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1.
Animal ; 18(9): 101273, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39153441

RESUMEN

This study addresses the critical issue of high-temperature stress in Japanese flounder (Paralichthys olivaceus), a factor threatening both their survival and the growth of the aquaculture industry. The research aims to identify genetic markers associated with high-temperature tolerance, unravel the genetic regulatory mechanisms, and lay the foundation for breeding Japanese flounder with increased resistance to high temperatures. In this study, using a genome-wide association study was performed to identify single nucleotide polymorphisms (SNPs) and genes associated with high-temperature tolerance for Japanese flounder using 280 individuals with 342 311 high-quality SNPs. The traits of high-temperature tolerance were defined as the survival time and survival status of Japanese flounder at high water temperature (31℃) for 15 days cultivate. A genome-wide association study identified six loci on six chromosomes significantly correlated with survival time under high-temperature stress. Six candidate genes were successfully annotated. Additionally, 34 loci associated with survival status were identified and mapped to 15 chromosomes, with 22 candidate genes annotated. Functional analysis highlighted the potential importance of genes like traf4 and ppm1l in regulating apoptosis, impacting high-temperature tolerance in Japanese flounder. These findings provide a valuable theoretical framework for integrating molecular markers into Japanese flounder breeding programmes, serving as a molecular tool to enhance genetic traits linked to high-temperature tolerance in cultured Japanese flounder.

2.
Gynecol Oncol ; 189: 138-145, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39126895

RESUMEN

OBJECTIVE: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes. METHODS: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures. RESULTS: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%). CONCLUSIONS: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.

3.
Bull Math Biol ; 86(9): 115, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102074

RESUMEN

In this paper, we study the problem of cost optimisation of individual-based institutional incentives (reward, punishment, and hybrid) for guaranteeing a certain minimal level of cooperative behaviour in a well-mixed, finite population. In this scheme, the individuals in the population interact via cooperation dilemmas (Donation Game or Public Goods Game) in which institutional reward is carried out only if cooperation is not abundant enough (i.e., the number of cooperators is below a threshold 1 ≤ t ≤ N - 1 , where N is the population size); and similarly, institutional punishment is carried out only when defection is too abundant. We study analytically the cases t = 1 for the reward incentive under the small mutation limit assumption and two different initial states, showing that the cost function is always non-decreasing. We derive the neutral drift and strong selection limits when the intensity of selection tends to zero and infinity, respectively. We numerically investigate the problem for other values of t and for population dynamics with arbitrary mutation rates.


Asunto(s)
Conducta Cooperativa , Teoría del Juego , Conceptos Matemáticos , Motivación , Castigo , Recompensa , Humanos , Dinámica Poblacional/estadística & datos numéricos , Simulación por Computador , Densidad de Población , Mutación
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(7): 1266-1271, 2024 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-39051072

RESUMEN

OBJECTIVE: To investigate the association of triglyceride-glucose index (TyG) with non-alcoholic fatty liver disease (NAFLD) and its diagnostic value for NAFLD in non-obese individuals. METHODS: We retrospectively collected the data of non-obese individuals (BMI < 25 kg/m2) undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May, 2020 and December, 2023, who all received abdominal ultrasound examination for NAFLD screening. The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines (RCS), and LASSO regression was used for variable screening; the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression. The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic (ROC) curves and sensitivity analysis. RESULTS: A total of 3723 non-obese subjects were enrolled in this study, including 432 (11.6%) patients with NAFLD. Compared with the healthy individuals, the patients with NAFLD had significant elevations of systolic and diastolic blood pressures, total cholesterol, triglycerides, LDL-C, blood uric acid, fasting blood glucose, and TyG index and a decreased HDL-C level (P < 0.05). Multivariate logistic regression revealed that for each one-unit increase of TyG, the risk of non-obese NAFLD increased by 2.2 folds (OR=3.22, 95% CI: 2.53-4.12, P < 0.001). Compared with a TyG index in the lowest quartile Q1, a TyG index in the Q2, Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds (OR=2.52, 95% CI: 1.20-5.95), 3.56 folds (OR=4.56, 95% CI: 2.28-10.46), and 8.66-folds (OR=9.66, 95% CI: 4.83-22.18), respectively. The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk (P for nonlinear= 0.019). For diagnosing non-obese NALFD, TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0% and a specificity of 71.2%. CONCLUSION: An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.


Asunto(s)
Glucemia , Enfermedad del Hígado Graso no Alcohólico , Triglicéridos , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Estudios Retrospectivos , Triglicéridos/sangre , Femenino , Glucemia/análisis , Masculino , Factores de Riesgo , Curva ROC , Modelos Logísticos , Persona de Mediana Edad , Índice de Masa Corporal , Adulto , Obesidad/sangre , Obesidad/complicaciones , Valor Predictivo de las Pruebas
6.
Eur Rev Med Pharmacol Sci ; 28(12): 3805, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38946387

RESUMEN

Eur Rev Med Pharmacol Sci 2024; 28 (2): 477-501-DOI: 10.26355/eurrev_202401_35047-PMID: 38305595, published online on January 31, 2024. After publication, the authors have found a mistake in the affiliation No. 1. Affiliation No. 1 has been corrected as follows: The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/35047.

7.
Neurooncol Adv ; 6(1): vdae058, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887507

RESUMEN

Background: The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS. Methods: Transcriptomic analysis of a murine schwannoma allograft model and immunohistochemical analysis of 17 human VS were performed. MMP9 abundance was assessed in mouse and human schwannoma cell lines. Transwell studies were performed to evaluate the effect of MMP9 on schwannoma invasion in vitro. Plasma biomarkers were identified from a multiplexed proteomic analysis in 45 prospective VS patients and validated in primary culture. The therapeutic efficacy of MMP9 inhibition was evaluated in a mouse schwannoma model. Results: MMP9 was the most highly upregulated protease in mouse schwannomas and was significantly enriched in adherent VS, particularly around tumor vasculature. High levels of MMP9 were found in plasma of patients with adherent VS. MMP9 outperformed clinical and radiographic variables to classify adherent VS with outstanding discriminatory ability. Human schwannoma cells secreted MMP9 in response to TNF-α which promoted cellular invasion and adhesion protein expression in vitro. Lastly, MMP9 inhibition decreased mouse schwannoma growth in vivo. Conclusions: We identify MMP9 as a preoperative biomarker to classify adherent VS. MMP9 may represent a new therapeutic target in adherent VS associated with poor surgical outcomes that lack other viable treatment options.

8.
Intensive Care Med ; 50(7): 1064-1074, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38748266

RESUMEN

PURPOSE: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI). METHODS: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months. RESULTS: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients. CONCLUSIONS: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention.


Asunto(s)
Enfermedad Crítica , Fragilidad , Evaluación Geriátrica , Unidades de Cuidados Intensivos , Humanos , Anciano , Estudios Prospectivos , Enfermedad Crítica/terapia , Enfermedad Crítica/mortalidad , Masculino , Femenino , Fragilidad/complicaciones , Fragilidad/epidemiología , Persona de Mediana Edad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Anciano de 80 o más Años , Anciano Frágil/estadística & datos numéricos , Estudios de Cohortes , Cuidados Críticos/métodos , Cuidados Críticos/estadística & datos numéricos , Prevalencia
9.
Clin Radiol ; 79(8): e1021-e1030, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38821757

RESUMEN

AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.


Asunto(s)
Tejido Adiposo , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Angiografía Coronaria/métodos , Tejido Adiposo/diagnóstico por imagen , Anciano , Tejido Adiposo Epicárdico
10.
Zhonghua Xue Ye Xue Za Zhi ; 45(2): 121-127, 2024 Feb 14.
Artículo en Chino | MEDLINE | ID: mdl-38604787

RESUMEN

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios de Casos y Controles , Infecciones por Citomegalovirus , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos
11.
Zhonghua Xue Ye Xue Za Zhi ; 45(1): 22-27, 2024 Jan 14.
Artículo en Chino | MEDLINE | ID: mdl-38527834

RESUMEN

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Sinusitis , Adulto , Femenino , Humanos , Masculino , Anfotericina B , Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Voriconazol , Niño , Adolescente , Adulto Joven , Persona de Mediana Edad
12.
J Emerg Med ; 66(3): e341-e345, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38403563

RESUMEN

BACKGROUND: The estimated serum osmolality is a measurement of solutes in the blood, including sodium, glucose, and urea, but also includes ethanol and toxic alcohols (e.g., methanol, ethylene glycol, diethylene glycol, isopropyl alcohol, propylene glycol) when present. These rarely measured toxic alcohols can elevate the serum osmolality, giving the true measured osmolality. The difference between that and a calculated osmolality is the osmolal gap, which can be elevated in many clinical scenarios such as renal failure, ingestion of toxic alcohols, diabetic ketoacidosis, shock, and others. CASE REPORT: We report a patient with a history of alcohol use disorder who came to the Emergency Department with an abnormally elevated osmolal gap in the setting of altered mental status. The patient's increased osmolal gap was further investigated while he was promptly treated with fomepizole, thiamine, and urgent hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the differential diagnosis for substances that increase the osmolal gap with respective ranges of elevation. This case demonstrates that although osmolal gap elevation is often attributed to the presence of toxic alcohols, other common etiologies may account for the gap, including acute renal failure and multiple myeloma.


Asunto(s)
Alcoholismo , Cetoacidosis Diabética , Mieloma Múltiple , Masculino , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Etanol , Metanol , Glicol de Etileno , Concentración Osmolar
14.
Eur Rev Med Pharmacol Sci ; 28(2): 477-501, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38305595

RESUMEN

OBJECTIVE: Retinopathy of prematurity (ROP) is an eye disease with the potential to cause blindness, primarily affecting premature infants with low birth weight. This study analyzed the etiology, primary location, and research advances in ROP. MATERIALS AND METHODS: We used bibliometric techniques and searched the Web of Science Core Collection for "retinopathy of prematurity." We found 4,018 original articles and reviews with 69,819 references. We analyzed the data using HistCite (12.03.17), VOSviewer (1.6.16), CiteSpace (6.1. R5), and the Bibliometrix Package (4.1.0). RESULTS: The amount of literature in this area has increased between 2001-2021. An analysis of references and journal co-citations highlights this field's most influential articles and related topics. Hellström, from the University of Gothenburg (Sweden), is the most prolific researcher; Harvard University is the most prolific research institution, and the USA is the most productive country. "Threshold ROP" and "cryotherapy" are the keywords with the highest burst strength. The future research hotspots are artificial intelligence, zone II, ROP development, ranibizumab, and type 1 retinopathy. CONCLUSIONS: This article offers a comprehensive review of the present status of ROP research, along with insights into emerging concepts and potential international collaborations in this field.


Asunto(s)
Retinopatía de la Prematuridad , Humanos , Recién Nacido , Inteligencia Artificial , Bibliometría , Ceguera , Recien Nacido Prematuro
15.
J Prev Alzheimers Dis ; 11(1): 196-213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38230733

RESUMEN

BACKGROUND: Aging is considered a key risk factor for Alzheimer's disease (AD). This study aimed to identify and validate potential aging-related genes associated with AD using bioinformatics analysis. METHODS: Datasets GSE36980 and GSE5281 were selected to screen differentially expressed genes (DEGs), and the immune cell correlation analysis and GSEA analysis of DEGs were performed. The intersection with senescence genes was taken as differentially expressed senescence-related genes (DESRGs), and the GSE44770 dataset was used for further validation. The potential biological functions and signaling pathways were determined by GO and KEGG, and the hub genes were identified by 12 algorithms in Cytohubba. The expression of 10 hub genes in different brain regions was determined and single-cell sequencing analysis was performed, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed. RESULTS: A total of 2137 DEGs were screened from the GSE36980 and GSE5281 datasets, and 278 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 29 DESRGs, including 14 senescence suppressor genes and 15 senescence inducible genes. The top 10 hub genes, including MDH1, CKB, PSMD14, SMARCA4, PEBP1, DDB2, ITPKB, ATF7IP, YAP1, and EWSR1 were screened. Furthermore, four diagnostic genes were identified: PMSD14, PEBP1, ITPKB, and ATF7IP. The ROC analysis showed that the respective area under the curves (AUCs) of PMSD14, PEBP1, ITPKB, and ATF7IP were 0.732, 0.701, 0.747, and 0.703 in the GSE36980 dataset and 0.870, 0.817, 0.902, and 0.834 in the GSE5281 dataset. In the GSE44770 dataset, PMSD14 (AUC, 0.838) and ITPKB (AUC, 0.952) had very high diagnostic values in the early stage of AD. Finally, based on these diagnostic genes, we found that the drug Abemaciclib is a targeted drug for the treatment of age-related AD. Flutamide can aggravate aging-related AD. CONCLUSION: The results of this study suggest that cellular SRGs might play an important role in AD. PMSD14, PEBP1, ITPKB, and ATF7IP have the potential as specific biomarkers for the early diagnosis of AD.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/genética , Envejecimiento/genética , Algoritmos , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción , Transactivadores , Complejo de la Endopetidasa Proteasomal
16.
Eur Rev Med Pharmacol Sci ; 28(1): 107-117, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38235898

RESUMEN

OBJECTIVE: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood. MATERIALS AND METHODS: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method. RESULTS: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk. CONCLUSIONS: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field.


Asunto(s)
Dermatitis Atópica , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Humanos , Dermatitis Atópica/genética , Ácidos Docosahexaenoicos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana
17.
Zhonghua Er Ke Za Zhi ; 62(2): 129-137, 2024 Feb 02.
Artículo en Chino | MEDLINE | ID: mdl-38264812

RESUMEN

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.


Asunto(s)
Displasia Broncopulmonar , Hipertensión Pulmonar , Enfermedades del Prematuro , Síndrome de Dificultad Respiratoria del Recién Nacido , Recién Nacido , Lactante , Niño , Humanos , Femenino , Embarazo , Recien Nacido Prematuro , Estudios Retrospectivos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Sufrimiento Fetal , Modelos Estadísticos , Pronóstico , Placenta , Edad Gestacional , Corticoesteroides
18.
Curr Nutr Rep ; 13(1): 15-22, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38194079

RESUMEN

PURPOSE OF REVIEW: Falls are a major global public health issue and the second cause of unintentional injury death. Nutrition may be an important factor for falls prevention in adults, but most previous studies examined the associations between single nutrients and falls. The use of dietary patterns is an alternative method to measure whole diet and its relationship with health outcomes. Therefore, we aimed to systematically review all evidence relating to dietary pattern impacts on falls and/or falls risk in adults. RECENT FINDINGS: This systematic review was registered on the PROSPERO (CRD42020171987). Four databases (Medline, Embase, Cochrane Library, CINAHL Complete) were used for searching potential articles on 18th December 2021 and updated the search on 10th July 2023. We included any quantitative study reporting associations between dietary patterns and falls and/or falls risk in healthy adults ≥ 18 years and publishing in English as full text and peer-reviewed. Of 2866 potential articles, five studies (two cross-sectional, three cohorts) were included for the evidence synthesis. The risk of bias was low in cohort studies. Dietary patterns were derived using both "a priori" or "empirical" approaches, and self-report questionnaires used for falls/falls risk in most studies. Associations between dietary patterns and falls/falls risk were inconsistent results by sex and study design. The effect of dietary patterns on reducing falls/falls risk is not clear in the included studies, so this association needs to be confirmed in future research.


Asunto(s)
Accidentes por Caídas , Patrones Dietéticos , Adulto , Femenino , Humanos , Masculino , Accidentes por Caídas/prevención & control , Factores de Riesgo
19.
Zhonghua Nei Ke Za Zhi ; 62(11): 1295-1302, 2023 Nov 01.
Artículo en Chino | MEDLINE | ID: mdl-37935495

RESUMEN

Objective: To investigate the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mitigating the adverse prognosis associated with central nervous system leukemia (CNSL) and to assess the significance of prophylactic intrathecal injection. Methods: A retrospective cohort analysis was conducted involving 30 patients with acute leukemia who had a history of CNSL who underwent allo-HSCT at Peking University People's Hospital between September 2012 and March 2018 (referred to as the CNSL-positive group). In addition, 90 patients with acute leukemia were selected from the same period who underwent allo-HSCT without a history of CNSL (referred to as the CNSL-negative group) and a rigorous 1∶3 matching was performed based on disease type, disease status, and transplantation type to form the control group. The prognosis between the two groups was compared using Kaplan-Meier analysis and the high-risk factors for CNSL relapse post-transplant were identified through Cox proportional-hazards model. Results: The median age of patients in the CNSL-negative group was significantly higher than that of patients in the CNSL-positive group (32 years vs. 24 years, P=0.014). No significant differences were observed in baseline data, including sex, disease type, disease status at transplantation, donor-recipient relationship, and human leukocyte antigen consistency between the two groups. The median follow-up time was 568 days (range: 21-1 852 days). The 4-year cumulative incidence of relapse (71.4%±20.9% vs. 29.3%±11.5%, P=0.005) and the cumulative incidence of CNSL post-transplant (33.6%±9.2% vs. 1.2%±1.2%, P<0.001) were significantly higher in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival rate in the CNSL-positive group was significantly lower than that in the CNSL-negative group (23.1%±17.0% vs. 71.5%±11.6%, P<0.001). However, no significant differences were observed in the 4-year cumulative transplant-related mortality and overall survival rates between the two groups (both P>0.05). Multivariate analysis revealed that a history of CNSL before transplantation (HR=25.050, 95%CI 3.072-204.300, P=0.003) was identified as high-risk factors for CNSL relapse post-transplant. Conversely, haploidentical transplantation was associated with a reduced risk of CNSL relapse post-transplant (HR=0.260, 95%CI 0.073-0.900, P=0.034). Within the CNSL-positive group, seven patients received prophylactic intrathecal therapy after transplantation, and their CNSL relapse rate was significantly lower than that of the 23 patients who did not receive intrathecal therapy after transplantation (0/7 vs. 9/23, P=0.048). Conclusions: Patients with a history of CNSL have a higher risk of relapse and experience poorer leukemia-free survival following transplantation. The use of prophylactic intrathecal injection shows promise in mitigating CNSL relapse rates, although further validation through prospective studies is necessary to substantiate these observations.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Pronóstico , Estudios Retrospectivos , Estudios Prospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia Mieloide Aguda/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Recurrencia , Sistema Nervioso Central
20.
J Math Biol ; 87(5): 77, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884760

RESUMEN

In this paper, we rigorously study the problem of cost optimisation of hybrid (mixed) institutional incentives, which are a plan of actions involving the use of reward and punishment by an external decision-maker, for maximising the level (or guaranteeing at least a certain level) of cooperative behaviour in a well-mixed, finite population of self-regarding individuals who interact via cooperation dilemmas (Donation Game or Public Goods Game). We show that a mixed incentive scheme can offer a more cost-efficient approach for providing incentives while ensuring the same level or standard of cooperation in the long-run. We establish the asymptotic behaviour (namely neutral drift, strong selection, and infinite-population limits). We prove the existence of a phase transition, obtaining the critical threshold of the strength of selection at which the monotonicity of the cost function changes and providing an algorithm for finding the optimal value of the individual incentive cost. Our analytical results are illustrated with numerical investigations. Overall, our analysis provides novel theoretical insights into the design of cost-efficient institutional incentive mechanisms for promoting the evolution of cooperation in stochastic systems.


Asunto(s)
Teoría del Juego , Motivación , Humanos , Conducta Cooperativa , Castigo , Recompensa , Evolución Biológica
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