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1.
J Cancer Surviv ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700620

RESUMO

PURPOSE: The impact of adverse childhood experiences (ACEs) on health-related quality of life (HRQOL) is increasingly recognized, however, this has not been studied in cancer survivors in the United States. This study investigates if ACEs are associated with HRQOL in cancer survivors. METHODS: We conducted a cross-sectional analysis of the 2020 Behavioral Risk Factor Surveillance System from states that administered ACEs and Cancer Survivorship modules. Eligibility criteria included being a cancer survivor and not currently receiving cancer treatment. Primary exposure was number of ACEs (categorized as 0, 1-2, 3, or ≥ 4). Primary outcomes were self-reported measures of HRQOL including worse overall health and ≥ 14 unhealthy days (mentally or physically) per month. Mantel-Haenszel stratified analyses were performed and prevalence ratios were adjusted for age. RESULTS: Of 5,780 participants, 62.0% were female and 67.8% were ≥ 65 years. Prevalence of worse overall health was 22.5% for individuals with no ACEs compared to 30.2% for 2-3 ACEs (aPR = 1.4, 95% CI 1.2, 1.5) and 38.5% for ≥ 4 ACEs (aPR = 1.7, 95% CI 1.5, 2.0). Prevalence of ≥ 14 unhealthy days was 18.1% with no ACEs compared to 21.0% for 1 ACE (aPR = 1.3, 95% CI 1, 1.3), 29.0% for 2-3 ACEs (aPR = 1.6, 95% CI 1.4, 1.8), and 44.8% for ≥ 4 ACEs (aPR = 2.2, 95% CI 2.0, 2.5). CONCLUSIONS: Our study provides novel evidence of the association of multiple ACEs with higher prevalence of poor HRQOL in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Screening for ACEs is warranted in all patients to guide targeted interventions to improve HRQOL and mitigate the impact of ACEs on HRQoL in cancer survivors.

2.
J Cardiothorac Surg ; 19(1): 275, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702716

RESUMO

BACKGROUND: Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels. METHODS: We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging. RESULTS: All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed. CONCLUSION: The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.


Assuntos
Neoplasias Pulmonares , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Humanos , Masculino , Pneumonectomia/métodos , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/cirurgia , Idoso , Excisão de Linfonodo/métodos , Duração da Cirurgia , Adulto , Tempo de Internação , Estudos de Viabilidade
3.
J Bone Oncol ; 46: 100601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38706714

RESUMO

Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule shows anti-tumor potential by playing a central role in the inhibition of several kinases related to cell cycle regulation and cytokinesis. In this study, systematic review demonstrated the feasibility and pharmacological mechanism of anti-tumor effect of reversine. Firstly, we grafted MNNG/HOS, U-2 OS, MG-63 osteosarcoma cell aggregates onto chicken embryonic chorioallantoic membrane (CAM) to examine the tumor volume of these grafts after reversine treatment. Following culture, reversine inhibited the growth of osteosarcoma cell aggregates on CAM significantly. In vitro experiment, reversine suppressed osteosarcoma cell viability, colony formation, proliferation, and induced apoptosis and cell cycle arrest at G0-G1 phase. Scratch wound assay demonstrated that reversine restrained cell migration. Reversine increased the protein expression of E-cadherin. The mRNA expression of Rac1, RhoA, CDC42, PTK2, PXN, N-cadherin, Vimentin in MNNG/HOS, U-2 OS and MG-63 cells were suppressed and PTEN increased after reversine treatment. Network pharmacology prediction, molecular docking and systematic review revealed MEK1 can be used as an effective target for reversine to inhibit osteosarcoma. Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.

4.
Chemosphere ; 359: 142259, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723692

RESUMO

6-Methylquinoline (6-MQ) is identified as a high-concentration organic compound pervasive in shale gas wastewater (SGW) and poses a significant risk of environmental pollution. In response, this study aimed to address these challenges by introducing an innovative electrochemical membrane constructed with multi-walled carbon nanotubes (CNTs) for the removal of 6-MQ. The investigation systematically explored the impact of voltage, initial pollutant concentration, and salinity on the performance of the electrochemical CNTs filter. It was found a positive correlation between removal efficiency and increasing voltage and salinity levels. Conversely, as the initial concentration of pollutants increased, the efficiency showed a diminishing trend. The electrochemical CNTs filter exhibited remarkable efficacy in both adsorption removal and electrochemical oxidation of 6-MQ. Notably, the CNTs membrane exhibited robust adsorption capabilities, evidenced by the sustained adsorption of 6-MQ for over 33 h. Furthermore, applying an electrochemical oxidation voltage of 3 V consistently maintained a removal rate exceeding 34.0% due to both direct and indirect oxidation, underscoring the sustained efficacy of the electrochemical membranes. Besides, real wastewater experiments, while displaying a reduction in removal efficiency compared to synthetic wastewater experiments, emphasized the substantial potential of the electrochemical CNTs filter for practical applications. This study underscores the significant promise of electrochemical membranes in addressing low molecular weight contaminants in SGW, contributing valuable insights for advancing SGW treatment strategies.

5.
BMC Infect Dis ; 24(1): 494, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745289

RESUMO

BACKGROUND: Brain-heart infusion agar supplemented with 4 µg/mL of vancomycin (BHI-V4) was commonly used for the detection of heterogeneous (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA). However, its diagnostic value remains unclear. This study aims to compare the diagnostic accuracy of BHI-V4 with population analysis profiling with area under the curve (PAP-AUC) in hVISA/VISA. METHODS: The protocol of this study was registered in INPLASY (INPLASY2023120069). The PubMed and Cochrane Library databases were searched from inception to October 2023. Review Manager 5.4 was used for data visualization in the quality assessment, and STATA17.0 (MP) was used for statistical analysis. RESULTS: In total, eight publications including 2153 strains were incorporated into the meta-analysis. Significant heterogeneity was evident although a threshold effect was not detected across the eight studies. The summary receiver operating characteristic (SROC) was 0.77 (95% confidence interval [CI], 0.74-0.81). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic score and diagnostic odds ratio were 0.59 (95% CI: 0.46-0.71), 0.96 (95%CI: 0.83-0.99), 14.0 (95% CI, 3.4-57.1), 0.43 (95%CI, 0.32-0.57), 3.48(95%CI, 2.12-4.85) and 32.62 (95%CI, 8.31-128.36), respectively. CONCLUSION: Our study showed that BHI-V4 had moderate diagnostic accuracy for diagnosing hVISA/VISA. However, more high-quality studies are needed to assess the clinical utility of BHI-V4.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus , Vancomicina , Humanos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico , Vancomicina/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Sensibilidade e Especificidade , Resistência a Vancomicina , Meios de Cultura , Área Sob a Curva
6.
Fitoterapia ; 175: 105945, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575091

RESUMO

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

7.
Plant Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568844

RESUMO

Tobacco (Nicotiana tabacum L.) belongs to the family Solanaceae, an economically significant crop (Zhou et al. 2023). Twelve samples with leaf spots were collected in Keti Village, Changshun County, Zunyi City, Guizhou province, China in 2022. Twenty-five percent of the samples had dry lesions near the leaf tip which resulted leaf tip blight after development. Fungi were isolated by a previous method (Wei et al. 2022). Six Alternaria strains were obtained and preserved in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. Among them, one strain YZU 221477 showed distinct cultural characteristics out of five A. alternata strains, which was again determined by growing on potato dextrose agar (PDA) at 25°C for 7 days in dark to evaluate. The colonies (60 mm in diameter) were white cottony in the center surrounded by vinaceous purple. To examine the morphology, mycelia were inoculated onto potato carrot agar (PCA) at 22°C, following an 8 h light/16 h dark photoperiod (Simmons 2007). Conidia were obclavate or ovoid, normally 3-5 conidial units per chain, 20-38 × 10-16.5 µm, 3 to 5 transverse septa, beakless or a short beak (4-30 µm). The observation results were consistent with those of A. gossypina (Zhang 2003). Total genomic DNA was extracted using the CTAB method and seven gene regions including internal transcribed spacer of rDNA (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1 alpha (TEF1), RNA polymerase second largest subunit (RPB2), Alternaria major allergen gene (Alt a 1), endopolygalacturonase (EndoPG) and an anonymous gene region (OPA10-2) were amplified with ITS5/ITS4, gpd1/gpd2, EF1-728F/EF1-986R, RPB2-5F/RPB2-7cR, Alt-for/Alt-rev, PG3/PG2b and OPA10-2L/OPA10-2R primers, respectively. All sequences were deposited in GenBank (ITS: OR710806; GAPDH: PP057862; TEF1: PP158601; RPB2: PP057863; Alt a 1: PP057865; EndoPG: PP057861; OPA10-2: PP057864). Combining with relevant sequences retrieved from the NCBI database were used for the phylogenetic analysis. Maximum Likelihood (ML) tree was constructed with RAxML v.7.2.8 employing GTRCAT model using 1000 bootstrap (BS) replicates to assess statistical support. The results indicated that the present strain grouped with A. gossypina (type strain of CBS 104.32) supported with 73% bootstrap values, also having a support of 0.83 Bayesian posterior probabilities values. Based on morphology and molecular evidence, the strain YZU 221477 is identified as Alternaria gossypina. Pathogenicity was examined to fulfill Koch's postulates. Mycelial plugs (6 mm diameter) of the present strain and A. alternata cultivated on PDA were taken from the margin and inoculated onto viable tobacco leaves (Cultivar: Yunyan 87, n=3) growing forty days, while controls were inoculated with sterile PDA. The assay was conducted three times. The plants were maintained at 25°C with humidity levels over 85% in a greenhouse. Leaves were evaluated after 7 days, necrotic spots encircled by yellow halos were on both inoculums, except controls. Pathogen re-isolation confirmed that it was the same as inoculated fungus based on morphology. A. gossypina was firstly found on cotton (Hopkins 1931), late reported to induce disease on Minneola, Nopalea, Hibiscus, Citrus, Solanum and Ageratina. To our knowledge, this is the first report of A. gossypina causing tobacco leaf tip blight in China, and it also provides a basis for controlling of tobacco leaf tip blight.

8.
Sci Rep ; 14(1): 8575, 2024 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609450

RESUMO

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Genômica , Biomarcadores Tumorais/genética , Microambiente Tumoral
9.
Mov Disord ; 39(5): 798-813, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38465843

RESUMO

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. OBJECTIVE: The objective of the study is to clarify the core features and influence factors of CRD patients in China. METHODS: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. RESULTS: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. CONCLUSIONS: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.


Assuntos
Mutação , Fenótipo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Mutação/genética , Genótipo , Disfunção Cognitiva/genética , Imageamento por Ressonância Magnética , Transtornos Parkinsonianos/genética , Idoso , Idade de Início , Adulto Jovem , Receptor de Fator Estimulador de Colônias de Macrófagos
10.
Food Funct ; 15(7): 3653-3668, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38487897

RESUMO

Intestinal ischemia-reperfusion (IIR) injury leads to inflammation and oxidative stress, resulting in intestinal barrier damage. Probiotics, due to their anti-inflammatory and antioxidant properties, are considered for potential intervention to protect the intestinal barrier during IIR injury. Bifidobacterium longum, a recognized probiotic, has targeted effects on IIR injury, but its mechanisms of action are not yet understood. To investigate the mechanism of Bifidobacterium longum intervention in IIR injury, we conducted a study using a rat IIR injury model. The results showed that Bifidobacterium longum could alleviate inflammation and oxidative stress induced by IIR injury by suppressing the NF-κB inflammatory pathway and activating the Keap1/Nrf2 signaling pathway. Bifidobacterium longum GL001 also increased the abundance of the gut microbiota such as Oscillospira, Ouminococcus, Corynebacterium, Lactobacillus, and Akkermansia, while decreasing the abundance of Allobaculum, [Prevotella], Bacteroidaceae, Bacteroides, Shigella, and Helicobacter. In addition, Bifidobacterium longum GL001 reversed the changes in amino acids and bile acids induced by IIR injury and reduced the levels of DL-cysteine, an oxidative stress marker, in intestinal tissue. Spearman correlation analysis showed that L-cystine was positively correlated with Lactobacillus and negatively correlated with Shigella, while DL-proline was positively correlated with Akkermansia. Moreover, bile acids, cholic acid and lithocholic acid, were negatively correlated with Lactobacillus and positively correlated with Shigella. Therefore, Bifidobacterium longum GL001 may alleviate IIR injury by regulating the gut microbiota to modulate intestinal lipid peroxidation and bile acid metabolism.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Probióticos , Traumatismo por Reperfusão , Ratos , Animais , Bifidobacterium longum/fisiologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Lactobacillus/metabolismo , Inflamação , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
11.
J Hazard Mater ; 470: 134134, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38554514

RESUMO

Microbial remediation of cadmium-contaminated soil offers advantages like environmental friendliness, cost-effectiveness, and simple operation. However, the efficacy of this remediation process relies on obtaining dominant strains and a comprehensive understanding of their Cd adsorption mechanisms. This study identified two Cd-resistant bacteria, Burkholderia sp. 1-22 and Bacillus sp. 6-6, with significant growth-promoting effects from rice rhizosphere soil. The strains showed remarkable Cd resistance up to ∼200 mg/L and alleviated Cd toxicity by regulating pH and facilitating bacterial adsorption of Cd. FTIR analysis showed crucial surface functional groups, like carboxyl and amino groups, on bacteria played significant roles in Cd adsorption. The strains could induce CdCO3 formation via a microbially induced calcium precipitation (MICP) mechanism, confirmed by SEM-EDS, X-ray analysis, and elemental mapping. Pot experiments showed these strains significantly increased organic matter and enzyme activity (e.g., urease, sucrase, peroxidase) in the rhizosphere soil versus the control group. These changes are crucial for restricting Cd mobility. Furthermore, strains 6-6 and 1-22 significantly enhance plant root detoxification of Cd, alleviating toxicity. Notably, increased pH likely plays a vital role in enhancing Cd precipitation and adsorption by strains, converting free Cd into non-bioavailable forms.


Assuntos
Bacillus , Burkholderia , Cádmio , Oryza , Rizosfera , Microbiologia do Solo , Poluentes do Solo , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Cádmio/toxicidade , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Burkholderia/metabolismo , Adsorção , Bacillus/metabolismo , Biodegradação Ambiental , Concentração de Íons de Hidrogênio , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
12.
Sensors (Basel) ; 24(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474929

RESUMO

An exhaust gas recirculation (EGR) valve is used to quickly and dynamically adjust the amount of recirculated exhaust gas, which is critical for improving engine fuel economy and reducing emissions. To address problems relating to the precise positioning of an electromotive (EM) valve under slowly varying plant dynamics and uncertain disturbances, we propose a servo control system design based on linear active disturbance rejection control (LADRC) for the EGR EM valve driven by a limited angle torque motor (LATM). By analyzing the structure of the LATM and the transmission, the dynamic model of the system is derived. In addition, to solve the problems caused by slowly varying plant dynamics and uncertain disturbances, we combine the effects of uncertain model parameters and external disturbances as the total disturbance, which is estimated in real time by an extended state observer (ESO) and then compensated. In addition, accurate angular information is obtained using a non-contact magnetic angle measurement method, and a high-speed digital communication channel is established to help implement a closed-loop position control system with improved responsiveness and accuracy. Simulation and experimental results show that the proposed servo system design can effectively ensure the precision and real-time performance of the EM valve under slowly changing plant dynamics and uncertain disturbances. The proposed servo system design achieves a full-stroke valve control accuracy of better than 0.05 mm and a full-stroke response time of less than 100 ms. The controlled valve also has good robustness under shock-type external disturbances and excellent airflow control capability. The repeatability of the airflow control is generally within 5%, and the standard deviation is less than 0.2 m3/h.

13.
Nutr Res ; 125: 79-90, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38552503

RESUMO

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

14.
ACS Nano ; 18(8): 6612-6622, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38359901

RESUMO

To perform multiplex profiling of single cells and eliminate the risk of potential sample loss caused by centrifugation, we developed a microfluidic flow cytometry and mass spectrometry system (µCytoMS) to evaluate the drug uptake and induced protein expression at the single cell level. It involves a microfluidic chip for the alignment and purification of single cells followed by detection with laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). Biofunctionalized nanoprobes (BioNPs), conjugating ∼3000 6-FAM-Sgc8 aptamers on a single gold nanoparticle (AuNP) (Kd = 0.23 nM), were engineered to selectively bind with protein tyrosine kinase 7 (PTK7) on target cells. PTK7 expression induced by oxaliplatin (OXA) uptake was assayed with LIF, while ICP-MS measurement of 195Pt revealed OXA uptake of the drug in individual cells, which provided further in-depth information about the drug in relation to PTK7 expression. At an ultralow flow of ∼0.043 dyn/cm2 (20 µL/min), the chip facilitates the extremely fast focusing of BioNPs labeled single cells without the need for centrifugal purification. It ensures multiplex profiling of single cells at a throughput speed of 500 cells/min as compared to 40 cells/min in previous studies. Using a machine learning algorithm to initially profile drug uptake and marker expression in tumor cell lines, µCytoMS was able to perform in situ profiling of the PTK7 response to the OXA at single-cell resolution for tests done on clinical samples from 10 breast cancer patients. It offers great potential for multiplex single-cell phenotypic analysis and clinical diagnosis.


Assuntos
Nanopartículas Metálicas , Microfluídica , Humanos , Citometria de Fluxo , Ouro , Biomarcadores , Espectrometria de Massas/métodos , Moléculas de Adesão Celular , Receptores Proteína Tirosina Quinases
15.
Nat Commun ; 15(1): 1131, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326351

RESUMO

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.


Assuntos
Inteligência Artificial , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Radiologistas , Neoplasias Hepáticas/diagnóstico por imagem
16.
Clin Nucl Med ; 49(3): 289-291, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306383

RESUMO

ABSTRACT: Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.


Assuntos
Neoplasias Cerebelares , Radioisótopos de Flúor , Hemangioblastoma , Neoplasias Renais , Octreotida/análogos & derivados , Compostos Organometálicos , Doença de von Hippel-Lindau , Masculino , Humanos , Adulto , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico por imagem , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Renais/patologia
17.
J Sleep Res ; : e14168, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380761

RESUMO

Perioperative sleep disturbance may increase delirium risk. However, the role of perioperative sleep disturbance in delirium following total joint arthroplasty remains unclear. This prospective cohort study aimed to observe the delirium risk in patients with sleep disturbances. After excluding pre-existing sleep disturbances, older patients scheduled for total joint arthroplasty from July 17, 2022, to January 12, 2023, were recruited. Preoperative sleep disturbance or postoperative sleep disturbance was defined as a Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) score of <50 during hospitalisation. A cut-off score of 25 was used to classify the severity of sleep disturbance. The primary outcome was the incidence of postoperative delirium. In all, 11.6% of cohort patients (34/294) developed delirium. After multivariate analysis, a preoperative Day 1 RCSQ score of ≤25 (odds ratio [OR] 3.62, 95% confidence interval [CI] 1.19-10.92; p = 0.02), occurrence of sleep disturbances (OR 2.76, 95% CI 1.19-6.38; p = 0.02) and RCSQ score of ≤25(OR 2.91, 95% CI 1.33-6.37; p = 0.007) postoperatively were strong independent predictors of delirium. After sensitivity analysis for daily delirium, a postoperative Day 1 RCSQ score of ≤25 (OR 9.27, 95% CI 2.72-36.15; p < 0.001) was associated with a greater risk of delirium on postoperative Day 1, with a reasonable discriminative area under the curve of 0.730. We concluded that postoperative but not preoperative sleep disturbances may be an independent factor for delirium risk. Sleep disturbance on the first night after surgery was a good predictor of subsequent delirium, no matter the nature of self-reported sleep disturbance.

18.
Blood ; 143(19): 1965-1979, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38271660

RESUMO

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML.


Assuntos
Classe Ib de Fosfatidilinositol 3-Quinase , Leucemia Mieloide Aguda , Células-Tronco Neoplásicas , Via de Pentose Fosfato , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Humanos , Camundongos , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Classe Ib de Fosfatidilinositol 3-Quinase/genética , Autorrenovação Celular , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética
19.
Curr Med Sci ; 44(1): 134-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273178

RESUMO

OBJECTIVE: SUMO-specific protease 3 (SENP3), a member of the SUMO-specific protease family, reverses the SUMOylation of SUMO-2/3 conjugates. Dysregulation of SENP3 has been proven to be involved in the development of various tumors. However, its role in mantle cell lymphoma (MCL), a highly aggressive lymphoma, remains unclear. This study was aimed to elucidate the effect of SENP3 in MCL. METHODS: The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR, Western blotting or immunohistochemistry. MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs. Cell proliferation was assessed by CCK-8 assay, and cell apoptosis was determined by flow cytometry. mRNA sequencing (mRNA-seq) was used to investigate the underlying mechanism of SENP3 knockdown on MCL development. A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo. RESULTS: SENP3 was upregulated in MCL patient samples and cells. Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis. Meanwhile, the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown. Furthermore, the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model. CONCLUSION: SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.


Assuntos
Linfoma de Célula do Manto , Adulto , Animais , Humanos , Camundongos , Apoptose/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Modelos Animais de Doenças , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Camundongos Nus , Proteínas do Tecido Nervoso , Peptídeo Hidrolases/uso terapêutico , RNA Mensageiro , Proteínas Wnt/uso terapêutico
20.
Eur Arch Otorhinolaryngol ; 281(6): 2893-2903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38206390

RESUMO

INTRODUCTION: Currently, age-related hearing loss has become prevalent, awareness and screening rates remain dismally low. Duing to several barriers, as time, personnel training and equipment costs, available hearing screening tools do not adequately meet the need for large-scale hearing detection in community-dwelling older adults. Therefore, an accurate, convenient, and inexpensive hearing screening tool is needed to detect hearing loss, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. OBJECTIVES: The study harnessed "medical big data" and "intelligent medical management" to develop a multi-dimensional screening tool of age-related hearing loss based on WeChat platform. METHODS: The assessment of risk factors was carried out by cross-sectional survey, logistic regression model and receiver operating characteristic (ROC) curve analysis. Combining risk factor assessment, Hearing handicap inventory for the elderly screening version and analog audiometry, the screening software was been developed by JavaScript language and been evaluated and verified. RESULTS: A total of 401 older adults were included in the cross-sectional study. Logistic regression model (univariate, multivariate) and reference to literature mention rate of risk factors, 18 variables (male, overweight/obesity, living alone, widowed/divorced, history of noise, family history of deafness, non-light diet, no exercising habit, smoking, drinking, headset wearer habit, hypertension, diabetes, hyperlipidemia, cardiovascular and cerebrovascular diseases, hyperuricemia, hypothyroidism, history of ototoxic drug use) were defined as risk factors. The area under the ROC curve (AUC) of the cumulative score of risk factors for early prediction of age-related hearing loss was 0.777 [95% CI (0.721, 0.833)]. The cumulative score threshold of risk factors was defined as 4, to classify the older adults into low-risk (< 4) and high-risk (≥ 4) hearing loss groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the screen tool were 100%, 65.5%, 71.8%, and 100.0%, respectively. The Kappa index was 0.6. CONCLUSIONS: The screening software enabled the closed loop management of real-time data transmission, early warning, management, whole process supervision of the hearing loss and improve self-health belief in it. The software has huge prospects for application as a screening approach for age-related hearing loss.


Assuntos
Programas de Rastreamento , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , Programas de Rastreamento/métodos , Fatores de Risco , Pessoa de Meia-Idade , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Curva ROC , Idoso de 80 Anos ou mais , Presbiacusia/diagnóstico , Presbiacusia/epidemiologia , Medição de Risco/métodos , Modelos Logísticos , Vida Independente
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