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1.
Database (Oxford) ; 20242024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137906

RESUMEN

Cancer stemness plays an important role in cancer initiation and progression, and is the major cause of tumor invasion, metastasis, recurrence, and poor prognosis. Non-coding RNAs (ncRNAs) are a class of RNA transcripts that generally cannot encode proteins and have been demonstrated to play a critical role in regulating cancer stemness. Here, we developed the ncStem database to record manually curated and predicted ncRNAs associated with cancer stemness. In total, ncStem contains 645 experimentally verified entries, including 159 long non-coding RNAs (lncRNAs), 254 microRNAs (miRNAs), 39 circular RNAs (circRNAs), and 5 other ncRNAs. The detailed information of each entry includes the ncRNA name, ncRNA identifier, disease, reference, expression direction, tissue, species, and so on. In addition, ncStem also provides computationally predicted cancer stemness-associated ncRNAs for 33 TCGA cancers, which were prioritized using the random walk with restart (RWR) algorithm based on regulatory and co-expression networks. The total predicted cancer stemness-associated ncRNAs included 11 132 lncRNAs and 972 miRNAs. Moreover, ncStem provides tools for functional enrichment analysis, survival analysis, and cell location interrogation for cancer stemness-associated ncRNAs. In summary, ncStem provides a platform to retrieve cancer stemness-associated ncRNAs, which may facilitate research on cancer stemness and offer potential targets for cancer treatment. Database URL: http://www.nidmarker-db.cn/ncStem/index.html.


Asunto(s)
Neoplasias , Células Madre Neoplásicas , ARN no Traducido , Humanos , Neoplasias/genética , Neoplasias/metabolismo , ARN no Traducido/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Bases de Datos de Ácidos Nucleicos , Bases de Datos Genéticas , Curaduría de Datos/métodos , MicroARNs/genética , MicroARNs/metabolismo
2.
Aesthetic Plast Surg ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179657

RESUMEN

OBJECTIVE: To investigate the application and therapeutic efficacy of a novel cartilage framework: the external septa framework in East Asian rhinoplasty. METHODS: From November 2021 to April 2023, Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital, Central South University, treated 41 patients with autologous costal cartilage rhinoplasty using an innovation external septal framework. The surgical open approach used an inverted V-shaped trans-columellar incision and marginal incision. The sixth or seventh costal cartilage was harvested to form the nasal columella support grafts (strut), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft are connected in a way of tongue in groove to form a external septum framework to support and lengthen the tip. A cap graft is used to shape the tip of the nose, the rectus abdominis fascia is used to cover the tip of the nose, and the shield grafts are used to augment the inferior lobules. ePTFE was sculpted according to the degree of augment of the nasal dorsum and implanted on the dorsal to augment the nasal dorsum. Clinical outcomes were assessed through standard facial photographs taken during the preoperative and follow-up periods, and a postoperative satisfaction survey was completed with regular follow-up using the rhinoplasty outcome evaluation scale (ROE) and visual analogue scale (VAS). Results of objective and subjective measurements before and after surgery were compared utilizing paired-sample t tests. Values of P < 0.05 were considered significant. Nasal framework's objective evaluation outcomes were assessed by measuring the patients' preoperative and postoperative nasolabial angle, nasal length, and nasal tip projection. (The distance between the pronasale and the alar-cheek junction was calculated as the tip projection.) The comparison of preoperative and postoperative nasolabial angle and nasal length was performed using the paired-sample t test, and the comparison of nasal tip projection was performed using the Wilcoxon signed rank-sum test for the comparison of paired samples. Values of P < 0 .05 were considered significant. RESULTS: A total of 41 patients were treated, including 9 males and 32 females, ranging in age from 17 to 48 years(32.8 ± 1.5 years old), In the study, an average follow-up period of 19.85 ± 4.88 months was observed (range 12-29 months). There was no long-term or short-term complication observed. The aesthetic outcome of all cases such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and bulbous tip was satisfactory. Patient satisfaction evaluation: The ROE scale was (11.85 ± 2.46) preoperatively and (17.43 ± 2.15) postoperatively. The VAS scores were (4.86 ± 1.60) preoperatively and (8.48 ± 1.25) postoperatively. The difference of ROE scale and VAS scores among the patients was statistically significant (P < 0. 05), and 88.9% of patients were satisfied following those procedures. In terms of nasolabial angle, preoperative and postoperative measurements of 41 patients were (86.11 ± 2.25)° and (98.66 ± 1.90)°, respectively, and the difference of nasolabial angle was statistically significant (P < 0.05); nasal length measurements were 39.43 ± 1.55 mm (37.95-43.51 mm) preoperatively and 42.17 ± 1.46 mm (40.23-45.62 mm) postoperatively; in terms of nasal tip projection, preoperative and postoperative measurements of median values were 1.84(1.73,2.01) cm and 2.15(2.02,2.32) cm, respectively; and the difference between preoperative and postoperative values was statistically significant (P < 0.05). CONCLUSIONS: The innovative cartilage framework-external septal framework, avoids the dissection of septa and absorption of septal cartilage with compression of ESG, it is easy to be performed, and it is also stable and strong to achieve in good aesthetic result. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors  www.springer.com/00266 .

3.
Adv Sci (Weinh) ; : e2403158, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953329

RESUMEN

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+-mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

4.
Environ Pollut ; 358: 124523, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38986763

RESUMEN

Halogenated flame retardants in farmlands were observed to inhibit the growth of exposed crops. This study aimed to elucidate the mechanism of inhibition on rice by employing four representative polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). The exposure to these contaminants at 200 nM led to a decrease of 0.63-0.95 fold in rice below-ground biomass and 0.49-0.66 fold in yield, and a corresponding 4%-10% increase in soluble sugars in leaves. PBDEs and PCBs were found to significantly disrupt the synthesis, decomposition, and transport of sugars in leaves, the three pivotal determinants of crop growth. Notably, these compounds promoted a 1.41- to 7.60-fold upregulation of the triose phosphate translocator, significantly enhancing soluble sugar synthesis. Conversely, a 0.45-0.97 fold downregulation was observed for sucrose transporters, thus impeding the leaf-to-shoot efflux of soluble sugars. Furthermore, PBDEs and PCBs were favorably bound to fructose-1,6-bisphosphate aldolase (FBA), inducing its substrate-specific dysfunction in fructose-1,6-diphosphate decomposition (3%-14%). Overall, PBDE and PCB exposure promoted a notable intracellular accumulation of soluble sugars in rice leaves, a typical symptom of plant diabetes, since the intensified synthesis of soluble sugars in leaves and the repressed decomposition and transportation of soluble sugars to other storage organs, thus impeding crop growth. This study provided an insightful understanding of the toxic effects and molecular mechanisms of halogenated flame retardants, highlighting their role in abnormal sugar accumulation and growth inhibition in crops and offering vital information for the risk assessment and administration of these compounds to guarantee the safety of agricultural products.


Asunto(s)
Éteres Difenilos Halogenados , Oryza , Bifenilos Policlorados , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Éteres Difenilos Halogenados/metabolismo , Bifenilos Policlorados/metabolismo , Azúcares/metabolismo , Hojas de la Planta/metabolismo , Contaminantes del Suelo/metabolismo , Retardadores de Llama/metabolismo , Transporte Biológico
5.
FASEB J ; 38(13): e23760, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38924449

RESUMEN

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.


Asunto(s)
Hiponatremia , Síndrome de Secreción Inadecuada de ADH , Proteínas de Transporte de Membrana , Ratones Noqueados , Transportadores de Urea , Animales , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Diuréticos/farmacología , Hiponatremia/tratamiento farmacológico , Hiponatremia/metabolismo , Síndrome de Secreción Inadecuada de ADH/tratamiento farmacológico , Síndrome de Secreción Inadecuada de ADH/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Ratones Endogámicos C57BL , Concentración Osmolar , Ratas Sprague-Dawley , Sodio/metabolismo
6.
Sci Rep ; 14(1): 13480, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866837

RESUMEN

The long-term trends in maternal and child health (MCH) in China and the national-level factors that may be associated with these changes have been poorly explored. This study aimed to assess trends in MCH indicators nationally and separately in urban and rural areas and the impact of public policies over a 30‒year period. An ecological study was conducted using data on neonatal mortality rate (NMR), infant mortality rate (IMR), under-five mortality rate (U5MR), and maternal mortality ratio (MMR) nationally and separately in urban and rural areas in China from 1991 to 2020. Joinpoint regression models were used to estimate the annual percentage changes (APC), average annual percentage changes (AAPC) with 95% confidence intervals (CIs), and mortality differences between urban and rural areas. From 1991 to 2020, maternal and child mortalities in China gradually declined (national AAPC [95% CI]: NMRs - 7.7% [- 8.6%, - 6.8%], IMRs - 7.5% [- 8.4%, - 6.6%], U5MRs - 7.5% [- 8.5%, - 6.5%], MMRs - 5.0% [- 5.7%, - 4.4%]). However, the rate of decline nationally in child mortality slowed after 2005, and in maternal mortality after 2013. For all indicators, the decline in mortality was greater in rural areas than in urban areas. The AAPCs in rate differences between rural and urban areas were - 8.5% for NMRs, - 8.6% for IMRs, - 7.7% for U5MRs, and - 9.6% for MMRs. The AAPCs in rate ratios (rural vs. urban) were - 1.2 for NMRs, - 2.1 for IMRs, - 1.7 for U5MRs, and - 1.9 for MMRs. After 2010, urban‒rural disparity in MMR did not diminish and in NMR, IMR, and U5MR, it gradually narrowed but persisted. MCH indicators have declined at the national level as well as separately in urban and rural areas but may have reached a plateau. Urban‒rural disparities in MCH indicators have narrowed but still exist. Regular analyses of temporal trends in MCH are necessary to assess the effectiveness of measures for timely adjustments.


Asunto(s)
Salud Infantil , Mortalidad del Niño , Mortalidad Infantil , Salud Materna , Mortalidad Materna , Población Rural , Población Urbana , Humanos , China/epidemiología , Salud Infantil/tendencias , Femenino , Lactante , Salud Materna/tendencias , Mortalidad Infantil/tendencias , Preescolar , Mortalidad del Niño/tendencias , Mortalidad Materna/tendencias , Niño , Recién Nacido , Masculino
7.
J Nanobiotechnology ; 22(1): 359, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907216

RESUMEN

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.


Asunto(s)
Materiales Biocompatibles , Inmunoterapia , Macrófagos , Periodontitis , Humanos , Periodontitis/tratamiento farmacológico , Periodontitis/terapia , Materiales Biocompatibles/química , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Animales , Inmunoterapia/métodos , Sistemas de Liberación de Medicamentos/métodos
8.
J Hazard Mater ; 476: 134953, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38908176

RESUMEN

The widespread introduction of organic compounds into environments poses significant risks to ecosystems. Assessing the adverse effects of organic contaminants on crops is crucial for ensuring food safety. However, laboratory research is often time-consuming and costly, and machine learning (ML) methods can offer a viable solution to address these challenges. This study aimed at developing a ML model that incorporates chemical descriptors to predict the phytotoxicity of organic contaminants on rice. A dataset was compiled by gathering published experimental data on the phytotoxicity of 60 organic compounds, with a focus on morphological inhibition, photosynthesis perturbation, and oxidative stress. Four ML models (RF, SVM, GBM, ANN) were developed using chemical molecular descriptors (CMD) and the Molecular ACCess System (MACCS) keys. RF-MACCS model demonstrated the highest fitness, achieving an R2 value of 0.79 and an RMSE of 0.14. Feature importance analysis highlighted nAtom, HBA, logKow, and TPSA as the most influential CMDs in our model. Additionally, substructures containing oxygen atoms, carbonyl group and carbon chains with nitrogen and oxygen atoms were identified as significant factors associated with phytotoxicity. This data-driven study could aid in predicting the phytotoxicity of organic contaminants on crops and evaluating the potential risks of emerging contaminants in agroecosystems.


Asunto(s)
Aprendizaje Automático , Oryza , Oryza/efectos de los fármacos , Oryza/crecimiento & desarrollo , Compuestos Orgánicos/toxicidad , Fotosíntesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes del Suelo/toxicidad
9.
Environ Int ; 187: 108737, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38735075

RESUMEN

DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1-71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87-95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (log2FC = -4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.


Asunto(s)
Metilación de ADN , Oryza , Sulfonamidas , Metilación de ADN/efectos de los fármacos , Oryza/genética , Oryza/metabolismo , Sulfonamidas/toxicidad , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Contaminantes del Suelo/toxicidad
10.
Sci Rep ; 14(1): 11633, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773186

RESUMEN

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.


Asunto(s)
Adenoma , Colonoscopía , Neoplasias Colorrectales , Estilo de Vida , Nomogramas , Humanos , Neoplasias Colorrectales/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adenoma/diagnóstico , Estudios Retrospectivos , Anciano , Factores de Riesgo , Adulto , Modelos de Riesgos Proporcionales , Curva ROC
11.
Vascular ; : 17085381241257161, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805192

RESUMEN

OBJECTIVES: The purpose of this study was to investigate the hemodynamic consequences of thoracic endovascular aortic repair which reconstructed left subclavian artery by chimney stent (ch-TEVAR). METHODS: Two patients who underwent thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) reconstruction using chimney stents were selected. Preoperative and postoperative CTA images were collected to reconstruct hemodynamic models for comparing and analyzing blood pressure, blood flow velocity, and wall shear stress in the aortic arch and its major branches. Concurrently, morphological alterations and position of chimney stent were also assessed. RESULTS: After the reconstruction of LSA in ch-TEVAR, no endoleak was seen, but the stent in LSA was compressed. The blood flow velocity of the LSA increased and disordered, the pressure was reduced, and the WSS was increased. Even more, there were a large amount of turbulence found in the LSA of one case, and its LSA was blocked. CONCLUSION: Chimney stent reduces the occurrence of endoleak due to its excellent deformation ability, but the compressed stent has a greater impact on the hemodynamics of LSA and eventually leads to LSA occlusion; in order to keep the LSA unobstructed, it is necessary to pay attention to the position of the chimney stent and keep it straight and do not fold or twist. Chimney stent has little influence on the aortic arch and the rest of the aortic arch branches.

12.
J Immunother Cancer ; 12(4)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38641349

RESUMEN

BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy. METHOD: 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy. RESULTS: After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041). CONCLUSION: Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted. STATEMENT: The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Metabolómica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
13.
Heliyon ; 10(7): e28586, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38576569

RESUMEN

Whole genome doublings (WGD), a hallmark of human cancer, is pervasive in breast cancer patients. However, the molecular mechanism of the complete impact of WGD on survival and treatment response in breast cancer remains unclear. To address this, we performed a comprehensive and systematic analysis of WGD, aiming to identify distinct genetic alterations linked to WGD and highlight its improvement on clinical outcomes and treatment response for breast cancer. A linear regression model along with weighted gene co-expression network analysis (WGCNA) was applied on The Cancer Genome Atlas (TCGA) dataset to identify critical genes related to WGD. Further Cox regression models with random selection were used to optimize the most useful prognostic markers in the TCGA dataset. The clinical implication of the risk model was further assessed through prognostic impact evaluation, tumor stratification, functional analysis, genomic feature difference analysis, drug response analysis, and multiple independent datasets for validation. Our findings revealed a high aneuploidy burden, chromosomal instability (CIN), copy number variation (CNV), and mutation burden in breast tumors exhibiting WGD events. Moreover, 247 key genes associated with WGD were identified from the distinct genomic patterns in the TCGA dataset. A risk model consisting of 22 genes was optimized from the key genes. High-risk breast cancer patients were more prone to WGD and exhibited greater genomic diversity compared to low-risk patients. Some oncogenic signaling pathways were enriched in the high-risk group, while primary immune deficiency pathways were enriched in the low-risk group. We also identified a risk gene, ANLN (anillin), which displayed a strong positive correlation with two crucial WGD genes, KIF18A and CCNE2. Tumors with high expression of ANLN were more prone to WGD events and displayed worse clinical survival outcomes. Furthermore, the expression levels of these risk genes were significantly associated with the sensitivities of BRCA cell lines to multiple drugs, providing valuable insights for targeted therapies. These findings will be helpful for further improvement on clinical outcomes and contribution to drug development in breast cancer.

14.
Aesthetic Plast Surg ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609657

RESUMEN

BACKGROUND: Alar base is the basal part where the two sides of the nose and the upper lip are connected. Alar base depression affects the overall facial contour by making the nasolabial folds deepen, the nasolabial angle smaller, the center of the face flat, etc. Despite the rapid development of rhinoplasty, controversy still exists regarding the treatment of alar base depression. This systematic review aims to evaluate the efficacy and safety of two prevalent techniques-diced autologous cartilage and mass cartilage-for addressing alar base depression. METHODS: A systematic review was conducted by searching the literature published in PubMed, Embase and Web of Science, Cochrane from January 2000 to April 2023 with the key words 'alar base depression or depressed alar base' and 'alar base augmentation,' and 2 investigators independently screened the retrieved literature according to inclusion and exclusion criteria. RESULTS: A total of 269 articles were obtained through database search. After removing duplicates, reading titles and abstracts, and finally reviewing the full text, 6 articles were included in the final study, including 165 patients. CONCLUSIONS: The results demonstrate that both diced autologous cartilage and mass cartilage techniques exhibit favorable outcomes in correcting alar base depression. Diced autologous cartilage offers better malleability, lighter border contours, and a more natural appearance. On the other hand, diced autologous cartilage seems to offer superior long-term effects, while mass cartilage presents certain surgical procedural advantages. Also, compared to diced cartilage, mass cartilage may have a lower rate of long-term resorption and a lower risk of displacement. This review emphasizes the need for personalized treatment selection based on individual patient characteristics. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

15.
Int J Med Robot ; 20(1): e2618, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38536711

RESUMEN

PURPOSE: This work presents the design and preliminary validation of a Magnetic Resonance (MR) conditional robot for lumbar injection for the treatment of lower back pain. METHODS: This is a 4-degree-of-freedom (DOF) robot that is 200 × 230 × 130 mm3 in volume and has a mass of 0.8 kg. Its lightweight and compact features allow it to be directly affixed to patient's back, establishing a rigid connection, thus reducing positional errors caused by patient movements during treatment. RESULTS: To validate the positioning accuracy of the needle by the robot, an electromagnetic (EM) tracking system and a needle with an EM sensor embedded in the tip were used for the free space evaluation with position accuracy of 0.88 ± 0.46 mm and phantom mock insertions using the Loop-X CBCT scanner with target position accuracy of 3.62 ± 0.92 mm. CONCLUSION: Preliminary experiments demonstrated that the proposed robot showed improvements and benefits in its rotation range, flexible needle adjustment, and sensor protection compared with previous and existing systems, offering broader clinical applications.


Asunto(s)
Robótica , Humanos , Imagen por Resonancia Magnética , Agujas , Espectroscopía de Resonancia Magnética , Inyecciones Espinales
16.
Epidemiol Infect ; 152: e48, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38468382

RESUMEN

China faces challenges in meeting the World Health Organization (WHO)'s target of reducing hepatitis B virus (HBV) infections by 95% using 2015 as the baseline. Using Global Burden of Disease (GBD) 2019 data, joinpoint regression models were used to analyse the temporal trends in the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of acute HBV (AHBV) infections in China from 1990 to 2019. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort on AHBV infection risk, while the Bayesian age-period-cohort (BAPC) model was applied to predict the annual number and ASIRs of AHBV infections in China through 2030. The joinpoint regression model revealed that CIRs and ASIRs decreased from 1990 to 2019, with a faster decline occurring among males and females younger than 20 years. According to the age-period-cohort model, age effects showed a steep increase followed by a gradual decline, whereas period effects showed a linear decline, and cohort effects showed a gradual rise followed by a rapid decline. The number of cases of AHBV infections in China was predicted to decline until 2030, but it is unlikely to meet the WHO's target. These findings provide scientific support and guidance for hepatitis B prevention and control.


Asunto(s)
Hepatitis B , Masculino , Femenino , Humanos , Teorema de Bayes , Hepatitis B/epidemiología , Virus de la Hepatitis B , Incidencia , China/epidemiología
17.
Environ Pollut ; 346: 123667, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38428795

RESUMEN

Thermal desorption (TD) remediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sites is known for its high energy consumption and cost implications. The key to solving this issue lies in analyzing the PAHs desorption process, defining remediation endpoints, and developing prediction models to prevent excessive remediation. Establishing an accurate prediction model for remediation efficiency, which involves a systematic consideration of soil properties, TD parameters, and PAH characteristics, poses a significant challenge. This study employed a machine learning approach for predicting the remediation efficiency based on batch experiment results. The results revealed that the extreme gradient boosting (XGB) model yielded the most accurate predictions (R2 = 0.9832). The importance of features in the prediction process was quantified. A model optimization scheme was proposed, which involved integrating features based on their relevance, importance, and partial dependence. This integration not only reduced the number of input features but also enhanced prediction accuracy (R2 = 0.9867) without eliminating any features. The optimized XGB model was validated using soils from sites, demonstrating a prediction error of less than 30%. The optimized XGB model aids in identifying the most optimal conditions for thermal desorption to maximize the remediation efficiency of PAH-contaminated sites under relative cost and energy-saving conditions.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Contaminantes del Suelo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Suelo , Biodegradación Ambiental
18.
ACS Macro Lett ; 13(3): 273-279, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38345474

RESUMEN

The immune system can recognize and respond to pathogens of various shapes. Synthetic materials that can change their shape have the potential to be used in vaccines and immune regulation. The ability of supramolecular assemblies to undergo reversible transformations in response to environmental stimuli allows for dynamic changes in their shapes and functionalities. A meticulously designed oligo(azobenzene-graft-mannose) was synthesized using a stepwise iterative method and "click" chemistry. This involved integrating hydrophobic and photoresponsive azobenzene units with hydrophilic and bioactive mannose units. The resulting oligomer, with its precise structure, displayed versatile assembly morphologies and chiralities that were responsive to light. These varying assembly morphologies demonstrated distinct capabilities in terms of inhibiting the proliferation of cancer cells and stimulating the maturation of dendritic cells. These discoveries contribute to the theoretical comprehension and advancement of photoswitchable bioactive materials.


Asunto(s)
Compuestos Azo , Manosa , Compuestos Azo/química , Química Clic , Interacciones Hidrofóbicas e Hidrofílicas
19.
J Orthop Surg Res ; 19(1): 2, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38167456

RESUMEN

BACKGROUND: Osteoarthritis is a chronic disease mainly involving the damage of articular cartilage and the whole articular tissue, which is the main cause of disability in the elderly. To explore more effective treatment measures, this study analyzed the regulatory role and molecular mechanism of lncRNA LINC00665 (LINC00665) in the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), providing a valuable theoretical basis for the pathogenesis and patient treatment of osteoarthritis. METHODS: Osteoarthritis tissues and healthy tissues were obtained from 52 patients with osteoarthritis and 34 amputated patients without osteoarthritis, and the levels of LINC00665 and miR-214-3p were assessed by RT-qPCR. BMSCs were cultured and induced chondrogenic differentiation. The proliferation ability of BMSCs was detected by CCK-8 method, and the apoptosis level of BMSCs was evaluated by flow cytometry. The content of proteoglycan-glycosaminoglycan (GAG) in cartilage matrix was determined by Alcian blue staining. In addition, the binding relationship between LINC00665 and miR-214-3p was verified by luciferase reporter assay, and the molecular mechanism was further analyzed. RESULTS: In osteoarthritis tissues, LINC00665 was elevated and miR-214-3p was down-regulated. With the chondrogenic differentiation of BMSCs, the level of GAG increased, and LINC00665 expression gradually decreased, while miR-214-3p level was on the contrary. After transfection of pcDNA3.1-LINC00665 in BMSCs, cell proliferation capacity was decreased, apoptosis rate was increased, and GAG content was reduced. Moreover, LINC00665 sponged miR-214-3p and negatively regulate its expression. Transfection of pcDNA3.1-LINC00665-miR-214-3p mimic changed the regulation of pcDNA3.1-LINC00665 on the viability and chondrogenic differentiation of BMSCs. CONCLUSIONS: Overexpression of lncRNA LINC00665 inhibited the proliferation and chondrogenic differentiation of BMSCs by targeting miR-214-3p. The LINC00665/miR-214-3p axis may improve joint damage and alleviate the progression of osteoarthritis.


Asunto(s)
Cartílago Articular , Células Madre Mesenquimatosas , MicroARNs , Osteoartritis , ARN Largo no Codificante , Humanos , Anciano , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Condrocitos/metabolismo , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Cartílago Articular/metabolismo , Células Cultivadas , Osteoartritis/metabolismo , Proliferación Celular/genética , Células de la Médula Ósea/metabolismo
20.
Echocardiography ; 41(1): e15738, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38284672

RESUMEN

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Embólico , Cardiopatías , Embolia Intracraneal , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Accidente Cerebrovascular Embólico/complicaciones , Atrios Cardíacos/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico , Ecocardiografía , Factores de Riesgo , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/complicaciones
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