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1.
Diabetes Metab Syndr Obes ; 17: 2583-2595, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946912

RESUMO

Purpose: The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD. Patients and Methods: The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD. Results: After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92-2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥25 kg/m2] and non-obese (BMI<25 kg/m2), and older (age≥45 years) and younger (age<45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P<0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings. Conclusion: This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.

4.
BMC Infect Dis ; 24(1): 714, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033158

RESUMO

BACKGROUND: Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. METHODS: The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. RESULTS: Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. CONCLUSION: This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.


Assuntos
Loa , Loíase , Humanos , Loíase/epidemiologia , Loíase/tratamento farmacológico , Loíase/diagnóstico , Loíase/parasitologia , Masculino , Adulto , Feminino , Animais , Pessoa de Meia-Idade , Pequim/epidemiologia , Loa/isolamento & purificação , Viagem , Adulto Jovem , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/parasitologia , Doenças Transmissíveis Importadas/diagnóstico , África/epidemiologia
5.
Infect Immun ; : e0023224, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037247

RESUMO

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.

6.
Front Endocrinol (Lausanne) ; 15: 1403452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036046

RESUMO

Objective: Diabetes is a significant risk factor for acute heart failure, associated with an increased risk of mortality. This study aims to analyze the prognostic significance of admission blood glucose (ABG) on 30-day mortality in Chinese patients with acute decompensated heart failure (ADHF), with or without diabetes. Methods: This retrospective study included 1,462 participants from the JX-ADHF1 cohort established between January 2019 to December 2022. We conducted multivariate cox regression, restricted cubic spline, receiver operating characteristic curve analysis, and mediation analysis to explore the association and potential mechanistic pathways (inflammation, oxidative stress, and nutrition) between ABG and 30-day mortality in ADHF patients, with and without diabetes. Results: During the 30-day follow-up, we recorded 20 (5.36%) deaths in diabetic subjects and 33 (3.03%) in non-diabetics. Multivariate Cox regression revealed that ABG was independently associated with 30-day mortality in ADHF patients, with a stronger association in diabetics than non-diabetics (hazard ratio: Model 1: 1.71 vs 1.16; Model 2: 1.26 vs 1.19; Model 3: 1.65 vs 1.37; Model 4: 1.76 vs 1.33). Further restricted cubic spline analysis indicated a U-shaped relationship between ABG and 30-day mortality in non-diabetic ADHF patients (P for non-linearity < 0.001), with the lowest risk at ABG levels approximately between 5-7 mmol/L. Additionally, receiver operating characteristic analysis demonstrated that ABG had a higher predictive accuracy for 30-day mortality in diabetics (area under curve = 0.8751), with an optimal threshold of 13.95mmol/L. Finally, mediation analysis indicated a significant role of inflammation in ABG-related 30-day mortality in ADHF, accounting for 11.15% and 8.77% of the effect in diabetics and non-diabetics, respectively (P-value of proportion mediate < 0.05). Conclusion: Our study confirms that ABG is a vital indicator for assessing and predicting 30-day mortality risk in ADHF patients with diabetes. For ADHF patients, both with and without diabetes, our evidence suggests that physicians should be alert and closely monitor any changes in patient conditions when ABG exceeds 13.95 mmol/L for those with diabetes and 7.05 mmol/L for those without. Timely adjustments in therapeutic strategies, including endocrine and anti-inflammatory treatments, are advisable.


Assuntos
Glicemia , Diabetes Mellitus , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Feminino , Masculino , Prognóstico , Estudos Retrospectivos , Glicemia/análise , Idoso , Pessoa de Meia-Idade , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , Fatores de Risco , Doença Aguda , China/epidemiologia , Seguimentos , Admissão do Paciente
7.
Front Nutr ; 11: 1392268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036498

RESUMO

Objective: Nutritional status is closely associated with the prognosis of heart failure. This study aims to assess the relationship between the Controlling Nutritional Status (CONUT) score and in-hospital mortality among patients with acute decompensated heart failure (ADHF) in Jiangxi, China. Methods: A retrospective cohort study was conducted. Multivariable Cox regression models and restricted cubic spline regression were employed to evaluate the relationship between the CONUT score and in-hospital mortality in ADHF patients from Jiangxi, China. The predictive value of the CONUT score for in-hospital mortality in ADHF patients was analyzed using receiver operating characteristic curves. Subgroup analyses were performed to identify risk dependencies of the CONUT score in specific populations. Results: The study included 1,230 ADHF patients, among whom 44 (3.58%) mortality events were recorded. After adjusting for confounding factors, a positive correlation was found between the CONUT score and the risk of in-hospital mortality in ADHF patients. Restricted cubic spline regression analysis indicated a non-linear relationship between the CONUT score and the risk of in-hospital mortality in ADHF patients, estimating a rapid increase in mortality risk when the CONUT score exceeded 5. Receiver operating characteristic analysis demonstrated a good predictive value of the CONUT score for all-cause mortality events in ADHF patients [area under the curve = 0.7625, optimal threshold = 5.5]. Additionally, a relatively higher risk associated with the CONUT score was observed in male patients and those with concomitant cerebral infarction. Conclusion: This study reveals a positive correlation between the CONUT score and the risk of in-hospital mortality in ADHF patients. Based on the findings of this study, we recommend maintaining a CONUT score below 5 for patients with ADHF in Jiangxi, China, as it may significantly contribute to reducing the risk of in-hospital all-cause mortality.

8.
Clin Transl Sci ; 17(2): e13718, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39052984

RESUMO

This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX-081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug-resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600 mg, N = 52) and a multiple ascending dose (MAD) arm (200 to 400 mg, N = 30). The influence of food was evaluated using a 400 mg dose within an SAD cohort. Plasma concentrations of WX-081 and M3 (main metabolite of WX-081) were analyzed using a validated liquid-chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT0-t), terminal half-life, and clearance of WX-081 ranged from 18.87 to 52.8 h, 31.39 to 236.57 h, and 6.4 to 80.34 L/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC0-t) of WX-081 showed dose-proportional increases in the SAD arm. The disparity between fasted and fed states of WX-081 was significant (p < 0.05), with fed dosing resulting in a 984.07% higher AUC0-t and 961.55% higher maximum plasma concentration. In both the SAD and MAD arms, one case each exhibited a 1 degree atrioventricular block. No QTc elongation was observed, and adverse events were not dose-dependent. Favorable exposure, tolerability, safety, and an extended MRT0-t suggest that WX-081 holds promise as a phase II development candidate for drug-resistant TB treatment.


Assuntos
Antituberculosos , Interações Alimento-Droga , Voluntários Saudáveis , Humanos , Adulto , Masculino , Antituberculosos/farmacocinética , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/sangue , Adulto Jovem , Feminino , Relação Dose-Resposta a Droga , Pessoa de Meia-Idade , Área Sob a Curva , Meia-Vida , China , Povo Asiático , Estudos Cross-Over , População do Leste Asiático
9.
Appl Opt ; 63(12): 3079-3091, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38856451

RESUMO

In most existing studies based on fringe projector profilometry (FPP), the whole scenario is reconstructed, or the ideal experimental settings are established to segment the object easily. However, in real industrial scenarios, automated object detection and segmentation are essential to perform object-level measurement. To address the problem, a dual-wavelet feature interaction network (DWFI-Net) is developed in this paper to perform object phase-valid region segmentation, where both the background and shadow are removed. In our work, the modulation and wrapped phase maps are considered as inputs innovatively. The modulation maps provide abundant structures and textures, while the wrapped phase maps complement and enhance shadows and edges. An adaptive wavelet feature interaction (AWFI) module is presented to learn and fuse the features, where discrete wavelet transformation (DWT) is applied to decompose the features. An edge-aware discrete cosine transformation (EDCT) module is developed as a decoder, where the discrete cosine transformation (DCT) is applied to interpret the fused features. Qualitative and quantitative experiments are performed to verify the superiority of our DWFI-Net and its effectiveness on object-level three-dimensional measurement based on FPP.

10.
J Inflamm Res ; 17: 4001-4016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915806

RESUMO

Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.

11.
Front Endocrinol (Lausanne) ; 15: 1393644, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915891

RESUMO

Objective: Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF). Methods: A total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients. Results: During the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08-14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (<0.24) and the 30-day mortality rate before the fourth quartile, with the lowest 30-day mortality risk in ADHF patients around an AIP of -0.1. Furthermore, mediation analysis suggested significant mediating effects of inflammation and nutrition on the 30-day mortality rate in ADHF patients related to AIP, with inflammation accounting for approximately 24.29% and nutrition for about 8.16% of the mediation effect. Conclusion: This retrospective cohort analysis reveals for the first time the association between AIP and the 30-day mortality rate in ADHF patients. According to our findings, maintaining an AIP around -0.1 in ADHF patients could be crucial for improving poor prognoses from a medical perspective. Additionally, for ADHF patients with high AIP, it is important to assess and, if necessary, enhance nutritional support and anti-inflammatory treatment.


Assuntos
Aterosclerose , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Aterosclerose/mortalidade , Aterosclerose/sangue , Aterosclerose/complicações , Prognóstico , Seguimentos , Biomarcadores/sangue , Doença Aguda , Estudos de Coortes , Fatores de Risco
12.
J Thorac Dis ; 16(5): 3461-3471, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883625

RESUMO

Background and Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, which leads to cardiac decompensation, cardiovascular and cerebrovascular infarction, and other thromboembolic diseases. AF is one of the most common comorbidities of valvular heart disease, especially in mitral valve disease. At the time of their mitral valve surgery, 20-42% of patients have AF. It is beneficial to maintain postoperative sinus rhythm and minimize complications when AF surgery is performed concurrently with mitral valve surgery. This review describes the surgical management of AF in mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. The aim of this review is to enable more patients with AF to receive more appropriate and individualised treatment. Methods: A narrative review was conducted on the literature on PubMed, Embase including all relevant studies published until November 2023. Key Content and Findings: This review focuses on the surgical management of AF during mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. Conclusions: Mitral valve surgery combined with AF surgery facilitates the maintenance of postoperative sinus rhythm in patients, reduces the risk of postoperative stroke, and improves survival. Advances in ablation technology have reduced the difficulty of the procedure, making it possible for more patients to undergo surgical ablation. In the future, it will be possible to tailor specific lesion sets and ablation modalities for individual patients. This would make surgical treatment of AF more effective and applicable to a larger population of patients with AF and mitral valve disease.

13.
J Thorac Dis ; 16(5): 3472-3483, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883655

RESUMO

Background and Objective: Atrial fibrillation (AF) is a prevalent clinical arrhythmia with a high incidence of disability and mortality. Autonomic nervous system (ANS) plays a crucial role in the onset and persistence of AF, and can lead to electrophysiological changes and alterations in atrial structure. Both animal models and clinical findings suggest that parasympathetic and sympathetic activity within the cardiac ANS could induce atrial remodeling and AF. Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting AF. Given the challenges faced by conventional pharmacological and atrial ablation techniques in the treatment of AF, increasing attention has been paid to autonomic intervention strategies for AF. Current research has demonstrated that the frequency and severity of AF episodes can be significantly reduced by modulating the activity of ANS. ANS neuromodulation is expected to lead more effective and personalized treatment options for patients with AF. The objective of this review is to provide a broader perspective for future related studies by reviewing preclinical and clinical studies of neuromodulation methods for the treatment of AF, searching for relevant approaches to treat AF, as well as identifying the strengths and weaknesses demonstrated by current relevant studies, and providing researchers with a broader overview of the latest neurological treatments for AF. Methods: A narrative review was conducted on the literature on PubMed, WanFang data, and Google Scholar, including all relevant studies published until November 2023. Key Content and Findings: In this review, we delve into the innervation of cardiac autonomic nerves, the role of the ANS in the development and maintenance of AF, and the current neuromodulation methods for AF treatment. These methods include stellate ganglion (SG) resection or ablation, vagus nerve stimulation (VNS), thoracic subcutaneous nerve stimulation (ScNS), renal denervation (RDN) therapy, ganglionated plexus (GP) ablation, and epicardial botulinum toxin or CaCl2 injection. More and more research suggests that neuromodulation methods for the treatment of AF have broad prospects. Conclusions: ANS plays a crucial role in AF development and maintenance through cardiac autonomic nerve remodeling. Modulating ANS activity can significantly reduce AF frequency and severity, offering more personalized treatment options. Current research on autonomic interventions for AF shows promise for more effective and personalized treatments.

14.
J Matern Fetal Neonatal Med ; 37(1): 2361278, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38835155

RESUMO

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse perinatal outcomes. Previous studies have demonstrated that the placenta of an ICP pregnancy differs in morphology and gene expression from the placenta of a normal pregnancy. To date, however, the genetic mechanism by which ICP affects the placenta is poorly understood. Therefore, the aim of this study was to investigate the differences in main cell types, gene signatures, cell ratio, and functional changes in the placenta between ICP and normal pregnancy. METHODS: Single-cell RNA sequencing (scRNA-seq) technology was used to detect the gene expression of all cells at the placental maternal-fetal interface. Two individuals were analyzed - one with ICP and one without ICP. The classification of cell types was determined by a graph-based clustering algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R software phyper () function and DAVID website. The differentially expressed genes (DEGs) encoding transcription factors (TFs) were identified using getorf and DIAMOND software. RESULTS: We identified 14 cell types and 22 distinct cell subtypes that showed unique functional properties. Additionally, we found differences in the proportions of fibroblasts 1, helper T (Th) cells, extravillous trophoblasts, and villous cytotrophoblasts, and we observed heterogeneity of gene expression between ICP and control placentas. Furthermore, we identified 263 DEGs that belonged to TF families, including zf-C2H2, HMGI/HMGY, and Homeobox. In addition, 28 imprinted genes were preferentially expressed in specific cell types, such as PEG3 and PEG10 in trophoblasts as well as DLK1 and DIO3 in fibroblasts. CONCLUSIONS: Our results revealed the differences in cell-type ratios, gene expression, and functional changes between ICP and normal placentas, and heterogeneity was found among cell subgroups. Hence, the imbalance of various cell types affects placental activity to varying degrees, indicating the complexity of the cell networks that form the placental tissue system, and this alteration of placental function is associated with adverse events in the perinatal period.


Assuntos
Colestase Intra-Hepática , Placenta , Complicações na Gravidez , Análise de Célula Única , Humanos , Feminino , Gravidez , Análise de Célula Única/métodos , Placenta/metabolismo , Estudos de Casos e Controles , Colestase Intra-Hepática/genética , Complicações na Gravidez/genética , Análise de Sequência de RNA , Adulto
15.
ESC Heart Fail ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867498

RESUMO

AIMS: The value of the systemic immune-inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). METHODS: This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi-acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan-Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose-response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. RESULTS: The Kaplan-Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII < 980 × 109/L, log-rank P < 0.001). After adjusting for various confounding factors, a higher SII was associated with an increased risk of 30 day mortality in ADHF patients [hazard ratio (HR) = 2.03, 95% confidence interval (CI): 1.34-3.08]. Further restricted cubic spline analysis revealed a non-linear dose-response relationship between the two (P for non-linear = 0.006). Receiver operating characteristic analysis demonstrated that SII had a high accuracy in predicting 30 day mortality events in ADHF patients (AUC = 0.7479), and the optimal predictive threshold was calculated to be 980 × 109/L, a sensitivity of 0.7547 and a specificity of 0.7234. CONCLUSIONS: This study found a significant positive association between SII and 30 day all-cause mortality in ADHF patients. We determined the SII cut-off point for predicting 30 day all-cause mortality in patients with ADHF to be 980 × 109/L.

16.
Sci Rep ; 14(1): 13981, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886481

RESUMO

Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis and hepatocellular carcinoma, but its pathogenesis has not been fully elucidated. Mutations in the HBV preS/S genes can lead to impaired secretion of either HBsAg or S-protein resulting in the accumulation of defective viruses or S protein in cells. In our previous work, the M133S mutation was present in the HBV S gene of maintenance hemodialysis (MHD) patients with OBI. In this study, we investigated the potential role of amino acid substitutions in S proteins in S protein production and secretion through the construction of mutant S gene plasmids, structural prediction, transcriptome sequencing analysis, and in vitro functional studies. Protein structure prediction showed that the S protein M133S mutant exhibited hydrophilic modifications, with greater aggregation and accumulation of the entire structure within the membrane phospholipid bilayer. Differential gene enrichment analysis of transcriptome sequencing data showed that differentially expressed genes were mainly concentrated in protein processing in the endoplasmic reticulum (ER). The expression of heat shock family proteins and ER chaperone molecules was significantly increased in the wild-type and mutant groups, whereas the expression of mitochondria-associated proteins was decreased. Immunofluorescence staining and protein blotting showed that the endoplasmic reticulum-associated protein PDI, the autophagy marker LC3, and the lysosome-associated protein LAMP2 co-localized with the S proteins in the wild-type and mutant strains, and their expression was increased. The mitochondria-associated TOMM20 protein was also co-expressed with the S protein, but expression was significantly reduced in the mutant. The M133S mutation in the S gene is expressed as a defective and misfolded protein that accumulates in the endoplasmic reticulum causing secretion-impaired endoplasmic reticulum stress, which in turn triggers mitochondrial autophagy and recruits lysosomes to fuse with the autophagosome, leading to mitochondrial clearance. This study preliminarily demonstrated that the mutation of M133S in the S gene can cause OBI and is associated with disease progression, providing a theoretical basis for the diagnosis and treatment of OBI.


Assuntos
Estresse do Retículo Endoplasmático , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B , Mitofagia , Diálise Renal , Humanos , Mitofagia/genética , Hepatite B/virologia , Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/complicações , Vírus da Hepatite B/genética , Estresse do Retículo Endoplasmático/genética , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Masculino , Mutação , Feminino , Pessoa de Meia-Idade , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/genética , Substituição de Aminoácidos , Adulto
17.
BMC Cardiovasc Disord ; 24(1): 264, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773437

RESUMO

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.


Assuntos
Causas de Morte , Doença da Artéria Coronariana , Avaliação Geriátrica , Desnutrição , Avaliação Nutricional , Estado Nutricional , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Idoso , Medição de Risco , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico , Desnutrição/diagnóstico , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Tempo , Fatores Etários , Idoso de 80 Anos ou mais , Japão/epidemiologia
18.
Natl Sci Rev ; 11(6): nwae115, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38707202

RESUMO

Multi-boron-embedded multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters show promise for achieving both high color-purity emission and high exciton utilization efficiency. However, their development is often impeded by a limited synthetic scope and excessive molecular weights, which challenge material acquisition and organic light-emitting diode (OLED) fabrication by vacuum deposition. Herein, we put forward a B‒N covalent bond-involved π-extension strategy via post-functionalization of MR frameworks, leading to the generation of high-order B/N-based motifs. The structurally and electronically extended π-system not only enhances molecular rigidity to narrow emission linewidth but also promotes reverse intersystem crossing to mitigate efficiency roll-off. As illustrated examples, ultra-narrowband sky-blue emitters (full-width at half-maximum as small as 8 nm in n-hexane) have been developed with multi-dimensional improvement in photophysical properties compared to their precursor emitters, which enables narrowband OLEDs with external quantum efficiencies (EQEmax) of up to 42.6%, in company with alleviated efficiency decline at high brightness, representing the best efficiency reported for single-host OLEDs. The success of these emitters highlights the effectiveness of our molecular design strategy for advanced MR-TADF emitters and confirms their extensive potential in high-performance optoelectronic devices.

19.
Front Cardiovasc Med ; 11: 1338156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742174

RESUMO

Objective: While hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear. Methods: A retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves. Results: After adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices. Conclusion: Among the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.

20.
BMC Endocr Disord ; 24(1): 66, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730299

RESUMO

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.


Assuntos
Índice de Massa Corporal , Lipídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lipídeos/sangue , Análise de Mediação , Adulto , Estudos de Coortes , Fatores de Risco , Biomarcadores/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , HDL-Colesterol/sangue , Idoso , Diabetes Mellitus Tipo 2/sangue , Triglicerídeos/sangue , Seguimentos , Prognóstico
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