskeletal motors kinesin and myosin and exceeds mechanical loads that are estimated to oppose transcriptional elongation in vivo. The data are consistent with efficient conversion of the free energy liberated by RNA synthesis into mechanical work.
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RNA Polimerases Dirigidas por DNA/fisiologia , Escherichia coli/enzimologia , Transcrição Gênica , Fenômenos Biofísicos , Biofísica , DNA Bacteriano/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/genética , Interferometria , Microesferas , Nucleotídeos/metabolismo , Moldes Genéticos , TermodinâmicaRESUMO
RNA polymerase (RNAP) moves along DNA while carrying out transcription, acting as a molecular motor. Transcriptional velocities for single molecules of Escherichia coli RNAP were measured as progressively larger forces were applied by a feedback-controlled optical trap. The shapes of RNAP force-velocity curves are distinct from those of the motor enzymes myosin or kinesin, and indicate that biochemical steps limiting transcription rates at low loads do not generate movement. Modeling the data suggests that high loads may halt RNAP by promoting a structural change which moves all or part of the enzyme backwards through a comparatively large distance, corresponding to 5 to 10 base pairs. This contrasts with previous models that assumed force acts directly upon a single-base translocation step.
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RNA Polimerases Dirigidas por DNA/química , Modelos Químicos , Proteínas Motores Moleculares/química , Transcrição Gênica , DNA Bacteriano/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/enzimologia , Matemática , Proteínas Motores Moleculares/metabolismo , RNA Bacteriano/biossíntese , RNA Mensageiro/biossíntese , Moldes Genéticos , TermodinâmicaRESUMO
BACKGROUND: Endoscopy has been introduced into cardiac surgery employing robotic systems. We have developed a new-minimally invasive approach that combines these two technologies for secundum atrial septal defect (ASD). The purpose of this study is to evaluate the efficacy of this approach, paying particular attention to its cosmetic effects. METHODS: Between November 2004 and April 2006, 22 patients (aged 18 to 62) with ASDs (with sizes 10 to 39 mm) were treated with occlusion apparatus with endoscopy and robotic arm (AESOP 3000, Computer Motion Inc., Santa Barbara, CA, USA) assist. RESULTS: All ASDs were successfully occluded with a mean device size of 26.8 mm (12 to 42 mm). Procedure time was ranged from 30 to 60 minutes. The ICU stay was less than 1 day and hospital stays was 3 to 7 days. No postoperative mortality was noted. During follow-up of 2 to 19 months, no major morbidities occurred. CONCLUSIONS: Endoscopic ASD occlusion assisted with robotic is safe and effective with rapid recovery. The cosmetic effect is better results than conventional surgical repair.
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Procedimentos Cirúrgicos Cardiovasculares/métodos , Comunicação Interatrial/cirurgia , Robótica/métodos , Toracoscopia/métodos , Toracotomia/métodos , Adolescente , Adulto , Procedimentos Cirúrgicos Cardiovasculares/instrumentação , Feminino , Comunicação Interatrial/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Robótica/instrumentação , Toracotomia/instrumentação , Ultrassonografia , Adulto JovemRESUMO
Deep brain stimulation (DBS) in the basal ganglia has been introduced to treat movement disorders. The effects of pallidal DBS on the neural oscillations in the globus pallidus interna (GPi) and the subthalamic nucleus (STN) of the same subject remains unclear. In this study, the DBS electrodes were bilaterally implanted in the GPi and STN in patients with Tourette's syndrome (TS). The local field potentials were simultaneously recorded from the GPi and STN during pallidal DBS with 130 Hz, 60 microseconds, and 1V/2V/2.5V voltages. The time-frequency characteristics were analyzed across the conditions of resting, stimulation and post-stimulation. The results showed that alpha and beta oscillation existed in the basal ganglia and the beta oscillation was attenuated by pallidal stimulation. The attenuations are significantly different among 1V/2V/2.5V voltages. The results suggest that beta oscillations may have physiological function in resisting tics in TS. Thus, the oscillation- and symptom-guided intelligent DBS needs to be investigated.
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OBJECTIVE: Diabetic nephropathy (DN) is a major diabetic micro-vascular complication, and podocyte apoptosis induced by high glucose (HG) is a typical early feature of DN. Studies have shown that microRNAs (miRNAs) play a crucial role in the pathogenesis of DN. The purpose of the current study was to explore the role and molecular mechanism of miR-770-5p in podocyte apoptosis in DN. PATIENTS AND MATERIALS AND METHODS: In vitro podocyte model of DN was conducted by treatment conditionally immortalized mouse podocytes with HG (30 mM D-glucose). The level of miR-770-5p in podocytes was detected using quantitative real-time PCR (qRT-PCR), and protein levels were measured using Western blot assay in our current study. The relationship between miR-770-5p and TP53 regulated inhibitor of apoptosis 1 (TRIAP1) was revealed by TargetScan and dual luciferase reporter assay. Cell proliferation ability and cell apoptosis were determined by using cell counting kit-8 (CCK-8) assay and flow cytometer (FCM), respectively. RESULTS: We found that miR-770-5p was significantly upregulated in podocytes under HG condition. TRIAP1 was a target gene of miR-770-5p and it was down-regulated in podocytes by HG treatment. Further analysis indicated that HG induced cell proliferation ability reduction, cell apoptosis enhancement and apoptotic peptidase activating factor 1(APAF1)/Caspase9 pathway exaltation in podocytes were prevented by miR-770-5p down-regulation. More importantly, the results showed that all the effects of miR-770-5p inhibitor on HG induced podocytes were eliminated by TRIAP1 silencing. S.-Z. Zhang, X.-J. Qiu, S.-S. Dong, L.-N. Zhou, Y. Zhu, M.-D. Wang, L.-W. Jin We showed that miR-770-5p was upregulated in the in vitro model of DN, and it might promote the development of DN through regulating podocyte apoptosis by targeting TRIAP1.
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Apoptose , Nefropatias Diabéticas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Modelos Biológicos , Podócitos/metabolismo , Animais , Linhagem Celular , Nefropatias Diabéticas/patologia , Glucose/farmacologia , Humanos , Camundongos , Podócitos/patologia , Ligação ProteicaRESUMO
Thyroid cancer is the most common malignant tumor in endocrine surgery. Surgery is the first choice for most patients with thyroid cancer. Da Vinci robot system as the auxiliary system is the most advanced endoscopic surgery, largely to fill the cavity mirror device cannot bend, complex operation and so on insufficiency, has now become an important way of surgical treatment of thyroid cancer, and its curative effect, high safety, but because of the economic cost is higher, is currently not widespread popularity.
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The replisome is a multiprotein molecular machinery responsible for the replication of DNA. It is composed of several specialized proteins each with dedicated enzymatic activities, and in particular, helicase unwinds double-stranded DNA and DNA polymerase catalyzes the synthesis of DNA. Understanding how a replisome functions in the process of DNA replication requires methods to dissect the mechanisms of individual proteins and of multiproteins acting in concert. Single-molecule optical-trapping techniques have proved to be a powerful approach, offering the unique ability to observe and manipulate biomolecules at the single-molecule level and providing insights into the mechanisms of molecular motors and their interactions and coordination in a complex. Here, we describe a practical guide to applying these techniques to study the dynamics of individual proteins in the bacteriophage T7 replisome, as well as the coordination among them. We also summarize major findings from these studies, including nucleotide-specific helicase slippage and new lesion bypass pathway in T7 replication.
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Replicação do DNA/genética , DNA Polimerase Dirigida por DNA/química , Pinças Ópticas , Imagem Individual de Molécula/métodos , Bacteriófago T7/genética , DNA/química , DNA Helicases/química , Escherichia coli/enzimologia , Escherichia coli/genética , Ligação ProteicaRESUMO
In order to evaluate the effect of penile enhancement, we retrospectively reviewed the data of the patients operated with autologous dermal graft implantation combined with a modified penile degloving procedure. The patients with the complaints of small penis, asking for penile augmentation, and normal erectile function were psychologically screened and enrolled. Data of follow-up visit including patient demographics, medical history, surgical procedure, patient-reported outcomes were analysed. In all, 30 eligible persons were operated. After degloving of the penis, the suspensory ligament was incised and the tunica albuginea was fixed to the proximal tunica dartos at the penile base. Then, the dermis graft was implanted on the dorsal surface of the tunica albuginea. The file of follow-up visit was available in 17 (57%) patients. The mean age was 23.7 years (19-35 years) and the mean follow-up was 13 months (range, 4-24 months). During the follow-up period, the average gain in the penis length was 2.7 cm in flaccid and 0.8 cm in erection, respectively. And the average gain in the penis circumference was 1.5 cm in flaccid and 1.2 cm in erection, respectively. Also, psychosexual sexual self-esteem and confidence of the patients were significantly improved (p < 0.001). Overall, 13 (76%) patients reported satisfaction with the penile appearance. We believe that the surgery is both safe and effective in the enhancement of the penis, however, further clinical studies with a larger patient population are necessary.