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BACKGROUND: Severe acute pancreatitis (SAP) is a familiar critical disease in the intensive care unit (ICU) patients. Nursing staff are important spiritual pillars during the treatment of patients, and in addition to routine nursing, more attention needs be paid to the patient's psychological changes. AIM: To investigate the effects of psychological intervention in ICU patients with SAP. METHODS: One hundred ICU patients with SAP were hospitalized in the authors' hospital between 2020 and 2023 were selected, and divided into observation and control groups per the hospitalization order. The control and observation groups received routine nursing and psychological interventions, respectively. Two groups are being compared, using the Self-rating Anxiety Scale (SAS), Self-Determination Scale (SDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and 36-item Short Form Health Survey (SF-36) scores; nursing satisfaction of patients; ICU care duration; length of stay; hospitalization expenses; and the incidence of complications. RESULTS: After nursing, the SDS, SAS, and APACHE II scores in the experimental group were significantly lower than in the control group (P < 0.05). The SF-36 scores in the observation group were significantly higher than those in the control group (P < 0.05). The nursing satisfaction of patients in the experimental group was 94.5%, considerably higher than that of 75.6% in the control group (P < 0.05). The ICU care duration, length of stay, and hospitalization expenses in the observation group were significantly lower than those in the control group, and the incidence of complications was lower (P < 0.05). CONCLUSION: For patients with SAP, the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.
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INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.
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Histerectomía , Investigación Cualitativa , Calidad de Vida , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/psicología , Neoplasias del Cuello Uterino/cirugía , Persona de Mediana Edad , Adulto , Histerectomía/psicología , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Calidad de Vida/psicología , China , Entrevistas como Asunto/métodos , Anciano , Adaptación PsicológicaRESUMEN
Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.
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Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.
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Electroacupuntura , Factores de Intercambio de Guanina Nucleótido , Canales Iónicos , Síndrome del Colon Irritable , Animales , Factores de Intercambio de Guanina Nucleótido/genética , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Hiperalgesia/terapia , Canales Iónicos/genética , Síndrome del Colon Irritable/terapia , Ratones , Serotonina/metabolismoRESUMEN
Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.
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Adenocarcinoma , Subunidades beta de Inhibinas/metabolismo , Neoplasias Pancreáticas , Adenocarcinoma/genética , Animales , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 14 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/patología , Fenotipo , Pronóstico , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores , Neoplasias PancreáticasRESUMEN
Based on the story of Chinese idiom, paodingjieniu (a magical and skilled form of craftsmanship) as the breakthrough point, this paper discusses the both paoding (cook) and the experienced acupuncture practitioner have the same high skills and explores the potential relationship between mind-regulation in treatment with acupuncture and flow theory. It is believed that the skills of ancient acupuncture practitioner in mind-regulation with acupuncture is not only a kind of "Tao" mode, but also a state of "flow". By the discussion on mind-regulation and flow theory, modern people may have more clear recognition on the mind regulation in treatment with acupuncture so as to better determine the therapeutic methods of acupuncture for mind-regulation.
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Terapia por Acupuntura , Medicina Tradicional China , Puntos de Acupuntura , Humanos , Relaciones Metafisicas Mente-CuerpoRESUMEN
AIMS: The impaired angiogenesis is one of the main factors affecting the healing of diabetic foot ulcer (DFU) wounds. Maggot debridement therapy (MDT) promotes granulation tissue growth and angiogenesis during DFU wound healing. Non-coding microRNAs can also promote local angiogenesis in DFU wounds by regulating wound repairing related gene expression. The purpose of this study was to investigate the mechanism of microRNAs in MDT promoting DFU wound angiogenesis. METHODS: In this study, we applied MDT to treat DFU wound tissue and detect the expression of the miR-17-92 cluster. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with maggot excretions/secretions (ES), the miR-17-92 cluster and the predicted target gene expression were measured. Tube formation assay and cell scratch assay were performed when inhibition of miR-18a/19a or overexpression of thrombospondin-1 (TSP-1) were used in this study. RESULTS: miR-18a/19a transcription significantly up-regulated and TSP-1 expression down-regulated in patients wound tissue and in HUVECs. Inhibition of miR-18a/19a or overexpression of TSP-1 partially blocked the migration and tube formation ability stimulated by ES. CONCLUSION: Targeted activation of miR-18a/19a transcription levels and subsequent regulation of TSP-1 expression may be a novel therapeutic strategy for DFU.
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Desbridamiento/métodos , Pie Diabético/terapia , Larva/metabolismo , MicroARNs/metabolismo , Cicatrización de Heridas , Animales , Diabetes Mellitus/terapia , Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , MicroARNs/genética , Neovascularización Fisiológica , Trombospondina 1/genética , Trombospondina 1/metabolismoRESUMEN
OBJECTIVE: Identify the molecular mechanism of inflammatory stimuli induced pancreatic cancer progression. METHODS: RNA-seq, microarray assay and bioinformatics analyses were used to identify differentially expressed genes. Immunohistochemical staining was performed to evaluate CD68, CD163, ß-catenin, CD103, CCL3 markers. Quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter assay, apoptosis assay, wound healing assay and immunofluorescence were performed to study the relationship of inflammatory stimuli and WNT/ß-catenin pathway. RESULTS: Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/ß-catenin pathway. Inflammatory stimuli could activate WNT/ß-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear ß-catenin expression of CD68-high group was much higher than CD68-low group (P < 0.05), as same as CD163 (P < 0.05). Inflammatory stimuli downregulated the expression of CCL3 via WNT/ß-catenin pathway and inhibited the chemotaxis of CD103 dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/ß-catenin pathway. Transforming growth factor-ß promoted malignant biological behavior of pancreatic cancer cells through WNT/ß-catenin pathway-dependent mechanism. CONCLUSIONS: Our present study provided a novel mechanism involved in the inflammation-driven cancer progression through tumor immune escape and downstream gene regulation of WNT/ß-catenin pathway-dependent manner.
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Apoptosis/genética , Inflamación/genética , Macrófagos/metabolismo , Neoplasias Pancreáticas/genética , Vía de Señalización Wnt/genética , beta Catenina/genética , Anciano , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Células Cultivadas , Progresión de la Enfermedad , Técnica del Anticuerpo Fluorescente/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/metabolismo , Ratones Endogámicos C57BL , Ratones Desnudos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , beta Catenina/metabolismoRESUMEN
BACKGROUND: The objective of this study was to improve the understanding of primary pulmonary lymphoma (PPL) for clinicians. METHODS: We enrolled 27 patients diagnosed with PPL in the First Affiliated Hospital of Soochow University from January 2000 to December 2016. The clinical manifestations, imaging findings, pathologic features, treatments and prognosis of the patients were collected. RESULTS: The male to female ratio was 1.5:1 and the average age was 54.6 ± 15.7 years old. Nine patients were asymptomatic. The main manifestations were cough, expectoration, bloody sputum and fever. The imaging findings presented as nodule, mass, pneumonia or consolidation. There were 2 cases of Hodgkin's lymphoma, 18 cases of non-Hodgkin's lymphoma and 7 cases of undifferentiated lymphoma. Non-Hodgkin's lymphoma cases were divided into T-cell lymphoma (nâ¯=â¯2), mucosa-associated lymphoid tissue lymphoma (MALT) (nâ¯=â¯11), diffuse large B-cell lymphoma (nâ¯=â¯3), small B-cell lymphoma (nâ¯=â¯1) and plasmacytoid B-cell lymphoma (nâ¯=â¯1). Ten MALT cases survived and 1 diffuse large B-cell lymphoma case has been in stable condition for 71 months after surgery and chemotherapy. The international prognostic index was related to the prognosis of PPL. CONCLUSIONS: The clinical manifestations and imaging findings of PPL were nonspecific. The prognosis of MALT was better than other types of PPL. The International prognostic index can be used for predicting the prognosis of PPL.
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Neoplasias Pulmonares , Linfoma , Adulto , Anciano , China , Femenino , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Linfoma/clasificación , Linfoma/diagnóstico , Linfoma/patología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.
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ADN (Citosina-5-)-Metiltransferasas/genética , Mutación , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/genética , ADN Metiltransferasa 3A , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patologíaRESUMEN
Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR. Protein levels were tested by western blotting, flow cytometry and immunohistochemistry. Migration was determined using a wound-healing assay. Stemness was further confirmed using a plate clone formation assay. We found that Rg3 repressed the growth and stemness of CRC cells both in vitro and in vivo. Rg3 also impaired the migration of CRC cells in vitro. Rg3 downregulated the expressions of angiogenesis-related genes, and repressed the vascularization of CRC xenografts. In addition, Rg3 strengthened the cytotoxicity of 5-Fluorouracil and oxaliplatin against orthotopic xenografts in vivo. Moreover, Rg3 downregulated the expressions of B7-H1 and B7-H3, high expressions of which were associated with reduced overall survival (OS) of CRC patients. Hence, Rg3 not only repressed the growth and stemness of CRC cells, but could also remodel the tumor microenvironment through repressing angiogenesis and promoting antitumor immunity. Therefore, Rg3 could be a novel therapeutic for the CRC treatment.
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Neoplasias Colorrectales/tratamiento farmacológico , Ginsenósidos/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Sinergismo Farmacológico , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacología , Ginsenósidos/administración & dosificación , Células HCT116 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/farmacología , Oxaliplatino , Distribución Aleatoria , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aberrant expression of long noncoding RNAs (lncRNAs) is implicated in cancer development and progression. However, the clinical significance and mechanism by which NONHSAT062994 regulates colorectal cancer (CRC) is unknown. We here reported that NONHSAT062994 was significantly downregulated in human CRC tissues and cell lines. Moreover, its expression was inversely correlated with tumor size and overall survival (OS) time in CRC patients. In CRC cells, the overexpression and knockdown of NONHSAT062994 inhibited and enhanced CRC cell growth, respectively, in vitro and in vivo. Mechanistically, NONHSAT062994 functioned as a tumor suppressor to inhibit CRC cell growth by inactivating Akt signaling. Notably, the NONHSAT062994 expression status was negatively correlated with the Akt downstream targets c-Myc and Cyclin D1 in clinical CRC samples. The current findings suggest that NONHSAT062994 plays a critical role in the development of CRC by regulating Akt signaling, and identified a candidate prognostic biomarker or potential therapeutic target for CRC patients.
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Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC. To verify the genomic characteristics of pancreatic SCC, we employed in-solution hybrid capture targeting 137 cancer-related genes accompanied by high throughput sequencing (HTS) to compare the different genetic variants in SCC and AC of pancreas. We compared the genetic alterations of known biomarkers of pancreatic adenocarcinoma in different pancreatic cancer tissues, and identified nine mutated genes in SCC of pancreas: C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, TET2, and nine genes (ABCB1, CSF1R, CYP2C18, FBXW7, ITPA, KIAA0748, SOD2, SULT1A2, ZNF142) that are mutated in pancreatic AC. This study may have taken one step forward on the discovery of potential biomarkers for the targeted treatment of SCC of the pancreas.
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Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pancreáticas/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Diferencial , Ontología de Genes , Humanos , Mutación INDEL , Inmunohistoquímica , Queratina-5/metabolismo , Queratina-6/metabolismo , Mutación , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Polimorfismo de Nucleótido Simple , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The case that aggregation has a large influence on the structure and fluorescent properties of 5-(4-(1,2,2-triphenylvinyl)phenyl)thiophene-2-carbaldehyde (P4 TA) is investigated in detail herein by employing quantum mechanics and molecular mechanics. Besides the isolated molecule, the aggregated molecule in water and in the crystalline state was studied by focusing on the comparison of photoelectronic properties, including the geometrical and electronic structures at ground and excited states, emission and internal conversation properties. For the aggregation state, the intermolecular interaction was used to explain the difference in structure, emission color and intensity of different polymorphs. The noticeable contribution from low-frequency region, corresponding to the four phenyl rings twisting vibration, to the Huang-Rhys factor and reorganization energy, as well as the possible potential energy surface crossing between S0 and S1 states for isolated molecules was considered as the reason of its aggregation-induced emission (AIE) performance. Importantly, the aggregation process in water simulated at the same time helps us to have a deeper understanding of the AIE behavior of P4 TA, which also provides another perspective to explore the AIE phenomenon in theory.
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BACKGROUND: miR-126 may increase angiogenesis in patients with diabetic foot ulcers (DFUs) treated with maggot debridement therapy (MDT). METHODS: Real-time quantitative PCR was used to detect expression of miR-126 mRNA in the peripheral blood among the non-diabetic population, type 2 diabetes mellitus patients without DFU, and patients with DFUs of type 2 diabetes mellitus. The expression of miR-126 mRNA in the peripheral blood of patients with DFUs was observed before and after MDT. Finally, human umbilical vein endothelial cells (HUVEC) were utilized to explore miR-126 mRNA expression with maggot excretions/secretions (ES). RESULTS: In the patients with DFUs, the miR-126 mRNA expression level in the peripheral blood was less than that type 2 diabetes mellitus patients without DFU, and much lower than that in the non-diabetic population (P<0.001). The miR-126 expression level was significantly increased in those DFU patients treated with MDT (P<0.05). Finally, using HUVEC co-cultured with ES, we showed the ES increased miR-126 expression in vitro (P<0.001). CONCLUSION: MDT upregulates the miR-126 expression in the peripheral blood of patients with DFUs.
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Terapia Biológica/métodos , Terapias Complementarias , Desbridamiento/métodos , Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/terapia , Dípteros/fisiología , MicroARNs/agonistas , Anciano , Animales , Secreciones Corporales/fisiología , Células Cultivadas , China , Técnicas de Cocultivo , Pie Diabético/sangre , Pie Diabético/metabolismo , Pie Diabético/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Regulación de la Expresión Génica , Vida Libre de Gérmenes , Hospitales Urbanos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Larva/fisiología , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
BACKGROUND: C-reactive protein (CRP) exerts prothrombotic effects through dissociating from pentameric CRP (pCRP) into modified or monomeric CRP (mCRP). However, although the high prevalence of venous thromboembolism (VTE) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been identified, it remains unclear whether the high levels of circulating pCRP potentially contribute to this hypercoagulable state in AAV. ANCA can induce the generation of neutrophil extracellular traps (NETs). In this study, the NETs-dependent generation of mCRP from pCRP and the influences of mCRP on the activation of coagulation system and inflammatory response in AAV were investigated. RESULTS: NETs were induced after TNF-α primed neutrophils were incubated with ANCA-containing IgG. After ANCA-induced netting neutrophils were incubated statically with platelet-rich plasma (PRP) containing mCRP (60 µg/mL), the proportion of platelets expressing CD62p increased significantly, while no increased CD62p expression of platelets was observed after static incubation with PRP containing pCRP (60 µg/mL). Under flow conditions, perfusing immobilized ANCA-induced netting neutrophils with pCRP-containing PRP caused platelets activation and mCRP deposition. The newly generated mCRP induced platelets activation on ANCA-induced netting neutrophils, enhanced D-dimer formation, and enhanced high mobility group box 1 secretion by platelets. CONCLUSIONS: Under flow conditions, ANCA-induced netting neutrophils can activate platelets and then prompt the formation of mCRP on activated platelets. Then the newly generated mCRP can further enhance the activation of platelets, the process of thrombogenesis, and the inflammatory response. So the high level of circulating pCRP is not only a sensitive marker for judging the disease activity, but also a participant in the pathophysiology of AAV.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/metabolismo , Proteína C-Reactiva/metabolismo , Neutrófilos/inmunología , Multimerización de Proteína , Tromboembolia Venosa/sangre , Coagulación Sanguínea/inmunología , Células Cultivadas , Trampas Extracelulares , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Proteínas HMGB/metabolismo , Hemodinámica , Humanos , Inflamación/inmunología , Selectina-P/metabolismo , Activación Plaquetaria , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: IgA nephropathy (IgAN) may progress to renal failure for some patients without any clinical risk factors and it is not unusual to find severe pathologic damage in clinically mild IgAN. We therefore investigated whether urinary kidney injury molecule-1 (KIM-1) was related to pathologic involvement in clinically mild IgAN. METHODS: Urinary KIM-1/creatinine of 51 IgAN patients with normotension, normal renal function and proteinuria < 1.0 g/24 h were tested. Relationships between urinary KIM-1 and pathologic features were analyzed. RESULTS: Eighteen of the 51 patients had elevated urinary KIM-1. The tubular atrophy/interstitial fibrosis was more severe in patients with elevated urinary KIM-1 than that in patients with normal urinary KIM-1 (T0/T1/T2, 13/5/0 vs. 33/0/0, P = 0.004). Proportion of glomeruli containing cresecents was higher in patients with elevated urinary KIM-1 than that in patients with normal urinary KIM-1 (50% vs. 18%, P = 0.026). Urinary KIM-1 correlated with the proportion of total crescents (R = 0.303, p = 0.031) and fibrous crescents (R = 0.456, p = 0.001), but did not correlate with the proportion of cellular crescents or fibrocellular crescents. Although the proportion of vascular lesions was higher in patients with elevated urinary KIM-1 (44.4%) than that in patients with normal urinary KIM-1 (18.1%), the difference was not significant (p = 0.057). There was no difference of the response to treatment between patients with and without elevated urinary KIM-1 during a short-term follow-up. CONCLUSIONS: Urinary KIM-1 is a reflection of tubularinstitial injury. For patients with clinically mild IgAN, high urinary KIM-1 is related to relatively severe pathologic involvement on renal biopsy.