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1.
Fish Shellfish Immunol ; 151: 109696, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871144

RESUMEN

The hepatopancreas is the biggest digestive organ in Amphioctopus fangsiao (A. fangsiao), but also undertakes critical functions like detoxification and immune defense. Generally, pathogenic bacteria or endotoxin from the gut microbiota would be arrested and detoxified in the hepatopancreas, which could be accompanied by the inevitable immune responses. In recent years, studies related to cephalopods immune have been increasing, but the molecular mechanisms associated with the hepatopancreatic immunity are still unclear. In this study, lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, was used for imitating bacteria infection to stimulate the hepatopancreas of A. fangsiao. To investigate the immune process happened in A. fangsiao hepatopancreas, we performed transcriptome analysis of hepatopancreas tissue after LPS injection, and identified 2615 and 1943 differentially expressed genes (DEGs) at 6 and 24 h post-injection, respectively. GO and KEGG enrichment analysis showed that these DEGs were mainly involved in immune-related biological processes and signaling pathways, including ECM-receptor interaction signaling pathway, Phagosome signaling pathway, Lysosome signaling pathway, and JAK-STAT signaling pathways. The function relationships between these DEGs were further analyzed through protein-protein interaction (PPI) networks. It was found that Mtor, Mapk14 and Atm were the three top interacting DEGs under LPS stimulation. Finally, 15 hub genes involving multiple KEGG signaling pathways and PPI relationships were selected for qRT-PCR validation. In this study, for the first time we explored the molecular mechanisms associated with hepatopancreatic immunity in A. fangsiao using a PPI networks approach, and provided new insights for understanding hepatopancreatic immunity in A. fangsiao.


Asunto(s)
Perfilación de la Expresión Génica , Hepatopáncreas , Lipopolisacáridos , Transcriptoma , Animales , Lipopolisacáridos/farmacología , Hepatopáncreas/inmunología , Perfilación de la Expresión Génica/veterinaria , Inmunidad Innata/genética , Transducción de Señal
2.
Mikrochim Acta ; 191(7): 368, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833176

RESUMEN

A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.


Asunto(s)
Colorimetría , Límite de Detección , Plaguicidas , Teléfono Inteligente , Colorimetría/métodos , Plaguicidas/análisis , Compuestos Organofosforados/análisis , Compuestos Organofosforados/química , Malatión/análisis , Malatión/química , Oxidorreductasas/química , Hierro/química , Fosfatasa Ácida/análisis , Fosfatasa Ácida/química , Bencidinas
3.
J Nanobiotechnology ; 21(1): 120, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37024939

RESUMEN

Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of "antigen multi-copy display" and "calcium carbonate (CaCO3) biomineralization" to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Humanos , Polvos , Linfocitos T CD8-positivos , Biomineralización , Células Presentadoras de Antígenos , Neoplasias/tratamiento farmacológico , Vacunas contra el Cáncer/uso terapéutico , Inmunoterapia/métodos , Microambiente Tumoral
4.
Int J Mol Sci ; 24(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37833923

RESUMEN

RNA N6-methyladenosine (m6A) modification is one of the principal post-transcriptional modifications and plays a dynamic role in testicular development and spermatogenesis. However, the role of m6A in porcine testis is understudied. Here, we performed a comprehensive analysis of the m6A transcriptome-wide profile in Shaziling pig testes at birth, puberty, and maturity. We analyzed the total transcriptome m6A profile and found that the m6A patterns were highly distinct in terms of the modification of the transcriptomes during porcine testis development. We found that key m6A methylated genes (AURKC, OVOL, SOX8, ACVR2A, and SPATA46) were highly enriched during spermatogenesis and identified in spermatogenesis-related KEGG pathways, including Wnt, cAMP, mTOR, AMPK, PI3K-Akt, and spliceosome. Our findings indicated that m6A methylations are involved in the complex yet well-organized post-transcriptional regulation of porcine testicular development and spermatogenesis. We found that the m6A eraser ALKBH5 negatively regulated the proliferation of immature porcine Sertoli cells. Furthermore, we proposed a novel mechanism of m6A modification during testicular development: ALKBH5 regulated the RNA methylation level and gene expression of SOX9 mRNA. In addition to serving as a potential target for improving boar reproduction, our findings contributed to the further understanding of the regulation of m6A modifications in male reproduction.


Asunto(s)
Epigenoma , Transcriptoma , Porcinos , Masculino , Animales , Fosfatidilinositol 3-Quinasas/metabolismo , Maduración Sexual , Testículo/metabolismo , ARN/metabolismo
5.
Molecules ; 28(23)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38067490

RESUMEN

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.


Asunto(s)
Glucosa , Ramnosa , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Glicoproteínas/metabolismo , Citosol/metabolismo
6.
Cancer Immunol Immunother ; 71(9): 2239-2254, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35124713

RESUMEN

OBJECTIVE: A complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC) will be provided in this network meta-analysis. METHODS: We searched 14 randomized clinical trials (RCTs) including 9572 NSCLC patients by PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Randomized pairwise and network meta-analyses were used to compare the incidence of severe immune-related adverse events (irAEs) across different ICIs-based treatments using risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: For severe dermatologic irAEs, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab + ipilimumab + platinum (79.1%), pembrolizumab (75.2%), nivolumab + ipilimumab (72.9%), camrelizumab + platinum (64.9%), atezolizumab + platinum (47.4%), nivolumab (44.2%), durvalumab (40.5%), pembrolizumab + platinum (15.5%), platinum-based chemotherapy (10.3%). For severe colitis, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab + platinum (72.4%), nivolumab (63.1%), atezolizumab + platinum (56.9%), durvalumab (56.6%), pembrolizumab (54.9%), pembrolizumab + platinum (38.6%), platinum-based chemotherapy (7.4%). For severe endocrine irAEs, the corresponding ranking of incidences of the nine groups from high to low was: durvalumab (74.3%), atezolizumab + platinum (54.5%), nivolumab + ipilimumab (54.0%), camrelizumab + platinum (51.7%), nivolumab + ipilimumab + platinum (51.6%), pembrolizumab + platinum (49.8%), pembrolizumab (49.2%), nivolumab (46.3%), platinum-based chemotherapy (18.6%). For severe pneumonitis, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab (84.3%), pembrolizumab (84.1%), durvalumab (66.1%), camrelizumab + platinum (61.4%), atezolizumab + platinum (50%), pembrolizumab + platinum (43.4%), platinum-based chemotherapy (16.2%), atezolizumab (6.2%). For severe hepatitis, the corresponding ranking of incidences of the eight groups from high to low was: pembrolizumab (68.8%), nivolumab + ipilimumab + platinum (65%), pembrolizumab + platinum (64.6%), durvalumab (57.9%), nivolumab (47.1%), atezolizumab + platinum (43.4%), camrelizumab + platinum (42%), platinum-based chemotherapy (11.2%). CONCLUSIONS: In addition to platinum-based chemotherapy, pembrolizumab + platinum for severe dermatologic irAEs and colitis, nivolumab for severe endocrine irAEs, atezolizumab for severe pneumonitis, camrelizumab + platinum for severe hepatitis may be associated with lower rates of irAEs than other immune-based regimens.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Colitis , Neoplasias Pulmonares , Neumonía , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Colitis/inducido químicamente , Humanos , Inhibidores de Puntos de Control Inmunológico , Ipilimumab/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Metaanálisis en Red , Nivolumab/efectos adversos , Neumonía/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Exp Dermatol ; 31(10): 1533-1542, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35661430

RESUMEN

Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.


Asunto(s)
Queloide , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proliferación Celular , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Queloide/metabolismo , Factor de Transcripción STAT3/metabolismo , Trombospondina 1/metabolismo
8.
Arch Toxicol ; 96(6): 1729-1737, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35237847

RESUMEN

Choline metabolism alteration is considered as a metabolic hallmark in cancer, reflecting the complex interactions between carcinogenic signaling pathways and cancer metabolism, but little is known about whether genetic variants in the metabolism pathway contribute to the susceptibility of bladder cancer. Herein, a case-control study comprising 580 patients and 1,101 controls was carried out to analyze the association of bladder cancer with genetic variants on candidate genes involved in the choline metabolism pathway using unconditional logistic regression. Gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied for differential gene expression analysis. Cox regression was also applied to estimate the role of candidate genes on bladder cancer prognosis. Our results demonstrated that C allele of rs6810830 in ENPP6 was a significant protective allele of bladder cancer, compared to the T allele [Odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.86, P = 7.14 × 10-5 in additive model]. Besides, we also found that the expression of ENPP6 remarkably decreased in bladder tumors compared with normal tissues. Moreover, high expression of ENPP6 was associated with worse overall survival (OS) in bladder cancer patients [hazard ratio (HR) with their 95% CI 1.39 (1.02-1.90), P = 0.039]. In conclusion, our results suggested that SNP rs6810830 (T > C) in ENPP6 might be a potential susceptibility loci for bladder cancer, and these findings provided novel insights into the underlying mechanism of choline metabolism in cancers.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Estudios de Casos y Controles , China , Colina , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología
9.
Arch Gynecol Obstet ; 306(4): 1147-1160, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35435483

RESUMEN

PURPOSE: This meta-analysis investigated the relationships between the CD44+/CD24- phenotype and tumor size, lymph node metastasis, distant metastasis, disease-free survival (DFS), and overall survival (OS) in 8036 postoperative breast cancer patients enrolled in 23 studies. METHODS: A literature search of PubMed, Medline, Cochrane, Embase, and PMC was conducted to identify eligible studies. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed to evaluate the relationships between the CD44+/CD24- phenotype and the pathological and biological characteristics of breast cancer patients, and the combined hazard ratios (HRs) and 95% CIs were calculated to evaluate the relationships between CD44+/CD24- and DFS and OS of breast cancer patients using Stata12.0 software. RESULTS: The CD44+/CD24- phenotype were not related to the tumor size (tumor size > 2.0 vs ≤ 2.0 cm, combined OR = 0.98, 95% CI 0.68-1.34, p = 0.792) and did not promote lymph node metastasis (lymph node metastasis vs. no lymph node metastasis, OR = 0.92, 95% CI 0.67-1.27, p = 0.626) and distant metastasis (distant metastasis vs no distant metastasis, combined OR = 3.88, 95% CI 0.93-16.24, p = 0.064). The CD44+/CD24- phenotype was negatively correlated with postoperative DFS (HR = 1.67, 95% CI 1.35-2.07, p < 0.00001) and OS (combined HR = 1.52, 95% CI 1.21-1.91, p = 0.0004). CONCLUSION: These results suggested expression of the CD44+/CD24- phenotype cannot be used as a reliable indicator of the tumor size, lymph node metastasis, and distant metastasis, however, it can be used be a potential therapeutic targets of DFS, OS in breast cancer patients.


Asunto(s)
Antígeno CD24 , Receptores de Hialuranos , Biomarcadores de Tumor/metabolismo , Antígeno CD24/genética , Antígeno CD24/metabolismo , Supervivencia sin Enfermedad , Humanos , Receptores de Hialuranos/metabolismo , Metástasis Linfática , Pronóstico , Modelos de Riesgos Proporcionales
10.
Org Biomol Chem ; 19(40): 8722-8726, 2021 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-34590648

RESUMEN

Recently, by constructing a haloalkyl chain, a new class of solid-state spiropyrans showing advanced photochromic activity has been developed, but the tailoring effect of the haloalkyl chain on photochromism is unclear. Here, the photochromism of solid-state spiropyrans with different chain lengths and end substituents is investigated, which gives a clear correlation between the chain length/end substituent and the thermodynamic stability of zwitterionic merocyanine. This work provides a useful designing strategy for tailoring the photochromism of solid-state spiropyrans.

11.
J Nanobiotechnology ; 19(1): 426, 2021 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-34922541

RESUMEN

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a "lactate treatment plant" (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.


Asunto(s)
Radical Hidroxilo/metabolismo , Ácido Láctico/metabolismo , Nanopartículas/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Catálisis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cobre/química , Glutatión/química , Humanos , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Radical Hidroxilo/química , Muerte Celular Inmunogénica/efectos de los fármacos , Ácido Láctico/química , Ratones , Oxigenasas de Función Mixta/química , Oxigenasas de Función Mixta/metabolismo , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Polietileneimina/química , Microambiente Tumoral
12.
Arch Toxicol ; 95(1): 299-309, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32964246

RESUMEN

Recently N6-Methyladenosine (m6A) has been identified to guide the interaction of RNA-binding protein hnRNP C and their target RNAs, which is termed as m6A-switches. We systematically investigated the association between genetic variants in m6A-switches and bladder cancer risk. A two-stage case-control study was performed to systematically calculate the association of single nucleotide polymorphisms (SNPs) in 2798 m6A-switches with bladder cancer risk in 3,997 subjects. A logistic regression model was used to assess the effects of SNPs on bladder cancer risk. A series of experiments were adopted to explore the role of genetic variants of m6A-switches. We identified that rs5746136 (G > A) of SOD2 in m6A-switches was significantly associated with the reduced risk of bladder cancer (additive model in discovery stage: OR = 0.80, 95% CI 0.69-0.93, P = 3.6 × 10-3; validation stage: adjusted OR = 0.88, 95% CI 0.79-0.99, P = 3.0 × 10-2; combined analysis: adjusted OR = 0.85, 95% CI 0.78-0.93, P = 4.0 × 10-4). The mRNA level of SOD2 was remarkably lower in bladder cancer tissues than the paired adjacent samples. SNP rs5746136 may affect m6A modification and regulate SOD2 expression by guiding the binding of hnRNP C to SOD2, which played a critical tumor suppressor role in bladder cancer cells by promoting cell apoptosis and inhibiting proliferation, migration and invasion. In conclusion, our findings suggest the important role of genetic variants in m6A modification. SOD2 polymorphisms may influence the expression of SOD2 via an m6A-hnRNP C-dependent mechanism and be promising predictors of bladder cancer risk.


Asunto(s)
Adenosina/análogos & derivados , Polimorfismo de Nucleótido Simple , Superóxido Dismutasa/genética , Neoplasias de la Vejiga Urinaria/genética , Adenosina/genética , Adenosina/metabolismo , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Fenotipo , Medición de Riesgo , Factores de Riesgo , Superóxido Dismutasa/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/etnología , Neoplasias de la Vejiga Urinaria/metabolismo
13.
Pharmacol Res ; 160: 105194, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32937178

RESUMEN

OBJECTIVE: The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials assessing the efficacy of PD-1/PD-L1 inhibitors relative to platinum-based chemotherapy for advanced NSCLC in PubMed, EMBASE, and Cochrane libraries from 2015 to 2020 were searched, along with review of studies at American Society of Clinical Oncology (ASCO) and European society for Medical Oncology (ESMO). Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) and odds ratios (OR) for adverse events (AE) were calculated using STATA and Revman software. RESULTS: PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly improved OS (HR = 0.82, 95% CI:0.74-0.91, P = 0.01 or HR = 0.74, 95% CI:0.67-0.82, P = 0.001). PD-1/PD-L1 inhibitors alone did not benefit PFS (HR = 0.99, 95% CI: 0.89-1.10, P = 0.892), while combination therapy led to prolonged PFS (HR = 0.61, 95% CI: 0.56-0.67, P < 0.001). Subgroup analysis showed that in NSCLC with PD-L1 ≥ 50%, treatment with PD-1/PD-L1 inhibitors alone significantly improved both PFS and OS. In patients subjected to the combined treatment regimen, we observed significant differences in PFS among groups stratified by PD-L1 expression (p < 0.001), immune drug type (p = 0.029), gender (p = 0.014) and liver metastasis (p = 0.035) and OS among groups stratified by immune drug type (p < 0.001), gender (P = 0.001) and smoking status (P = 0.041). Safety analysis showed that combination therapy increased chemotherapy-induced adverse events (AE), while PD-1/PD-L1 inhibitors alone were associated with a lower incidence of any grade of treatment-related AEs (TRAE). A higher incidence of Grade 3-5 TRAEs and hypothyroidism was observed with PD-1 inhibitors than PD-L1 inhibitors. CONCLUSIONS: First-line treatment of advanced NSCLC with immune monotherapy or immunochemotherapy confers a greater survival benefit than chemotherapy alone. Combination of chemotherapy with PD-1/PD-L1 inhibitors leads to an increase in adverse events, and PD-1 inhibitors offer enhanced survival benefits and fewer adverse events than PD-L1 inhibitors. Remarkably, female patients undergoing combination therapy had longer overall survival than male patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Platino/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(3): 276-279, 2020 Mar 08.
Artículo en Zh | MEDLINE | ID: mdl-32621441

RESUMEN

We introduce the background of Shanghai medical purchasing service and supervision platform (later we call it "open platform") and the effect of its implementation. We also analyze the problems occurred by medical institutions in the management of supplies, explore how to use open platform to strengthen the management of medical supplies, further optimize the structure of supplies, standardize the clinical reasonable use and charges, and ensure the quality, safety and traceability of supplies.


Asunto(s)
Equipos y Suministros , China
15.
Sensors (Basel) ; 19(5)2019 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-30857140

RESUMEN

Intelligent medical service system integrates wireless internet of things (WIoT), including medical sensors, wireless communications, and middleware techniques, so as to collect and analyze patients' data to examine their physical conditions by many personal health devices (PHDs) in real time. However, large amount of malicious codes on the Android system can compromise consumers' privacy, and further threat the hospital management or even the patients' health. Furthermore, this sensor-rich system keeps generating large amounts of data and saturates the middleware system. To address these challenges, we propose a fog computing security and privacy protection solution. Specifically, first, we design the security and privacy protection framework based on the fog computing to improve tele-health and tele-medicine infrastructure. Then, we propose a context-based privacy leakage detection method based on the combination of dynamic and static information. Experimental results show that the proposed method can achieve higher detection accuracy and lower energy consumption compared with other state-of-art methods.


Asunto(s)
Internet , Tecnología de Sensores Remotos/métodos , Tecnología Inalámbrica , Seguridad Computacional
16.
Biol Pharm Bull ; 40(12): 2146-2152, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-28978811

RESUMEN

Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is one of the new therapeutic strategies for treating ischemic stroke. However, the poor survival rate of transplanted BMSCs in ischemic tissue limits the therapeutic efficacy of this approach. Oxidative stress is a major mechanism underlying the pathogenesis of brain ischemia and has a negative impact on the survival of transplanted BMSCs. Tetramethylpyrazine (TMP) has been reported to possess potent antioxidant activity. In the present study, we aimed to investigate the protective effects of TMP pretreatment on BMSCs survival of hydrogen peroxide (H2O2)-induced apoptosis in vitro and to elucidate the potential antiapoptotic mechanisms of TMP pretreatment on BMSCs. BMSCs were pretreated with TMP (10, 25, 50, 100, and 200 µmol/L) for 24 h and then exposed to 500 µmol/L of H2O2 for 24 h. We found that TMP pretreatment significantly increased cell viability and decreased cell apoptosis and intracellular reactive oxygen species (ROS) generation. Furthermore, the protective effects of TMP were related to increased Bcl-2 expression, attenuated Bax expression, and enhanced levels of phosphorylated Akt (p-Akt) and extracellular regulated protein kinases1/2 (p-ERK1/2). Further studies found that these beneficial effects of TMP were significantly blocked by wortmannin (an inhibitor of phosphoinositide-3 kinase (PI3K)) or PD98059 (an inhibitor of ERK1/2). In conclusion, our results confirm that TMP protects BMSCs against H2O2-induced apoptosis by regulating the PI3K/Akt and ERK1/2 signaling pathways, suggesting that TMP may be used in combination with BMSCs to improve cell survival for the treatment of ischemic stroke.


Asunto(s)
Apoptosis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Sustancias Protectoras/farmacología , Pirazinas/farmacología , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Isquemia Encefálica/terapia , Supervivencia Celular/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Masculino , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/fisiología , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/terapia
17.
Water Sci Technol ; 2017(1): 300-309, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29698244

RESUMEN

This study prepared a carboxylate-functionalized sugarcane bagasse (CF-SCB) from sugarcane bagasse (SCB) via a simple and low-toxicity chemical modification to enhance its capacity for adsorbing methylene blue (MB) from aqueous solutions. The success of chemical modification was confirmed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), the pore area and porosity, and zeta potential measurement analysis. The adsorption capacity of CF-SCB was investigated at different pHs, ionic strengths, temperatures, contact times and initial dye concentrations. Equilibrium data were best described by the Langmuir isotherm model, and the maximum monolayer adsorption capacity of CF-SCB (296.74 mg g-1) was greatly improved compared with SCB (77.16 mg g-1) at 30 °C. The thermodynamic study indicated that MB adsorption onto CF-SCB was a spontaneous, endothermic and entropy increased process. Adsorption kinetics followed a pseudo-second-order mode, and the adsorption mechanism was based on electrostatic interactions. The reusability study showed that CF-SCB had reasonably good reuse potential. All the results suggested that CF-SCB has high potential to be used as an effective and renewable adsorbent for MB removal from wastewater.


Asunto(s)
Celulosa/química , Azul de Metileno/química , Saccharum/química , Contaminantes Químicos del Agua/química , Adsorción , Cinética , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Termodinámica , Tiazinas , Aguas Residuales , Purificación del Agua
18.
J Affect Disord ; 362: 661-669, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39019221

RESUMEN

BACKGROUND: According to the healthy context paradox, the negative effects of peer victimization on core self-evaluation and depressive symptoms may vary in different levels of classroom-level victimization. However, previous studies have not investigated this issue using a longitudinal study design. OBJECTIVE: The present study used a longitudinal design to examine why and under what conditions peer victimization was associated with adolescents' depressive symptoms. METHOD: A large number of Chinese adolescents (Time 1: N = 4164, 50.3 % girls, Mage = 12.89, SDage = 0.77; Time 2: N = 4001, 50.4 % girls, Mage = 14.39, SDage = 0.75) were followed for one and a half years. RESULTS: Results showed that adolescents who were victimized in healthy contexts were more depressed and were at an increased risk of reporting more negative core self-evaluation than those victimized in unhealthy contexts. Moreover, core self-evaluation served as a mediator between peer victimization and depressive symptoms. LIMITATIONS: This study included two waves of data, which limited the exploration of dynamic relationships between peer victimization and depressive symptoms. In addition, the self-reported data weakened the objectivity of the results. Finally, this study neglected the effects of different dimensions of peer victimization on depressive symptoms. CONCLUSIONS: The healthy context paradox of peer victimization is identified in China, highlighting that future interventions of peer victimization should pay more attention to specific remaining victimized and self-devaluing individuals in healthy contexts.


Asunto(s)
Acoso Escolar , Víctimas de Crimen , Depresión , Grupo Paritario , Humanos , Femenino , Adolescente , Estudios Longitudinales , Masculino , Depresión/psicología , Víctimas de Crimen/psicología , China , Acoso Escolar/psicología , Autoevaluación (Psicología) , Niño , Autoinforme , Pueblos del Este de Asia
19.
J Affect Disord ; 350: 721-727, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38272359

RESUMEN

Although childhood maltreatment has been suggested to play an important role in developing Internet addiction among adolescents, little is known about the mediating and moderating mechanisms underlying this association. The present study investigated (a) the mediating role of maladaptive cognitive emotion regulation strategy (MCERS) in the association between childhood maltreatment and Internet addiction, and (b) the moderating role of peer support in the relationship between childhood maltreatment and Internet addiction. A sample of 4163 Chinese adolescents (50.3 % females, Mage = 14.25, SD = 1.53) were recruited. The moderated mediation model showed that MCERS mediated the relationship between childhood maltreatment and Internet addiction. Furthermore, the mediating process was moderated by peer support. Interestingly, peer support can protect adolescents from being affected by higher levels of MCERS while it displays limited protective effect when adolescents suffered from higher levels of childhood maltreatment. These findings indicate that reducing the MCERS and enhancing peer support can contribute to the alleviation of negative influences of childhood maltreatment on Internet addiction.


Asunto(s)
Conducta Adictiva , Maltrato a los Niños , Regulación Emocional , Femenino , Humanos , Adolescente , Masculino , Niño , Trastorno de Adicción a Internet/epidemiología , Conducta Adictiva/epidemiología , Conducta Adictiva/psicología , China/epidemiología , Internet
20.
Foods ; 13(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38928865

RESUMEN

The study used headspace solid-phase microextraction coupled with gas chromatography-time-of-flight mass spectrometry (HS-SPME-GC-TOF-MS) to analyze volatile compounds in leaves and fruits of Amomum tsaoko, Amomum paratsaoko, and Amomum koenigii. The composition and aroma of distinct metabolites were analyzed using multivariate statistical methods. A total of 564 volatile compounds were identified from three species of the genus Amomum, which were further divided into nine categories: terpenoids, carboxylic acids, alcohols, hydrocarbons, aldehydes, ketones, phenols, ethers, and other compounds. Terpenoids and alcohols were the most abundant. The content and types of compounds vary in A. tsaoko, A. paratsaoko, and A. koenigii, so mixing or substituting them is not advisable. We selected 45 metabolites based on the criteria of the variable importance in projection values (VIP > 1.5) and one-way ANOVA (p < 0.05). The top 19 metabolites with the most significant VIP values were chosen. Interestingly, (Z)-2-decenal was only found in Amomum koenigii, while nitroethane and nonanal were only present in cultivated A. tsaoko. Additionally, linalool, cineole, and (D)-limonene were the main components affecting the aroma of three species of the genus Amomum. The volatile components identified in this study provide a theoretical basis for analyzing the unique flavor of A. tsaoko, A. paratsaoko, and A. koenigii.

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