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TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.
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Linfoma de Células B Grandes Difuso , Proteína p53 Supresora de Tumor , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Humanos , Proteína p53 Supresora de Tumor/genética , Pronóstico , Mutación Missense/genética , Mutación/genética , Microambiente Tumoral/genética , Masculino , Femenino , Factores de Riesgo , Persona de Mediana EdadRESUMEN
Zero-dimensional (0D) hybrid metal halides have been emerged as room-temperature phosphorescence (RTP) materials, but synchronous optimization of multiple phosphorescence performance in one structural platform remains less resolved, and stable RTP activity in aqueous medium is also unrealized due to serious instability toward water and oxygen. Herein, we demonstrated a photophysical tuning strategy in a new 0D hybrid zinc halide family of (BTPP)2ZnX4 (BTPP = benzyltriphenylphosphonium, X = Cl and Br). Infrequently, the delicate combination of organic and inorganic species enables this family to display multiple ultralong green afterglow and efficient self-trapped exciton (STE) associated cyan phosphorescence. Compared with inert luminescence of [BTPP]+ cation, incorporation of anionic [ZnX4]2- effectively enhance the spin-orbit coupling effect, which significantly boosts the photoluminescence quantum yield (PLQY) up to 30.66% and 54.62% for afterglow and phosphorescence, respectively. Synchronously, the corresponding luminescence lifetime extend to 143.94 ms and 0.308 µs surpassing the indiscernible phosphorescence of [BTPP]X salt. More importantly, this halide family presents robust RTP emission with nearly unattenuated PLQY in water and harsh condition (acid and basic aqueous solution) over half a year. The highly efficient integrated afterglow and STE phosphorescence as well as ultrahigh aqueous state RTP realize multiple anti-counterfeiting applications in wide chemical environments.
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BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.
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BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.
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Aspergilosis Broncopulmonar Alérgica , Aspergillus fumigatus , Biomarcadores , Glucocorticoides , Óxido Nítrico , Humanos , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Femenino , Masculino , Glucocorticoides/uso terapéutico , Adulto , Pronóstico , Biomarcadores/análisis , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Aspergillus fumigatus/inmunología , Persona de Mediana Edad , Estudios Retrospectivos , Inmunoglobulina E/sangre , Estudios Prospectivos , Prueba de Óxido Nítrico Exhalado Fraccionado , Inmunoglobulina GRESUMEN
The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Mutación , Humanos , Linfoma de Células B Grandes Difuso/líquido cefalorraquídeo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/líquido cefalorraquídeo , Biomarcadores de Tumor/genética , Anciano , Adulto , ADN Tumoral Circulante/líquido cefalorraquídeo , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Pronóstico , Anciano de 80 o más Años , Adulto Joven , Estudios ProspectivosRESUMEN
OBJECTIVES: The glow discharge plasma (GDP) procedure has proven efficacy in grafting allylamine onto zirconia dental implant surfaces to enhance osseointegration. This study explored the enhancement of zirconia dental implant properties using GDP at different energy settings (25, 50, 75, 100, and 200 W) both in vitro and in vivo. MATERIALS AND METHODS: In vitro analyses included scanning electron microscopy, wettability assessment, energy-dispersive X-ray spectroscopy, and more. In vivo experiments involved implanting zirconia dental implants into rabbit femurs and later evaluation through impact stability test, micro-CT, and histomorphometric measurements. RESULTS: The results demonstrated that 25 and 50 W GDP allylamine grafting positively impacted MG-63 cell proliferation and increased alkaline phosphatase activity. Gene expression analysis revealed upregulation of OCN, OPG, and COL-I. Both 25 and 50 W GDP allylamine grafting significantly improved zirconia's surface properties (p < .05, p < .01, p < .001). However, only 25 W allylamine grafting with optimal energy settings promoted in vivo osseointegration and new bone formation while preventing bone level loss around the dental implant (p < .05, p < .01, p < .001). CONCLUSIONS: This study presents a promising method for enhancing Zr dental implant surface's bioactivity.
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Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.
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Background/purpose: 3D-printed bone tissue engineering is becoming recognized as a key approach in dentistry for creating customized bone regeneration treatments fitting patients bone defects requirements. 3D bioprinting offers an innovative method to fabricate detailed 3D structures, closely emulating the native bone micro-environment and better bone regeneration. This study aimed to develop an 3D-bioprintable scaffold using a combination of alginate and ß-tricalcium phosphate (ß-TCP) with the Cellink® BioX printer, aiming to advance the field of tissue engineering. Materials and methods: The physical and biological properties of the resulting 3D-printed scaffolds were evaluated at 10 %, 12 %, and 15 % alginate combined with 10 % ß-TCP. The scaffolds were characterized through printability, swelling behavior, degradability, and element analysis. The biological assessment included cell viability, alkaline phosphatase (ALP) activity. Results: 10 % alginate/ß-TCP 3D printed at 25 °C scaffold demonstrated the optimal condition for printability, swelling capability, and degradability of cell growth and nutrient diffusion. Addition of ß-TCP particles significantly improved the 3D printed material viscosity over only alginate (P < 0.05). 10 % alginate/ß-TCP enhanced MG-63 cell's proliferation (P < 0.05) and alkaline phosphatase activity (P < 0.001). Conclusion: This study demonstrated in vitro that 10 % alginate/ß-TCP bioink characteristic for fabricating 3D acellular bioprinted scaffolds was the best approach. 10 % alginate/ß-TCP bioink 3D-printed scaffold exhibited superior physical properties and promoted enhanced cell viability and alkaline phosphatase activity, showing great potential for personalized bone regeneration treatments.
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Background/purpose: Oral health is related to general health and a person's overall well-being. The aim of the present study was to explore the association between oral health status and bite force among young adults. Materials and methods: Maximum bite force (MBF) was measured using Dental Prescale II in conjunction with a pressure-sensitive film and bite force analyzer in 40 young adults aged 20 to 40. Supragingival dental plaque was collected and cultured. Plaque weight, pH, and colony counts were assessed. The decayed, missing, and filled teeth index (DMFT) and body mass index (BMI) were recorded. Results: Bite force was negatively correlated with the number of missing teeth and the sum of missing and filled teeth. When the filled-to-remaining-teeth ratio (F/R ratio) was less than 8%, the bite force was significantly higher compared to an F/R ratio of 8-25%. Additionally, the amount of total bacteria was positively correlated with total bite force, and the quantity of Streptococcus mutans (S. mutans) along with total bacteria was positively correlated with bite force in the molar region (∗P < 0.05). The molar region predominantly contributed to bite force. Conclusion: Elevated levels of cariogenic bacteria may increase the risk of tooth loss, subsequently leading to reduced bite force. This reduction in bite force can further impact the efficiency of chewing function and, consequently, the quality of life. An F/R ratio above 8% could be easily calculated clinically and could serve as a guide to identify patients, particularly young adults, at risk of reduced bite force.
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INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
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Aspergilosis Broncopulmonar Alérgica , Linfocitos B , Líquido del Lavado Bronquioalveolar , Células Th2 , Humanos , Masculino , Femenino , Aspergilosis Broncopulmonar Alérgica/inmunología , Adulto , Células Th2/inmunología , Persona de Mediana Edad , Estudios de Casos y Controles , Linfocitos B/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T Reguladores/inmunología , Asma/inmunología , Células Th17/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement is a procedure that can effectively treat complications of portal hypertension, such as variceal bleeding and refractory ascites. However, there have been no specific studies on predicting long-term survival after TIPS placement. AIM: To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS. METHODS: A retrospective analysis was conducted on a cohort of 224 patients who underwent TIPS implantation. Through univariate and multivariate Cox regression analyses, various factors were examined for their ability to predict survival at 6 years after TIPS. Consequently, a composite score was formulated, encompassing the indication, shunt reasonability, portal venous pressure gradient (PPG) after TIPS, percentage decrease in portal venous pressure (PVP), indocyanine green retention rate at 15 min (ICGR15) and total bilirubin (Tbil) level. Furthermore, the performance of the newly developed Cox (NDC) model was evaluated in an internal validation cohort and compared with that of a series of existing models. RESULTS: The indication (variceal bleeding or ascites), shunt reasonability (reasonable or unreasonable), ICGR15, postoperative PPG, percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement. The NDC model incorporated these parameters and successfully identified patients at high risk, exhibiting a notably elevated mortality rate following the TIPS procedure, as observed in both the training and validation cohorts. Additionally, in terms of predicting the long-term survival rate, the performance of the NDC model was significantly better than that of the other four models [Child-Pugh, model for end-stage liver disease (MELD), MELD-sodium and the Freiburg index of post-TIPS survival]. CONCLUSION: The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis, help identify high-risk patients and guide follow-up management after TIPS implantation.
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SCOPE: Breast milk has the potential to prevent childhood obesity by providing probiotics, but there are still instances of obesity in breastfed children. METHODS AND RESULTS: This study investigates the difference in intestinal flora structure between breastfed children with obesity (OB-BF) and normal-weight breastfed children (N-BF). Building upon this foundation, it employs both cell and mouse models to identify an antiobesity strain within the fecal matter of N-BF children and explore its underlying mechanisms. The results reveal a reduction in lactobacillus levels within the intestinal flora of OB-BF children compared to N-BF children. Consequently, Lactobacillus plantarum H-72 (H-72) is identified as a promising candidate due to its capacity to stimulate glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine cells (ECCs). In vivo, H-72 effectively increases serum GLP-1 concentration, reduces food intake, regulates the expression of genes related to energy metabolism (SCD-1, FAS, UCP-1, and UCP-3), and regulates gut microbiota structure in mice. Moreover, the lipoteichoic acid of H-72 activates toll-like receptor 4 to enhanced GLP-1 secretion in STC-1 cells. CONCLUSIONS: L. plantarum H-72 is screened out for its potential antiobesity effect, which presents a potential and promising avenue for future interventions aimed at preventing pediatric obesity in breastfed children.
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Microbioma Gastrointestinal , Obesidad Infantil , Probióticos , Humanos , Niño , Animales , Ratones , Femenino , Lactancia Materna , Intestinos , Péptido 1 Similar al Glucagón/metabolismo , Probióticos/farmacologíaRESUMEN
Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (EBV+ DLBCL) predicts poor prognosis and CD30 expression aggravates the worse consequences. Here, we reported that CD30 positivity was an independent prognostic indicator in EBV+ DLBCL patients in a retrospective cohort study. We harnessed CRISPR/Cas9 editing to engineer the first loss-of-function models of CD30 deficiency to identify that CD30 was critical for EBV+ DLBCL growth and survival. We established a pathway that EBV infection mediated CD30 expression through EBV-encoded latent membrane protein 1 (LMP1), which involved NF-κB signaling. CRISPR CD30 knockout significantly repressed BCL2 interacting protein 3 (BNIP3) expression and co-IP assay indicated a binding between CD30 and BNIP3. Moreover, silencing of CD30 induced mitochondrial dysfunction and suppressed mitophagy, resulting in the accumulation of damaged mitochondria by depressing BNIP3 expression. Additionally, CRISPR BNIP3 knockout caused proliferation defects and increased sensitivity to apoptosis. All the findings reveal a strong relationship between mitophagy and adverse prognosis of EBV+ DLBCL and discover a new regulatory mechanism of BNIP3-mediated mitophagy, which may help develop effective treatment regimens with anti-CD30 antibody brentuximab vedotin to improve the prognosis of CD30+ EBV+ DLBCL patients.
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Infecciones por Virus de Epstein-Barr , Linfoma de Células B Grandes Difuso , Enfermedades Mitocondriales , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Estudios Retrospectivos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Mitofagia , Enfermedades Mitocondriales/complicaciones , Proteínas de la Membrana/genética , Proteínas Proto-Oncogénicas/genéticaRESUMEN
BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.
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Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Distribución Tisular , Pronóstico , Insuficiencia Renal Crónica/terapia , LípidosRESUMEN
Researchers have recently found that N6-methyladenosine (m6A) is a type of internal posttranscriptional modification that is essential in mammalian mRNA. However, the features of m6A RNA methylation in acute intracerebral hemorrhage (ICH) remain unknown. To explore differential methylations and to discover their functions in acute ICH patients, we recruited three acute ICH patients, three healthy controls, and an additional three patients and healthy controls for validation. The m6A methylation levels in blood samples from the two groups were determined by ultrahigh-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was employed to identify differences in m6A modification, and the differentially expressed m6A-modified genes were confirmed by MeRIP-qPCR. We found no significant differences in the total m6A levels between the two groups but observed differential methylation peaks. Compared with the control group, the coding genes showing increased methylation following acute ICH were mostly involved in processes connected with osteoclast differentiation, the neurotrophin signaling pathway, and the spliceosome, whereas genes with reduced m6A modification levels after acute ICH were found to be involved in the B-cell and T-cell receptor signaling pathways. These results reveal that differentially m6A-modified genes may influence the immune microenvironments in acute ICH.
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Adenosina/análogos & derivados , Hemorragia Cerebral , Metilación de ARN , Animales , Humanos , Hemorragia Cerebral/genética , Linfocitos B , MamíferosRESUMEN
BACKGROUND: Portal hypertension (PHT) in patients with alcoholic cirrhosis causes a range of clinical symptoms, including gastroesophageal varices and ascites. The hepatic venous pressure gradient (HVPG), which is easier to measure, has replaced the portal venous pressure gradient (PPG) as the gold standard for diagnosing PHT in clinical practice. Therefore, attention should be paid to the correlation between HVPG and PPG. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. METHODS: Between January 2017 and June 2020, 134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures. Correlations were assessed using Pearson's correlation coefficient to estimate the correlation coefficient (r) and determination coefficient (R2). Bland-Altman plots were constructed to further analyze the agreement between the measurements. Disagreements were analyzed using paired t tests, and P values < 0.05 were considered statistically significant. RESULTS: In this study, the correlation coefficient (r) and determination coefficient (R2) between HVPG and PPG were 0.201 and 0.040, respectively (P = 0.020). In the 108 patients with no collateral branch, the average wedged hepatic venous pressure was lower than the average portal venous pressure (30.65 ± 8.17 vs. 33.25 ± 6.60 mmHg, P = 0.002). Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography (19.4%), while the average PPG was significantly higher than the average HVPG (25.94 ± 7.42 mmHg vs 9.86 ± 7.44 mmHg; P < 0.001). The differences between HVPG and PPG < 5 mmHg in the collateral vs no collateral branch groups were three cases (11.54%) and 44 cases (40.74%), respectively. CONCLUSION: In most patients, HVPG cannot accurately represent PPG. The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.
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OBJECTIVE: This study aimed to compare the hemorheological and inflammatory changes before and after coronary artery bypass graft (CABG) surgery, as factors such as hypothermia, hemodilution, transfusion, and other variables affect blood viscosity and inflammation during the procedure. METHODS: A total of 25 patients who underwent CABG surgery were enrolled in this study. Whole blood was collected just before the CABG (D0), 2 days after surgery (D2), and 5 days after surgery (D5). The plasma viscosity (PV) and whole blood viscosity (WBV) were measured at shear rates ranging from 0.1 to 1000 s-1 using a rheometer, and the mean values were compared. Inflammatory markers were also assessed and analyzed in relation to the hemorheological changes. RESULTS: Compared with the baseline values, the PV significantly increased after 5 days. WBV showed a significant increase on day 2 and after 5 days. The WBV and fibrinogen were significantly correlated on day 2 and day 5 but not before surgery. Inflammatory markers such as CRP, WBC, platelets, and fibrinogen also demonstrated notable changes in relation to the hemorheological alterations. CONCLUSIONS: This study highlights the crucial finding that hyperviscosity, characterized by elevated PV and WBV, persists for almost one week after on-pump CABG surgery. Understanding the interplay between inflammation and hemorheological properties during the postoperative period is crucial for optimizing patient care. Future research should focus on exploring the underlying mechanisms and potential therapeutic interventions to mitigate the impact of inflammation on blood viscosity and improve patient outcomes following CABG surgery.
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Background/purpose: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methods: Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. Results: We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Conclusion: Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.
Asunto(s)
Carcinoma Hepatocelular , Infecciones por VIH , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Incidencia , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Cirrosis Hepática/epidemiologíaRESUMEN
We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002-1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003-1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006-1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009-1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029-1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.