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1.
Geriatr Orthop Surg Rehabil ; 15: 21514593241280912, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220251

RESUMEN

Introduction: Non-attendance with scheduled postoperative follow-up visits remains a common issue in orthopaedic clinical research. The objective of this study was to identify the risk factors associated with loss to follow-up among elderly patients with hip-fracture postoperatively. Methods: A retrospective analysis of 1-year post-surgery was performed on patients aged over 60 years who underwent hip-fracture surgery from January 2017 to March 2019. Based on their completion of the appointed follow-up schedule, the patients were classified into 2 groups: the Loss to Follow-up (LTFU) Group and the Follow-up (FU) Group. Clinical outcomes were evaluated by Functional Recovery Score (FRS) questionnaires. Telephone interviews were conducted with patients lost to follow-up to determine the reasons for non-attendance. A comparative analysis of baseline characteristics between the 2 groups was implemented, with further exploration of statistical differences through logistic regression. Results: A total of 992 patients met the inclusion criteria were included in this study, of which 189 patients, accounting for 19.1%, were lost to follow-up 1 year postoperatively. The mean age of the patients in the LTFU Group was 82.0 years, significantly higher than the 76.0 years observed in the FU Group (P < 0.001). The FRS for the LTFU Group was marginally higher than that of the FU group (84.0 vs 81.0), with no significant difference (P = 0.060). Logistic regression analysis identified several significant predictors of noncompliance, including advanced age at surgery, femoral neck fracture, hip arthroplasty, long distance from residence to hospital, and the reliance on urban-rural public transportation for reaching the hospital. Conclusion: Postoperative follow-up loss was prevalent among elderly patients with hip fractures. Our study indicated a constellation of risk factors contributing to noncompliance, including advanced age, transportation difficulties, long travel distance, femoral neck fracture and hip arthroplasty surgery.

2.
Adv Healthc Mater ; : e2402596, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39252661

RESUMEN

The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme-like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high-glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro-computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.

3.
Biomed Pharmacother ; 179: 117375, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278186

RESUMEN

The perioperative period encompasses all phases of patient care from the decision to perform surgery until full recovery. Ferroptosis, a newly identified type of regulated cell death, influences a wide array of diseases, including those affecting the prognosis and regression of surgical patients, such as ischemia-reperfusion injury and perioperative cognitive dysfunction. This review systematically examines perioperative factors impacting ferroptosis such as surgical trauma-induced stress, tissue hypoxia, anesthetics, hypothermia, and blood transfusion. By analyzing their intrinsic relationships, we aim to improve intraoperative management, enhance perioperative safety, prevent complications, and support high-quality postoperative recovery, ultimately improving patient outcomes.

4.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1590-1598, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39235017

RESUMEN

Soil organic matter serves as a crucial indicator for soil quality. Albic soil, characterized by a barrier layer, exhibits limitations in organic matter content, which can adversely affect crop growth and development. To elucidate the impact of deep mixing of various organic materials on the redistribution of organic matter in the surface soil of albic soil could provide theoretical and technical insights for establishing suitable plough layers for albic soil in Northeast China. We conducted a two-year positioning experiment in Shuangyashan, Heilongjiang Province with five treatments, conventional shallow tillage (0-15 cm, CK), inversion tillage (0-35 cm) without or with straw return (T35 and T35+S), inversion tillage with cattle manure (T35+M) and cattle manure plus maize straw (T35+S+M). The results showed that soil fertilization via deep mixing of organic materials to a depth of 35 cm significantly increased maize yield in albic soil, with the T35+S+M treatment demonstrating the most pronounced effect, yielding an average production of 2934.76 kg·hm-2. Compared to CK, the T35 treatment resulted in a significant 8.4% decrease in organic matter content in the tillage layer, a significant 7.6% increase in organic matter in the sub-tillage layer, and a relative richness degree of soil organic matter in the sub-tillage layer increased by 17.5%. Deep mixed return of organic materials following deep ploughing markedly increased organic matter content of the plough layer, with organic matter conversion ranging from 16.3% to 31.0%. In comparison to the T35 treatment, there was no significant increase in soil organic matter content in the T35+S tillage layer and sub-tillage layer. Conversely, soil organic matter content increased by 4.6% and 6.9% in the T35+M and T35+S+M treatments, with corresponding increase of 11.2% and 15.4% in sub-tillage layer, respectively. Additionally, the soil organic matter richness index in sub-tillage layer increased by 2.5% and 5.1%, respectively. There was a significant positive correlation between organic matter content in the entire plough layer and maize yield, with a contribution rate of 17.5%. Therefore, the utilization of organic fertilizer or a combination of organic fertilizer and straw deep mixing can quickly fertilize albic soil by increasing soil organic matter content in both the whole tillage layer (0-35 cm) and the sub-tillage layer (15-35 cm).


Asunto(s)
Agricultura , Fertilizantes , Compuestos Orgánicos , Suelo , Zea mays , Suelo/química , Compuestos Orgánicos/análisis , China , Zea mays/crecimiento & desarrollo , Agricultura/métodos , Fertilizantes/análisis , Estiércol , Productos Agrícolas/crecimiento & desarrollo
5.
Cureus ; 16(7): e64322, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130890

RESUMEN

Background Patients utilize online health information to inform their medical decision-making. YouTube is one of the most popular media platforms with abundant health-related resources, yet the quality of the disseminated information remains unclear. This study aims to evaluate the quality and reliability of content pertaining to diverticulosis and diverticulitis on YouTube. Methods One author queried the terms "diverticulosis," "diverticulitis," "acute diverticulitis," and "chronic diverticulitis" on YouTube. The first 50 videos per search were selected for analysis. Duplicates, non-English videos, or procedural content were excluded. Video characteristics including view count, likes, comments, duration, days since upload, view ratio, video power index, and video sources (professional organizations (POs), health information websites (HIWs), and entertainment/independent users (EIUs)) were collected. Videos were scored using the mDISCERN and Global Quality Score (GQS). Results Sixty-four videos were included. DISCERN scores significantly differed between POs (n=20, mean=4.35), HIWs (n=29, mean=2.97), and EIUs (n=15, mean=1.83). GQS also significantly differed between POs (n=20, mean=4.47), HIWs (n=29, mean=3.62), and EIUs (n=15, mean=2.5). Video characteristics significantly differed between groups, with most user engagement seen in EIUs. Conclusion POs and HIWs disseminate higher quality health information about diverticular disease on YouTube. The higher viewer engagement with EIUs is concerning, as these sources were found to have lower quality content. Although YouTube has the capability to provide valuable information on diverticulosis and diverticulitis, enhanced content screening is needed to ensure accuracy and validation.

6.
Zhonghua Nan Ke Xue ; 30(5): 387-396, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-39210486

RESUMEN

OBJECTIVE: To explore the potential causal relationship between gut microbiota and teratozoospermia. METHODS: We searched the database of Genome-Wide Association Study (GWAS) for gut microbiota- and teratozoospermia-related data. We used gut microbiota as an exposure factor, determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance, and derived the outcome variables from the European data on teratozoospermia, with a sample size of 85 716, including 915 cases and 209 006 controls. Using inverse-variance weighting (IVW), MR-Egger regression and the weighted median estimator (WME), we performed two-sample Mendelian randomization (MR) analysis on the retrieved data, and estimated the causal relationship between gut microbiota and teratozoospermia based on the ß value. RESULTS: Two-sample MR analysis indicated that the class Erysipelotrichia, family Erysipelotrichaceae, family Streptococcaceae, genus Coprococcusl, genus Ruminococcaceae UCG009, genus Streptococcus, order Clostridialesm and order Erysipelotrichales were causally related with the increased risk, while the family Porphyromonadaceae with the decreased risk of teratozoospermia. CONCLUSION: The class Erysipelotrichia, family Erysipelotrichaceae, family Streptococcaceae, genus Coprococcusl, genus Ruminococcaceae UCG009, genus Streptococcus, order Clostridialesm and order Erysipelotrichales are one of the causes of teratozoospermia, related to the increased risk of the condition, while the family Porphyromonadaceae has a protective effect on sperm morphology, reducing the risk of teratozoospermia.


Asunto(s)
Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Teratozoospermia , Humanos , Masculino , Teratozoospermia/genética
7.
J Phys Chem B ; 128(31): 7627-7638, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39073136

RESUMEN

Rosemary is one of the most promising, versatile, and studied natural preservatives. Carnosic acid (CA) and carnosol (CARN), as the primary active ingredients of rosemary extracts, have little difference in structure, but their antioxidant activities vary significantly, depending on the system studied. The underlying molecular mechanisms remain unclear. By means of optical spectroscopies, stopped-flow, laser photolysis, and density functional theory (DFT) calculations, we have compared CA and CARN between their reaction dynamics of radical scavenging, metal ion chelation, and oxidation inhibition in lipid emulsion and beef, as well as between their interactions with ß-carotene (ß-Car). For reference, 3-isopropyl catechol (IC), which is structurally similar to the active groups of CA and CARN, was studied in parallel. It is found for CA that the intramolecular hydrogen bond can boost the acidity of its phenol hydroxyl and that the synergistic effect with ß-Car can substantially enhance its antioxidation activity in the model systems of lipid and meat via the CA-to-ß-Car electron transfer reaction. The substitution of A and B rings on the catechol group in both CA and CARN limits browning caused by their formation of oxidative products as antioxidants.


Asunto(s)
Abietanos , Antioxidantes , Teoría Funcional de la Densidad , Enlace de Hidrógeno , Rosmarinus , Abietanos/química , Abietanos/farmacología , Rosmarinus/química , Antioxidantes/química , Antioxidantes/farmacología , beta Caroteno/química , Bovinos , Animales , Oxidación-Reducción
8.
BMC Endocr Disord ; 24(1): 106, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978006

RESUMEN

BACKGROUND: Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited. METHOD: We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analysed. RESULTS: During the study period, 1059 patients were admitted for STIs (88% required surgery). DM was an independent risk factor for LOS. Diabetic patients presented with higher body-mass index (28 vs. 26), larger abscess size (24 vs. 14 cm2) and had a longer length of stay (4.4 days vs. 2.9 days). They also underwent a higher proportion of wide debridement and application of negative pressure wound therapy (42% vs. 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs. 4). Diabetic patients were two times more likely to present with carbuncles (p = 0.02). CONCLUSION: The incidence of STIs among DM patients represent a significant disease burden, surgeons should consider intensive patient counselling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based upon lifestyle modification and glucose control.


Asunto(s)
Infecciones de los Tejidos Blandos , Humanos , Masculino , Femenino , Estudios Retrospectivos , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/complicaciones , Persona de Mediana Edad , Anciano , Diabetes Mellitus/epidemiología , Factores de Riesgo , Adulto , Tiempo de Internación/estadística & datos numéricos , Incidencia , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Complicaciones de la Diabetes/epidemiología , Estudios de Seguimiento
9.
PLoS One ; 19(7): e0307862, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39042654

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0152112.].

10.
J Acoust Soc Am ; 156(1): 548-559, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39024384

RESUMEN

Conventional near-field acoustic holography based on compressive sensing either does not fully exploit the underlying block-sparse structures of the signal or suffers from a mismatch between the actual and predefined block structure due to the lack of prior information about block partitions, resulting in poor accuracy in sound field reconstruction. In this paper, a pattern-coupled Bayesian compressive sensing method is proposed for sparse reconstruction of sound fields. The proposed method establishes a hierarchical Gaussian-Gamma probability model with a pattern-coupled prior based on the equivalent source method, transforming the sound field reconstruction problem into recovering the sparse coefficient vector of the equivalent source strengths within the compressive sensing framework. A set of hyperparameters is introduced to control the sparsity of each element in the sparse coefficient vector of the equivalent source strengths, where the sparsity of each element is determined by both its own hyperparameters and those of its immediate neighbors. This approach enables the promotion of block sparse solutions and achieves better performance in solving for the sparse coefficient vector of the equivalent source strengths without prior information of block partitions. The effectiveness and superiority of the proposed method in reconstructing sound fields are verified by simulations and experiments.

11.
J Hepatol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992769

RESUMEN

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

12.
Phys Chem Chem Phys ; 26(28): 19217-19227, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38957117

RESUMEN

An inverse sandwich structure has been computationally predicted for uranium boride and extended to the series of actinide elements (An) from Th to Cm. The electronic structure and chemical bonding of these novel compounds have been analyzed using density functional theory and multireference wave-function based methods. We report the trends in electronic structure and bonding for An2B8, and found that (d-π)π and (d-p)δ are the most important factors in the stability of An2B8. The (f-p)δ bond provides extra stabilization for Pa2B8 and U2B8, owing to the extensive interactions of An-B8-An, resulting in a short distance for the Pa-Pa and U-U bonds.

13.
J Cell Mol Med ; 28(13): e18516, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38958577

RESUMEN

The progression of lung adenocarcinoma (LUAD) from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma (IAC) involves a complex evolution of tumour cell clusters, the mechanisms of which remain largely unknown. By integrating single-cell datasets and using inferCNV, we identified and analysed tumour cell clusters to explore their heterogeneity and changes in abundance throughout LUAD progression. We applied gene set variation analysis (GSVA), pseudotime analysis, scMetabolism, and Cytotrace scores to study biological functions, metabolic profiles and stemness traits. A predictive model for prognosis, based on key cluster marker genes, was developed using CoxBoost and plsRcox (CPM), and validated across multiple cohorts for its prognostic prediction capabilities, tumour microenvironment characterization, mutation landscape and immunotherapy response. We identified nine distinct tumour cell clusters, with Cluster 6 indicating an early developmental stage, high stemness and proliferative potential. The abundance of Clusters 0 and 6 increased from AAH to IAC, correlating with prognosis. The CPM model effectively distinguished prognosis in immunotherapy cohorts and predicted genomic alterations, chemotherapy drug sensitivity, and immunotherapy responsiveness. Key gene S100A16 in the CPM model was validated as an oncogene, enhancing LUAD cell proliferation, invasion and migration. The CPM model emerges as a novel biomarker for predicting prognosis and immunotherapy response in LUAD patients, with S100A16 identified as a potential therapeutic target.


Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Progresión de la Enfermedad , Neoplasias Pulmonares , Aprendizaje Automático , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Análisis de la Célula Individual/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Perfilación de la Expresión Génica
14.
J Mater Chem B ; 12(30): 7367-7383, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38940905

RESUMEN

The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone injury repair has been insufficient. In this study, we designed an injectable poly(L-lactic acid) (PLLA) porous microsphere that forms calcium phosphate crystals on its surface by binding to melatonin, followed by bionanomimetic mineralization in vitro. The microsphere is injectable and degradable, and its release of melatonin (MT) and calcium phosphate (CaP) crystals promotes macrophage M2 polarization, reprogramming of macrophages, and enhanced osteogenesis. After LPS stimulation, the proportion of M2-polarized macrophages in the MS@CaP@MT group was 39.2 ± 2.7%, significantly higher than that in other groups (P < 0.05). Further, in the MS@CaP@MT group, rats exhibited bone mineral densities of 129.4 ± 12.8 mg cc-1 at 2 weeks and 171.6 ± 13.6 mg cc-1 at 4 weeks in the defect area, which were significantly higher than those in other groups (P < 0.05). Using an animal model of femoral condylar defects, we demonstrated that MT PLLA porous microspheres loaded with calcium phosphate crystals can improve the immune microenvironment and form a microsphere-centered osteogenesis model. This significantly accelerates bone defect repair and provides a potential strategy for bone defect treatment.


Asunto(s)
Fosfatos de Calcio , Macrófagos , Melatonina , Microesferas , Poliésteres , Fosfatos de Calcio/química , Animales , Melatonina/farmacología , Melatonina/química , Poliésteres/química , Porosidad , Ratas , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratas Sprague-Dawley , Regeneración Ósea/efectos de los fármacos , Células RAW 264.7 , Masculino , Propiedades de Superficie , Tamaño de la Partícula , Osteogénesis/efectos de los fármacos
15.
Nat Commun ; 15(1): 3755, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704385

RESUMEN

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.


Asunto(s)
Anticoagulantes , Escherichia coli , Heparina , Sulfotransferasas , Sulfotransferasas/metabolismo , Sulfotransferasas/genética , Heparina/metabolismo , Heparina/biosíntesis , Anticoagulantes/metabolismo , Anticoagulantes/química , Escherichia coli/genética , Escherichia coli/metabolismo , Ingeniería Metabólica/métodos , Humanos , Polisacáridos/metabolismo , Polisacáridos/biosíntesis , Polisacáridos/química , Mutagénesis Sitio-Dirigida , Ingeniería de Proteínas/métodos , Disacáridos/metabolismo , Disacáridos/biosíntesis , Disacáridos/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética
16.
Heliyon ; 10(7): e28826, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596127

RESUMEN

Oral microecological dysregulation has been shown to be associated with various immune system disorders. Henoch-schonlein purpura (HSP) is an autoimmune small vessel inflammatory disease in children of uncertain etiology, and studies have suggested that streptococcal infection may be an influential factor in its development. However, the relationship between oral microecological dysregulation and HSP has not been clearly studied so far. In this study, an epidemiological survey on the oral health status of children with HSP was investigated in this paper, and collected dental plaque from four groups of children for 16SrDNA high-throughput sequencing to analyze the composition and changes of oral microbial diversity among different groups. The results showed that the oral health status of children with HSP was poor, except for the incidence of caries in the 5-year-old group, the caries rate and dmfs/DMFS in the 3,4 and 5-year-old groups were higher than the same age in the fourth Chinese Oral Health Epidemiological Survey. Moreover, the development of HSP is accompanied by disturbances in the oral microbiota; a decrease in the number of Firmicutes which producing butyric acid may be closely associated with the development of HSP; changes in the abundance of Streptococcus and Neisseria may be a risk factor for the development of HSP.

17.
Int Urol Nephrol ; 56(9): 3047-3055, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38642210

RESUMEN

PURPOSE: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.


Asunto(s)
Glomerulonefritis Membranosa , Inmunosupresores , Aprendizaje Automático , Proteinuria , Tacrolimus , Humanos , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/complicaciones , Tacrolimus/uso terapéutico , Proteinuria/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , China , India , Adulto , Pueblos del Este de Asia
18.
Curr Pharm Des ; 30(18): 1419-1432, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38639271

RESUMEN

OBJECTIVES: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration. METHODS: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen. RESULTS: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively. CONCLUSION: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.


Asunto(s)
Ciclosporina , Inmunosupresores , Método de Montecarlo , Síndrome Nefrótico , Espironolactona , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Espironolactona/administración & dosificación , Espironolactona/farmacocinética , Ciclosporina/administración & dosificación , Ciclosporina/farmacocinética , Niño , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Preescolar
19.
Sci Rep ; 14(1): 9881, 2024 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688977

RESUMEN

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.


Asunto(s)
Biomarcadores de Tumor , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias , Microambiente Tumoral , Proteínas de Unión al GTP rab3 , Humanos , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Mutación , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/diagnóstico , Neoplasias/patología , Pronóstico , Proteínas de Unión al GTP rab3/genética , Proteínas de Unión al GTP rab3/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética
20.
J Cell Mol Med ; 28(9): e18357, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38683127

RESUMEN

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP-sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP-q-PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter -299 to -157 region. It was further verified that pcDNA3.1 (-)-cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy-related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.


Asunto(s)
Envejecimiento , Proteína 5 Relacionada con la Autofagia , Autofagia , Núcleo Celular , Miocardio , Troponina I , Troponina I/metabolismo , Troponina I/genética , Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Envejecimiento/metabolismo , Envejecimiento/genética , Animales , Miocardio/metabolismo , Humanos , Núcleo Celular/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Ratones , Células HEK293 , Masculino , Regiones Promotoras Genéticas , Regulación de la Expresión Génica , Miocitos Cardíacos/metabolismo , Ratones Noqueados
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