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Breast cancer (bc) is the second most common type of human malignancies with highest morbidity and mortality in the female population. Therefore, it is essential to develop novel and effective therapies for bc treatment. The main aim of the current study is to investigate the functions of CEBPB and THBS2 in bc and the underlying mechanism. Reverse transcription-quantitative real-time polymerase chain reaction and western blot were performed for the measurement of ribonucleic acids and proteins. Function and mechanism assays were, respectively, conducted for the evaluation of bc biological behaviors and exploration of the potential correlation of genes. According to bioinformatics analyses and experimental results, THBS2, up-regulated in bc tissues and cell lines, could facilitate cell migration, invasion and EMT in bc. CEBPB was validated to facilitate miR-29a-3p transcription, thus negatively modulating THBS2 expression. The results of rescue experiments reflected that CEBPB could regulate the malignant behaviors of bc cells via THBS2. Furthermore, CEBPB was ascertained to inhibit the transcription of B3GALTL to affect THBS2 protein O-fucosylation and secretion. The interaction between THBS2 and ITGB1 was confirmed, and THBS2 was found to activate the PI3K/AKT signaling pathway. To conclude, CEBPB could restrain bc cell migration, invasion and EMT via inhibition on THBS2 expression and O-fucosylation.
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Neoplasias da Mama , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , Neoplasias da Mama/metabolismo , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteína beta Intensificadora de Ligação a CCAAT/genéticaRESUMO
BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.
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Biomarcadores , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/sangue , Masculino , Feminino , Idoso , Biomarcadores/sangue , Biomarcadores/análise , Prognóstico , Pessoa de Meia-Idade , Proteômica/métodos , Estudos de Coortes , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/análise , Metabolômica/métodos , MultiômicaRESUMO
Background Sepsis-induced acute kidney injury (S-AKI) is a common complication in critically ill patients. Therefore, reliable biomarkers for predicting S-AKI outcomes are necessary. Serum cell-free DNA (cfDNA) is a circulating extracellular DNA fragment used as a noninvasive screening tool for many diseases, including sepsis. This study aimed to investigate the prognostic value of cfDNA in S-AKI patients and its relationship with some other parameters.Methods A total of 89 S-AKI patients admitted to the intensive care unit (ICU) from June 2021 to December 2021 were enrolled in this study. The patients were categorized into the low cfDNA group (< 855 ng/ml) and high cfDNA group (≥ 855 ng/ml) and were followed up for three months. CfDNA was extracted from serum and quantified using Quant-iT PicoGreen dsDNA Reagent.Results Overall survival was significantly lower in the high cfDNA group than in the low cfDNA group (Log-Rank p = 0.012). Univariate Cox proportional hazard model showed that cfDNA was significantly associated with all-cause mortality (HR [hazard ratio] 2.505, 95% CI [95% confidence interval] 1.184-5.298, p = 0.016). Also, serum cfDNA was a significant risk factor for all-cause mortality after adjusting for covariates (HR 2.191, 95% CI 1.017-4.721, p = 0.045). Moreover, cfDNA was positively correlated with several baseline parameters, including serum creatine, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and International Normalized Ratio.Conclusion High serum cfDNA level is associated with higher mortality among the S-AKI population, indicating that cfDNA is a valuable biomarker for S-AKI prognosis.
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Injúria Renal Aguda , Ácidos Nucleicos Livres , Sepse , Humanos , Biomarcadores , Prognóstico , Unidades de Terapia Intensiva , Injúria Renal Aguda/epidemiologia , Sepse/complicações , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the effects of resveratrol (RSV) on ovarian morphology, plasma anti-Müllerian hormone (AMH) and insulin-like growth factor 1 levels (IGF-1), and oxidative stress parameters in rats with polycystic ovary syndrome (PCOS). METHODS: Forty-six rats were randomly divided into a normal control (n = 12), a PCOS model control (n = 12), a rosiglitazone (RSG, n = 11), and an RSV group (n = 11). The PCOS model was established in the latter three groups by rejection of epidehydroandrosterone. The rats in the normal control and PCOS model control groups were treated by gavage of normal saline and those in the RSG and RSV groups by intragastric administration of RSG at 10 mg/(kg·d) and RSV at 3.0 mg/(kg·d), respectively. After 4 weeks of treatment, the ovarian histology was observed under the light microscope, the levels of plasma AMH and IGF-1 measured by ELISA, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the ovarian tissue detected using the Ellman, Sun and AEBI methods, respectively. RESULTS: After a 4-week treatment, statistically significant differences were observed in the above indicators between the normal control and PCOS model control groups (P<0.05). The rats treated with RSG and RSV also showed significant differences in these parameters from the model controls (P<0.05). CONCLUSION: RSV can enhance the local antioxidant capacity of the ovary, reduce the levels of AMH and IGF-1, and improve the morphology of the ovarian tissue in rats with PCOS, indicating its potential value in the treatment of PCOS.
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Antioxidantes , Fator de Crescimento Insulin-Like I , Ovário , Estresse Oxidativo , Síndrome do Ovário Policístico , Resveratrol , Estilbenos , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Feminino , Resveratrol/farmacologia , Ratos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Hormônio Antimülleriano/sangue , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Catalase/metabolismo , Ratos Sprague-Dawley , Modelos Animais de Doenças , Rosiglitazona/farmacologiaRESUMO
BACKGROUND: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. CASE PRESENTATION: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. CONCLUSION: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.
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Tumor Carcinoide , Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Tumores Neuroendócrinos , Neoplasias Ovarianas , Feminino , Humanos , Adulto , Idoso , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Prognóstico , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patologia , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapiaRESUMO
PURPOSE: Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer characteristic of high recurrence rate and poor prognosis. According to previous studies and bioinformatics prediction, PGM5P3-AS1 has been found to be significantly down-regulated in TNBC cells. In addition, cell ferroptosis has become a hotspot in breast cancer research and TNBC has been reported to be more sensitive to ferroptosis than receptor positive breast cancer. Hence, we aim at exploring the molecular mechanism of PGM5P3-AS1 in TNBC cells and further explore whether PGM5P3-AS1 can inhibit TNBC progression via promoting cell ferroptosis. METHODS: The expression of genes in TNBC cells was verified by RT-qPCR assay. Functional assays were taken to evaluate the impact PGM5P3-AS1 may exert on TNBC progression. The regulatory pattern of PGM5P3-AS1 on cell ferroptosis in TNBC was validated through mechanism assays. RESULTS: PGM5P3-AS1 was proved to be down-regulated in TNBC cells and suppressed TNBC cell proliferation as well as migration. PGM5P3-AS1 promoted cell ferroptosis in TNBC by recruiting RNA-binding protein (RBP) NOP58 to stabilize MAP1LC3C mRNA, and thus inhibiting TNBC progression. CONCLUSION: PGM5P3-AS1 regulated MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of TNBC.
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Ferroptose , Proteínas Associadas aos Microtúbulos , RNA Antissenso , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Associadas aos Microtúbulos/genética , RNA Antissenso/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to play significant roles in regulating gene expression in tumorigenesis, including breast cancer (BC). This study was designed to explore the role and underlying molecular mechanisms of circMMP11 in BC. METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used for examining expression of circMMP11, microRNA-625-5p (miR-625-5p), and Zinc finger E-box binding homeobox-2 (ZEB2). The protein expression of ZEB2, Vimentin, and E-cadherin was assessed by western blot assay. The proliferation ability of BC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The transwell assay was used to measure migration and invasion of BC cells. The apoptotic cells were examined by flow cytometry assay. The interaction association among circMMP11, miR-625-5p, and ZEB2 was confirmed by RNA pull-down and dual-luciferase report assays. A xenograft experiment was established to clarify the role of circMMP11 silencing in vivo. RESULTS: We found that circMMP11 and ZEB2 were overexpressed in BC tissues and cells compared with controls. The suppression of circMMP11 or ZEB2 repressed proliferation, migration, and invasion while induced apoptosis of BC cells. Additionally, miR-625-5p, interacted with ZEB2, was a target of circMMP11 in BC cells. CircMMP11 regulated the expression of ZEB2 by targeting miR-625-5p. Knockdown of circMMP11-mediated effects on BC cells could be abolished by overexpression of ZEB2. Consistently, silencing of circMMP11 impeded the tumor growth in vivo. CONCLUSIONS: CircMMP11/miR-625-5p/ZEB2 axis affected proliferation, migration, invasion, and apoptosis of BC cells through the mechanism of competing endogenous RNAs (ceRNA), indicating that circMMP11 was an oncogenic circRNA in BC.
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BACKGROUND: The number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes. METHODS: A retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤ 35 years of age with pathologically confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastasis-free intervals. RESULTS: We identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤ 35 years of age. The overall 5-year LR, RR, and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P = 0.028 and P = 0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P = 0.004 and P = 0.007, respectively). Patients with HR-/HER2+ status had a significantly higher LR (HR 20.4; 95% CI, 11.8-35.4) and DM (HR 37.2; 95% CI, 24.6-56.3) at 10 years. Breast-conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%. CONCLUSIONS: The rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR-/HER2+ tumors.
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Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the epidemiological features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Shijiazhuang, China. METHODS: Based on the information officially announced on the official website of the Health Commission of Hebei Province, epidemiological data were collected from 133 children, aged 0-18 years, who were diagnosed with SARS-CoV-2 infection in Shijiazhuang from January 2 to January 30, 2021. A statistical analysis was performed for general status, regional distribution, presence or absence of clusters, and results of SARS-CoV-2 nucleic acid tests. RESULTS: Among the 133 children with SARS-CoV-2 infection, there were 65 boys and 68 girls, with a male/female ratio of 0.96:1. The youngest age of onset was 3 months and 7 days, and the mean age of onset was (9±5) years. Of all the 133 children, 90(67.7%) were the first confirmed case of SARS-CoV-2 infection among their family members. Of all the children, 108(81.2%) came from the Gaocheng District in Shijiazhuang, among whom 38(28.6%) were from Xiaoguozhuang Village where the first patient with a confirmed diagnosis lived. SARS-CoV-2 nucleic acid test at week 2 after the outbreak showed positive results in 88 children (66.2%), and only 5 children had clinical symptoms before positive SARS-CoV-2 results were obtained. Of all the 133 children, 19(14.3%) were found positive in the first SARS-CoV-2 nucleic acid test after the outbreak, and 70(52.6%) had positive results for ≥4 times. There were 98 school students with infection, among whom 74(75.5%) were the first confirmed case in their family, and among 35 non-school students, 16(45.7%) were the first confirmed case in their family (P < 0.05). CONCLUSIONS: Among the children confirmed with SARS-CoV-2 infection in Shijiazhuang, there is a high proportion of children who are the first confirmed case in their family, and the children are mainly distributed in the rural areas of Gaocheng. Most of these children are students, so the prevention and control of cluster infection in schools should be taken seriously. There are often no symptoms before SARS-CoV-2 nucleic acid test, with a low positive rate of the first nucleic acid test, which increases the difficulty of early discovery of the epidemic.
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COVID-19 , SARS-CoV-2 , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Instituições AcadêmicasRESUMO
Cumulative evidence suggests that the heat shock protein 90 (Hsp90) co-chaperone UNC-45 myosin chaperone A (UNC45A) contributes to tumorigenesis and that its expression in cancer cells correlates with proliferation and metastasis of solid tumors. However, the molecular mechanism by which UNC45A regulates cancer cell proliferation remains largely unknown. Here, using siRNA-mediated gene silencing and various human cells, we report that UNC45A is essential for breast cancer cell growth, but is dispensable for normal cell proliferation. Immunofluorescence microscopy, along with gene microarray and RT-quantitative PCR analyses, revealed that UNC45A localizes to the cancer cell nucleus, where it up-regulates the transcriptional activity of the glucocorticoid receptor and thereby promotes expression of the mitotic kinase NIMA-related kinase 7 (NEK7). We observed that UNC45A-deficient cancer cells exhibit extensive pericentrosomal material disorganization, as well as defects in centrosomal separation and mitotic chromosome alignment. Consequently, these cells stalled in metaphase and cytokinesis and ultimately underwent mitotic catastrophe, phenotypes that were rescued by heterologous NEK7 expression. Our results identify a key role for the co-chaperone UNC45A in cell proliferation and provide insight into the regulatory mechanism. We propose that UNC45A represents a promising new therapeutic target to inhibit cancer cell growth in solid tumor types.
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Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Quinases Relacionadas a NIMA/biossíntese , Proteínas de Neoplasias/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/patologia , Feminino , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Células MCF-7 , Mitose/genética , Quinases Relacionadas a NIMA/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética , Células PC-3RESUMO
The study aims to investigate whether there is difference in pre-treatment white matter parameters in treatment-resistant and treatment-responsive schizophrenia. Diffusion tensor imaging (DTI) was acquired from 60 first-episode drug-naïve schizophrenia (39 treatment-responsive and 21 treatment-resistant schizophrenia patients) and 69 age- and gender-matched healthy controls. Imaging data was preprocessed via FSL software, then diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted. Besides, structural network matrix was constructed based on deterministic fiber tracking. The differences of diffusion parameters and topology attributes between three groups were analyzed using analysis of variance (ANOVA). Compared with healthy controls, treatment-responsive schizophrenia showed altered white matter mainly in anterior thalamus radiation, splenium of corpus callosum, cingulum bundle as well as superior longitudinal fasciculus. While treatment-resistant schizophrenia patients showed white matter abnormalities in anterior thalamus radiation, cingulum bundle, fornix and pontine crossing tract relative to healthy controls. Treatment-resistant schizophrenia showed more severe white matter abnormalities in anterior thalamus radiation compared with treatment-responsive patients. There was no significant difference in white matter network topological attributes among the three groups. The performance of support vector machine (SVM) showed accuracy of 63.37% in separating the two patient subgroups ( P = 0.04). In this study, we showed different patterns of white matter alterations in treatment-responsive and treatment-resistant schizophrenia compared with healthy controls before treatment, which may help guiding patient identification, targeted treatment and prognosis improvement at baseline drug-naïve state.
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Esquizofrenia , Substância Branca , Anisotropia , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Esquizofrenia/diagnóstico por imagemRESUMO
This study aimed to investigate the regulatory mechanism of linc00161/miR-128/MAPK1 axis on drug resistance of ovarian cancer. Methods: the differentially expressed lncRNAs were screened based on microarray analysis. The expression of linc00161, miR-128 and MAPK1 in ovarian cancer-resistant tissues and cells was tested qRT-PCR, whereas MAPK1 protein expression was examined via western blot in the ovarian cancer resistant cells. The targeted relationship between miR-128 and linc00161 as well as the relationship between miR-128 and MAPK1 were testified by Dual luciferase gene reporter assay. The influence of miR-128 and MAPK1 on the proliferation of ovarian cancer-resistant cells was demonstrated by CCK-8 and colony formation assay. The effect of linc00161 on ovarian cancer was demonstrated by xenograft tumor model in vivo. Results: Linc00161 was highly expressed in ovarian cancer-resistant tissues and SKOV3/DDP cells while the miR-128 displayed a lower expression. Overexpression of linc00161 increased the colony formation ratio in SKOV3 cells, whereas sh-linc00161 reduced colony formation ratio in SKOV3/DDP cells. MAPK1 was highly expressed in ovarian cancer-resistant tissues and cells and could be regulated by linc00161 and miR-128. The proliferation ability of SKOV3 cell was enhanced after transfected with miR-128 inhibitor, whereas that of SKOV3/DDP cells was attenuated by miR-128 mimics. In addition, the colony formation ratio of SKOV3 cells co-transfected with DDP + MAPK1 + sh-linc00161 decreased. The colony formation ratio of SKOV3/DDP cells also declined after transfected with DDP+ MAPK1. Linc00161 regulated the drug resistance of ovarian cancer via modulating microRNA-128/MAPK1. In vivo, sh-linc00161 inhibited the tumor growth.
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Biomarcadores Tumorais/análise , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Animais , Apoptose , Proliferação de Células , Feminino , Seguimentos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis. METHODS: A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90. CONCLUSIONS: Urinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.
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Coinfecção/epidemiologia , Citocinas/sangue , Sepse/epidemiologia , Idoso , Coinfecção/imunologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/imunologia , Sepse/mortalidadeRESUMO
5-FU-based chemotherapy is recently most recommended as the first-line treatment for gastric cancer (GC). However, 5-FU resistance is common for many postoperative GC patients. Homeobox A13 (HOXA13) is a member of homeobox genes highly expressed in many human tumors. Its potential roles and mechanisms of resistance to 5-FU in GC are poorly understood. In this study, we discovered that HOXA13 played an oncogenic role in vivo and in vitro. The patients with HOXA13 overexpression were closely related with poor prognosis and more prone to be resistant to 5-FU. Moreover, dehydrogenase/reductase 2 (DHRS2) was identified as a downstream gene of HOXA13. HOXA13 played a role of carcinogenesis through directly down-regulating DHRS2 to increase MDM2. Furthermore, HOXA13 conferred 5-FU resistance through MRP1 by a p53-dependent pathway. Therefore, HOXA13 might serve as a potential signature that recognized patients who were insensitive to 5-FU, and timely recommended them to other chemotherapy regimens.
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Oxirredutases do Álcool/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/uso terapêutico , Proteínas de Homeodomínio/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Idoso , Oxirredutases do Álcool/metabolismo , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Carbonil Redutase (NADPH) , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Objective Although intraoperative cell salvage (ICS) has been widely used to reduce the demand for allogeneic blood transfusion, patients who use ICS approach still have not completely avoided chances of blood transfusion. This study aims to investigate the rate of allogeneic red blood cell(RBC) transfusion in patients receiving ICS, and to evaluate irrationality of allogeneic RBC transfusion and its risk factors.Methods Medical records of all patients associated with ICS approach from January 2013 to July 2014 were retrospectively reviewed. Theoretical hemoglobin level after reinfusion of salvaged RBC at the end of operations was estimated. Irrational transfusion was defined as initiating allogeneic transfusion with theoretical hemoglobin above 100 g/L. The clinical variables, including the surgical department, gender, age, body weight, ratio of blood loss to estimated blood volume(EBV), salvaged blood volume and preoperative hemoglobin level were subsequently compared between patients who received rational transfusion and those did not. Logistic regression was performed to identify the risk factors for irrationality of allogeneic RBC transfusion in these patients.Results Of 1487 patients with ICS approach in this study, the rate of allogeneic RBC transfusion was 31.4%(467/1487), and the rate of irrational allogeneic RBC transfusion was 26.0% (341/1313). Patients with irrational transfusion were younger (t=4.656, P<0.001), with lower body weight (t=3.910, P<0.001) and slightly lower preoperative HGB level (t=2.822, P=0.005) than those with rational transfusion, but had significantly larger salvaged blood volume (U=-10.926, P<0.001) and higher ratio of blood loss to EBV (U=-17.067, P<0.001), disregarding whether they preoperatively met anemia criteria or not (U=-1.396, P=0.163). Preoperative hemoglobin level (OR=1.975, P=0.005) and the ratio of blood loss/EBV (OR=5.392, P<0.001) were independent risk factors leading to the irrational allogeneic RBC transfusion.Conclusions The irrationality of allogeneic RBC transfusion existed in ICS patients, which may be associated with the preoperative hemoglobin level and the ratio of blood loss to EBV. Determining the HGB levels before transfusion is required to avoid unnecessary blood administration. Doctors should keep their knowledge in blood management updated and improve their awareness of rational transfusion for a better patients care.
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Transfusão de Sangue/métodos , Transfusão de Eritrócitos/métodos , Recuperação de Sangue Operatório/métodos , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To study the efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus obstruction. METHODS: According to the time from admission to the treatment via fiber bronchoscope, the children with MPP who were found to have airway mucus obstruction under a fiber bronchoscope were randomly divided into early intervention group (≤3 days; n=40) and late intervention group (>3 days; n=56). The two groups were compared in terms of clinical data and imaging recovery.The children were followed for 1-3 months. RESULTS: Of the 96 children, 38 were found to have the formation of plastic bronchial tree, among whom 10 were in the early intervention group and 28 were in the late intervention group (P=0.01). Compared with the late intervention group, the early intervention group had a shorter duration of fever, length of hospital stay, and time to the recovery of white blood cell count and C-reactive protein (P<0.05), as well as a higher atelectasis resolution rate (P<0.05). Compared with the late intervention group, the early intervention group had a higher percentage of children with a ≥ 60% absorbed area of pulmonary consolidation at discharge. After 3 months of follow-up, the early intervention group had a higher percentage of children with a ≥ 90% absorbed area of pulmonary consolidation than the late intervention group (80% vs 55%; P=0.01), and the early intervention group had a lower incidence rate of atelectasis than the late intervention group (P<0.05). CONCLUSIONS: Early treatment via fiber bronchoscope can shorten the course of the disease and reduce complications and sequelae in MPP children with airway mucus obstruction.
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Obstrução das Vias Respiratórias/terapia , Broncoscópios , Pneumonia por Mycoplasma/complicações , Criança , Pré-Escolar , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , MucoRESUMO
To provide a theoretical basis for alpine source lake protection, ten samples were taken from each lake annually from 2012 to 2015. Each year, the various species of nitrogen and phosphorus nutrients were measured. The average contents of nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus, and total nitrogen in the four lakes are 0.195-0.0 mg/L, 0.038-0.143 mg/L, 0.004-0.168 mg/L, 0.006-0.740 mg/L, and 0.050-0.547 mg/L, respectively. The total phosphorus contents in Eling Lake, Longbao Lake and Sea Star were higher than Class I water quality standards, and the total nitrogen contents in Eling Lake, Sea Star and Zhaling Lake were higher than Class I water quality standards as well. The concentration contour maps of the nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus and total nitrogen showed that the indicators of the four lakes in the east, the west, and the center of the lake did not have the same trend. From 2012 to 2015, each of the measured nutrients showed a rising trend year by year. The four lakes are polluted by both endogenous and exogenous pollution, and it is necessary to limit the exogenous pollution and protect the alpine lakes immediately.
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Monitoramento Ambiental , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise , China , Lagos/química , Análise Espaço-Temporal , TibetRESUMO
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a relatively rare malignant tumor and early diagnosis and appropriate treatment for ASPS are essential for a good prognosis. PURPOSE: To retrospectively review the clinical presentation and computed tomography (CT) and magnetic resonance imaging (MRI) findings of ASPS so as to improve the accuracy of imaging diagnosis. MATERIAL AND METHODS: Fourteen patients with pathologically proven ASPS were enrolled. Their clinical and imaging findings were retrospectively reviewed. RESULTS: The median age of the patients was 29 years (range, 13-37 years). Most tumors were located in the soft tissues of the trunk and lower limbs. The median maximal diameter of the masses was 91 mm. Thirteen masses presented with ovoid or irregular shapes. Eleven masses had less clear boundaries. Compared with the adjacent muscles, the masses were isodense or hypodense on CT, hypo-, iso-, or hyperintense on T1-weighted images, and heterogeneous hyperintense on T2-weighted images. Intense enhancement was seen after contrast agent administration, with prominent intra- or peri-tumoral feeders on CT or flow voids on MRI. By the end of the last follow-up, 13 patients had distant metastasis and three patients had local recurrence. CONCLUSION: ASPS should be included in the differential diagnosis when a bulky, heterogeneous soft tissue mass in the trunk and the lower limbs with intense enhancement after contrast administration and prominent intra- or peri-tumoral feeders on CT or flow voids on MRI is seen, particularly in young patients.
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Imageamento por Ressonância Magnética , Sarcoma Alveolar de Partes Moles/diagnóstico por imagem , Sarcoma Alveolar de Partes Moles/patologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/patologia , Masculino , Radiografia Torácica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tórax/patologia , Adulto JovemRESUMO
We applied resting-state functional magnetic resonance imaging(rfMRI)combined with graph theory to analyze 90 regions of the infantile small world neural network of the whole brain.We tried to get the following two points clear:1 whether the parameters of the node property of the infantile small world neural network are correlated with the level of infantile intelligence development;2 whether the parameters of the infantile small world neural network are correlated with the children's baseline parameters,i.e.,the demographic parameters such as gender,age,parents' education level,etc.Twelve cases of healthy infants were included in the investigation(9males and 3females with the average age of 33.42±8.42 months.)We then evaluated the level of infantile intelligence of all the cases and graded by Gesell Development Scale Test.We used a Siemens 3.0T Trio imaging system to perform resting-state(rs)EPI scans,and collected the BOLD functional Magnetic Resonance Imaging(fMRI)data.We performed the data processing with Statistical Parametric Mapping 5(SPM5)based on Matlab environment.Furthermore,we got the attributes of the whole brain small world and node attributes of 90 encephalic regions of templates of Anatomatic Automatic Labeling(ALL).At last,we carried out correlation study between the above-mentioned attitudes,intelligence scale parameters and demographic data.The results showed that many node attributes of small world neural network were closely correlated with intelligence scale parameters.Betweeness was mainly centered in thalamus,superior frontal gyrus,and occipital lobe(negative correlation).The r value of superior occipital gyrus associated with the individual and social intelligent scale was-0.729(P=0.007);degree was mainly centered in amygdaloid nucleus,superior frontal gyrus,and inferior parietal gyrus(positive correlation).The r value of inferior parietal gyrus associated with the gross motor intelligent scale was 0.725(P=0.008);efficiency was mainly centered in inferior frontal gyrus,inferior parietal gyrus,and insular lobe(positive correlation).The r value of inferior parietal gyrus associated with the language intelligent scale was 0.738(P=0.006);Anoda cluster coefficient(anodalCp)was centered in frontal lobe,inferior parietal gyrus,and paracentral lobule(positive correlation);Node shortest path length(nlp)was centered in frontal lobe,inferior parietal gyrus,and insular lobe.The distribution of the encephalic regions in the left and right brain was different.However,no statistical significance was found between the correlation of monolithic attributes of small world and intelligence scale.The encephalic regions,in which node attributes of small world were related to other demographic indices,were mainly centered in temporal lobe,cuneus,cingulated gyrus,angular gyrus,and paracentral lobule areas.Most of them belong to the default mode network(DMN).The node attributes of small world neural network are widely related to infantile intelligence level,moreover the distribution is characteristic in different encephalic regions.The distribution of dominant encephalic is in accordance the related functions.The existing correlations reflect the ever changing small world nervous network during infantile development.
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Mapeamento Encefálico , Encéfalo/fisiologia , Rede Nervosa/fisiologia , Córtex Cerebral , Pré-Escolar , Feminino , Lobo Frontal , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Occipital , Lobo ParietalRESUMO
Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.