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Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.
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Colo do Útero , Displasia do Colo do Útero , Vagina , Humanos , Feminino , Colo do Útero/anormalidades , Colo do Útero/cirurgia , Colo do Útero/patologia , Vagina/anormalidades , Vagina/cirurgia , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/patologia , Tubas Uterinas/cirurgia , Tubas Uterinas/anormalidades , Tubas Uterinas/patologia , Anormalidades CongênitasRESUMO
Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P< 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported. Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938. Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance.
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Doença das Coronárias , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Idoso , Doença das Coronárias/epidemiologia , Doença das Coronárias/sangue , Pessoa de Meia-Idade , Senilidade Prematura/epidemiologia , Fatores de Risco , Envelhecimento , Triglicerídeos/sangue , China/epidemiologia , Adenosina Desaminase/metabolismo , Ureia/sangueRESUMO
The increasingly urgent issue of climate change is driving the development of carbon dioxide (CO2) capture and separation technologies in flue gas after combustion. The monolithic adsorbent stands out in practical adsorption applications for its simplified powder compaction process while maintaining the inherent balance between energy consumption for regeneration and selectivity for adsorption. However, optimizing the adsorption capacity and selectivity of CO2 separation materials remains a significant challenge. Herein, we synthesized monolithic polymer networks (N-CMPs) with triphenylamine adsorption sites, acid-base environment tolerance, and precise narrow microchannel pore systems for the selective sieving of CO2 and particulate matter (PM) in flue gas. The inherent continuous covalent bonding of N-CMPs, along with their highly delocalized π-π conjugated porous framework, ensures the stability of the monolithic polymer network's adsorption and separation capabilities under wet and acid-base conditions. Specifically, under the conditions of 1 bar at 273 K, the CO2 adsorption capacity of N-CMP-1 is 3.35 mmol/g. Attributed to the highly polar environment generated by triphenylamine and the inherent high micropore/mesopore ratio, N-CMPs exhibit an excellent ideal adsorbed solution theory (IAST) selectivity for CO2/N2 under simulated flue gas conditions (CO2/N2 = 15:85). Dynamic breakthrough experiments further visualize the high separation efficiency of N-CMPs in practical adsorption applications. Moreover, under acid-base conditions, N-CMPs achieve a capture efficiency exceeding 99.76 % for PM0.3, enabling the selective separation of CO2 and PM in flue gas. In fact, the combined capture of hazardous PM and CO2 from the exhaust gases produced by the combustion of fossil fuels will play a pivotal role in mitigating climate change and environmental issues until low-carbon and alternative energy technologies are widely adopted.
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BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.
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Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.
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Antibacterianos , Antineoplásicos , Catequina , Cobre , Nanocompostos , Antibacterianos/farmacologia , Antibacterianos/química , Cobre/química , Cobre/farmacologia , Nanocompostos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Animais , Camundongos , Humanos , Catequina/química , Catequina/farmacologia , Catequina/análogos & derivados , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/efeitos dos fármacos , Fotoquimioterapia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/microbiologia , Ensaios de Seleção de Medicamentos Antitumorais , Staphylococcus aureus/efeitos dos fármacos , Terapia Fototérmica , Tamanho da Partícula , Escherichia coli/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Propriedades de Superfície , Proliferação de Células/efeitos dos fármacosRESUMO
Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.
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Proteínas Substratos do Receptor de Insulina , Sistema de Sinalização das MAP Quinases , Mutação , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Animais , Malformações do Desenvolvimento Cortical do Grupo I/genética , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neurônios/metabolismo , Neurônios/patologia , Movimento Celular/genética , Células HEK293 , Feminino , Displasia Cortical Focal , EpilepsiaRESUMO
OBJECTIVES: To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. METHODS: SH-SY5Y cells were divided into control group, low concentration (0.1 µM and 1 µM) adapalene groups, and high concentration (10 µM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker ßIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. RESULTS: Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of ßIII-tubulin and NFH increased in the 1 µM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). CONCLUSIONS: Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.
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Neuroblastoma , Tubulina (Proteína) , Humanos , Neurônios , Diferenciação Celular , Apoptose , Linhagem Celular TumoralRESUMO
BACKGROUND: The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined. RESULTS: Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001). CONCLUSION: Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.
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Fibrose Pulmonar Idiopática , Metformina , Piridonas , Humanos , Camundongos , Animais , Metformina/farmacologia , Metformina/uso terapêutico , Pulmão/patologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Superóxido Dismutase/farmacologia , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: ⢠The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. ⢠Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. ⢠The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Linfonodos/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologiaRESUMO
OBJECTIVES: To assess image quality and liver metastasis detection of reduced-dose dual-energy CT (DECT) with deep learning image reconstruction (DLIR) compared to standard-dose single-energy CT (SECT) with DLIR or iterative reconstruction (IR). METHODS: In this prospective study, two groups of 40 participants each underwent abdominal contrast-enhanced scans with full-dose SECT (120-kVp images, DLIR and IR algorithms) or reduced-dose DECT (40- to 60-keV virtual monochromatic images [VMIs], DLIR algorithm), with 122 and 106 metastases, respectively. Groups were matched by age, sex ratio, body mass index, and cross-sectional area. Noise power spectrum of liver images and task-based transfer function of metastases were calculated to assess the noise texture and low-contrast resolution. The image noise, signal-to-noise ratios (SNR) of liver and portal vein, liver-to-lesion contrast-to-noise ratio (LLR), lesion conspicuity, lesion detection rate, and the subjective image quality metrics were compared between groups on 1.25-mm reconstructed images. RESULTS: Compared to 120-kVp images with IR, 40- and 50-keV VMIs with DLIR showed similar noise texture and LLR, similar or higher image noise and low-contrast resolution, improved SNR and lesion conspicuity, and similar or better perceptual image quality. When compared to 120-kVp images with DLIR, 50-keV VMIs with DLIR had similar low-contrast resolution, SNR, LLR, lesion conspicuity, and perceptual image quality but lower frequency noise texture and higher image noise. For the detection of hepatic metastases, reduced-dose DECT by 34% maintained observer lesion detection rates. CONCLUSION: DECT assisted with DLIR enables a 34% dose reduction for detecting hepatic metastases while maintaining comparable perceptual image quality to full-dose SECT. CLINICAL RELEVANCE STATEMENT: Reduced-dose dual-energy CT with deep learning image reconstruction is as accurate as standard-dose single-energy CT for the detection of liver metastases and saves more than 30% of the radiation dose. KEY POINTS: ⢠The 40- and 50-keV virtual monochromatic images (VMIs) with deep learning image reconstruction (DLIR) improved lesion conspicuity compared with 120-kVp images with iterative reconstruction while providing similar or better perceptual image quality. ⢠The 50-keV VMIs with DLIR provided comparable perceptual image quality and lesion conspicuity to 120-kVp images with DLIR. ⢠The reduction of radiation by 34% by DLIR in low-keV VMIs is clinically sufficient for detecting low-contrast hepatic metastases.
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Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Estudos Prospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Doses de Radiação , Processamento de Imagem Assistida por Computador/métodosRESUMO
There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , MicroRNAs , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Luciferases , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/genéticaRESUMO
Objective: Focal cortical dysplasia (FCD) is the most common pathological cause for pediatric epilepsy, with frontal lobe epilepsy (FLE) being the most prevalent in the pediatric population. We attempted to utilize radiomic and morphological methods on MRI and PET to detect FCD in children with FLE. Methods: Thirty-seven children with FLE and 20 controls were included in the primary cohort, and a five-fold cross-validation was performed. In addition, we validated the performance in an independent site of 12 FLE children. A two-stage experiments including frontal lobe and subregions were employed to detect the lesion area of FCD, incorporating the asymmetric feature between the left and right hemispheres. Specifically, for the radiomics approach, we used gray matter (GM), white matter (WM), GM and WM, and the gray-white matter boundary regions of interest to extract features. Then, we employed a Multi-Layer Perceptron classifier to achieve FCD lesion localization based on both radiomic and morphological methods. Results: The Multi-Layer Perceptron model based on the asymmetric feature exhibited excellent performance both in the frontal lobe and subregions. In the primary cohort and independent site, the radiomics analysis with GM and WM asymmetric features had the highest sensitivity (89.2 and 91.7%) and AUC (98.9 and 99.3%) in frontal lobe. While in the subregions, the GM asymmetric features had the highest sensitivity (85.6 and 79.7%). Furthermore, relying on the highest sensitivity of GM and WM asymmetric features in frontal lobe, when integrated with the subregions results, our approach exhibited overlaps with GM asymmetric features (55.4 and 52.4%), as well as morphological asymmetric features (54.4 and 53.8%), both in the primary cohort and at the independent site. Significance: This study demonstrates that a two-stage design based on the asymmetry of radiomic and morphological features can improve FCD detection. Specifically, incorporating regions of interest for GM, WM, GM, and WM, and the gray-white matter boundary significantly enhances the localization capabilities for lesion detection within the radiomics approach.
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Background: Glucose metabolism (GM) plays a crucial role in cancer cell proliferation, tumor growth, and survival. However, the identification of glucose metabolism-related genes (GMRGs) for effective prediction of prognosis in head and neck squamous cell carcinoma (HNSC) is still lacking. Methods: We conducted differential analysis between HNSC and Normal groups to identify differentially expressed genes (DEGs). Key module genes were obtained using weighted gene co-expression network analysis (WGCNA). Intersection analysis of DEGs, GMRGs, and key module genes identified GMRG-DEGs. Univariate and multivariate Cox regression analyses were performed to screen prognostic-associated genes. Independent prognostic analysis of clinical traits and risk scores was implemented using Cox regression. Gene set enrichment analysis (GSEA) was used to explore functional pathways and genes between high- and low-risk groups. Immune infiltration analysis compared immune cells between the two groups in HNSC samples. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Quantitative real-time fluorescence PCR (qRT-PCR) validated the expression levels of prognosis-related genes in HNSC patients. Results: We identified 4973 DEGs between HNSC and Normal samples. Key gene modules, represented by black and brown module genes, were identified. Intersection analysis revealed 76 GMRG-DEGs. Five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) were identified. A nomogram incorporating age, lymph node status (N), and risk score was constructed for survival prediction in HNSC patients. Immune infiltration analysis showed significant differences in five immune cell types (Macrophages M0, memory B cells, Monocytes, Macrophages M2, and Dendritic resting cells) between the high- and low-risk groups. GDSC database analysis identified 53 drugs with remarkable differences between the groups, including A.443654 and AG.014699. DNMT1 and MTHFD2 were up-regulated, while MPZ was down-regulated in HNSC. Conclusion: Our study highlights the significant association of five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) with HNSC. These findings provide further evidence of the crucial role of GMRGs in HNSC.
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Metabolismo dos Carboidratos , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/genética , GlucoseRESUMO
Background: Malnutrition is prevalent in patients with pulmonary tuberculosis (PTB) and is associated with a poor prognosis. Objective: This study aims to assess the prevalence and risk factors of malnutrition in patients with PTB. Methods: Studies related to the prevalence and risk factors of malnutrition in patients with PTB were searched through PubMed, Embase, Web of Science, and Cochrane Library databases from January 1990 to August 2022, and two researchers screened the literature, evaluated the quality, and extracted data independently. A random-effects model was used to pool the effect sizes and 95% confidence intervals. Subgroup analysis, meta-regression analysis, and sensitivity analysis were further performed to identify sources of heterogeneity and evaluate the stability of the results. Publication bias was assessed by Doi plot, Luis Furuya-Kanamori (LFK) asymmetry index, funnel plot, and Egger's tests. Results: A total of 53 studies involving 48, 598 participants were identified in this study. The prevalence of malnutrition was 48.0% (95% CI, 40.9-55.2%). Subgroup analysis revealed that malnutrition was more common among male gender (52.3%), bacterial positivity (55.9%), family size over 4 (54.5%), drug resistance (44.1%), residing in rural areas (51.2%), HIV infection (51.5%), Asian (51.5%), and African (54.5%) background. The prevalence of mild, moderate, and severe malnutrition was 21.4%, 14.0%, and 29.4%, respectively. Bacterial positivity (OR = 2.08, 95% CI 1.26-3.41), low income (OR = 1.44, 95% CI 1.11-1.86), and residing in rural areas (OR = 1.51, 95% CI 1.20-1.89) were risk factors of malnutrition in patients with PTB. However, male (OR = 1.04, 95% CI 0.85-1.26) and drinking (OR = 1.17, 95% CI 0.81-1.69) were not risk factors for malnutrition in patients with PTB. Due to the instability of sensitivity analysis, HIV infection, age, family size, smoking, and pulmonary cavity need to be reevaluated. Meta-regression suggested that sample size was a source of heterogeneity of prevalence. The Doi plot and LFK asymmetry index (LFK = 3.87) indicated the presence of publication bias for prevalence, and the funnel plot and Egger's test showed no publication bias for risk factors. Conclusion: This meta-analysis indicated that malnutrition was prevalent in patients with PTB, and bacterial positivity, low income, and those residing in rural areas were risk factors for malnutrition. Therefore, clinical workers should pay attention to screening the nutritional status of patients with PTB and identifying the risk factors to reduce the incidence of malnutrition and provide nutritional interventions early to improve the prognosis in patients with PTB.
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PLC-ß is widely distributed in eukaryotic cells and is the key enzyme in phosphatidylinositol signal transduction pathway. The cellular functions regulated by its four subtypes (PLC-ß1, PLC-ß2, PLC-ß3, PLC-ß4) play an important role in maintaining homeostasis of organism. PLC-ß and its related signals can promote or inhibit the occurrence and development of cancer by affecting the growth, differentiation and metastasis of cells, while targeted intervention of PLC-ß1-PI3K-AKT, PLC-ß2/CD133, CXCR2-NHERF1-PLC-ß3, Gαq-PLC-ß4-PKC-MAPK and so on can provide new strategies for the precise prevention and treatment of malignant tumors. This paper reviews the mechanism of PLC-ß in various tumor cells from four aspects: proliferation and differentiation, invasion and metastasis, angiogenesis and protective measures.
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Purpose: This study aimed to investigate the value of quantified extracellular volume fraction (fECV) derived from dual-energy CT (DECT) for predicting the survival outcomes of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Materials and methods: A total of 63 patients with HCC who underwent DECT before treatment were retrospectively included. Virtual monochromatic images (VMI) (70 keV) and iodine density images (IDI) during the equilibrium phase (EP) were generated. The tumor VMI-fECV and IDI-fECV were measured and calculated on the whole tumor (Whole) and maximum enhancement of the tumor (Maximum), respectively. Univariate and multivariate Cox models were used to evaluate the effects of clinical and imaging predictors on overall survival (OS) and progression-free survival (PFS). Results: The correlation between tumor VMI-fECV and IDI-fECV was strong (both p< 0.001). The Bland-Altman plot between VMI-fECV and IDI-fECV showed a bias of 5.16% for the Whole and 6.89% for the Maximum modalities, respectively. Increasing tumor VMI-fECV and IDI-fECV were positively related to the effects on OS and PFS (both p< 0.05). The tumor IDI-fECV-Maximum was the only congruent independent predictor in patients with HCC after TACE in the multivariate analysis on OS (p = 0.000) and PFS (p = 0.028). Patients with higher IDI-fECV-Maximum values had better survival rates above the optimal cutoff values, which were 35.42% for OS and 29.37% for PFS. Conclusion: The quantified fECV determined by the equilibrium-phase contrast-enhanced DECT can potentially predict the survival outcomes of patients with HCC following TACE treatment.
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As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma, accounting for approximately 75% of the total number of patients with renal cell carcinoma. Currently, the clinical treatment of ccRCC involves targeted therapy, immunotherapy, and a combination of the two. In immunotherapy, PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment. However, as treatment progresses, some patients gradually develop resistance to immunotherapy. Meanwhile, other patients experience great side effects after immunotherapy, resulting in a survival status far lower than the expected survival rate. Based on these clinical problems, many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results. We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Neoplasias Renais/tratamento farmacológicoRESUMO
The role of ferroptosis in human acute lymphoblastic leukemia and its possible molecular mechanisms of action are still unknown. In this study, harvested Molt-4 cells were exposed to different concentrations of erastin, and their proliferation capacity was tested by using the cell counting kit-8 assay. Lipid peroxidation levels were detected through flow cytometry. Mitochondrial alterations were observed through transmission electron microscopy. The expression levels of SLC7A11, glutathione peroxidase 4 (GPX4), and mitogen-activated protein kinase (MAPK) were detected by using quantitative real-time PCR and Western blot analysis. This study found that erastin inhibited the growth of Molt-4 cells. This inhibitory effect could be partially reversed by the ferroptosis inhibitor Ferrostatin-1 and the p38 MAPK inhibitor. The mitochondria of Molt-4 cells treated with erastin shortened and condensed. Compared with those in the control group, the levels of reactive oxygen species and malondialdehyde had increased, whereas the levels of glutathione had decreased in the treatment group. The treatment of Molt-4 cells with erastin decreased the levels of SLC7A11 and GPX4 mRNA and increased the expression levels of p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase. These findings suggested that erastin caused the ferroptosis of Molt-4 cells. This process may be correlated with the inhibition of the cystine/glutamate antiporter system and GPX4 and the activation of p38 MAPK and ERK1/2.
Assuntos
Ferroptose , Humanos , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Piperazinas/farmacologia , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.