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OBJECTIVE: To investigate the factors affecting the efficacy of ultrasound (US)-guided percutaneous microwave ablation (PMWA) for adenomyosis with abnormal uterine bleeding (AUB-A). METHODS: Baseline data of patients with AUB-A who underwent US-guided PMWA treatment between October 2020 and October 2021, including demography characteristics, laboratory and imaging examination results were retrospectively analyzed. 3D reconstruction of magnetic resonance imaging (MRI) was applied to quantitatively assess the local treatment responses, including ratio of non-perfusion volume to adenomyosis volume (NPVr), ablation rate of the endometrial-myometrial junction (EMJ), and surface area (SA) of the ablated part of the EMJ. Patients were followed up at 3, 6, and 12 months after treatment, and divided into two groups: group with complete relief (CR), and group with partial relief (PR) or no relief (NR). Data were compared between them. RESULTS: Thirty-one patients were analyzed with a mean age of 38.7 ± 6.8 years (range: 24-48): 48.4% (15/31), 63.3% (19/30), and 65.5% (19/29) achieved CR at 3, 6, and 12 months, respectively. In univariate analysis, compared with the PR/NR group, serum CA125 levels were significantly lower in CR group at 3 months, while ablation rates of EMJ and SA of the ablated part of the EMJ were significantly higher at the three time points. Other baseline characteristics and NPVr did not differ between the two groups. CONCLUSION: Baseline CA125 and ablation rate of the EMJ and SA of the ablated part of the EMJ are associated with the outcome of AUB-A patients after US-guided PMWA treatment.
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Adenomiose , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adenomiose/complicações , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Ultrassonografia de Intervenção , Hemorragia UterinaRESUMO
PURPOSE: To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery. METHODS: Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method. RESULTS: The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice. CONCLUSIONS: This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.
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Antineoplásicos Fitogênicos/administração & dosagem , Portadores de Fármacos/química , Hidrogéis/química , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacocinética , Linhagem Celular Tumoral , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Ácido Hialurônico/química , Camundongos , Nanopartículas/química , Neoplasias/patologia , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Laryngeal squamous-cell carcinoma (LSCC) is the second most common malignant tumor of head and neck squamous cell carcinoma. The study was aimed to identify key long non-coding RNAs (lncRNAs) biomarkers for LSCC. METHODS: Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between LSCC and adjacent tissues were obtained based on The Cancer Genome Atlas. DElncRNA-DEmRNAs co-expression and DElncRNA-nearby-target DEmRNA interaction networks were constructed. Receiver operating characteristic and survival analysis were performed. A published dataset were as used to validate the result of bioinformatics analysis. RESULTS: We obtained 1103 DEmRNAs and 306 DElncRNAs between LSCC and adjacent tissues. A total of 338 DElncRNA-DEmRNA co-expression pairs and 229 DElncRNA-nearby-target DEmRNA pairs were obtained. Ten DElncRNAs and six DEmRNAs has great diagnostic value for LSCC. HOXB9 has potential prognostic value for LSCC. The results of GSE84957 validation were generally consistent with our results. CONCLUSION: Our study provided clues for understanding the mechanism and developing potential biomarkers for LSCC.
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Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Bases de Dados Factuais , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Neoplasias Laríngeas/mortalidade , Prognóstico , Reprodutibilidade dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most malignant head and neck carcinomas with unique epidemiological features. In this study, we aimed to identify the novel NPC-related genes and biological pathways, shedding light on the potential molecular mechanisms of NPC. METHODS: Based on Gene Expression Omnibus (GEO) database, an integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in NPC compared to normal control. The genes which were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction (PPI) network construction were used to uncover biological functions of DEGs. RESULTS: Two DNA methylation and five gene expression datasets were incorporated. A total of 1074 genes were up-regulated and 939 genes were down-regulated in NPC were identified. A total of 719 differential methylation CpG sites (DMCs) including 1 hypermethylated sites and 718 hypomethylated sites were identified. Among which, 11 genes were both DEGs and DMGs in NPC. Pathways in cancer, p53 signaling pathway and Epstein-Barr virus infection were three pathways significantly enriched pathways in DEmRNAs of NPC. The PPI network of top 50 DEGs were consisted of 191 nodes and 191 edges. CONCLUSIONS: Our study was helpful to elucidate the underlying mechanism of NPC and provide clues for therapeutic methods.
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Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo , Infecções por Vírus Epstein-Barr/genética , Redes Reguladoras de Genes/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Mapas de Interação de Proteínas , Transdução de SinaisRESUMO
Bats can be divided into frugivory, nectarivory, insectivory, and sanguivory based on their diets, and are therefore ideal wild animal models to study the relationship between diets and intestinal microflora. Early studies of bat gut bacteria showed that the diversity and structure of intestinal bacterial communities in bats are closely related to dietary changes. Worthy of note, intestinal microbes are composed of bacteria, fungi, protozoa, and archaea. Although the number of gut fungi is much lower than that of gut bacteria, they also play an important role in maintaining the host homeostasis. However, there are still few reports on the relationship between the gut mycobiota and the dietary habits of the host. In addition, bats have also been shown to naturally transmit pathogenic viruses and bacteria through their feces and saliva, but fungal infections from bat are less studied. Here, we used high-throughput sequencing of bacterial 16S and eukaryotic 18S rRNA genes in the V4 and V9 regions to characterize fecal bacterial and fungal microbiota in phytophagous and insectivorous bats in South China. The results show that the gut microbiota in bats were dominated by bacterial phyla Proteobacteria, Firmicutes, Tenericutes and Bacteroidetes, and fungal phyla Ascomycota and Basidiomycota. There was a significant difference in the diversity of bacterial and fungal microbiota between the groups, in addition to specific bacteria and fungi populations on each of them. Of note, the number of fungi in the feces of herbivorous bats is relatively higher. Most of these fungi are foodborne and are also pathogens of humans and other animals. Thus, bats are natural carriers of fungal pathogens. The current study expands the understanding of the bat gut bacterial and fungal mycobiota and provides further insight into the transmission of fungal pathogens.
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Ração Animal , Quirópteros , Fezes/microbiologia , Microbiota , Animais , Bactérias/classificação , Bactérias/genética , Biodiversidade , China , Feminino , Fungos/classificação , Fungos/genética , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 18S/genéticaRESUMO
The tumor vascular barrier and tumor stroma barrier become the two main obstacles in the in vivo delivery of nanomedicines. In this study, to overcome the two barriers, we used iNGR, a tumor-penetrating peptide, to modify the liposomes to increase their accumulation and penetration in tumor tissues. First, iNGR-modified sterically stabilized liposomes (iNGR-SSL) were prepared, which showed vesicle sizes of about 100 nm and narrow size distribution. The uptake of iNGR-SSL by U87MG cells and HUVECs were significantly more than that of unmodified liposome. The in vivo imaging study demonstrated that iNGR modification remarkably increased the accumulation of the liposome in orthotopic tumor tissues of animal model. The immunofluorescence staining analysis proved that iNGR-SSL could penetrate through tumor blood vessels and into the deep tumor tissues. The cytotoxicity of iNGR-modified doxorubicin-loaded liposomes (iNGR-SSL/DOX) on U87MG and HUVECs cells in vitro was significantly enhanced than that of unmodified doxorubicin-loaded liposomes (SSL/DOX). The iNGR-SSL/DOX also showed comparatively (p < 0.05) stronger cytotoxicity on tumor than SSL/DOX, which should be resulted from the increased tumor accumulation and penetration mediated by iNGR. This study proved that iNGR peptide modification might be an effective method to enhance the tumor penetrating ability of liposomes in tumor tissue and their antitumor effect.
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Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Glioblastoma/tratamento farmacológico , Lipossomos/química , Oligopeptídeos/química , Linhagem Celular Tumoral , Citometria de Fluxo , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana , Humanos , Microscopia Eletrônica de TransmissãoRESUMO
The use of exogenous carbon monoxide releasing molecules (CORMs) provides promise for clinical application; however, the hazard potential of CORMs in vivo remains poorly understood. The developmental toxicity of CORM-3 was investigated by exposure to concentrations ranging from 6.25 to 400 µmol/L during 4-144 h post fertilization. Toxicity endpoints of mortality, spontaneous movement, heart rate, hatching rate, malformation, body length, and larval behavior were measured. CORM-3 disrupted the progression of zebrafish larval development at concentrations exceeding 50 µmol/L, resulting in embryonic developmental toxicity.
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Cardiotônicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Peixe-Zebra/embriologia , Animais , Monóxido de Carbono/farmacologia , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Peixe-Zebra/metabolismoRESUMO
Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves' turtle (Chinemys reevesii) have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH) cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp), comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS) of the turtle's GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO) cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH) gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves' turtle might correlate with downregulated gene expression.
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Clonagem Molecular/métodos , Hormônio do Crescimento/genética , Íntrons , Proteínas de Répteis/genética , Tartarugas/metabolismo , Animais , Células CHO , Linhagem Celular , Embrião de Galinha , Cricetinae , Cricetulus , Regulação da Expressão Gênica , Células HEK293 , Humanos , Filogenia , Ratos , Especificidade da Espécie , Tartarugas/genéticaRESUMO
The effects of introns, especially the first intron, on the regulation of gene expression remains unclear. Therefore, the objective of the present study was to investigate the transcriptional regulatory function of intron 1 on the chicken growth hormone (cGH) gene in the rat pituitary tumor cell line (GH4-C1). Transient transfection using first-intron-inserted cGH complete coding sequences (CDSs) and non-intron-inserted cGH CDS plasmids, quantitative RT-PCR (qRT-PCR) and western blot assays were used to detect the expression of cGH. The reporter gene assay was also used to investigate the effect of a series of fragments in the first intron of cGH on gene expression in GH4-C1. All of the results revealed that a 200-bp fragment located in the +485/+684 region of intron 1 was essential for repressing the expression of cGH. Further informatics analysis showed that there was a cluster of 13 transcriptional factor binding sites (TFBSs) in the +485/+684 region of the cGH intron 1. Disruption of a glucocorticoid response-like element (the 19-nucleotide sequence 5'-AGGCTTGACAGTGACCTCC-3') containing a T-box motif (TGACCT) located within this DNA fragment increased the expression of the reporter gene in GH4-C1. In addition, an electrophoretic mobility shift assay (EMSA) revealed a glucocorticoid receptor (GR) protein of rat binding to the glucocorticoid response-like element. Together, these results indicate that there is a negative glucocorticoid response-like element (nGRE) located in the +591/+609 region within the first intron of cGH, which is essential for the down-regulation of cGH expression.
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Regulação da Expressão Gênica , Hormônio do Crescimento/genética , Íntrons , Receptores de Glucocorticoides/genética , Elementos de Resposta , Somatotrofos/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Galinhas , Éxons , Glucocorticoides/farmacologia , Hormônio do Crescimento/metabolismo , Humanos , Fases de Leitura Aberta , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Ratos , Receptores de Glucocorticoides/metabolismo , Somatotrofos/efeitos dos fármacos , Somatotrofos/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Transfecção , TransgenesRESUMO
OBJECTIVE: To evaluate the bio-safety of graphene quantum dots (GQDs), we studied its effects on the embryonic development of zebrafish. METHODS: In vivo, biodistribution and the developmental toxicity of GQDs were investigated in embryonic zebrafish at exposure concentrations ranging from 12.5-200 µg/mL for 4-96 h post-fertilization (hpf). The mortality, hatch rate, malformation, heart rate, GQDs uptake, spontaneous movement, and larval behavior were examined. RESULTS: The fluorescence of GQDs was mainly localized in the intestines and heart. As the exposure concentration increased, the hatch and heart rate decreased, accompanied by an increase in mortality. Exposure to a high level of GQDs (200 µg/mL) resulted in various embryonic malformations including pericardial edema, vitelline cyst, bent spine, and bent tail. The spontaneous movement significantly decreased after exposure to GQDs at concentrations of 50, 100, and 200 µg/mL. The larval behavior testing (visible light test) showed that the total swimming distance and speed decreased dose-dependently. Embryos exposed to 12.5 µg/mL showed hyperactivity while exposure to higher concentrations (25, 50, 100, and 200 µg/mL) caused remarkable hypoactivity in the light-dark test. CONCLUSION: Low concentrations of GQDs were relatively non-toxic. However, GQDs disrupt the progression of embryonic development at concentrations exceeding 50 µg/mL.
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Embrião não Mamífero/efeitos dos fármacos , Grafite/toxicidade , Pontos Quânticos/toxicidade , Peixe-Zebra/embriologia , Animais , Comportamento Animal , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Grafite/administração & dosagem , Grafite/química , Larva/efeitos dos fármacos , Pontos Quânticos/administração & dosagem , Pontos Quânticos/químicaRESUMO
This study was undertaken to investigate the synergistic effects of methylprednisolone (MP) administration and transplantation of amniotic membrane mesenchymal stem cells (AM-MSCs) following T11 spinal cord clip compressive injury in rats. The combination treatment with MP (50 mg/kg) and delayed transplantation of AM-MSCs after rat spinal cord injury, significantly reduced (1) myeloperoxidase activity, (2) the proinflammatory cytokines: tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-17, interferon-γ and (3) the cell apoptosis [terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) staining, and caspase-3, Bax and Bcl-2 expressions]; increased: (1) the levels of the anti-inflammatory cytokines (IL-10 and transforming growth factor-ß1) and (2) the survival rate of AM-MSCs in the injury site. The combination therapy significantly ameliorated the recovery of limb function (evaluated by Basso, Beattie and Bresnahan score). Taken together, our results demonstrate that MP in combination with AM-MSCs transplantation is a potential strategy for reducing secondary damage and promoting functional recovery following spinal cord injury.
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Âmnio/transplante , Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais/métodos , Metilprednisolona/administração & dosagem , Traumatismos da Medula Espinal/terapia , Âmnio/citologia , Animais , Apoptose/fisiologia , Terapia Combinada/métodos , Feminino , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
AIM: This study aims to investigate the comparative effects of the team-based learning methodology against conventional teaching practices on the educational outcomes of nursing students. BACKGROUND: The team-based learning instructional strategy represents a significant pedagogical innovation in nursing education. This approach initiates with foundational knowledge, uses predetermined questions for guidance and adopts both intra-group and inter-group dialogues as mechanisms of learning. It accentuates the creativity and pragmatism of students, thereby enhancing their communicative and collaborative competencies. Although this methodology has garnered recognition among nursing education practitioners in recent years, consensus on its pedagogical efficacy remains elusive. DESIGN: The investigation was structured as a systematic review and meta-analysis. METHODS: In August 2024, a comprehensive search was executed across several databases, including PubMed, Embase, The Cochrane Library, Web of Science, OVID, Scoups and CNKI, to identify studies that satisfied predetermined criteria for inclusion and exclusion. The process entailed screening studies against the criteria, extracting pertinent data and assessing the quality of the studies prior to performing a meta-analysis. The review protocol of this study was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024513238). RESULTS: From an initial pool of 3191 articles, 29 were selected for meta-analysis following a meticulous screening process. Findings indicated that the team-based learning methodology significantly outperformed traditional teaching approaches in enhancing nursing students' final examination scores and practical skills. Moreover, it was observed to bolster self-directed learning and critical thinking capabilities among students. Nonetheless, the impact of team-based learning on improving problem-solving skills and communication skills warrants additional verification. CONCLUSION: The investigation concludes that the team-based learning approach is efficacious in enriching nursing students' theoretical and practical proficiencies, alongside promoting self-directed learning and critical thinking. However, given the constrained number and quality of the studies included, these findings necessitate corroboration through further high-caliber research.
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Nine Pezizomycotina strains were isolated from rotten dead branches and leaves collected from Guizhou Province. To obtain their accurate taxonomic placement, we provided the morphological characteristics of conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, SSU, LSU and tub2 gene sequences, confirmed our strains represented three novel species, Peglioniafalcata, Neoascochytapseudofusiformis and Neomicrosphaeropsiscylindrica. Peglioniafalcata produced falcate conidia and Neoa.pseudofusiformis generated fusiform conidia, while Neom.cylindrica possessed cylindrical conidia. The phylogenetic results also supported them as novel taxa. All the new species in the present study were found as saprophytic on forest litter with high rainfall, which suggest they may have a certain effect on nutrient decomposition and redistribution in forest ecosystems. Thus, it opened a way for further research on related ecological roles and their application production.
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OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .
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BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.
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Metabolismo Energético , Leptina , Obesidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adiponectina/genética , Adiponectina/metabolismo , Estudos de Casos e Controles , Metabolismo Energético/genética , Leptina/sangue , Leptina/genética , Leptina/metabolismo , Mutação com Perda de Função , Proteínas de Membrana/genética , Obesidade/genética , Obesidade/metabolismo , Sobrepeso/genética , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismoAssuntos
Lobectomia Temporal Anterior/efeitos adversos , Epilepsia/complicações , Meningioma/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Paralisia Pseudobulbar/etiologia , Neoplasias da Base do Crânio/cirurgia , Epilepsia/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Meningioma/complicações , Meningioma/diagnóstico por imagem , Neoplasias da Base do Crânio/complicações , Neoplasias da Base do Crânio/diagnóstico por imagemRESUMO
Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear. Methods: Cdk5 kinase activity was measured by [γ-32P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa. Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression. Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.
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OBJECTIVE: To evaluate the efficacy and safety of percutaneous microwave ablation (PMWA) for treating adenomyosis in the posterior uterine wall. METHODS: Thirty-six patients with symptomatic adenomyosis in the posterior uterine wall who had been subjected to PMWA were retrospectively enrolled in this study. 20 patients who had no ideal transabdominal puncture path due to the retroverted or retroflexed uterine position were treated with PMWA combined with Yu's uteropexy (Group 1). The other 16 patients were treated with PMWA only (Group 2). The non-perfused volume (NPV) ratio, symptomatic relief rate, recurrence rate, changes in clinical symptom scores, economic cost, and complications were compared. RESULTS: The mean NPV ratio for the 36 patients was 90.2±18.3%, and the percentage of patients who obtained complete relief of dysmenorrhea and menorrhagia was 81.3% (26/32), and 69.6% (16/23) respectively. The recurrence rate was 11.1% (4/36). No major complication was observed. Minor complications included lower abdominal pain, fever, vaginal discharge, nausea, and/or vomiting after ablation, with incidences of 55.6%, 41.7%, 47.2%, and 19.4% respectively. Subgroup analysis showed no significant difference in the median value of NPV ratio, symptomatic relief rate of dysmenorrhea and menorrhagia, changes in clinical symptom scores, recurrence rate and economic cost between the two groups (all p > 0.05). CONCLUSION: PMWA is an effective and safe treatment for adenomyosis in the posterior uterine wall. ADVANCES IN KNOWLEDGE: This study focused on the ultrasound-guided PMWA treatment for adenomyosis in the posterior uterine wall. Yu's uteropexy, a new ancillary technique allowing safe PMWA for deep posterior uterine wall lesions in retroverted uterus, expanded the indications of PMWA for symptomatic adenomyosis.
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Adenomiose , Menorragia , Feminino , Humanos , Adenomiose/cirurgia , Adenomiose/patologia , Dismenorreia , Estudos Retrospectivos , Micro-Ondas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia. However, an alternative treatment approach is needed for patients who cannot tolerate general anesthesia. We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia. CASE SUMMARY: A 46-year-old female suffered from abnormal uterine bleeding, severe anemia, and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma. She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency. A new individualized combined treatment, consisting uterine artery embolization (UAE), percutaneous microwave ablation (PMWA) of the pedicle and the endometrium, and transvaginal removal of the leiomyoma by twisting, was performed. The lesion was completely removed successfully under local anesthesia without any major complications. The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life. CONCLUSION: UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.
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The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization. However, the in vivo distribution and release of siRNA still cannot be effectively monitored. In this study, based on the fluorescence resonance energy transfer (FRET) principle, a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds (Au-DR-siRNA), which were then wrapped with lipid nanoparticles (LNPs) for monitoring the release behaviour of siRNA in vivo. The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells, the fluorescence of Cy5 would change from quenched state to activated state, showing the location and time of siRNA release. Besides, the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds. Therefore, this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA, but also a siRNA delivery system for treating and diagnosing tumors.