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1.
J Adv Res ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38862035

RESUMO

INTRODUCTION: Frailty Index (FI) is a common measure of frailty, which has been advocated as a routine clinical test by many guidelines. The genetic and phenotypic relationships of FI with cardiovascular indicators (CIs) and behavioral characteristics (BCs) are unclear, which has hampered ability to monitor FI using easily collected data. OBJECTIVES: This study is designed to investigate the genetic and phenotypic associations of frailty with CIs and BCs, and further to construct a model to predict FI. METHOD: Genetic relationships of FI with 288 CIs and 90 BCs were assessed by the cross-trait LD score regression (LDSC) and Mendelian randomization (MR). The phenotypic data of these CIs and BCs were integrated with a machine-learning model to predict FI of individuals in UK-biobank. The relationships of the predicted FI with risks of type 2 diabetes (T2D) and neurodegenerative diseases were tested by the Kaplan-Meier estimator and Cox proportional hazards model. RESULTS: MR revealed putative causal effects of seven CIs and eight BCs on FI. These CIs and BCs were integrated to establish a model for predicting FI. The predicted FI is significantly correlated with the observed FI (Pearson correlation coefficient = 0.660, P-value = 4.96 × 10-62). The prediction model indicated "usual walking pace" contributes the most to prediction. Patients who were predicted with high FI are in significantly higher risk of T2D (HR = 2.635, P < 2 × 10-16) and neurodegenerative diseases (HR = 2.307, P = 1.62 × 10-3) than other patients. CONCLUSION: This study supports associations of FI with CIs and BCs from genetic and phenotypic perspectives. The model that is developed by integrating easily collected CIs and BCs data in predicting FI has the potential to monitor disease risk.

2.
J Immunother Cancer ; 12(6)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908858

RESUMO

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Melanoma , Piridinas , Humanos , Masculino , Feminino , Melanoma/tratamento farmacológico , Melanoma/patologia , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/farmacologia , Piridinas/efeitos adversos , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mucosa/efeitos dos fármacos , Mucosa/patologia
3.
Front Microbiol ; 15: 1373013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835486

RESUMO

Background: This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. Methods: We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1ß, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed. Results: A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors. Conclusion: O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.

4.
Breast ; 76: 103762, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38924994

RESUMO

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.

5.
J Biophotonics ; : e202400119, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38932695

RESUMO

Image Photoplethysmography (IPPG) technology is a noncontact physiological parameter detection technology, which has been widely used in heart rate (HR) detection. However, traditional imaging devices still have issues such as narrower receiving spectral range and inferior motion detection performance. In this paper, we propose a HR detection method based on multi-spectral video. Our method combining multispectral imaging with IPPG technology provides more accurate physiological information. To realize real-time evaluation of HR directly from facial multispectral videos, we propose a new end-to-end neural network, namely IPPGResNet18. The IPPGResNet18 model was trained on the multispectral video dataset from which better results were achieved: MAE = 2.793, RMSE = 3.695, SD = 3.707, p = 0.304. The experimental results demonstrate a high accuracy of HR detection under motion state using this detection method. In respect of real-time monitoring of HR during movement, our method is obviously superior to the conventional technical solutions.

6.
Postgrad Med ; : 1-11, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38912825

RESUMO

OBJECTIVE: The aim of this study is to examine the perception, willingness to engage, and demand of community residents regarding the 'internet + nursing service' in a designated pilot area, aiming to offer insights for the widespread adoption of the 'internet + nursing service' throughout China. METHODS: A survey pertaining to the 'internet + nursing service' was conducted from March to April 2022. The study specifically targeted residents within two sub-districts of a city in the Jiangsu province. The sampling technique employed in this study was stratified random sampling. RESULTS: Out of a total of 400 community residents selected from two sub-districts in this region, 378 provided valid responses, resulting in an effective rate of 94.5%. Within the study cohort, 80 participants (21.16%) demonstrated familiarity with the concept of 'internet + nursing service.' Additionally, 231 participants (61.11%) conveyed their willingness to adopt such services. Regarding service preferences, the primary demands were for health guidance, vital sign monitoring, and basic care. Challenges in implementing the service were attributed to concerns related to medical risks, personal safety for both nurses and patients, and potential breaches of privacy. CONCLUSIONS: Residents in the pilot area exhibited a moderate awareness of the 'internet + nursing service,' with a relatively high willingness to embrace the program. There is a need for further refinement of pertinent laws, widespread dissemination of policies, and enhancements in the quality of nursing services. These measures aim to ensure that a greater number of community residents can avail themselves of improved home-based nursing services.

7.
EFORT Open Rev ; 9(6): 458-466, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828978

RESUMO

Purpose: For many decades, patients recovering from wound closure have been instructed not to bathe. Although studies have shown that earlier postoperative bathing does not increase the risk of wound infection, it remains rare in practice for patients to be allowed earlier postoperative bathing. We performed this meta-analysis to determine how earlier bathing affected rates of wound infection, other complications, and patient satisfaction. Methods: This systematic review conforms to PRISMA guidelines. The PubMed, EMBASE, Medline, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception dates to December 31, 2022. We estimated pooled values for the efficacy of trial of earlier bathing versus delayed bathing using the odds ratio and their associated 95% CI, and we used the I 2 statistic to assess heterogeneity between studies contributing to these estimates. Results: Of the 1813 articles identified by our search, 11 randomized controlled trials including 2964 patients were eligible for inclusion. The incidence of wound infection did not differ significantly between the earlier bathing and delayed bathing groups, nor did rates of other wound complications such as redness and swelling, or wound dehiscence. However, the incidence of hematoma in the delayed bathing group was higher than in the earlier bathing group. Reported patient satisfaction was significantly higher in the earlier bathing group. Conclusion: The medical community, health authorities, and government should create and disseminate clinical practice guidelines to guide patients to evidence-based beneficial treatment.

8.
Water Res ; 259: 121848, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824797

RESUMO

Chronic exposure to elevated geogenic arsenic (As) and fluoride (F-) concentrations in groundwater poses a significant global health risk. In regions around the world where regular groundwater quality assessments are limited, the presence of harmful levels of As and F- in shallow groundwater extracted from specific wells remains uncertain. This study utilized an enhanced stacking ensemble learning model to predict the distributions of As and F- in shallow groundwater based on 4,393 available datasets of observed concentrations and forty relevant environmental factors. The enhanced model was obtained by fusing well-suited Extreme Gradient Boosting, Random Forest, and Support Vector Machine as the base learners and a structurally simple Linear Discriminant Analysis as the meta-learner. The model precisely captured the patchy distributions of groundwater As and F- with an AUC value of 0.836 and 0.853, respectively. The findings revealed that 9.0% of the study area was characterized by a high As risk in shallow groundwater, while 21.2% was at high F- risk identified as having a high risk of fluoride contamination. About 0.2% of the study area shows elevated levels of both of them. The affected populations are estimated at approximately 7.61 million, 34.1 million, and 0.2 million, respectively. Furthermore, sedimentary environment exerted the greatest influence on distribution of groundwater As, with human activities and climate following closely behind at 29.5%, 28.1%, and 21.9%, respectively. Likewise, sedimentary environment was the primary factor affecting groundwater F- distribution, followed by hydrogeology and soil physicochemical properties, contributing 27.8%, 24.0%, and 23.3%, respectively. This study contributed to the identification of health risks associated with shallow groundwater As and F-, and provided insights into evaluating health risks in regions with limited samples.


Assuntos
Arsênio , Monitoramento Ambiental , Fluoretos , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , Fluoretos/análise , Arsênio/análise , Poluentes Químicos da Água/análise , China
9.
Phytomedicine ; 131: 155775, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838401

RESUMO

BACKGROUND: The cyclin-dependent kinase 4 (CDK4) interacts with its canonical and non-canonical substrates modulating the cell cycle in tumor cells. However, the potential substrates and the beyond-cell-cycle-regulated functions of CDK4 in colon cancer (CC) are still unknown. Hernandezine (HER) is previously verified to induce G0/G1 phase arrest and autophagic cell death in human cancer cells, which implies that HER might target G0/G1 phase-related proteins, including CDK4. PURPOSE: The present study tried to investigate the glycolytic metabolism and oxidative stress functions of CDK4 in colon cancer. Furthermore, the inhibitory effects and potential binding sites of HER on CDK4, as well as its anti-tumor activity were investigated in CC cells. METHODS: The mass spectrometry assay was performed to identify potential endogenous substrates of CDK4 and the correlation between glycolytic metabolic rate and CDK4 level in COAD patient tissues. Meanwhile, after inhibiting the activity or the expression of CDK4, the binding capacity of CDK4 to PKM2 and NRF2 and the latter two protein distributions in cytoplasm and nucleus were detected in CC cells. In vitro, the regulatory effects of the CDK4-PKM2-NRF2 axis on glycolysis and oxidative stress were performed by ECAR, OCR, and ROS assay. The inhibitory effect of HER on CDK4 activity was explored in CC cells and the potential binding sites were predicted and testified in vitro. Furthermore, tumor growth inhibition of HER by suppressing the CDK4-PKM2-NRF2 axis was also investigated in vitro and in vivo. RESULTS: PKM2 and NRF2 were identified as endogenous substrates of CDK4 and, high-expressed CDK4 was associated with low-level glycolysis in COAD. In vitro, inactivated CDK4 facilitated CDK4-PKM2-NRF2 complex formation which resulted in 1) inhibited PKM2 activity and retarded the glycolytic rate; 2) cytoplasm-detained NRF2 failed to transcript anti-oxidative gene expressions and induced oxidant stress. Additionally, as a CDK4 inhibitor, HER developed triple anti-tumor effects including induced G0/G1 phase arrest, suppressed glycolysis, and disrupted the anti-oxidative capacity of CC cells. CONCLUSION: The results first time revealed that CDK4 modulated glycolytic and anti-oxidative capacity of CC cells via bound to its endogenous substrates, PKM2 and NRF2. Additionally, 140Asp145Asn amino acid sites of CDK4 were potential targets of HER. HER exerts anti-tumor activity by inhibited the activity of CDK4, promoted the CDK4-PKM2-NRF2 complex formation in the CC cells.


Assuntos
Proteínas de Transporte , Neoplasias do Colo , Quinase 4 Dependente de Ciclina , Proteínas de Membrana , Fator 2 Relacionado a NF-E2 , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Quinase 4 Dependente de Ciclina/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Animais , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Linhagem Celular Tumoral , Proteínas de Transporte/metabolismo , Glicólise/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Feminino
10.
Cancer Med ; 13(12): e7413, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38925621

RESUMO

OBJECTIVE: To address the question of axillary lymph node staging in ductal carcinoma in situ with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. RESULTS: Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. CONCLUSION: The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.


Assuntos
Axila , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Linfonodos , Metástase Linfática , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Intraductal não Infiltrante/terapia , Carcinoma Intraductal não Infiltrante/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Invasividade Neoplásica , Micrometástase de Neoplasia/patologia
11.
J Cell Mol Med ; 28(9): e18374, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722288

RESUMO

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.


Assuntos
Neoplasias da Mama , Organoides , Medicina de Precisão , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Organoides/efeitos dos fármacos , Organoides/patologia , Organoides/metabolismo , Medicina de Precisão/métodos , Animais , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Pessoa de Meia-Idade
12.
Cancer Lett ; 593: 216956, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38735381

RESUMO

Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.


Assuntos
Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Neoplasias de Cabeça e Pescoço , Inibidores de Proteínas Quinases , Fator de Transcrição STAT3 , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Animais , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Feminino , Masculino , Camundongos Nus , Camundongos , Proteína do Retinoblastoma/metabolismo , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fosforilação
13.
Aging (Albany NY) ; 16(9): 8086-8109, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38728245

RESUMO

BACKGROUND: Research has shown a connection between vasculogenic mimicry (VM) and cancer progression. However, the functions of genes related to VM in the emergence and progression of TNBC have not been completely elucidated. METHODS: A survival risk model was constructed by screening biomarkers using DESeq2 and WGCNA based on public TNBC transcriptome data. Furthermore, gene set enrichment analysis was performed, and tumor microenvironment and drug sensitivity were analyzed. The selected biomarkers were validated via quantitative PCR detection, immunohistochemical staining, and protein detection in breast cancer cell lines. Biomarkers related to the proliferation and migration of TNBC cells were validated via in vitro experiments. RESULTS: The findings revealed that 235 target genes were connected to the complement and coagulation cascade pathways. The risk score was constructed using KCND2, NRP1, and VSTM4. The prognosis model using the risk score and pathological T stage yielded good validation results. The clinical risk of TNBC was associated with the angiogenesis signaling pathway, and the low-risk group exhibited better sensitivity to immunotherapy. Quantitative PCR and immunohistochemistry indicated that the expression levels of KCND2 in TNBC tissues were higher than those in adjacent nontumor tissues. In the TNBC cell line, the protein expression of KCND2 was increased. Knockdown of KCND2 and VSTM4 inhibited the proliferation and migration of TNBC cells in vitro. CONCLUSIONS: In this study, three VM-related biomarkers were identified, including KCND2, NRP1, and VSTM4. These findings are likely to aid in deepening our understanding of the regulatory mechanism of VM in TNBC.


Assuntos
Biomarcadores Tumorais , Neovascularização Patológica , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Feminino , Prognóstico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Proliferação de Células/genética , Neuropilina-1/genética , Neuropilina-1/metabolismo , Movimento Celular/genética , Transcriptoma , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo
14.
Nat Commun ; 15(1): 4106, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750031

RESUMO

China's extensive planted forests play a crucial role in carbon storage, vital for climate change mitigation. However, the complex spatiotemporal dynamics of China's planted forest area and its carbon storage remain uncaptured. Here we reveal such changes in China's planted forests from 1990 to 2020 using satellite and field data. Results show a doubling of planted forest area, a trend that intensified post-2000. These changes lead to China's planted forest carbon storage increasing from 675.6 ± 12.5 Tg C in 1990 to 1,873.1 ± 16.2 Tg C in 2020, with an average rate of ~ 40 Tg C yr-1. The area expansion of planted forests contributed ~ 53% (637.2 ± 5.4 Tg C) of the total above increased carbon storage in planted forests compared with planted forest growth. This proactive policy-driven expansion of planted forests has catalyzed a swift increase in carbon storage, aligning with China's Carbon Neutrality Target for 2060.

15.
Clin Lab ; 70(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747931

RESUMO

BACKGROUND: The goal of the study was to provide an individual and precise genetic and molecular biological basis for the early prevention, diagnosis, and treatment of local FH by analyzing the risk factors for the development of FH in Han and Mongolian patients in the Hulunbuir, comparing the lipid levels of FH patients of the two ethnicities, and assessing differences in mutations to two genes between the two ethnic groups. METHODS: Twenty cases each of Han Chinese and Mongolian healthy controls and fifty patients who each met the inclusion criteria from November 2021 to December 2022 in five general hospitals in Hulunbuir were selected. Multifactor logistic analysis was used to analyze the risk factors associated with the development of FH. We used t-tests to analyze statistical differences in lipid levels between the groups, and Sanger sequencing to detect the dis-tribution of common mutation sites of PCSK9 and APOB in all study subjects. The mutation rates and differences between regions and ethnic groups were summarized and compared. RESULTS: 1) Gender, age, alcohol consumption, dietary status, and a family history of FH were risk factors associated with the development of FH. 2) TC, LDL-C, and APOB were significantly higher in Mongolian cases than Han cases (p < 0.05). sdLDL-C was not statistically different between the two ethnicities (p > 0.05). 3) We detected four (8%) heterozygous mutations at the PCSK9 gene E670G mutation site in the Han case group and a total of nine (18%) mutations at this site in the Mongolian cases, including one (2%) homozygous and eight (16%) heterozygous mutations. One case of a heterozygous mutation was detected in the Mongolian control group. We detected a total of ten (20%) mutations at the APOB gene rs1367117 mutation site in the Han case group, including eight (16%) heterozygous and two (4%) homozygous mutations, 11 cases (22%) of heterozygous mutations in the Mongolian case group, two cases of heterozygous mutations in the Han control group, and one case of a heterozygous mutation in the Mongolian control group. 4) The D374Y and S127R mutation sites of PCSK9 and the R3500Q mutation site of APOB were not detected in any of the study subjects. CONCLUSIONS: The mutation sites of the PCSK9 and APOB genes in FH patients in Hulunbuir are different from other regions, and the mutation rate is higher than in other regions. Therefore, we recommend that the mutation sites of the PCSK9 and APOB genes described herein be used as clinical detection indicators to assist the diagnosis of FH in this region.


Assuntos
Apolipoproteína B-100 , Hiperlipoproteinemia Tipo II , Mutação , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/genética , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , China/epidemiologia , Apolipoproteína B-100/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/etnologia , Hiperlipoproteinemia Tipo II/diagnóstico , Povo Asiático/genética , Adulto , Mongólia/epidemiologia , Mongólia/etnologia , Estudos de Casos e Controles , Predisposição Genética para Doença , LDL-Colesterol/sangue , Etnicidade/genética , Idoso
17.
Mikrochim Acta ; 191(6): 321, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727732

RESUMO

The rapid and precise monitoring of peripheral blood miRNA levels holds paramount importance for disease diagnosis and treatment monitoring. In this study, we propose an innovative research strategy that combines the catalytic hairpin assembly reaction with SERS signal congregation and enhancement. This combination can significantly enhance the stability of SERS detection, enabling stable and efficient detection of miRNA. Specifically, our paper-based SERS detection platform incorporates a streptavidin-modified substrate, biotin-labeled catalytic hairpin assembly reaction probes, 4-ATP, and primer-co-modified gold nanoparticles. In the presence of miRNA, the 4-ATP and primer-co-modified gold nanoparticles can specifically recognize the miRNA and interact with the biotin-labeled CHA probes to initiate an interfacial catalytic hairpin assembly reaction. This enzyme-free high-efficiency catalytic process can accumulate a large amount of biotin on the gold nanoparticles, which then bind to the streptavidin on the substrate with the assistance of the driving liquid, forming red gold nanoparticle stripes. These provide a multitude of hotspots for SERS, enabling enhanced signal detection. This innovative design achieves a low detection limit of 3.47 fM while maintaining excellent stability and repeatability. This conceptually innovative detection platform offers new technological possibilities and solutions for clinical miRNA detection.


Assuntos
Biotina , Ouro , Limite de Detecção , Nanopartículas Metálicas , MicroRNAs , Análise Espectral Raman , MicroRNAs/sangue , MicroRNAs/análise , Nanopartículas Metálicas/química , Ouro/química , Análise Espectral Raman/métodos , Biotina/química , Humanos , Catálise , Estreptavidina/química
19.
World J Gastrointest Surg ; 16(5): 1336-1343, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38817276

RESUMO

BACKGROUND: Magnetic anchor technique (MAT) has been applied in laparoscopic cholecystectomy and laparoscopic appendectomy, but has not been reported in laparoscopic partial hepatectomy. AIM: To evaluate the feasibility of the MAT in laparoscopic left lateral segment liver resection. METHODS: Retrospective analysis was conducted on the clinical data of eight patients who underwent laparoscopic left lateral segment liver resection assisted by MAT in our department from July 2020 to November 2021. The Y-Z magnetic anchor devices (Y-Z MADs) was independently designed and developed by the author of this paper, which consists of the anchor magnet and magnetic grasping apparatus. Surgical time, intraoperative blood loss, intraoperative accidents, operator experience, postoperative incision pain score, postoperative complications, and other indicators were evaluated and analyzed. RESULTS: All eight patients underwent a MAT-assisted laparoscopic left lateral segment liver resection, including three patients undertaking conventional 5-port and five patients having a transumbilical single-port operation. The mean operation time was 138 ± 34.32 min (range 95-185 min) and the mean intraoperative blood loss was 123 ± 88.60 mL (range 20-300 mL). No adverse events occurred during the operation. The Y-Z MADs showed good workability and maneuverability in both tissue and organ exposure. In particular, the operators did not experience either a "chopstick" or "sword-fight" effect in the single-port laparoscopic operation. CONCLUSION: The results show that the MAT is safe and feasible for laparoscopic left lateral segment liver resection, especially, exhibits its unique abettance for transumbilical single-port laparoscopic left lateral segment liver resection.

20.
Ann Gen Psychiatry ; 23(1): 19, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730281

RESUMO

BACKGROUND: Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. OBJECTIVES: Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. METHODS: 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach's coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. RESULT: CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach 's of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. CONCLUSION: Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial.

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