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OBJECTIVE: The risk category of gastric gastrointestinal stromal tumors (GISTs) are closely related to the surgical method, the scope of resection, and the need for preoperative chemotherapy. We aimed to develop and validate convolutional neural network (CNN) models based on preoperative venous-phase CT images to predict the risk category of gastric GISTs. METHOD: A total of 425 patients pathologically diagnosed with gastric GISTs at the authors' medical centers between January 2012 and July 2021 were split into a training set (154, 84, and 59 with very low/low, intermediate, and high-risk, respectively) and a validation set (67, 35, and 26, respectively). Three CNN models were constructed by obtaining the upper and lower 1, 4, and 7 layers of the maximum tumour mask slice based on venous-phase CT Images and models of CNN_layer3, CNN_layer9, and CNN_layer15 established, respectively. The area under the receiver operating characteristics curve (AUROC) and the Obuchowski index were calculated to compare the diagnostic performance of the CNN models. RESULTS: In the validation set, CNN_layer3, CNN_layer9, and CNN_layer15 had AUROCs of 0.89, 0.90, and 0.90, respectively, for low-risk gastric GISTs; 0.82, 0.83, and 0.83 for intermediate-risk gastric GISTs; and 0.86, 0.86, and 0.85 for high-risk gastric GISTs. In the validation dataset, CNN_layer3 (Obuchowski index, 0.871) provided similar performance than CNN_layer9 and CNN_layer15 (Obuchowski index, 0.875 and 0.873, respectively) in prediction of the gastric GIST risk category (All P >.05). CONCLUSIONS: The CNN based on preoperative venous-phase CT images showed good performance for predicting the risk category of gastric GISTs.
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Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/cirurgia , Tomografia Computadorizada por Raios X/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Redes Neurais de Computação , Curva ROCRESUMO
PURPOSE: Colonoscopy is the gold standard for the diagnosis of colorectal cancer (CRC). Before a colonoscopy, an adequate bowel preparation (BP) is required. Currently, more novel regimens with different effects have been proposed and used successively. This network meta-analysis aims to compare the cleaning effects and patients' tolerability of several BP regimens. METHODS: We performed a network meta-analysis of randomized controlled trials including sixteen kinds of BP regimens. We searched PubMed, Cochrane Library, Embase, and Web of Science databases. The outcomes of this study were bowel cleansing effect and tolerance. RESULTS: We included a total of 40 articles with 13,064 patients. For the primary outcomes, polyethylene glycol (PEG) + ascorbic acid (Asc) + simethicone (Sim) (OR, 14.27, 95%CrI, 2.68-127.87) regimen is ranked first in Boston Bowel Preparation Scale (BBPS). PEG + Sim (OR, 2.0, 95%CrI 0.64-6.4) regimen is ranked first in Ottawa Bowel Preparation Scale (OBPS), but without significant differences. For the secondary outcomes, PEG + Sodium Picosulfate/Magnesium Citrate (SP/MC) (OR, 4.88e + 11, 95%CrI, 39.56-1.82e + 35) regimen is the best in cecal intubation rate(CIR). PEG + Sim (OR,1.5, 95%CrI, 1.0-2.2) regimen is ranked first in adenoma detection rate(ADR). Senna (OR, 3.23, 95%CrI, 1.04-9.97) and SP/MC (OR, 249.91, 95%CrI, 78.49-958.19) regimens are ranked first in abdominal pain and willingness to repeat, respectively. There is no significant difference in cecal intubation time (CIT), polyp detection rate (PDR), nausea, vomiting, and abdominal bloat. CONCLUSION: PEG + Asc + Sim regimen is more effective at cleaning the bowel. PEG + SP/MC will be helpful to increase CIR. For ADR, PEG + Sim regimen will be more helpful. In addition, PEG + Asc + Sim is the least likely to cause abdominal bloat, while Senna regimen is more likely to cause abdominal pain. Patients prefer to re-use the SP/MC regimen for bowel preparation.
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Catárticos , Colonoscopia , Humanos , Adulto , Catárticos/efeitos adversos , Ceco , Metanálise em Rede , Polietilenoglicóis/efeitos adversos , Simeticone , SenosídeosRESUMO
BACKGROUND: Cell division control 42 (CDC42) regulates atherosclerosis, blood lipids, and inflammation and thus affects coronary artery disease (CAD), but its utility in drug-coated balloon (DCB)-treated small-vessel CAD (SV-CAD) patients is unclear. This study intended to evaluate the change and prognostic role of CDC42 in SV-CAD patients underwent DCB. METHODS: Serum CDC42 was measured by enzyme-linked immunosorbent assay in 211 SV-CAD patients underwent DCB at baseline, day (D) 1, D3, and D7, as well as in 50 healthy controls (HCs). RESULTS: CDC42 was decreased in SV-CAD patients compared to HCs (P < 0.001), and it was negatively associated with total cholesterol (P = 0.015), low-density lipoprotein cholesterol (P = 0.003), C-reactive protein (P = 0.001), multivessel disease (P = 0.020), and American college of cardiology/American heart association type B2/C lesions (P = 0.039) in SV-CAD patients. Longitudinally, CDC42 decreased from baseline to D1 and then gradually increased to D7 (P < 0.001) in SV-CAD patients after DCB. Interestingly, high CDC42 (cut-off value = 500 pg/mL) at baseline (P = 0.047), D3 (P = 0.046), and D7 (P = 0.008) was associated with a lower accumulating target lesion failure (TLF) rate; high CDC42 at D3 (P = 0.037) and D7 (P = 0.041) was related to a lower accumulating major adverse cardiovascular event (MACE) rate in SV-CAD patients underwent DCB. Importantly, CDC42 at D7 (high vs. low) independently predicted lower accumulating TLF (hazard ratio (HR) = 0.145, P = 0.021) and MACE (HR = 0.295, P = 0.023) risks in SV-CAD patients underwent DCB. CONCLUSIONS: Circulating CDC42 level relates to milder disease conditions and independently estimates lower risks of TLF and MACE in SV-CAD patients underwent DCB, but further validation is still needed.
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Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , ColesterolRESUMO
OBJECTIVES: To explore added value of diffusion-weighted imaging (DWI) as an adjunct to Kaiser score (KS) for differentiation of benign from malignant lesions on breast magnetic resonance imaging (MRI). METHODS: Two hundred forty-six patients with 273 lesions (155 malignancies) were included in this retrospective study from January 2015 to December 2019. All lesions were proved by pathology. Two radiologists blind to pathological results evaluated lesions according to KS. Lesions with score > 4 were considered malignant. Four thresholds of ADC values -1.3 × 10-3mm2/s, 1.4 × 10-3mm2/s, 1.53 × 10-3mm2/s, and 1.6 × 10-3mm2/s were used to distinguish benign from malignant lesions. For combined diagnosis, a lesion with KS > 4 and ADC values below the preset cutoffs was considered as malignant; otherwise, it was benign. Sensitivity, specificity, and area under the curve (AUC) were compared between KS, DWI, and combined diagnosis. RESULTS: The AUC of KS was significantly higher than that of DWI alone (0.941 vs 0.901, p = 0.04). The sensitivity of KS (96.8%) and DWI (97.4 - 99.4%) was comparable (p > 0.05) while the specificity of KS (83.9%) was significantly higher than that of DWI (19.5-56.8%) (p < 0.05). Adding DWI as an adjunct to KS resulted in a 0-2.5% increase of specificity and a 0.1-1.3% decrease of sensitivity; however, the difference did not reach statistical significance (p > 0.05). CONCLUSION: KS showed higher diagnostic performance than DWI alone for discrimination of breast benign and malignant lesions. DWI showed no additional value to KS for characterizing breast lesions. KEY POINTS: ⢠KS showed higher diagnostic performance than DWI alone for differentiation of benign from breast malignant lesions. ⢠DWI alone showed a high sensitivity but a low specificity for characterizing breast lesions. ⢠Diagnostic performance did not improve using DWI as an adjunct to KS.
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Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The aim of the present study was to explore the brain active characteristics of patients with irritable bowel syndrome with diarrhea (IBS-D) using resting-state functional magnetic resonance imaging technology. METHODS: Thirteen IBS-D patients and fourteen healthy controls (HC) were enrolled. All subjects underwent head MRI examination during resting state. A voxel-based analysis of fractional amplitude of low frequency fluctuation (fALFF) maps between IBS-D and HC was performed using a two-sample t-test. The relationship between the fALFF values in abnormal brain regions and the scores of Symptom Severity Scale (IBS-SSS) were analyzed using Pearson correlation analysis. RESULTS: Compared with HC, IBS-D patients had lower fALFF values in the left medial superior frontal gyrus and higher fALFF values in the left hippocampus and right precuneus. There was a positive correlation between the duration scores of IBS-SSS and fALFF values in the right precuneus. CONCLUSION: The altered fALFF values in the medial superior frontal gyri, left hippocampus and right precuneus revealed changes of intrinsic neuronal activity, further revealing the abnormality of gut-brain axis of IBS-D.
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Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Diarreia/fisiopatologia , Síndrome do Intestino Irritável/diagnóstico por imagem , Síndrome do Intestino Irritável/fisiopatologia , Imageamento por Ressonância Magnética , Dor Abdominal/fisiopatologia , Adulto , Estudos de Casos e Controles , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Diarreia/etiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/psicologia , Masculino , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto JovemRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the health and lifespan of the elderly worldwide. Recently, the correlation between AD and type 2 diabetes mellitus (T2DM) has received intensive attention, and a promising new anti-AD strategy is the use of anti-diabetic drugs. Oxyntomodulin (Oxm) is a peptide hormone and growth factor that acts on neurons in the hypothalamus. OXM activates glucagon-like peptide 1 (GLP-1) and glucagon (Gcg) receptors, facilitates insulin signaling and has neuroprotective effects against Aß1-42-induced cytotoxicity in primary hippocampal neurons. Here, we tested the effects of the protease-resistant analogue (D-Ser2)Oxm on spatial memory and synaptic plasticity and the underlying molecular mechanisms in the APP/PS1 transgenic mouse model of AD. The results showed that (D-Ser2)Oxm not only alleviated the impairments of working memory and long-term spatial memory, but also reduced the number of Aß plaques in the hippocampus, and reversed the suppression of hippocampal synaptic long-term potentiation (LTP). Moreover, (D-Ser2)Oxm administration significantly increased p-PI3K/p-AKT1 expression and decreased p-GSK3ß levels in the hippocampus. These results are the first to show an in vivo neuroprotective role of (D-Ser2)Oxm in APP/PS1 mice, and this role involves the improvement of synaptic plasticity, clearance of Aß and normalization of PI3K/AKT/GSK3ß cell signaling in the hippocampus. This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD.
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Doença de Alzheimer/patologia , Peptídeo 1 Semelhante ao Glucagon/agonistas , Plasticidade Neuronal/efeitos dos fármacos , Oxintomodulina/farmacologia , Receptores de Glucagon/agonistas , Memória Espacial/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Hipocampo/efeitos dos fármacos , Insulina/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Oxintomodulina/uso terapêutico , Presenilina-1/genéticaRESUMO
BACKGROUND: The novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) has spread around the world. We aimed to recapitulate the clinical and CT imaging features of COVID-19 and their differences in three age groups. METHODS: The clinical and CT data of patients with COVID-19 (n = 307) that had been divided into three groups (Group 1: < 40 years old; Group 2: 40 ≤ age < 60 years old; Group 3: ≥ 60 years old) according to age were analyzed retrospectively. RESULTS: Of all patients, 114 (37.1%) had histories of epidemiological exposure, 48 (15.6%) were severe/critical cases, 31 had hypertension (10.1%), 15 had diabetes mellitus (4.9%), 3 had chronic obstructive pulmonary disease (COPD, 1%). Among the three groups, severe/critical type, hypertension and diabetes occurred more commonly in the elderly group compared with Group 1&2 (P < 0.05, respectively). Cough and chest tightness/pain were more commonly appeared in Group 2&3 compared with Group 1 (P < 0.05, respectively). Compared with Group 1 and 2, there were more abnormal laboratory examination indexes (including CRP increase, abnormal percentage of lymphocytes, neutrophils and monocytes) in Group 3 (P < 0.05, respectively). CT images revealed that more lobes were affected and more subpleural lesions were involved in the elderly group, besides, crazy paving sign, bronchodilatation and pleural thickening were more commonly seen in the elderly group, with significant difference between Group 1&2, Group 2&3 (P < 0.05, respectively). CONCLUSIONS: COVID-19 presented representative clinical manifestations, laboratory examinations and CT findings, but three age groups possessed their own specific characteristics. Grasping the clinical and CT features stratified by age will be helpful for early definite diagnosis of COVID-19.
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Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Fatores Etários , Idoso , Betacoronavirus/fisiologia , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
PURPOSE: To explore the value of the apparent diffusion coefficient (ADC) in assessing preoperative T staging of low rectal cancer and the correlation between ADC value and Ki-67 expression. METHODS: Data on 77 patients with a proven pathology of low rectal cancer were retrospectively analyzed. All patients underwent a magnetic resonance imaging scan 1 week prior to operation, and the mean ADC value was measured. All tumors were fully removed, and pathologic staging was determined. The Ki-67 expression was determined using immunohistochemical methods in all patients. The correlation between Ki-67 expression and ADC features was studied. RESULTS: A total of 77 patients with low rectal cancer were included in the study. The pathology type was adenocarcinoma. The numbers of patients with pathological stages T1, T2, T3, and T4 were 9, 23, 32, and 13, respectively. The ADC value of all tumors ranged from 0.60 to 1.20 mm2/s. The average Ki-67 proliferation index was 55.3% ± 20.2%. A significant difference was observed between the preoperative ADC value and pathological T staging of low rectal cancer (P < .01). The more advanced the T stage, the lower the detected ADC values were. A negative correlation was noted between the preoperative ADC value and Ki-67 proliferation index of rectal cancer (r = -0.71, P < .01). When the Ki-67 proliferation index increased, lower ADC values were detected. CONCLUSION: The ADC values can provide useful information on preoperative tumor staging and may facilitate evaluation of the biological behavior of low rectal cancer. The ADC values should be considered a sensitive image biomarker of rectal cancer.
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Adenocarcinoma/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Antígeno Ki-67/análise , Neoplasias Retais/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
Epidemiological studies show a positive correlation between the air levels of fine particulate matter (PM2.5) and cardiovascular disorders, but how PM2.5 affects cardiomyocytes has not been studied in great deal. The aim of the present study was to obtain an insight into the links among intracellular levels of reactive oxygen species (ROS), apoptosis and mitogen-activated protein kinases (MAPKs) in rat cardiac H9c2 cells exposed to PM2.5. H9c2 cells were incubated with PM2.5 at 100-800 µg ml(-1) to evaluate the effects of PM2.5 on cell viability, cell apoptosis, intracellular levels of ROS and expression of apoptosis-related proteins as well as activation of MAPKs. PM2.5 decreased cell viability, increased the cell apoptosis rate and intracellular ROS production in a concentration-dependent manner. PM2.5 decreased the Bcl-2/Bax ratio and increased cleaved caspase-3 levels. A Western blots study showed up-regulation of phosphorylated MAPKs including extracellular signal-regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK in the PM2.5-treated cells. The p38 MAPK inhibitor SB239063 attenuated whereas the ERKs inhibitor PD98059 augmented the effects of PM2.5 on apoptosis and the expression of related proteins. In conclusion, PM2.5 decreases cell viability and increases apoptosis by enhancing intracellular ROS production and activating the MAPKs signaling pathway in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5-induced cardiac injury.
Assuntos
Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Material Particulado/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Ratos , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Endothelial dysfunction and oxidative stress likely play roles in PM2.5-induced harmful effects. Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant that exerts protective effects on cardiovascular diseases (CVDs) in part by scavenging free radicals. The exposure to ambient fine particulate matter (PM2.5) is responsible for certain CVDs. The aim of the present study was to investigate whether EGCG could also inhibit PM2.5-induced oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in human umbilical vein endothelial cells (HUVECs). PM2.5 (200 µg/mL) increased both cell death and intracellular ROS levels significantly, whereas EGCG (50-400 µM) inhibited these effects in a concentration-dependent manner. Western blotting and PCR demonstrated that EGCG increased Nrf2 and HO-1 expression in HUVECs that had been exposed to PM2.5. PD98059 (a selective inhibitor of extracellular signal regulated kinase [ERK]-1/2) and SB203580 (a selective inhibitor of p38 MAPK), but not SP600125 (a selective inhibitor of c-jun N-terminal kinase [JNK]), attenuated the EGCG-induced Nrf2 and HO-1 expression. In addition, silencing Nrf2 abolished EGCG-induced Nrf2 and HO-1 upregulation and enhancement of cell viability. The present study suggests that EGCG protects HUVECs from PM2.5-induced oxidative stress injury by upregulating Nrf2/HO-1 via activation of the p38 MAPK and the ERK1/2 signaling pathways.
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Antioxidantes/farmacologia , Catequina/análogos & derivados , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/química , Catequina/química , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Concentração Inibidora 50 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Rattin, a specific derivative of humanin in rats, shares the ability with HN to protect neurons against amyloid ß (Aß) peptide-induced cellular toxicity. However, it is still unclear whether Rattin can protect against Aß-induced deficits in cognition and synaptic plasticity in rats. In the present study, we observed the effects of Rattin and Aß31-35 on the spatial reference memory and in vivo hippocampal Long-term potentiation of rats by using Morris water maze test and hippocampal field potential recording. Furthermore, the probable molecular mechanism underlying the neuroprotective roles of Rattin was investigated. We showed that intra-hippocampal injection of Rattin effectively prevented the Aß31-35-induced spatial memory deficits and hippocampal LTP suppression in rats; the Aß31-35-induced activation of Caspase-3 and inhibition of STAT3 in the hippocampus were also prevented by Rattin treatment. These findings indicate that Rattin treatment can protect spatial memory and synaptic plasticity of rats against Aß31-35-induced impairments, and the underlying protective mechanism of Rattin may be involved in STAT3 and Caspases-3 pathways. Therefore, application of Rattin or activation of its signaling pathways in the brain might be beneficial to the prevention of Aß-related cognitive deficits.
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Peptídeos beta-Amiloides/toxicidade , Potenciação de Longa Duração/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas/farmacologia , Doença de Alzheimer/metabolismo , Animais , Caspase 3/biossíntese , Modelos Animais de Doenças , Citometria de Fluxo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/biossínteseRESUMO
Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.
Assuntos
Menopausa Precoce , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , MicroRNAs , Insuficiência Ovariana Primária , Animais , Feminino , Camundongos , Antígenos CD28 , Interleucina-10/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/terapia , Insuficiência Ovariana Primária/induzido quimicamente , Proteínas Proto-Oncogênicas c-aktRESUMO
Premature ovarian insufficiency (POI) is a serious disease significantly affecting the physical and mental health of women of reproductive age, not just impacting fertility outcomes. Ovarian damage due to chemotherapy remains a major cause of this condition. Recent studies have indicated the involvement of the long non-coding RNA HOTAIR in the progression of various diseases, showcasing important biological functions, yet its role in POI remains unclear. We conducted microarray dataset analysis and qRT-PCR experiments, demonstrating downregulation of HOTAIR expression in ovarian tissue and granulosa cells. Various functional experiments using plasmids overexpressing HOTAIR confirmed its promotion of cisplatin-induced granulosa cell autophagy and proliferation. Mechanistically, dual-luciferase assays showed that HOTAIR modulates ATG14 levels in POI by binding miR-148b-3p, thereby enhancing levels of autophagy and proliferation. In this study, we first explored the impact of miR-148b-3p on POI and found that overexpression of miR-148b-3p reversed the promotion of autophagy and proliferation induced by HOTAIR overexpression. The inhibitory effect of miR-148b-3p inhibitor on KGN cell autophagy and proliferation improvement could also be reversed by silencing ATG14. Overall, our findings indicate the promoting role of HOTAIR in POI and its potential as a biomarker for POI by modulating the miR-148b-3p/ATG14 axis to improve mechanisms of autophagy and proliferation in POI.
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A novel microchannel heat sink (TFMCHS) with trapezoidal ribs and fan grooves was proposed, and the microchannel was manufactured using selective laser melting technology. Firstly, the temperature and pressure drop at different power levels were measured through experiments and then combined with numerical simulation to explore the complex flow characteristics within TFMCHSs and evaluate the comprehensive performance of microchannel heat sinks based on the thermal enhancement coefficient. The results show that, compared with rectangular microchannel heat sinks (RMCHSs), the average and maximum temperatures of TFMCHSs are significantly reduced, and the temperature distribution is more uniform. This is mainly caused by the periodic interruption and redevelopment of the velocity boundary layer and thermal boundary layer caused by ribs and grooves. And as the heating power increases, the TFMCHS has better heat dissipation performance. When P=33 W and the inlet flow rate is 32.5 mL/min, the thermal enhancement factor reaches 1.26.
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Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light-heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.
Assuntos
Nanopartículas , Terapia Fototérmica , Polímeros , Nanopartículas/uso terapêutico , Imagem Óptica/métodos , Fototerapia , Linhagem Celular TumoralRESUMO
BACKGROUND: The study evaluated the protective effect of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against all-cause hospitalized pneumonia in children in Beijing. METHODS: Based on the vaccination record and inpatient medical record database of Beijing, children born in 2017 in Beijing, matched by age, gender, and district of the children with the ratio of 1:4, were selected as the vaccinated and unvaccinated groups according whether if vaccinated with PCV13. The incidence rate and 95 % confidence interval (95 %CI), vaccine effectiveness (VE) and direct medical costs of all-cause hospitalized pneumonia were calculated and compared within the same period of 12 months, 18 months, 24 months and 30 months after the birth of the child. RESULTS: The decreased incidence rates of all-cause hospitalized pneumonia were observed at the four points in the PCV13 vaccinated group compared to the unvaccinated group, which were significant at the points of 12 months (0.42 % vs. 0.72 %, P = 0.001), 18 months (0.90 % vs. 1.26 %, P = 0.002) and 24 months (1.37 % vs. 1.65 %, P = 0.046). The VE of PCV13 against all-cause hospitalized pneumonia within 12 months was the highest as 41.9 % (95 % CI 19.6 %, 58.0 %), followed by 29.3 % (95 % CI 11.4 %, 43.5 %) within 18 months, 17.1 % (95 % CI 0.3 %, 31.1 %) within 24 months and it almost disappeared within 30 months. The VE of 4-dose vaccination within 18 months and 24 months were 39.9 % (95 % CI 20.3 %, 54.7 %) and 27.2 % (95 % CI 8.6 %, 42.0 %), respectively. The median hospitalization cost of the children in the vaccinated group was higher at the four points but without significance. CONCLUSIONS: PCV13 had a certain protective effect on all-cause hospitalized pneumonia, and the booster immunization strategy had the best protective effect with great public health significance to enter the immunization program.
Assuntos
Infecções Pneumocócicas , Pneumonia Pneumocócica , Criança , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae , Pequim/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Pneumocócicas , Hospitalização , Vacinas ConjugadasRESUMO
BACKGROUND: Tendon-derived stem cells (TDSCs) are one of stem cells characterized by greater clonogenicity, tenogenesis, and proliferation capacity. Circ_0005736 has been shown to be decreased in Rotator cuff tendinopathy. Here, we investigated the function and relationship of circ_0005736 in TDSC tenogenic differentiation. METHODS: Transforming growth factor ß1 (TGF-ß1) was used to induce the tenogenic differentiation in TDSC. Cell proliferation, invasion and migration were evaluated by Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine, transwell, and wound healing assays, respectively. The detection of the levels of genes and proteins was performed by qRT-PCR and Western blot. The binding between miR-636 and circ_0005736 or MAPK1 (Mitogen-Activated Protein Kinase 1) was verified using dual-luciferase reporter assay and RIP assays. RESULTS: TGF-ß1 induced tenogenic differentiation by enhancing the production of tendon-specific markers and TDSC proliferation, invasion and migration. TGF-ß1 treatment promoted circ_0005736 expression, knockdown of circ_0005736 abolished TGF-ß1-induced tenogenic differentiation in TDSCs. Mechanistically, circ_0005736 acted as a sponge for miR-636 to up-regulate the expression of MAPK1, which was confirmed to be a target of miR-636 in TDSCs. Further rescue assays showed that inhibition of miR-636 could rescue circ_0005736 knockdown-induced suppression on TGF-ß1-caused tenogenic differentiation in TDSCs. Moreover, forced expression of miR-636 abolished TGF-ß1-caused tenogenic differentiation in TDSCs, which was rescued by MAPK1 up-regulation. CONCLUSION: Circ_0005736 enhanced TGF-ß1-induced tenogenic differentiation in TDSCs via increasing the production of tendon-specific markers and TDSC proliferation, invasion and migration through miR-636/MAPK1 axis.
Assuntos
MicroRNAs , Proteína Quinase 1 Ativada por Mitógeno , Fator de Crescimento Transformador beta1 , Tendões , Diferenciação CelularRESUMO
Bronchial lipoma is a rare benign tumor of the lung, which is often misdiagnosed due to concomitant pulmonary diseases. In addition, the coexistence of endobronchial lipoma and lung cancer is extremely unusual. To date, no related computed tomography (CT) images have been reported. The patient was a 53-year-old man, who was admitted to our hospital with cough, yellow phlegm, and fever for 1 week. The CT image showed an irregular mass in the medial segment of the right middle lobe (B4a) with surrounding ground glass opacity, and another solid nodule in the right lower lobe (B6b). Unfortunately, after 2 weeks of anti-inflammatory treatment, the bronchial invasion of the B4a nodule did not decrease significantly, so further bronchoscopy was carried out and tumor resection was performed using endoscopic mucosal resection with a ligation device (EMR-L). During the follow-up 4 months, it was found that the B6b nodule was marked enlargement and then removed. The lesions of the B4a and B6b were confirmed as endobronchial lipoma and squamous cell carcinoma (T1aN0M0) by histopathology and immunohistochemical staining, respectively, and no postoperative radiotherapy or chemotherapy was performed. Regrettably, after 29 months of follow-up, we observed recurrence and slow enlargement of the lipoma in its original location, progressive emphysema in both lungs, and solitary chest wall metastasis from the B6b squamous cell carcinoma that had been resected. Therefore, endobronchial endoscopy resection should be carefully selected for larger endobronchial lipoma. If it is accompanied by early squamous cell carcinoma (T1aN0M0), we still recommend active postoperative chemoradiotherapy.
Assuntos
Neoplasias Brônquicas , Carcinoma de Células Escamosas , Lipoma , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/cirurgia , Endoscopia , Broncoscopia , Lipoma/diagnóstico por imagem , Lipoma/cirurgiaRESUMO
Premature ovarian insufficiency, characterized by ovarian infertility and low fertility, has become a significant problem in developed countries due to its propensity for late delivery. It has been described that the vital role of lncRNA in the development and progression of POI. The aim of this work was to create a POI-based lncRNA-mRNA network (POILMN) to recognize key lncRNAs. Overall, differently expressed mRNAs (DEGs) and differently expressed lncRNAs (DELs) were achieved by using the AnnoProbe and limma R packages. POI-based lncRNA-mRNA network (POILMN) construction was carried out using the tinyarray R package and hypergeometric distribution. To identify key lncRNAs, we used CentiScaPe plug-in Cytoscape as a screening tool. In total, 244 differentially expressed lncRNAs (DELs) and 288 differentially expressed mRNAs (DEGs) were obtained in this study. Also, 177 lncRNA/mRNA pairs (including 39 lncRNAs and 86 mRNAs) were selected using the hypergeometric test. Finally, we identified four lncRNA (HCP5, NUTM2A-AS1, GABPB1-IT1, and SMIM25) intersections by topological analysis between two centralities (degree and betweenness), and we explored their subnetwork GO and KEGG pathway enrichment analysis. Here, we have provided strong evidence for a relationship with apoptosis, DNA repair damage, and energy metabolism terms and pathways in the key lncRNAs in our POI-based lncRNA-mRNA network. In addition, we evaluated the localization information of genes related to POI and found that genes were more distributed on chromosomes 15, 16, 17, and 19. However, more experiments are needed to confirm the functional significance of such predicted lncRNA/mRNA. In conclusion, our study identified four long non-coding RNA molecules that may be relevant to the progress of premature ovarian insufficiency.
RESUMO
A multifunctional semiconducting nanoagonist with high photothermic conversion efficiency (86.2%) and alkyl radical generation ability was developed. The nanoagonist demonstrated excellent anticancer performance through NIR-II light-triggered photothermic/thermodynamic combinational therapy both in vitro and in vivo.