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2.
Adv Healthc Mater ; : e2400938, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829702

RESUMEN

Ovarian cancer is the most lethal gynecologic cancer in developed countries. In the tumor microenvironment, the extracellular matrix (ECM) and flow shear stress are key players in directing ovarian cancer cells invasion. We use artificial ECM models based only on ECM proteins to build an ovarian tumor-on-chip to decipher the crosstalk between ECM and shear stress on the migratory behavior and cellular heterogeneity of ovarian tumor cells. This work shows that in the shear stress regime of the peritoneal cavity, the ECM plays a major role in driving individual or collective ovarian tumor cells migration. In the presence of basement membrane proteins, migration is more collective that on type I collagen regardless of shear stress. With increasing shear stress, individual cell migration was enhanced, while no significant impact on collective migration was measured. This highlights the central position that ECM and flow shear stress should hold in in vitro ovarian cancer models to deepen our understanding of cellular responses, and improve the development of ovarian cancer therapeutic platforms. In this frame, adding flow provides significant improvement in biological relevance over our previous work. Further steps for enhanced clinically relevance require not only multiple cell lines but patient-derived cells and sera. This article is protected by copyright. All rights reserved.

3.
Nanomaterials (Basel) ; 14(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38727394

RESUMEN

Iron redox flow batteries (IRFBs) are cost-efficient RFBs that have the potential to develop low-cost grid energy storage. Electrode kinetics are pivotal in defining the cycle life and energy efficiency of the battery. In this study, graphite felt (GF) is heat-treated at 400, 500 and 600 °C, and its physicochemical and electrochemical properties are studied using XPS, FESEM, Raman and cyclic voltammetry. Surface morphology and structural changes suggest that GF heat-treated at 500 °C for 6 h exhibits acceptable thermal stability while accessing the benefits of heat treatment. Specific capacitance was calculated for assessing the wettability and electrochemical properties of pristine and treated electrodes. The 600 °C GF has the highest specific capacitance of 34.8 Fg-1 at 100 mV s-1, but the 500 °C GF showed the best battery performance. The good battery performance of the 500 °C GF is attributed to the presence of oxygen functionalities and the absence of thermal degradation during heat treatment. The battery consisting of 500 °C GF electrodes offered the highest voltage efficiency of ~74%, Coulombic efficiency of ~94%, and energy efficiency of ~70% at 20 mA cm-2. Energy efficiency increased by 7% in a battery consisting of heat-treated GF in comparison to pristine GF. The battery is capable of operating for 100 charge-discharge cycles with an average energy efficiency of ~ 67% for over 100 cycles.

4.
PLoS One ; 19(5): e0303435, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38696504

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0061677.].

5.
Molecules ; 29(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38731518

RESUMEN

Hemicellulose can be selectively removed by acid pretreatment. In this study, selective removal of hemicellulose was achieved using dilute sulfuric acid assisted by aluminum sulfate pretreatment. The optimal pretreatment conditions were 160 °C, 1.5 wt% aluminum sulfate, 0.7 wt% dilute sulfuric acid, and 40 min. A component analysis showed that the removal rate of hemicellulose and lignin reached 98.05% and 9.01%, respectively, which indicated that hemicellulose was removed with high selectivity by dilute sulfuric acid assisted by aluminum sulfate pretreatment. Structural characterizations (SEM, FTIR, BET, TGA, and XRD) showed that pretreatment changed the roughness, crystallinity, pore size, and functional groups of corn straw, which was beneficial to improve the efficiency of enzymatic hydrolysis. This study provides a new approach for the high-selectivity separation of hemicellulose, thereby offering novel insights for its subsequent high-value utilization.

6.
J Thorac Dis ; 16(4): 2482-2498, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38738219

RESUMEN

Background: Frailty is a medical syndrome caused by multiple factors, characterized by decreased strength, endurance, and diminished physiological function, resulting in increased susceptibility to dependence and/or death. Patients with chronic obstructive pulmonary disease (COPD) tend to be more vulnerable to frailty due to their physical and psychological burdens. Therefore, the aim of this study was to develop a reliable and accurate vulnerability risk prediction model for frailty in patients with COPD in order to improve the identification and prediction of patient frailty. The specific objectives of this study were to determine the prevalence of frailty in patients with COPD and develop a prediction model and evaluate its predictive power. Methods: Clinical information was analyzed using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database, and 34 indicators, including behavioral factors, health status, mental health parameters, and various sociodemographic variables, were examined in the study. The adaptive synthetic sampling technique was used for unbalanced data. Three methods, ridge regressor, extreme gradient boosting (XGBoost) classifier, and random forest (RF) regressor, were used to filter predictors. Seven machine learning (ML) techniques including logistic regression (LR), support vector machines (SVM), multilayer perceptron, light gradient-boosting machine, XGBoost, RF, and K-nearest neighbors were used to analyze and determine the optimal model. For customized risk assessment, an online predictive risk modeling website was created, along with Shapley additive explanation (SHAP) interpretations. Results: Depression, smoking, gender, social activities, dyslipidemia, asthma, and residence type (urban vs. rural) were predictors for the development of frailty in patients with COPD. In the test set, the XGBoost model had an area under the curve of 0.942 (95% confidence interval: 0.925-0.959), an accuracy of 0.915, a sensitivity of 0.873, and a specificity of 0.911, indicating that it was the best model. Conclusions: The ML predictive model developed in this study is a useful and easy-to-use instrument for assessing the vulnerability risk of patients with COPD and may aid clinical physicians in screening high-risk patients.

7.
Osteoporos Int ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38772921

RESUMEN

PURPOSE: The association between type 2 diabetes mellitus (T2DM), lifestyle factors, and the risk of osteoporosis (OP) is well-established. However, the impact of a healthy lifestyle on diabetes-related osteoporosis needs further investigation. Our objective was to explore if a combination of healthy lifestyle factors could mitigate the risk of OP in individuals with type 2 diabetes. METHODS: This longitudinal analysis included 237,725 middle-aged and older participants. An overall lifestyle score, ranging from 0 to 7, was calculated by assigning a point for each of the seven healthy lifestyle factors, including no current smoking, non-excessive alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and adequate sunshine exposure. RESULTS: During a median follow-up 12.21 years, 5760 OP cases were documented. Participants with T2DM showed a higher risk of OP than those without diabetes. Compared with participants without diabetes who had a lifestyle score of 6-7, the hazard ratios (HRs) for OP were 1.58 (95% CI 1.23-2.03), 1.62 (95% CI 1.16-2.25), and 2.58 (95% CI 1.64-4.05) for participants with T2DM who had a lifestyle score of 4, 3, and 0-2, respectively. There was a graded association between higher lifestyle scores and lower risks of incident OP among participants without diabetes as well as among those with T2DM. We estimated that the population attributable fraction for not adhering to 6-7 lifestyle behaviors was 15.7%. CONCLUSIONS: Participants with T2DM who adhered to a variety of healthy lifestyle factors demonstrated a substantially reduced risk of developing OP.

8.
Heliyon ; 10(10): e30717, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38774316

RESUMEN

As the adoption of solar hybrid systems continues to rise due to their potential to compensate for the fluctuation of solar irradiation, it becomes imperative to accurately evaluate their performance, considering the variation of off-design conditions. This paper introduces a detailed analysis method for evaluating the annual performance of a solar-MGT system under transient boundary conditions for a whole-year operation range. A hybrid system of a micro gas turbine, recuperator, and solar dish is considered, and an off-design simulation model is developed and verified with available experimental results. Two different configurations for a recuperated cycle are considered, and simulations are conducted for a test case in Pretoria, SA. The results for Jun.21 and Dec.21 as low and high solar energy days are reported with more details to compare the configurations and demonstrate the effect of ambient temperature on the heat loss of the solar receiver and the overall performance of the system. The alternative configuration reduces heat loss with a lower temperature receiver but has higher fuel consumption compared to the conventional configuration. Operating strategies for different hours of operation from 1 h to 24 h per day are simulated for 365 days, based on real meteorological data, and compared with the operating in solar available hours. It is shown that the whole-year simulation of the system considering the variation of boundary conditions can change the estimation of fuel consumption by 25 %.

9.
Med Phys ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38781536

RESUMEN

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) Pathology Committee introduced a histologic grading system for invasive lung adenocarcinoma (LUAD) in 2020. The IASLC grading system, hinging on the evaluation of predominant and high-grade histologic patterns, has proven to be practical and prognostic for invasive LUAD. However, there are still limitations in evaluating the prognosis of stage IA LUAD. Radiomics may serve as a valuable complement. PURPOSE: To establish a model that integrates IASLC grading and radiomics, aimed at predicting the prognosis of stage IA LUAD. METHODS: We conducted a retrospective analysis of 628 patients diagnosed with stage IA LUAD who underwent surgical resection between January 2015 and December 2018 at our institution. The patients were randomly divided into the training set (n = 439) and testing set (n = 189) at a ratio of 7:3. Overall survival (OS) and disease-free survival (DFS) were taken as the end points. Radiomics features were obtained by PyRadiomics. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO). The prediction models for OS and DFS were developed using multivariate Cox regression analysis, and the models were visualized through nomogram plots. The model's performance was evaluated using area under the curves (AUC), concordance index (C-index), calibration curves, and survival decision curve analysis (DCA). RESULTS: In total, nine radiomics features were selected for the OS prediction model, and 15 radiomics features were selected for the DFS prediction model. Patients with high radiomics scores were associated with a worse prognosis (p < 0.001). We built separate prediction models using radiomics or IASLC alone, as well as a combined prediction model. In the prediction of OS, we observed that the combined model (C-index: 0.812 ± 0.024, 3 years AUC: 0.692, 5 years AUC: 0.792) achieved superior predictive performance than the radiomics (C-index: 0.743 ± 0.038, 3 years AUC: 0.633, 5 years AUC: 0.768) and IASLC grading (C-index: 0.765 ± 0.042, 3 years AUC: 0.658, 5 years AUC: 0.743) models alone. Similar results were obtained in the models for DFS. CONCLUSION: The combination of radiomics and IASLC pathological grading proves to be an effective approach for predicting the prognosis of stage IA LUAD. This has substantial clinical relevance in guiding treatment decisions for early-stage LUAD.

10.
Med Mycol ; 62(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38710585

RESUMEN

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.


We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.


Asunto(s)
ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Meningitis Criptocócica , Humanos , Meningitis Criptocócica/mortalidad , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/microbiología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , ADN Viral/líquido cefalorraquídeo , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/líquido cefalorraquídeo , Anciano , Líquido Cefalorraquídeo/microbiología , Líquido Cefalorraquídeo/virología , Cryptococcus neoformans/genética , Cryptococcus neoformans/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Adulto Joven , China/epidemiología , Análisis de Supervivencia
11.
J Sci Food Agric ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785267

RESUMEN

BACKGROUND: Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). RESULTS: QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6ß levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION: In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.

12.
Waste Manag ; 183: 260-270, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38776828

RESUMEN

The landfill is one of the most important sources of microplastics (MPs). The pretreatment method is a precondition of microplastics study for the presence of complex substances in landfills. Therefore, it is essential to examine the impact of different pretreatment methods on the microplastics detection. A literature review and a comparison experiment on digestion solutions were performed to establish a comprehensive identification method for MPs in landfills. When exposed to of 30 % H2O2, minimal mass reduction of PE, PP and PET were 4.00 %, 3.00 % and 3.00 % respectively, and the least surface damage was observed in MPs, while exhibiting the most optimal peak value for infrared spectral characteristics. It is demonstrated that the effect of 30 % H2O2 dissolution was superior compared to 10 % KOH and 65 % HNO3. The method was subsequently utilized to investigate the distribution of MPs in a landfill. The dominant MPs were polyethylene (PE, 18.56-23.91 %), polyethylene terephthalate (PET, 8.80-18.66 %), polystyrene (PS, 10.31-18.09 %), and polypropylene (PP, 11.60-14.91 %). The comprehensive identification method of "NaCl density separation + 30 % H2O2 digestion + NaI density separation + sampling microscope + Mirco-FTIR" is suitable for the detection of MPs in landfills.


Asunto(s)
Residuos Sólidos , Instalaciones de Eliminación de Residuos , Eliminación de Residuos/métodos , Polietileno/análisis , Tereftalatos Polietilenos/análisis , Poliestirenos/análisis , Polipropilenos/análisis
13.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167208, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701956

RESUMEN

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.


Asunto(s)
Cardiomiopatías , Electroacupuntura , Exosomas , Lipopolisacáridos , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo , Exosomas/genética , Electroacupuntura/métodos , Ratones , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/terapia , Cardiomiopatías/patología , Cardiomiopatías/genética , Cardiomiopatías/prevención & control , Lipopolisacáridos/toxicidad , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
14.
J Exp Clin Cancer Res ; 43(1): 152, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38812060

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. METHODS: The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). RESULTS: HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. CONCLUSIONS: HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Homólogo de la Proteína Chromobox 5 , Histona Desacetilasa 1 , Factor de Transcripción STAT1 , Animales , Femenino , Humanos , Masculino , Ratones , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Línea Celular Tumoral , Proliferación Celular , Colangiocarcinoma/metabolismo , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Homólogo de la Proteína Chromobox 5/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histona Desacetilasa 1/metabolismo , Factor de Transcripción STAT1/metabolismo
15.
Front Immunol ; 15: 1310239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711515

RESUMEN

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.


Asunto(s)
Carcinoma Hepatocelular , Progresión de la Enfermedad , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , China , Anciano , Adulto , Estadificación de Neoplasias , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis , Resultado del Tratamiento , Pueblos del Este de Asia
17.
World J Gastrointest Oncol ; 16(4): 1626-1646, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38660634

RESUMEN

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

18.
Heliyon ; 10(7): e29214, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601586

RESUMEN

Objective: The study established a nomogram based on quantitative parameters of spectral computed tomography (CT) and clinical characteristics, aiming to evaluate its predictive value for preoperative lymphovascular invasion (LVI) in gastric cancer (GC). Methods: From December 2019 to December 2021, 171 patients with pathologically confirmed GC were retrospectively collected with corresponding clinical data and spectral CT quantitative data. Patients were divided into LVI-positive and LVI-negative groups based on their pathological results. The univariate and multivariate logistic regression analyses were used to identify the risk factors and construct a nomogram. The calibration curve and receiver operating characteristic (ROC) curve were adopted to evaluate the predictive accuracy of nomogram. Results: Four clinical characteristics or spectral CT quantitative parameters, including Borrmann classification (P = 0.039), CA724 (P = 0.007), tumor thickness (P = 0.031), and iodine concentration in the venous phase (VIC) (P = 0.004) were identified as independent factors for LVI in GC patients. The nomogram was established based on the four factors, which had a potent predictive accuracy in the training, internal validation and external validation cohorts, with the area under the ROC curve (AUC) of 0.864 (95% CI, 0.798-0.930), 0.964 (95% CI, 0.903-1.000) and 0.877 (95% CI, 0.759-0.996), respectively. Conclusion: This study constructed a comprehensive nomogram consisting spectral CT quantitative parameters and clinical characteristics of GC, which exhibited a robust efficiency in predicting LVI in GC patients.

19.
Org Lett ; 26(15): 3151-3157, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38564713

RESUMEN

A facile iron(II)-catalyzed radical [3 + 2] cyclization of N-aryl cyclopropylamines with various alkenes to access the structurally polyfunctionalized cyclopentylamine scaffolds has been developed. Using low-cost FeCl2·4H2O as catalyst, N-aryl cyclopropylamines could be utilized to react with a wide range of alkenes including exocyclic/acyclic terminal alkenes, cycloalkenes, alkenes from the natural-occurring compounds (Alantolactone, Costunolide), and known drugs (Ibuprofen, l-phenylalanine, Flurbiprofen) to obtain a variety of cyclopentylamines fused with different useful motifs in generally good yields and diastereoselectivities. The highlight of this protocol is also featured by no extra oxidant, no base, EtOH as the solvent, gram-scale synthesis, and further diverse transformations of the synthetic products. More importantly, an iron(II)-mediated hydrogen radical dissociation pathway was proposed based on the mechanism research experiments.

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