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PURPOSE: To assess the impact of incorporating internet-based resources and popular science workshops on self-care management among hemodialysis patients with arteriovenous fistula. DESIGN: A randomized controlled trial involving 110 hemodialysis patients with arteriovenous fistula, randomly assigned to either the experimental or control group. METHODS: The experimental group received self-management training utilizing internet resources and interactive workshops, while the control group received conventional health education methods. After the intervention, the self-management proficiency of both groups was assessed, including comprehension of arteriovenous fistula-related information, satisfaction levels, self-care abilities, engagement in functional exercises, quality of life, and other relevant factors. FINDINGS: Patients in the experimental group exhibited significantly greater proficiency in arteriovenous fistula self-management knowledge, higher levels of patient satisfaction, enhanced self-management abilities, improved functional exercise performance, and better overall quality of life compared to those in the control group (p < 0.05). CONCLUSIONS: The combination of internet resources and popular science workshops presents a novel and promising approach for educating and promoting self-care management among hemodialysis patients with arteriovenous fistula. This method holds potential for widespread dissemination and implementation in science education. CLINICAL EVIDENCE: The study demonstrates the tangible benefits of integrating internet-based resources and popular science workshops into self-management training for arteriovenous fistula among hemodialysis patients, as evidenced by improved knowledge, satisfaction, abilities, exercise performance, and quality of life in the experimental group compared to the control group.
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OBJECTIVE: To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. METHODS: The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. RESULTS: The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OSï¼P ï¼0.05ï¼. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. CONCLUSION: The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfócitos T CD4-Positivos , Linfoma Folicular , Rituximab , Humanos , Cloridrato de Bendamustina/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Doxorrubicina/administração & dosagem , Ciclofosfamida , Prednisona/administração & dosagem , Adulto , Prognóstico , Infecções , Resultado do Tratamento , VincristinaRESUMO
Spermatogenic cell heterogeneity is determined by the complex process of spermatogenesis differentiation. However, effectively revealing the regulatory mechanisms underlying mammalian spermatogenic cell development and differentiation via traditional methods is difficult. Advances in technology have led to the emergence of many single-cell transcriptome sequencing protocols, which have partially addressed these challenges. In this review, we detail the principles of 10x Genomics technology and summarize the methods for downstream analysis of single-cell transcriptome sequencing data. Furthermore, we explore the role of single-cell transcriptome sequencing in revealing the heterogeneity of testicular ecological niche cells, delineating the establishment and disruption of testicular immune homeostasis during human spermatogenesis, investigating abnormal spermatogenesis in humans, and, ultimately, elucidating the molecular evolution of mammalian spermatogenesis.
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Evolução Molecular , Análise de Sequência de RNA , Análise de Célula Única , Espermatogênese , Espermatogênese/genética , Animais , Análise de Célula Única/métodos , Masculino , Análise de Sequência de RNA/métodos , Humanos , Transcriptoma , TestículoRESUMO
Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.
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The significance of point-of-care testing (POCT) in early clinical diagnosis and personalized patient care is increasingly recognized as a crucial tool in reducing disease outbreaks and improving patient survival rates. Within the realm of POCT, biosensors utilizing magnetic nanoparticles (MNPs) have emerged as a subject of substantial interest. This review aims to provide a comprehensive evaluation of the current landscape of POCT, emphasizing its growing significance within clinical practice. Subsequently, the current status of the combination of MNPs in the Biological detection has been presented. Furthermore, it delves into the specific domain of MNP-based biosensors, assessing their potential impact on POCT. By combining existing research and spotlighting pivotal discoveries, this review enhances our comprehension of the advancements and promising prospects offered by MNP-based biosensors in the context of POCT. It seeks to facilitate informed decision-making among healthcare professionals and researchers while also promoting further exploration in this promising field of study.
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BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.
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Glucuronosiltransferase , Fígado , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Fígado/metabolismoRESUMO
Chronic graft-versus-host disease (cGVHD) is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation, with the incidence of 30%-70%. Unlike acute GVHD, cGVHD involves a large number of immune cells and cytokines in addition to T cell, which is activated abnormally by the donor, and cytokine storms, which characterized by infiltration of donor lymphocytes and damage to host target organ. Recent studies have further made progress in targeting related immune cells and cytokines. In this review, the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/terapia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Crônica , Citocinas/metabolismo , Imunidade Inata , Transplante Homólogo , Linfócitos T/imunologia , Imunidade Adaptativa , Síndrome de Bronquiolite ObliteranteRESUMO
Conventional two-dimensional (2D) cell culture techniques may undergo modifications in the future, as life scientists have widely acknowledged the ability of three-dimensional (3D) in vitro culture systems to accurately simulate in vivo biology. In recent years, researchers have discovered that microgravity devices can address many challenges associated with 3D cell culture. Stem cells, being pluripotent cells, are regarded as a promising resource for regenerative medicine. Recent studies have demonstrated that 3D culture in microgravity devices can effectively guide stem cells towards differentiation and facilitate the formation of functional tissue, thereby exhibiting advantages within the field of tissue engineering and regenerative medicine. Furthermore, We delineate the impact of microgravity on the biological behavior of various types of stem cells, while elucidating the underlying mechanisms governing these alterations. These findings offer exciting prospects for diverse applications.
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Medicina Regenerativa , Células-Tronco , Engenharia Tecidual , Ausência de Peso , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Humanos , Células-Tronco/citologia , Células-Tronco/fisiologia , Diferenciação Celular , Animais , Técnicas de Cultura de Células em Três Dimensões/métodos , Técnicas de Cultura de Células/métodosRESUMO
PURPOSE: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis, whether a causal relationship exists, and provides some evidence of causality. METHODS: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS). The authors used inverse variable weighting (IVW) as the primary analysis method. In addition, the authors simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. RESULTS: The results of the IVW method of MR analysis showed that 8 immunocyte phenotypes were positively associated with osteonecrosis [ P <0.05, odds ratio (OR) > 1]; 18 immunocyte phenotypes were negatively associated with osteonecrosis ( P <0.05, OR<1), none of which were heterogeneous or horizontally pleiotropic ( P > 0.05) or reverse causality. In addition to this, in reverse MR, osteonecrosis was positively associated with 10 additional immunocyte phenotypes ( P <0.05, OR > 1) and negatively associated with 14 immunocyte phenotypes ( P <0.05, OR<1). And none of them had heterogeneity and horizontal pleiotropy ( P > 0.05) or reverse causality. CONCLUSIONS: The authors demonstrated a complex causal relationship between multiple immune phenotypes and osteonecrosis through a comprehensive two-way, two-sample MR analysis, highlighting the complex pattern of interactions between the immune system and osteonecrosis.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteonecrose , Fenótipo , Humanos , Osteonecrose/genética , Osteonecrose/imunologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.
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Ferro , Neoplasias , Humanos , Morte Celular , Ferro/metabolismo , Ferritinas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Lisossomos/metabolismoRESUMO
Cancer patients are at high risk of malnutrition, which can lead to adverse health outcomes such as prolonged hospitalization, increased complications, and increased mortality. Accurate and timely nutritional assessment plays a critical role in effectively managing malnutrition in these patients. However, while many tools exist to assess malnutrition, there is no universally accepted standard. Although different tools have their own strengths and limitations, there is a lack of narrative reviews on nutritional assessment tools for cancer patients. To address this knowledge gap, we conducted a non-systematic literature search using PubMed, Embase, Web of Science, and the Cochrane Library from their inception until May 2023. A total of 90 studies met our selection criteria and were included in our narrative review. We evaluated the applications, strengths, and limitations of 4 commonly used nutritional assessment tools for cancer patients: the Subjective Global Assessment (SGA), Patient-Generated Subjective Global Assessment (PG-SGA), Mini Nutritional Assessment (MNA), and Global Leadership Initiative on Malnutrition (GLIM). Our findings revealed that malnutrition was associated with adverse health outcomes. Each of these 4 tools has its applications, strengths, and limitations. Our findings provide medical staff with a foundation for choosing the optimal tool to rapidly and accurately assess malnutrition in cancer patients. It is essential for medical staff to be familiar with these common tools to ensure effective nutritional management of cancer patients.
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Desnutrição , Neoplasias , Avaliação Nutricional , Estado Nutricional , Humanos , Neoplasias/complicações , Desnutrição/diagnósticoRESUMO
Microgravity is a primary challenge that need to overcome, when human travel to space. Our study provided evidence that Kupffer cells (KCs) are sensitive to simulated microgravity (SMG), and no similar research report has been found in the literature. Using transcriptome sequencing technology, it was showed that 631 genes were upregulated and 801 genes were downregulated in KCs after treatment under SMG for 3 days. The GO analysis indicated that the proliferation of KCs was affected when exposed to SMG for 3 days. CCK-8 assay confirmed that the proliferation of KCs was inhibited in the third day under the environment of SMG. Furthermore, we identified 8 key genes that affect the proliferation of KCs and predicted 2 transcription factors (TFs) that regulate the 8 key genes. Significantly, we found that microgravity could affect the expression of LMO2 and EZH2 to reduce the transcription of Racgap1, Ccna2, Nek2, Aurka, Plk1, Haus4, Cdc20, Bub1b, which resulting in the reduction in KCs proliferation. These finding suggested that the inhibition of KCs proliferation under microgravity may influence the homeostasis of liver, and LMO2 and EZH2 can be the targets in management of KCs' disturbance in the future practice of space medicine.
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Transcriptoma , Ausência de Peso , Humanos , Células de Kupffer , Proliferação de Células , Simulação de Ausência de Peso , Proteína Potenciadora do Homólogo 2 de Zeste , Proteínas Proto-Oncogênicas , Proteínas Adaptadoras de Transdução de Sinal , Proteínas com Domínio LIM/genéticaRESUMO
Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mø@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mø@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies.
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Neoplasias , Camundongos , Animais , Neoplasias/patologia , Macrófagos , Transferência Adotiva , Bactérias , Microambiente Tumoral , ImunoterapiaRESUMO
Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.
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Dor Crônica , Habenula , Camundongos , Animais , Área Tegmentar Ventral/metabolismo , Habenula/metabolismo , Depressão , Ácido gama-Aminobutírico/metabolismoRESUMO
A critical challenge of existing cancer vaccines is to orchestrate the demands of antigen-enriched furnishment and optimal antigen-presentation functionality within antigen-presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)-tumor hybrid cell-derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT-Exo-STING) for maximized tumor-specific T-cell immunity. These chimeric carriers are furnished with broad-spectrum antigen complexes to elicit a robust T-cell-mediated inflammatory program through direct self-presentation and indirect DC-to-T immunostimulatory pathway. This chimeric exosome-assisted delivery strategy possesses the merits versus off-the-shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue-homing capacity, even across the intractable blood-brain barrier (BBB), and the desired cytosolic entry for enhanced STING-activating signaling. The improved antigen-presentation performance with this nanovaccine-driven STING activation further enhances tumor-specific T-cell immunoresponse. Thus, DT-Exo-STING reverses immunosuppressive glioblastoma microenvironments to pro-inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT-Exo-STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post-operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm.
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Exossomos , Glioblastoma , Humanos , Glioblastoma/terapia , Linfócitos T , Apresentação de Antígeno , Imunoterapia/métodos , Microambiente TumoralRESUMO
Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.
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Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.
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Regulação Neoplásica da Expressão Gênica , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , ÍntronsRESUMO
OBJECTIVE: This study aimed to examine whether diabetes mellitus is causally associated with osteonecrosis. METHOD: Using publicly accessible genome-wide association study statistics, a bidirectional two-sample Mendelian randomization analysis was carried out. In order to determine whether diabetes has a causal effect on osteonecrosis and whether osteonecrosis has a causal effect on diabetes, we extracted six date on diabetes in Europeans from IEU OpenGWAS and GWAS Catalogue and osteonecrosis in Europeans from FinnGen. We then evaluated the data using inverse variance weighting, MR-Egger regression, weighted median, weighted mode, and simple mode. The results' stability and dependability were then evaluated using sensitivity analysis and heterogeneity analysis. Finally, meta-analysis is used to further confirm if there is a relationship between diabetes and osteonecrosis. RESULTS: When diabetes was used as an exposure factor, MR-Egger regression showed that directional fold product was unlikely to bias the results. Cochran's Q test showed only minor heterogeneity in a few data sets. Multidirectional tests Egger-intercept, MR-PRESSO and funnel plots for most data did not show multidirectional and asymmetry at the gene level. Most of the IVW results showed no causal relationship between diabetes mellitus and osteonecrosis. The results of meta-analysis of IVW methods further confirmed the absence of a causal relationship. Inverse MR analysis also showed no causal relationship between osteonecrosis and diabetes. CONCLUSION: Results of bidirectional MR analysis show no evidence of causal relationship between diabetes and osteonecrosis.
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Diabetes Mellitus , Osteonecrose , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Diabetes Mellitus/genética , NonoxinolRESUMO
A large number of studies have demonstrated that mRNA vaccine has been characterized as a technique with good safety, strong immunogenicity and high developmental potential, which makes it have broad prospects in immunotherapy. In recent years, the stability and in vivo delivery efficiency of mRNA vaccines have been largely addressed by the progresses in mRNA engineering and delivery innovation. And some mRNA vaccines are now clinical approved or in preclinical trials. Here, we summarize current knowledge on the research advances, technology, and application in major infectious diseases in humans and animals of mRNA vaccines, with the aim to provide a reference for improving the development of novel mRNA vaccines.