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1.
Heliyon ; 10(13): e33619, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39091940

RESUMEN

Objectives: Effective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. Methods: In total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. Results: Nine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. Conclusion: This multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

2.
Medicine (Baltimore) ; 103(31): e39076, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093767

RESUMEN

RATIONALE: Both spinal muscular atrophy (SMA) and Phenylketonuria (PKU) are caused by biallelic pathogenic mutations. However, there has been no report on case who suffering from both diseases simultaneously. SMA mainly affects the motor function while PKU may have an impact on both the intelligence and motor function. But if only 1 disease is treated while neglecting the other, the treatment effect will be compromised. Here, for the first time, we report a case from China diagnosed with both these diseases and treated properly. PATIENT CONCERNS: A boy was admitted to the Children's Hospital Affiliated to Shandong University (Jinan, China) due to "limb weakness for 19 months" when he was 22 months old. Considering that the child's motor function development is delayed, we made a comprehensive examinations including inherited metabolic diseases and found a significantly increase of phenylalanine concentration in the blood which indicating PKU. Combined with his typical clinical manifestations of SMA, target capture sequencing followed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) technologies were used for genetic confirmation. DIAGNOSES: SMA and PKU was confirmed. INTERVENTIONS: The child was treated with risdiplam and low phenylalanine formula immediately when he was diagnosed with both SMA and PKU. OUTCOMES: The child showed remarkable improvement in motor function and significant decrease of blood phenylalanine concentration after treatment. LESSONS: To our knowledge, this is the first reported case of SMA combined with PKU. This case expands our understanding of diagnosis for synchronous SMA and PKU and highlights the importance of comprehensive examinations and the utilizing of various genetic testing methods to make an accurate diagnosis of genetic diseases, which may help avoiding the progressive damage caused by certain genetic disease with insidious clinical symptoms.


Asunto(s)
Atrofia Muscular Espinal , Fenilcetonurias , Humanos , Fenilcetonurias/genética , Fenilcetonurias/complicaciones , Fenilcetonurias/diagnóstico , Masculino , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/complicaciones , Lactante , Pruebas Genéticas/métodos , Fenilalanina/sangre , Fenilalanina/genética
3.
Heliyon ; 10(13): e33938, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071710

RESUMEN

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an 'inside-out' growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3'UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3'UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the 'inside-out' growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

4.
Mol Cancer ; 23(1): 148, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39048965

RESUMEN

Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.


Asunto(s)
Enzimas Desubicuitinizantes , Neoplasias , Complejo de la Endopetidasa Proteasomal , Ubiquitinación , Humanos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Animales , Complejo de la Endopetidasa Proteasomal/metabolismo , Enzimas Desubicuitinizantes/metabolismo , Proteolisis , Ubiquitina/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Procesamiento Proteico-Postraduccional , Terapia Molecular Dirigida , Ubiquitina-Proteína Ligasas/metabolismo
5.
Health Place ; 89: 103310, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38991484

RESUMEN

While the restorative benefits of residential environments are known, the influence of residents' physical activity on their perceptions of restorativeness in different settlements is unclear. This study aimed to investigate the mediating and moderating roles of residents' physical activities and seasons on restorative perceptions using survey data from three settlements in Harbin, China, involving a baseline survey conducted in June 2023 and questionnaires administered at 30-day intervals from July to December 2023 (534 interviews). Residents' restorative perceptions and physical activity levels were highest in autumn, with settlement quality having a seasonal moderating effect and physical activity having a mediating effect.

6.
JCO Glob Oncol ; 10: e2400044, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38995686

RESUMEN

PURPOSE: To characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL. METHODS: On the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants. RESULTS: The post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year). CONCLUSION: This community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.


Asunto(s)
Neoplasias Esofágicas , Calidad de Vida , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/psicología , Masculino , Femenino , Persona de Mediana Edad , Anciano , China , Esofagectomía , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Adulto
7.
Integr Cancer Ther ; 23: 15347354241268271, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081216

RESUMEN

OBJECTIVE: Powerful adjuvant strategies are required to improve the survival of patients with completely resected stage ΙΙΙA non-small cell lung cancer (NSCLC). We aimed to compare the efficacy of traditional Chinese medicine (TCM) treatment versus observation after adjuvant chemotherapy in these patients. METHODS: Eligible patients were randomized 1:1 to receive either oral decoctions based on Qi-Yin syndrome differentiation (TCM group) or observation (observation group). The intervention lasted for 12 months. The primary endpoint was 1-year disease-free survival (DFS). Secondary endpoints were DFS, quality of life, regulatory T cells (Tregs), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on the surface of Tregs in peripheral blood. We used EORTC QLQ-LC43 to evaluate quality of life. RESULTS: Between Apr 29, 2019, and Nov 11, 2021, 75 patients were randomly assigned to oral decoctions based on Qi-Yin syndrome differentiation (n = 38) or observation (n = 37). The full analysis set included 35 patients in the TCM group and 35 in the observation group. After a median follow-up of 24.2 months, oral decoctions based on Qi-Yin syndrome differentiation improved DFS compared with observation (HR 0.378, 95% CI: 0.157-0.912; P = .03). One-year DFS was 82.1% in the TCM group and 61.9% in the observation group (P = .06). Three months after randomization, scores of total health, role function, emotional function, and social function in the TCM group were higher than those in the observation group (P < .01 for all), scores of fatigue, pain, insomnia, appetite loss, constipation, cough, and chest pain were lower than those in the observation group (P < .05 for all); there was no significant difference in the proportion of Tregs between the TCM group and the observation group (P = .58); the proportion of CTLA-4+Tregs in the TCM group was lower than that in the observation group (P = .046). There were no adverse events that occurred in both groups. CONCLUSIONS: Oral decoctions based on Qi-Yin syndrome differentiation after adjuvant chemotherapy prolonged DFS, reduced the risk of disease recurrence and metastasis, improved quality of life, and down-regulated the proportion of CTLA-4+Tregs in completely resected stage ΙΙΙA NSCLC patients. TRIAL REGISTRATION: Chinese Clinical Trial Register, No. ChiCTR1800019396. Date of registration: 9 November 2018.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Medicina Tradicional China , Calidad de Vida , Humanos , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Quimioterapia Adyuvante/métodos , Medicina Tradicional China/métodos , Anciano , Qi , Estadificación de Neoplasias , Supervivencia sin Enfermedad
9.
Clinics (Sao Paulo) ; 79: 100458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39084065

RESUMEN

BACKGROUND: The influences of Oxycodone (OXY) combined with Paclitaxel (PTX) on breast cancer cells are unclear. The present study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis, and migration of human breast cancer SKBR3 cells and the underlying mechanism. METHODS: The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. RESULTS: OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration, and invasion of SKBR3 cells as compared to the control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-Ⅱ, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with the control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. CONCLUSIONS: The present study indicates that OXY can enhance the antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Movimiento Celular , Proliferación Celular , Oxicodona , Paclitaxel , Humanos , Paclitaxel/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Línea Celular Tumoral , Oxicodona/farmacología , Movimiento Celular/efectos de los fármacos , Sinergismo Farmacológico , Supervivencia Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Reproducibilidad de los Resultados , Western Blotting
11.
Drug Des Devel Ther ; 18: 2891-2904, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006193

RESUMEN

Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.


Asunto(s)
Estudios Cruzados , Medicamentos Genéricos , Estradiol , Posmenopausia , Comprimidos , Equivalencia Terapéutica , Femenino , Humanos , Persona de Mediana Edad , Administración Oral , Pueblo Asiatico , China , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/efectos adversos , Pueblos del Este de Asia , Estradiol/farmacocinética , Estradiol/administración & dosificación , Estradiol/sangre , Estradiol/análogos & derivados , Voluntarios Sanos
12.
Gland Surg ; 13(5): 669-683, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38845839

RESUMEN

Background: Mammographic architectural distortion (AD) is usually subtle and has variable presentations and causes, which poses a diagnostic challenge for breast radiologists and consequently a complex decision-making challenge for clinicians and patients. Presently, there is no reliable imaging standard to differentiate between malignant and benign ADs preoperatively. This study aimed to perform a comprehensive analysis of detailed mammographic and ultrasonographic features and clinical characteristics to enhance the diagnostic and differential efficacy for AD lesions. The findings have the potential to boost the diagnostic confidence of breast radiologists when encountering with AD lesions and could be instrumental in refining clinical management strategies for ADs. Methods: This retrospective study included consecutive female patients with ADs on screening or diagnostic mammography from January 6, 2015, to December 28, 2018. The patient's clinical data, mammographic and ultrasonographic or "second look" ultrasonographic findings, and pathological results were reviewed. The continuous variables were analyzed using the t-test. The categorical variables were assessed using the Chi-square test or two-tailed Fisher's exact test. Logistic regression analyses were conducted to evaluate potential risk factors for pathologically proven malignant ADs. Machine learning model based on multimodal clinical and imaging features was constructed using R software. Results: Ultimately, 344 patients with 346 AD lesions were enrolled in the study (mean age: 47.40±10.07 years; range, 19-84 years). Of the ADs, 228 were malignant and 118 were non-malignant. Palpable AD on mammography was more likely to indicate malignancy than non-palpable AD (83.43% vs. 49.15%, P<0.001). AD associated with other mammographic findings was more likely to be malignant than pure AD (73.58% vs. 59.36%, P=0.005). Ultrasonography (US) correlates were observed in 345 of these 346 AD lesions. Among these US correlates, 63 (18.26%, 63/345) were detected by "second look" ultrasound. For the US correlates, the mammographic ADs that appeared as non-mass-like hypoechoic areas and masses on US were more likely to be malignant than those that appeared as other abnormalities (P<0.001). The sensitivity, specificity and diagnostic accuracy of the eXtreme Gradient Boosting (XGBoost) model based on clinical and comprehensive imaging features in differentiation of AD lesions in the validation set were 66.46%, 94.23% and 78.9%, respectively, and the AUC was 0.886 (95% confidence interval: 0.825-0.947). Conclusions: The application of mammograms-guided "second-look" ultrasound could enhance the detection of US correlates, particularly non-mass-like features. The comprehensive analysis based on clinical and multimodal imaging features could be beneficial in improving the diagnostic and differential efficacy for AD lesions detected on mammography and instrumental in refining clinical management strategies for ADs.

13.
J Proteome Res ; 23(7): 2343-2354, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38831540

RESUMEN

Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.


Asunto(s)
Desoxicitidina , Gemcitabina , Proteómica , Proteínas Quinasas Asociadas a Fase-S , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Humanos , Proteómica/métodos , Línea Celular Tumoral , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
14.
Pestic Biochem Physiol ; 202: 105936, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38879328

RESUMEN

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.


Asunto(s)
Beauveria , Beauveria/patogenicidad , Beauveria/genética , Beauveria/fisiología , Animales , Virulencia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Spodoptera/microbiología , Esporas Fúngicas , Larva/microbiología , Serina Proteasas/metabolismo , Serina Proteasas/genética , Control Biológico de Vectores , Fusarium/patogenicidad , Fusarium/genética
15.
iScience ; 27(6): 109965, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38832013

RESUMEN

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

16.
RSC Adv ; 14(24): 16912-16920, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38799222

RESUMEN

In this study, polypropylene/halloysite nanotube (PP/HNT) composite separators were prepared by coating HNTs treated with hydrochloric acid (HCl) of different concentrations on both sides of a PP separator. The effect of HNTs treated with hydrochloric acid (HCl) of different concentrations on the properties of PP/HNT composite separators was investigated. The results indicate that the PP/HNT composite separator exhibits higher electrolyte uptake and wettability than a commercial PP separator, resulting in a better electrochemical performance in Li/LiFePO4 cells. In particular, the PP/HNTs-1.2 M composite separator with HNTs treated with 1.2 M HCl exhibits the highest electrolyte uptake (384%) and ionic conductivity (1.03 mS cm-1). The cells assembled with a PP/HNTs-1.2 M composite separator deliver discharge capacities of 166 mA h g-1 (0.5 C) and 131 mA h g-1 (3 C) with attractive cycling performance (87.6% capacity retention after 100 cycles). HNTs treated with HCl of appropriate concentrations can significantly improve the properties of PP/HNT composite separators for application in lithium-ion batteries.

17.
Cardiovasc Diabetol ; 23(1): 182, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811950

RESUMEN

BACKGROUND: Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF). METHOD: 427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification. CONCLUSION: Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.


Asunto(s)
Biomarcadores , Glucemia , Insuficiencia Cardíaca , Triglicéridos , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Masculino , Femenino , Estudios Transversales , Triglicéridos/sangre , Persona de Mediana Edad , Anciano , Glucemia/metabolismo , Enfermedad Crónica , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico , Biomarcadores/sangre , Volumen Sistólico , Valor Predictivo de las Pruebas , Resistencia a la Insulina , Pronóstico , Tensión Longitudinal Global
18.
Clin Exp Med ; 24(1): 102, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758367

RESUMEN

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/ß/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/ß/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/ß/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/ß/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.


Asunto(s)
Proteínas de Unión al GTP , Inmunoterapia , Neoplasias , Humanos , Linfocitos T CD8-positivos/inmunología , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/inmunología , Inmunoterapia/métodos , Interferón-alfa/metabolismo , Interferón beta/metabolismo , Interferón gamma/metabolismo , Interleucina-15/genética , Neoplasias/inmunología , Neoplasias/terapia , Transducción de Señal
19.
Int Immunopharmacol ; 133: 112069, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38643710

RESUMEN

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.


Asunto(s)
Transporte Activo de Núcleo Celular , Catequina , FN-kappa B , Receptor de Muerte Celular Programada 1 , Linfocitos T , Animales , Femenino , Humanos , Ratones , Transporte Activo de Núcleo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular Tumoral , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo
20.
Artículo en Inglés | MEDLINE | ID: mdl-38581316

RESUMEN

Objective: To explore and evaluate the effect of the accountability rehabilitation nursing model in the care of patients with ischemic stroke and the impact on nursing satisfaction, in order to improve the quality of care for patients with ischemic stroke. Design: This study selected 92 patients with ischemic stroke who met the inclusion criteria as the study objects, and divided them equally into the control group (46 cases) and the research group (46 cases) using a random number table. Data were collected by questionnaire. Interventions: The control group received standard routine rehabilitation nursing care, while the study group underwent an accountable rehabilitation care model. In the accountable rehabilitation care model, distinct nursing practices and strategies were employed to enhance clinical outcomes, limb function, neurological function, quality of life, and nursing satisfaction. Key elements of this model may include personalized care plans, increased emphasis on patient engagement, targeted therapeutic interventions, and a systematic approach to care coordination. A comparative analysis was conducted before and after the intervention to highlight the nuanced differences in outcomes between the two groups, shedding light on the specific benefits and effectiveness of the accountable rehabilitation care model as opposed to routine rehabilitation care. Results: In terms of clinical outcomes, the ESS score of the study group after intervention was significantly higher than that of the control group, indicating a positive impact on overall health (P < .05); limb function assessed by upper and lower limb muscle strength scores improved in both groups after the intervention. There was a significant enhancement, in which the score of the study group was significantly higher than that of the control group (P < .05); the NIHSS score showed that compared with the control group, the neurological function of the study group was significantly improved (P < .05); the SS-QOL score was used The assessed quality of life also improved significantly in the study group, exceeding the scores in the control group (P < .05). In addition, the nursing satisfaction of the study group was significantly higher compared with the control group, which highlighted the positive acceptance of the responsible rehabilitation nursing model by nursing staff (P < .05). Together, these findings highlight the combined benefits of the intervention in enhancing clinical, functional, and subjective outcomes. Discussion: The study underscores the promising clinical benefits of the responsibility system rehabilitation nursing model for patients with ischemic stroke. Marked enhancements in clinical outcomes, limb and nerve function, quality of life, and nursing satisfaction indicate its potential to significantly improve patient care. The personalized and accountable approach, featuring tailored care plans and heightened emphasis on patient engagement, holds promise for fostering positive health outcomes and enhancing overall patient experiences. Integrating this model into routine stroke care protocols emerges as a pivotal strategy for optimizing rehabilitation processes and adopting a patient-centered approach. Despite these advantages, acknowledging study limitations, such as non-randomized participant allocation and the absence of blinding, is crucial to recognizing potential biases. The study's sample size and single-center focus may impact generalizability. Beyond ischemic stroke, the model's broader significance aligns with contemporary healthcare trends, emphasizing accountability, personalized care plans, and enhanced care coordination. Its potential adaptation to various healthcare settings, chronic disease management, and preventive care could contribute to improved patient outcomes and healthcare quality. Future research should explore scalability and sustainability across diverse healthcare settings, investigating applicability to different patient populations and medical conditions. Assessing long-term effects, including healthcare cost-effectiveness and patient adherence, is essential for a comprehensive understanding of impact. Furthermore, delving into the perspectives of healthcare providers and patients can refine and tailor implementation strategies for optimal outcomes. Results: After the intervention, The European Stroke Scale (ESS) score of the study group was higher than that of the control group. After the intervention, the muscle strength scores of the upper and lower limbs of the study group were significantly higher than those of the control group. After intervention, the National Institutes of Health Stroke Scale (NIHSS) score of the study group was lower than that of the control group. After intervention, the stroke-specific quality of life scale (SS-QOL) score of the study group was higher than that of the control group. The nursing satisfaction of the study group was higher than that of the control group after intervention (all P < .05). Conclusion: The results of the study showed that the responsibility system rehabilitation nursing mode showed significant effects in improving the limb function, neurological function and quality of life of patients with ischemic stroke, which could promote the disease outcome of patients, and the nursing satisfaction of patients was high, which was worthy of promotion.

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