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PURPOSE: The purpose of this study is to retrospect and summarize clinical efficiency and experience of the free superficial palmar branch of radial artery (SPBRA) flap for soft-tissue reconstruction in distal digital injury. METHOD: 13 patients with soft-tissue defect of finger, reconstructed by the free superficial palmar branch of radial artery (SPBRA) flap in our department from January 2020 to January 2022, were reviewed. After 6-12 months of follow-up, evaluated the treatment effect of the fingers reconstructed by SPBRA flap. RESULTS: All the flaps in our series application were survival uneventful, and all the donor sites were closed primarily without complications or obvious scarring. The flaps were soft in texture and satisfactory in appearance and function. The flaps with the median nerve palmar cutaneous branch had a good sensation recovery. Measurement of two-point discrimination (TPD) ranged from 6 to 10 mm. All patients were satisfied with the aesthetic appearance. According to the Evaluation Trial Standards of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, the results were graded as excellent in 11 cases and good in 2 cases. CONCLUSION: The SPBRA perforator flap has the advantages of simple operation, soft texture, good appearance and function, and is credible and useful for reconstructing various finger injuries.
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Traumatismos de los Dedos , Procedimientos de Cirugía Plástica , Arteria Radial , Traumatismos de los Tejidos Blandos , Humanos , Arteria Radial/trasplante , Masculino , Procedimientos de Cirugía Plástica/métodos , Adulto , Persona de Mediana Edad , Traumatismos de los Dedos/cirugía , Femenino , Traumatismos de los Tejidos Blandos/cirugía , Estudios Retrospectivos , Colgajo Perforante/irrigación sanguínea , Adulto Joven , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
The short-video application TikTok shows great potential for disseminating health information. We assessed the content, sources, and quality of information in videos related to nonalcoholic fatty liver disease (NAFLD) on TikTok. Our study aims to identify upload sources, content, and characteristic information for NAFLD videos on TikTok and further evaluate factors related to video quality. We investigated the top 100 videos related to NAFLD on TikTok and analyzed the upload sources, content, and characteristics of these videos. Evaluate video quality using the DISCERN tool and Global Quality Score (GQS). In addition, the correlation between video quality and video characteristics is further studied. In terms of video sources, the majority of NAFLD videos on TikTok (85/100, 85%) were posted by doctors, ensuring the professionalism of the content, and among the video content, disease knowledge was the most dominant video content, accounting for 57% (57/100) of all videos, and the average DISCERN and GQS scores of all 100 videos were 39.59 (SD 3.31) and 2.99 (SD 0.95), respectively. DISCERN and GQS data show that videos related to NAFLD do not have high-quality scores on TikTok, mainly fair (68/100, 68%) and moderate (49/100, 49%). In general, the quality of NAFLD video information from professional content and professional sources was higher than that of nonprofessional sources and nonprofessional content, the video quality of general surgeons was better than that of other department physicians, and the video quality of junior physicians was better than that of senior physicians. In terms of video correlation, durations, the number of fans, and the total number of works were negatively correlated with DISCERN scores (Râ <â 0, Pâ <â .05), while likes, comments, collections, shares, and days since upload were not significantly correlated with DISCERN and GQS scores (Pâ >â .05). The medical information on TikTok is not rigorous enough to guide patients to make accurate judgments, platforms should monitor and guide publishers to help promote and disseminate quality content.
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Enfermedad del Hígado Graso no Alcohólico , Grabación en Video , Humanos , Estudios Transversales , Difusión de la Información/métodosRESUMEN
Structural metamorphosis of metal-organic frameworks (MOFs) eliciting highly active metal-hydroxide catalysts has come to the fore lately, with much promise. However, the role of organic ligands leaching into electrolytes during alkaline hydrolysis remains unclear. Here, we elucidate the influence of organic carboxylate anions on a family of Ni or NiFe-based hydroxide type catalysts during the oxygen evolution reaction. After excluding interfering variables, i.e., electrolyte purity, Ohmic loss, and electrolyte pH, the experimental results indicate that adding organic anions to the electrolyte profoundly impacts the redox potential of the Ni species versus with only a negligible effect on the oxygen evolution activities. In-depth studies demonstrate plausible reasons behind those observations and allude to far-reaching implications in controlling electrocatalysis in MOFs, mainly where compositional modularity entails fine-tuning organic anions.
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A 5-year-old neutered female Korean domestic shorthair cat diagnosed with oral squamous cell carcinoma (SCC) presented to the hospital with severe oral purulent discharge, anorexia, and lethargy. Owing to extensive lesions, surgical excision and radiation therapy were not feasible. Instead, prior to metronomic therapy with toceranib, the patient received an intravenous injection of feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) (1 × 106 cells/10 mL of saline) to reduce inflammation. No acute side effects (such as fever, increased respiratory rate, diarrhea, and vomiting) were observed following stem cell therapy. For 6 days, purulent discharge, bleeding, swelling, a bad odor, and crust exfoliation in the tumor area on the face were dramatically reduced. However, the patient exhibited difficulty in voluntarily receiving foods, and weight loss persisted. Starting from the 7th day, purulent discharge, bleeding, and odor at the SCC area worsened again. Toceranib, low-dose NSAIDs (meloxicam, every other day), antibiotics (cefazoline), and gabapentin were administered; however, they were not effective in reducing the pus, bleeding, foul odor, and crust exfoliation at the SCC area. Symptoms of pain, weakness, and weight loss progressed, leading to the choice of euthanasia with the owner's consent approximately 1 month later. This case report reveals that allogeneic fUC-MSCs have a slight short-term effect on purulent discharge, bleeding, odor, and crust exfoliation and may be additional therapy for feline oral SCC.
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H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the GD2 disialoganglioside and chimeric antigen receptor modified T-cells targeting GD2 (GD2-CART) eradicate DMGs in preclinical models. Arm A of the Phase I trial NCT04196413 administered one IV dose of autologous GD2-CART to patients with H3K27M-mutant pontine (DIPG) or spinal (sDMG) diffuse midline glioma at two dose levels (DL1=1e6/kg; DL2=3e6/kg) following lymphodepleting (LD) chemotherapy. Patients with clinical or imaging benefit were eligible for subsequent intracerebroventricular (ICV) GD2-CART infusions (10-30e6 GD2-CART). Primary objectives were manufacturing feasibility, tolerability, and identification of a maximally tolerated dose of IV GD2-CART. Secondary objectives included preliminary assessments of benefit. Thirteen patients enrolled and 11 received IV GD2-CART on study [n=3 DL1(3 DIPG); n=8 DL2(6 DIPG/2 sDMG). GD2-CART manufacturing was successful for all patients. No dose-limiting toxicities (DLTs) occurred on DL1, but three patients experienced DLT on DL2 due to grade 4 cytokine release syndrome (CRS). Nine patients received ICV infusions, which were not associated with DLTs. All patients exhibited tumor inflammation-associated neurotoxicity (TIAN). Four patients demonstrated major volumetric tumor reductions (52%, 54%, 91% and 100%). One patient exhibited a complete response ongoing for >30 months since enrollment. Eight patients demonstrated neurological benefit based upon a protocol-directed Clinical Improvement Score. Sequential IV followed by ICV GD2-CART induced tumor regressions and neurological improvements in patients with DIPG and sDMG. DL1 was established as the maximally tolerated IV GD2-CART dose. Neurotoxicity was safely managed with intensive monitoring and close adherence to a management algorithm.
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The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium.
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Diferenciación Celular , Decidua , Endometrio , Reprogramación Metabólica , Células del Estroma , Animales , Bovinos , Femenino , Humanos , Ratones , Embarazo , Decidua/metabolismo , Decidua/citología , Endometrio/metabolismo , Endometrio/citología , Fibroblastos/metabolismo , Fibroblastos/citología , Células del Estroma/metabolismo , PorcinosRESUMEN
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48-0.85), 0.94 (0.72-1.23), 0.68 (0.50-0.92) and 1.62 (1.24-2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Incidencia , Factores de Riesgo , Inmunoglobulinas/sangre , Anciano , Estudios de CohortesRESUMEN
Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients. Comprehensive profiling of matched PDX and patient samples demonstrates that PDXs closely recapitulate parental tumors. By leveraging multi-lineage models, we reveal that the previously reported genomic disparities of PDX could be mainly attributed to intra-patient spatial heterogeneity instead of substantial model-independent genomic evolution. Moreover, DNA damage response pathway inhibitor (DDRi) screening uncovers heterogeneous responses across models. Prolonged iterative drug exposure recapitulates acquired drug resistance in initially sensitive models. Meanwhile, interrogation of induced drug-resistant (IDR) models reveals that suppressed interferon (IFN) response and activated Wnt/ß-catenin signaling contribute to acquired DDRi drug resistance.
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Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Animales , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Vía de Señalización Wnt/genética , Resistencia a Antineoplásicos/genética , Genómica/métodos , Bancos de Muestras Biológicas , Heterogeneidad Genética , Daño del ADN/genética , Interferones/metabolismo , Interferones/genética , Linaje de la Célula/genéticaRESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. At initial diagnosis, approximately 20% of patients are diagnosed with metastatic CRC (mCRC). Although the APCâAsef interaction is a well-established target for mCRC therapy, the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor. In this study, we identified a novel structural scaffold based on MAI inhibitors, the first-in-class APCâAsef inhibitors we reported previously. ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed, and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound. In addition, the cocrystal structure validated that the two-layer πâπ stacking interactions were essential for inhibitor stabilization in the bound state. Furthermore, in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APCâAsef interaction. These results provide an intrinsic structural basis to further explore drug-like molecules for APCâAsef-mediated CRC therapy.
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Beta diversity patterns along environmental gradients and underlying mechanisms constitute key research inquiries in biogeography. However, ecological processes often also influence the functional traits of biological communities, making the assessment of functional ß-diversity crucial. Ground beetles (Coleoptera: Carabidae) are one of the most species-rich groups in the insect community, displaying strong habitat specificity and morphological differences. In this study, we explored the patterns of taxonomic and functional beta diversity in ground beetle communities along the altitudinal gradient of warm-temperature forests. By partitioning beta diversity into turnover and nestedness components, we evaluated their relationship with spatial distance. Our findings indicate a decline in species and functional trait similarity with increasing elevation and geographic distance. Further analysis attributed both types of beta diversity in carabids to a combination of dispersal limitation and environmental filtering, with elevation and geographic distance emerging as significant factors. Interestingly, forest-type variations were found to have no impact on the beta diversity of these communities. Our study reveals the impact of environmental filtering and dispersal limitation on both taxonomic and functional beta-diversity, shedding light on carabid community assembly in localized warm-temperature forest areas in eastern China.
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Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616-0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P < .001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment.
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Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR - Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.
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Enzima Convertidora de Angiotensina 2 , Antivirales , COVID-19 , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , SARS-CoV-2 , Animales , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/virología , Ratones , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Humanos , Pulmón/virología , Pulmón/patología , Tratamiento Farmacológico de COVID-19 , Queratina-18/genética , Carga Viral , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/farmacología , Técnicas de Sustitución del Gen , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , FemeninoRESUMEN
PURPOSE: The consumption of added sugar has increased rapidly in recent years. Limited knowledge exists regarding the association between added sugar intake and muscle strength, although the latter is a predictor of physical disability in older adults. This study aimed to investigate the association between added sugar intake and longitudinal changes in handgrip strength among middle-aged and elderly Chinese adults. METHODS: This prospective cohort study included 5298 adults aged 40 years and older (62.6% men) from the TCLSIH (Tianjin Chronic Low-grade Systemic Inflammation and Health) cohort study. Added sugar intake was obtained through a frequency questionnaire containing 100 items of food. Handgrip strength is measured annually using a handheld digital dynamometer. Multivariate linear regression models were used to examine the association between added sugars intake and the annual changes in handgrip strength and weight-adjusted handgrip strength. RESULTS: In the fully adjusted model, the annual change in handgrip strength for one unit increase in total added sugar, solid added sugar, and liquid added sugar intake was -0.0353 kg, (95% confidence intervals (CI) -0.000148, -0.0000164; P = 0.01), -0.0348 kg (95% CI: -0.000227, -0.0000269; P = 0.01) and -0.0189 kg (95% CI -0.000187, 0.0000338; P = 0.17), respectively. Added sugar from bread and biscuits sources were remarkably associated with a decline in handgrip strength (ß = -0.0498; 95%CI -0.00281, -0.000787) and (ß = -0.0459; 95%CI 0.00158, 0.00733) (P < 0.01). CONCLUSIONS: Our data suggest that the higher the intake of solid added sugars, but not liquid sugars, were associated with the declined handgrip strength in the Chinese middle-aged and elderly population. In addition, the consumption of added sugars from bread and biscuits sources was also associated with a decline in grip strength.
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Fuerza de la Mano , Humanos , Fuerza de la Mano/fisiología , Masculino , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Anciano , Azúcares de la Dieta/administración & dosificación , China , Adulto , Dieta/estadística & datos numéricosRESUMEN
Fewer than 5 % glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4+ T cells (P = 0.031) and CD4+ Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8 % of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.
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Neoplasias Encefálicas , Supervivientes de Cáncer , Metilación de ADN , Glioblastoma , Mutación , Humanos , Glioblastoma/genética , Glioblastoma/patología , Femenino , Masculino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Persona de Mediana Edad , Anciano , Microambiente Tumoral/genética , Biomarcadores de Tumor/genética , Adulto , Secuenciación del Exoma , Isocitrato Deshidrogenasa/genética , Regulación Neoplásica de la Expresión Génica , Variaciones en el Número de Copia de ADNRESUMEN
Currently, the clinical treatment of bone cancer pain (BCP) is mainly related to its pathogenesis. The aim of the present study was to elucidate the potential role of N6-methyladenosine (m6A) in BCP in the spinal cord dorsal root ganglia (DRG) of BCP rats and its specific regulatory mechanism in N-methyl-d-aspartate receptor subunit 2B (NR2B). A rat model of BCP was constructed by tibial injection of Walker256 cells, and ALKBH5 and NR2B expression in the spinal cord DRG was detected. ALKBH5 was silenced or overexpressed in PC12 cells to verify the regulatory effect of ALKBH5 on NR2B. The specific mechanism underlying the interaction between ALKBH5 and NR2B was investigated using methylated RNA immunoprecipitation and dual-luciferase reporter gene assays. The results showed increased expression of m6A, decreased expression of ALKBH5, and increased expression of NR2B in the DRG of the BCP rat model. Overexpression of ALKBH5 inhibited NR2B expression, whereas interference with ALKBH5 caused an increase in NR2B expression. In NR2B, interference with ALKBH5 caused an increase in m6A modification, which caused an increase in NR2B. Taken together, ALKBH5 affected the expression of NR2B by influencing the stability of the m6A modification site of central NR2B, revealing that ALKBH5 is a therapeutic target for BCP.
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BACKGROUND: Peri-implantitis and periodontitis have similar immunological bioprocesses and inflammatory phenotypes. In the inflammatory process, the adaptive immune cells can drive the development of disease. This research investigated the differences and diagnostic significance of peri-implantitis and periodontitis in adaptive immune responses. METHODS: We acquired four GEO datasets of gene expressions in surrounding tissues in healthy person, healthy implant, periodontitis, and peri-implantitis patients. The structural characteristics and enrichment analyses of differential expression genes were examined. The adaptive immune landscapes in peri-implantitis and periodontitis were then evaluated using single sample gene set enrichment analysis. The STRING database and Cytoscape were used to identify adaptive hub genes, and the ROC curve was used to verify them. Finally, qRT-PCR method was used to verify the expression level of Hub gene in activated T cells on the titanium-containing or titanium-free culture plates. RESULTS: At the transcriptome level, the data of healthy implant, peri-implantitis and periodontitis were highly dissimilar. The peri-implantitis and periodontitis both exhibited adaptive immune response. Except for the activated CD4+T cells, there was no significant difference in other adaptive immune cells between peri-implantitis and periodontitis. In addition, correlation analysis showed that CD53, CYBB, and PLEK were significantly positively linked with activated CD4+T cells in the immune microenvironment of peri-implantitis, making them effective biomarkers to differentiate it from periodontitis. CONCLUSIONS: Peri-implantitis has a uniquely immunogenomic landscape that differs from periodontitis. This study provides new insights and ideas into the activated CD4+T cells and hub genes that underpin the immunological bioprocess of peri-implantitis.
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Inmunidad Adaptativa , Biología Computacional , Periimplantitis , Periodontitis , Humanos , Periimplantitis/genética , Periimplantitis/inmunología , Periimplantitis/diagnóstico , Periodontitis/genética , Periodontitis/inmunología , Periodontitis/diagnóstico , Inmunidad Adaptativa/genética , Biología Computacional/métodos , Transcriptoma , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.
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Estilo de Vida Saludable , Conducta Sedentaria , Sueño , Humanos , Femenino , Masculino , China/epidemiología , Estudios Prospectivos , Adulto , Sueño/fisiología , Factores de Riesgo , Persona de Mediana Edad , Ejercicio Físico , Hígado Graso/epidemiología , Pueblos del Este de AsiaRESUMEN
Accumulating studies suggest that splicing factors play important roles in many diseases including human cancers. Our study revealed that WBP11, a core splicing factor, is highly expressed in ovarian cancer (OC) tissues and associated with a poor prognosis. WBP11 inhibition significantly impaired the proliferation and mobility of ovarian cancer cells in vitro and in vivo. Furthermore, FOXM1 transcriptionally activated WBP11 expression by directly binding to its promoter in OC cells. Importantly, RNA-seq and alternative splicing event analysis revealed that WBP11 silencing decreased the expression of MCM7 by regulating intron 4 retention. MCM7 inhibition attenuated the increase in malignant behaviors of WBP11-overexpressing OC cells. Overall, WBP11 was identified as an oncogenic splicing factor that contributes to malignant progression by repressing intron 4 retention of MCM7 in OC cells. Thus, WBP11 is an oncogenic splicing factor with potential therapeutic and prognostic implications in OC.
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Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Intrones , Componente 7 del Complejo de Mantenimiento de Minicromosoma , Neoplasias Ováricas , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Femenino , Intrones/genética , Componente 7 del Complejo de Mantenimiento de Minicromosoma/genética , Componente 7 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Animales , Línea Celular Tumoral , Ratones , Proliferación Celular/genética , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Pronóstico , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Ratones Desnudos , Empalme Alternativo/genéticaRESUMEN
Background: To describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). Methods: Data on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. Results: From 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65-74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. Conclusion: Over the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.
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The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.