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1.
Materials (Basel) ; 17(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39274639

RESUMEN

In the present research, the impacts of Ce additions at various concentrations (0, 1.0, 3.4, and 4.0 wt.%) on the evolution of the microstructure, mechanical properties, and thermal conductivity of as-cast and as-extruded Mg-3Sn alloys were investigated. The findings demonstrate that adding Ce caused the creation of a new ternary MgSnCe phase in the magnesium matrix. Some new Mg17Ce2 phases are generated in the microstructure when Ce levels reach 4%. The thermal conductivity of the Mg-3Sn alloy is significantly improved due to Ce addition, and the Mg-3Sn-3.4Ce alloy exhibits the highest thermal conductivity, up to 133.8 W/(m·K) at 298 K. After extrusion, both the thermal conductivity and mechanical properties are further improved. The thermal conductivity perpendicular to the extrusion direction of Mg-3Sn-3.4Ce alloy could achieve 136.28 W/(m·K), and the tensile and yield strengths reach 264.3 MPa and 227.2 MPa, with an elongation of 7.9%. Adding Ce decreases the dissolved Sn atoms and breaks the eutectic α-Mg and Mg2Sn network organization, leading to a considerable increase in the thermal conductivity of as-cast Mg-3Sn alloys. Weakening the deformed grain texture contributed to the further enhancement of the thermal conductivity after extrusion.

2.
Transl Cancer Res ; 13(8): 4315-4323, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39262466

RESUMEN

Background: Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN. Methods: We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed in vivo experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways. Results: SIM treatment suppresses pNEN growth both in vitro and in vivo, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells. Conclusions: Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.

3.
Front Pharmacol ; 15: 1425940, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309004

RESUMEN

Objective: The World Health Organization advocated for enhanced integration of traditional medicine and complementary medicine into national healthcare systems across all countries. This study aims to explore the progress and challenges in integrated traditional Chinese and western medicine (ITCWM) in China over 20 years using nationwide data. Methods: This cross-sectional study examined various facets of ITCWM in China in terms of policies, resources, services, and funding. National policy documents from 2009 onwards were retrieved from official websites of the Chinese government. Data on ITCWM resources, services and subsidies from 2002 to 2021 were extracted from the China Statistical Yearbooks of Chinese Medicine and China Health Statistical Yearbooks. Research fund projects with the ITCWM discipline were collected from the database of National Natural Science Foundation of China. A mixed method of both quantitative and qualitative approaches was employed to present a comprehensive overview of the collected data. Results: This study presented five key findings. First, despite the issuance of 17 national policies by the Chinese government since 2009 to promote the development of traditional Chinese medicine (TCM), only three of them were specifically tailored for ITCWM. Second, although the average annual growth rates of ITCWM institutions, beds, and practitioners reached 0.35%, 10.56%, and 10.88% from 2002 to 2021, with more equitable allocation of ITCWM resources, the overall proportion of ITCWM remained below 5% in 2021. Third, progress has been made in ITCWM practices, yet service efficiency requires further enhancement. In 2021, ITCWM hospitals accounted for 2% of outpatient and emergency visits and 1.57% of hospital admissions among all hospitals, and 9.82% of delivered services were preventive healthcare services. Fourth, ITCWM served a crucial role in primary healthcare services, but its service capabilities need improvement. From 2007 to 2021, the average growth rates of ITCWM clinics, outpatient departments, and practitioners in outpatient departments were 13.30%, 2.57%, and 12.14%, respectively, while the proportion within TCM hospitals dropped. Lastly, despite the Chinese government's emphasis on financial investment and related project funding for ITCWM, it remained lower than that allocated to TCM and western medicine. Conclusion: ITCWM played a pivotal role in China's healthcare system to advance individuals' health and well-being across the lifespan. In the future, China will provide further support to enhance ITCWM health resources and improve service capability, and the strategic integration of ITCWM into the broader healthcare system will play a crucial role in achieving universal health coverage and the Sustainable Development Goals.

4.
Int J Nanomedicine ; 19: 9487-9502, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290860

RESUMEN

Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.


Asunto(s)
Ratones Endogámicos C57BL , Oligopéptidos , Neoplasias Pancreáticas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Puntos Cuánticos , Animales , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Fotoquimioterapia/métodos , Puntos Cuánticos/química , Puntos Cuánticos/administración & dosificación , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/administración & dosificación , Oligopéptidos/química , Oligopéptidos/farmacología , Ratones , Humanos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Calreticulina , Modelos Animales de Enfermedad , Citocinas/metabolismo
5.
Korean J Radiol ; 25(8): 756-766, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109502

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. RESULTS: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). CONCLUSION: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.


Asunto(s)
Microondas , Ablación por Radiofrecuencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Estudios Retrospectivos , Adulto , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Microondas/uso terapéutico , Ablación por Radiofrecuencia/métodos , Resultado del Tratamiento , Persona de Mediana Edad , Progresión de la Enfermedad , Estadificación de Neoplasias
6.
World J Gastroenterol ; 30(27): 3326-3335, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39086750

RESUMEN

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.


Asunto(s)
Hemorroides , Polidocanol , Recurrencia , Soluciones Esclerosantes , Escleroterapia , Humanos , Polidocanol/administración & dosificación , Polidocanol/uso terapéutico , Hemorroides/terapia , Hemorroides/diagnóstico , Hemorroides/cirugía , Persona de Mediana Edad , Femenino , Masculino , Estudios Prospectivos , Escleroterapia/métodos , Resultado del Tratamiento , Ligadura/métodos , Soluciones Esclerosantes/administración & dosificación , Adulto , Anciano , Índice de Severidad de la Enfermedad , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Satisfacción del Paciente , Dimensión del Dolor , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico
7.
Heliyon ; 10(12): e32516, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38994101

RESUMEN

Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P < 0.001). CHA2DS2-VASc score-stratified subgroup analysis showed similar cumulative event rates between the two groups in men and women with scores of 2 and 3 (intermediate risk for stroke), respectively, (P > 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P < 0.05). Conclusion: Men with a CHA2DS2-VASc score of 2 and women with a score of 3 had a relatively low incidence of stroke events after successful catheter ablation for AF and may be safe for anticoagulation cessation. Greater benefits from long-term OAC were observed in men with CHA2DS2-VASc score ≥3 and women with score ≥4.

8.
Eur Radiol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987399

RESUMEN

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

9.
Bioresour Technol ; 406: 131027, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925411

RESUMEN

In this study, the feasibility of promoting the lactic acid (LA) fermentation of food waste (FW) with iron tailings (ITs) addition was explored. The best LA yield was 0.91 g LA/g total sugar when 1 % ITs were added into the system. The mechanisms for promoting LA production were acidification alleviation effects and reduction equivalent supply of ITs. Furthermore, the addition of ITs promoted carbohydrate hydrolysis, and the carbohydrates digestibility reached 88.85 % in the 1 % ITs group. The ITs also affected the microbial communities, Lactococcus gradually replaced Streptococcus as the dominant genus, and results suggested that Lactococcus had a positive correlation with LA production and carbohydrate digestibility. Finally, the complex LAB in FW had significant effects on heavy metal removal from ITs, and the removal efficiency Cr, As, Pb, Cd, and Hg can reach 50.84 %, 26.72 %, 59.65 %, 49.75 % and 78.87 % in the 1 % ITs group, respectively.


Asunto(s)
Fermentación , Hierro , Ácido Láctico , Hierro/metabolismo , Ácido Láctico/metabolismo , Ácido Láctico/biosíntesis , Metales Pesados , Alimentos , Residuos , Hidrólisis , Concentración de Iones de Hidrógeno , Lactococcus/metabolismo , Alimento Perdido y Desperdiciado
10.
Artículo en Inglés | MEDLINE | ID: mdl-38905036

RESUMEN

OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PA + BCL-10 µM, PA + BCL-20 µM, and PA + BCL-50 µM groups. The PA group was treated with PA (200 µM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 µM, 20 µM, 50 µM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.

11.
Cancer Med ; 13(12): e7388, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38924330

RESUMEN

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores , Neoplasias del Sistema Biliar , Biomarcadores de Tumor , Curva ROC , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Carbohidratos Asociados a Tumores/sangre , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/sangre , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangre , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad
12.
World J Gastroenterol ; 30(19): 2575-2602, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38817665

RESUMEN

BACKGROUND: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited. AIM: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer. METHODS: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model. RESULTS: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes (SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma. CONCLUSION: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Pronóstico , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Procesamiento Proteico-Postraduccional , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/inmunología , Adenocarcinoma/metabolismo , Ácido Láctico/metabolismo , Simportadores/genética , Simportadores/metabolismo , Proliferación Celular/genética , Perfilación de la Expresión Génica , Masculino , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/terapia , Femenino , Animales , Transcriptoma
13.
Virulence ; 15(1): 2350775, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736041

RESUMEN

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.


Asunto(s)
Bacterias , Líquido del Lavado Bronquioalveolar , Microbiota , Faringe , ARN Ribosómico 16S , Síndrome de Dificultad Respiratoria , Sepsis , Humanos , Masculino , Femenino , Síndrome de Dificultad Respiratoria/microbiología , Persona de Mediana Edad , Faringe/microbiología , ARN Ribosómico 16S/genética , Líquido del Lavado Bronquioalveolar/microbiología , Anciano , Sepsis/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Alveolos Pulmonares/microbiología , Adulto , Unidades de Cuidados Intensivos , Microbioma Gastrointestinal
14.
Platelets ; 35(1): 2347331, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38722091

RESUMEN

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.


What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.


Asunto(s)
Criopreservación , Plasma Rico en Plaquetas , Cicatrización de Heridas , Plasma Rico en Plaquetas/metabolismo , Humanos , Criopreservación/métodos , Proliferación Celular , Movimiento Celular , Fibroblastos/metabolismo
15.
J Gastrointest Cancer ; 55(3): 1105-1110, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38668776

RESUMEN

BACKGROUND: Nanoparticle polymeric micellar paclitaxel (NPMP) is a novel Cremophor EL (CrEL)-free nanoparticle micellar formulation of paclitaxel. This study evaluated the efficacy and toxicity of NPMP in the treatment of patients with advanced gastric cancer (AGC). METHODS: Patients with histologically confirmed AGC in Jiangsu Cancer Hospital were retrospectively collected and divided into two groups. Patients in group A received NPMP at a total dose of 360 mg/m2 each cycle, and patients in group B were given paclitaxel at a dose of 210 mg/m2 each cycle. In addition, all patients received 5-fluorouracil at a dose of 0.75 g/m2 on days 1-4 and leucovorin at a dose of 200 mg/m2 on days 1-4 for at least 2 cycles. RESULTS: From January 2021 to May 2023, 63 patients (32 in group A and 31 in group B) could be evaluated for treatment response. A marked disparity in the overall response was observed between groups A and B, indicating statistical significance. The overall response rate was 31% in group A (10/32) and 10% in group B (3/31) (P = 0.034). Disease control rate was 91% in group A (29/32) and 81% in group B (25/31) (P = 0.440). No statistically significant difference in adverse reactions was observed between the two groups. However, the incidence of anemia, leucopenia, nausea, vomiting, diarrhea, liver dysfunction, and allergy in group A was notably lower than that in group B. CONCLUSIONS: NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.


Asunto(s)
Micelas , Nanopartículas , Paclitaxel , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Nanopartículas/administración & dosificación , Estudios Retrospectivos , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Resultado del Tratamiento , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación
16.
BMC Anesthesiol ; 24(1): 147, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632505

RESUMEN

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.


Asunto(s)
Propofol , Niño , Humanos , Anestesia General , Anestesia Intravenosa/métodos , Anestésicos Intravenosos , Propofol/uso terapéutico , Remifentanilo
17.
Front Neurol ; 15: 1368988, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665996

RESUMEN

Objective: Acupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis. Methods: This study evaluates academic publications retrieved from the Web of Science database (2010.01-2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps. Results: The final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010-2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis. Conclusion: This study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

18.
Brain Res ; 1836: 148882, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38521160

RESUMEN

Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 , decreasing the levels of iron and MDA, as well as increasing the activity of GSH and Nrf2. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.


Asunto(s)
Epilepsia , Ferroptosis , Hipocampo , Mitocondrias , Ratas Wistar , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Masculino , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Ferroptosis/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Dipéptidos/farmacología , Pilocarpina , Imidazoles/farmacología , Piridinas/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Oligopéptidos
19.
Nat Commun ; 15(1): 2392, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493166

RESUMEN

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI-AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI-AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI-AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI-LHCI among various photosynthetic organisms.


Asunto(s)
Complejos de Proteína Captadores de Luz , Complejo de Proteína del Fotosistema I , Complejo de Proteína del Fotosistema I/metabolismo , Complejos de Proteína Captadores de Luz/metabolismo , Ecosistema , Microscopía por Crioelectrón , Fotosíntesis
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 39-42, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38433629

RESUMEN

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT) rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180° counter-clockwise with the patient head turned to the right. Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intubation in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the sternum,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clockwise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were compared between the two groups. Results The 648 patients included 336 males and 312 females,with the age ranging from 39.0 to 75.0 years old and the average age of(54.6±9.0) years old.The success rate of first intubation was 80.3% in the 90° group and 75.0% in the 180° group,which showed no significant difference(P=0.109).The success rate of second intubation was higher in the 180° group than in the 90° group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P=0.585). Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.


Asunto(s)
Bronquios , Intubación Intratraqueal , Femenino , Masculino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Procedimientos Quirúrgicos Electivos , Hospitales , Tráquea
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