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2.
Nutr J ; 23(1): 48, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704549

RESUMO

BACKGROUND: Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia. METHODS: We conducted a cross-sectional study involving 13,636 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings. RESULTS: Higher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship. CONCLUSION: This study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.


Assuntos
Dieta , Hiperuricemia , Estilo de Vida , Inquéritos Nutricionais , Ácido Úrico , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Feminino , Masculino , Estudos Transversais , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Ácido Úrico/sangue , Dieta/métodos , Dieta/estatística & dados numéricos , Estresse Oxidativo , Prevalência , Idoso
3.
Med Image Anal ; 95: 103199, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38759258

RESUMO

The accurate diagnosis on pathological subtypes for lung cancer is of significant importance for the follow-up treatments and prognosis managements. In this paper, we propose self-generating hybrid feature network (SGHF-Net) for accurately classifying lung cancer subtypes on computed tomography (CT) images. Inspired by studies stating that cross-scale associations exist in the image patterns between the same case's CT images and its pathological images, we innovatively developed a pathological feature synthetic module (PFSM), which quantitatively maps cross-modality associations through deep neural networks, to derive the "gold standard" information contained in the corresponding pathological images from CT images. Additionally, we designed a radiological feature extraction module (RFEM) to directly acquire CT image information and integrated it with the pathological priors under an effective feature fusion framework, enabling the entire classification model to generate more indicative and specific pathologically related features and eventually output more accurate predictions. The superiority of the proposed model lies in its ability to self-generate hybrid features that contain multi-modality image information based on a single-modality input. To evaluate the effectiveness, adaptability, and generalization ability of our model, we performed extensive experiments on a large-scale multi-center dataset (i.e., 829 cases from three hospitals) to compare our model and a series of state-of-the-art (SOTA) classification models. The experimental results demonstrated the superiority of our model for lung cancer subtypes classification with significant accuracy improvements in terms of accuracy (ACC), area under the curve (AUC), positive predictive value (PPV) and F1-score.

4.
EMBO Mol Med ; 16(5): 1193-1219, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38671318

RESUMO

Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Poli I-C , Receptor 3 Toll-Like , Receptor 3 Toll-Like/metabolismo , Receptor 3 Toll-Like/agonistas , Animais , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Humanos , Camundongos , Poli I-C/farmacologia , Masculino , Feminino , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Camundongos Knockout , Pessoa de Meia-Idade
5.
Artigo em Inglês | MEDLINE | ID: mdl-38628818

RESUMO

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

6.
Front Cell Infect Microbiol ; 14: 1366472, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500502

RESUMO

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.


Assuntos
Obstrução das Vias Respiratórias , Mucormicose , Masculino , Humanos , Pessoa de Meia-Idade , Anfotericina B/uso terapêutico , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/patologia , Rhizopus oryzae , Necrose/patologia , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Tecido de Granulação/patologia , Tosse/patologia
7.
Surgery ; 175(5): 1321-1328, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429165

RESUMO

BACKGROUND: To investigate the role and mechanism of liver parenchyma transection in accelerating the regeneration of future liver remnants in rats with portal vein ligation (PVL). METHODS: Rats were randomly divided into the PVL group (90% PVL at the caudate lobe, right lobe , left lateral lobe and left median lobe), associating liver partition and portal vein ligation for staged hepatectomy (portal vein ligation with complete liver parenchyma transection [ALPPS]) group (90% PVL with 80 to 90% liver parenchyma transection), PVL + partial liver partition (PLP) group (90% PVL with 30 to 50% liver parenchyma transection), PVL + partition in the ligated lobe (PLL) group (90% PVL with 40 to 60% liver parenchyma transection in the portal vein ligated lobe), PVL + partition in the remnant lobe (PRL) group (90% PVL with 40 to 60% liver parenchyma transection in the remnant lobe), PVL + radiofrequency ablation (RFA) group (90% PVL with splenic ablation) and sham operation (sham) group. The animals were killed at 4 time points of postoperative days 1, 3, 5, and 7. Six rats were killed at each time point, with 24 rats in each group. The weights of the future liver remnant and whole liver were measured. Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were analyzed by using an automatic biochemical analyzer. Serum tumor necrosis factor-α, interleukin-6, and hepatocyte growth factor were measured by enzyme-linked immunosorbent assay. The expression of cell proliferating nuclear antigen (Ki67) and phosphorylated histone H3 was detected by immunohistochemistry, and the positive rate was calculated. RESULTS: The ALPPS group displayed the highest FLR weight to body weight ratio compared with that of the other groups (P < .05), and the partial liver split (PVL + PLP) group also displayed higher remnant weight to body weight ratio than the ectopic liver split (PVL + PLL and PVL + PRL) groups (P < .05). During the first 7 days after surgery the cytokine levels of the ALPPS, PVL + PLP, PVL + PLL and PVL + PRL groups were comparable (P > .05). The PVL + PLP, PVL + PLL, PVL + PRL and PVL + RFA groups showed similar necrotic areas in the portal vein ligated lobe (P > .05). A hemodynamic study revealed that a liver split along the demarcation line could further increase the portal pressure of the FLR and both the split site and completeness were associated with portal hemodynamic alternations and liver hypertrophy. Extrahepatic organ injury (eg, spleen ablation) also has a significant impact on portal hemodynamics and liver regeneration. CONCLUSION: Complete liver splitting along the demarcation line induced higher portal vein pressure and more rapid FLR hypertrophy than partial or ectopic liver splitting after PVL. The portal hemodynamic alterations after liver split rather than inflammatory cytokine release may be the major cause of ALPPS-induced rapid liver hypertrophy.


Assuntos
Neoplasias Hepáticas , Veia Porta , Ratos , Animais , Veia Porta/cirurgia , Veia Porta/patologia , Fígado/patologia , Hepatectomia , Regeneração Hepática , Hepatomegalia , Neoplasias Hepáticas/cirurgia , Hipertrofia/patologia , Ligadura , Citocinas , Peso Corporal
8.
Plant Commun ; : 100835, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38425040

RESUMO

Cucurbitacin IIa is a triterpenoid isolated exclusively from Hemsleya plants and a non-steroidal anti-inflammatory drug that functions as the main ingredient of prescription Hemslecin capsules and tablets in China. Synthetic biology provides new strategies for production of such valuable cucurbitacins at a large scale; however, the biosynthetic pathway of cucurbitacin IIa has been unknown, and the heterologous production of cucurbitacins in galactose medium has been expensive and low yielding. In this study, we characterized the functions of genes encoding two squalene epoxidases (HcSE1-2), six oxidosqualene cyclases (HcOSC1-6), two CYP450s (HcCYP87D20 and HcCYP81Q59), and an acyltransferase (HcAT1) in cucurbitacin IIa biosynthesis by heterologous expression in Saccharomyces cerevisiae and Nicotiana benthamiana. We achieved high-level production of the key cucurbitacin precursor 11-carbonyl-20ß-hydroxy-Cuol from glucose in yeast via modular engineering of the mevalonate pathway and optimization of P450 expression levels. The resulting yields of 46.41 mg/l 11-carbonyl-20ß-hydroxy-Cuol and 126.47 mg/l total cucurbitacin triterpenoids in shake flasks are the highest yields yet reported from engineered microbes. Subsequently, production of 11-carbonyl-20ß-hydroxy-Cuol by transient gene expression in tobacco resulted in yields of 1.28 mg/g dry weight in leaves. This work reveals the key genes involved in biosynthesis of prescription cucurbitacin IIa and demonstrates that engineered yeast cultivated with glucose can produce high yields of key triterpenoid intermediates. We describe a low-cost and highly efficient platform for rapid screening of candidate genes and high-yield production of pharmacological triterpenoids.

9.
Ital J Pediatr ; 50(1): 39, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38439018

RESUMO

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.


Assuntos
Povo Asiático , Ferro , Recém-Nascido , Feminino , Gravidez , Humanos , Estudos Prospectivos , Transferrinas , China/epidemiologia
10.
Nat Immunol ; 25(3): 525-536, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356061

RESUMO

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.


Assuntos
Doenças Autoimunes , Humanos , Citocinas , Epigenômica , Histona Desmetilases , Homeostase , Oxirredutases N-Desmetilantes , Histona Desmetilases com o Domínio Jumonji/genética
11.
Cancer Immunol Immunother ; 73(2): 26, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280084

RESUMO

Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.


Assuntos
Vacinas Anticâncer , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígenos de Neoplasias , Bevacizumab/uso terapêutico , Vacinas Anticâncer/farmacologia , Vacinas Anticâncer/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linfócitos T CD8-Positivos , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral
12.
Cytokine ; 173: 156441, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37995394

RESUMO

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.


Assuntos
Criptococose , Cryptococcus , MicroRNAs , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Piroptose/genética , Cryptococcus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Criptococose/metabolismo , Criptococose/patologia , Fatores de Transcrição Kruppel-Like
13.
Cell Rep Med ; 4(12): 101315, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38091986

RESUMO

Patients with hepatocellular carcinoma (HCC) at the same clinical stage can have extremely different prognoses, and molecular subtyping provides an opportunity for individualized precision treatment. In this study, genomic, transcriptomic, proteomic, and phosphoproteomic profiling of primary tumor tissues and paired para-tumor tissues from HCC patients (N = 160) are integrated. Proteomic profiling identifies three HCC subtypes with different clinical prognosis, which are validated in three publicly available external validation sets. A simplified panel of nine proteins associated with metabolic reprogramming is further identified as a potential subtype-specific biomarker for clinical application. Multi-omics analysis further reveals that three proteomic subtypes have significant differences in genetic alterations, microenvironment dysregulation, kinase-substrate regulatory networks, and therapeutic responses. Patient-derived cell-based drug tests (N = 26) show personalized responses for sorafenib in three proteomic subtypes, which can be predicted by a machine-learning response prediction model. Overall, this study provides a valuable resource for better understanding of HCC subtypes for precision clinical therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteômica , Multiômica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-38083011

RESUMO

Accurate liver tumor segmentation is a prerequisite for data-driven tumor analysis. Multiphase computed tomography (CT) with extensive liver tumor characteristics is typically used as the most crucial diagnostic basis. However, the large variations in contrast, texture, and tumor structure between CT phases limit the generalization capabilities of the associated segmentation algorithms. Inadequate feature integration across phases might also lead to a performance decrease. To address these issues, we present a domain-adversarial transformer (DA-Tran) network for segmenting liver tumors from multiphase CT images. A DA module is designed to generate domain-adapted feature maps from the non-contrast-enhanced (NC) phase, arterial (ART) phase, portal venous (PV) phase, and delay phase (DP) images. These domain-adapted feature maps are then combined with 3D transformer blocks to capture patch-structured similarity and global context attention. The experimental findings show that DA-Tran produces cutting-edge tumor segmentation outcomes, making it an ideal candidate for this co-segmentation challenge.


Assuntos
Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Algoritmos , Artérias , Fontes de Energia Elétrica , Generalização Psicológica
15.
Artigo em Inglês | MEDLINE | ID: mdl-38083466

RESUMO

Liver cancer has been one of the top causes of cancer-related death. For developing an accurate treatment strategy and raising the survival rate, the differentiation of liver cancers is essential. Multiphase CT recently acts as the primary examination method for clinical diagnosis. Deep learning techniques based on multiphase CT have been proposed to distinguish hepatic cancers. However, due to the recurrent mechanism, RNN-based approaches require expensive calculations whereas CNN-based models fail to explicitly establish temporal correlations among phases. In this paper, we proposed a phase difference network, termed as Phase Difference Network (PDN), to identify two liver cancer, hepatocellular carcinoma and intrahepatic cholangiocarcinoma, from four-phase CT. Specifically, the phase difference was used as interphase temporal information in a differential attention module, which enhanced the feature representation. Additionally, utilizing a multihead self-attention module, a transformer-based classification module was employed to explore the long-term context and capture the temporal relation between phases. Clinical datasets are used in experiments to compare the performance of the proposed strategy versus conventional approaches. The results indicate that the proposed method outperforms the traditional deep learning based methods.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Redes Neurais de Computação , Neoplasias Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Atenção , Tomografia Computadorizada por Raios X/métodos
16.
World J Clin Cases ; 11(29): 7248-7252, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37946755

RESUMO

BACKGROUND: Thyroglossal duct cysts (TDC) are common congenital deformities. Most of them are cysts formed by the thyroglossal ducts that do not disappear and degenerate in the early embryonic stage. TDC exists alone and is rarely complicated by other congenital embryonic malformations. Only a few reports of TDC with branchial cleft cysts, thyroid cancer, thyroid hematoma, and epidermoid cysts have been reported. Therefore, we report a patient with TDC and parathyroid cyst (PC), a rare disease that has never been reported. CASE SUMMARY: A 47-year-old woman presented to clinic in April 2021 with a neck tumor which she had noticed 5 d earlier. We perfected the relevant examinations, such as ultrasound and computed tomography, and resected the tumor. After surgical treatment, the pathology revealed a cervical thyroglossal duct cyst and a left lobe parathyroid cyst. The patient was followed up for 1 year without significant recurrence. CONCLUSION: We report a patient with a simultaneous TDC and a PC to explore the correlation between the two congenital anomalies.

17.
World J Clin Cases ; 11(29): 7253-7257, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37946756

RESUMO

BACKGROUND: Occult thyroid papillary carcinoma (OTPC) is typically characterized by initial presentation with cervical lymph node metastasis and can be detected through ultrasound. However, the initial and sole manifestation was a submandibular solid-cystic mass. High-frequency ultrasound, enhanced multislice computed tomography (CT) scan, and thyroid function tests revealed no abnormalities, which is relatively uncommon. CASE SUMMARY: A 24-year-old Chinese female, who studied at a university in Shandong Province, presented to the clinic in June 2019 with a right submandibular mass that she had noticed 2 mo earlier. Clinical examination revealed a 2-cm, nontender, movable solid-cystic mass in the submandibular region, with no palpable thyroid mass observed. Ultrasonography revealed a 2.0 cm × 1.1 cm solid-cystic mass in the right submandibular region, and the thyroid gland showed no abnormalities. CT scan and 131I whole body follow-up scan showed that there were no abnormalities in the thyroid. However, cytology and pathology showed papillary tumor cell clusters, consistent with papillary thyroid carcinoma. Thus, we performed total thyroidectomy and right neck lymph node dissection. The pathology revealed the thyroid was detected as classical thyroid micropapillary carcinoma, and lymph nodes of levels VI central and levels II, III, IV, V on the right side showed no tumor metastasis. The patient was followed up for 2 years without significant recurrence. CONCLUSION: The presentation of a submandibular solid-cystic mass as the primary and solitary indication of OTPC is relatively uncommon. Fine needle aspiration is advised for evaluating neck masses.

18.
Cell Discov ; 9(1): 118, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012147

RESUMO

Hydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of cardiovascular, neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2-Gi1 complexes with or without agonists, including the drugs niacin (2.69 Å) and acipimox (3.23 Å), the highly subtype-specific agonist MK-6892 (3.25 Å), and apo form (3.28 Å). Combined with molecular dynamics simulation and functional analysis, we have revealed the recognition mechanism of HCAR2 for different agonists and summarized the general pharmacophore features of HCAR2 agonists, which are based on three key residues R1113.36, S17945.52, and Y2847.43. Notably, the MK-6892-HCAR2 structure shows an extended binding pocket relative to other agonist-bound HCAR2 complexes. In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which shed light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects.

19.
World J Gastroenterol ; 29(35): 5094-5103, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37744290

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries. Despite advances in cancer treatment, the 5-year survival rate for patients with PDAC remains less than 5%. In recent years, neoadjuvant therapy (NAT) has emerged as a promising treatment option for many cancer types, including locally advanced PDAC, with the potential to improve patient outcomes. To analyze the role of NAT in the setting of locally advanced PDAC over the past decade, a systematic literature search was conducted using PubMed and Web of Science. The results suggest that NAT may reduce the local mass size, promote tumor downstaging, and increase the likelihood of resection. These findings are supported by the latest evidence-based medical literature and the clinical experience of our center. Despite the potential benefits of NAT, there are still challenges that need to be addressed. One such challenge is the lack of consensus on the optimal timing and duration of NAT. Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT. In conclusion, NAT has emerged as a promising treatment option for locally advanced PDAC. However, further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease. With continued advances in cancer treatment, there is hope of improving the outcomes of patients with PDAC in the future.


Assuntos
Carcinoma Ductal Pancreático , Segunda Neoplasia Primária , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante/efeitos adversos , Pâncreas , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas
20.
Radiat Oncol ; 18(1): 153, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723540

RESUMO

OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. RESULTS: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040). CONCLUSION: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Sinusite , Humanos , Carcinoma Nasofaríngeo/radioterapia , Estudos Retrospectivos , Sinusite/diagnóstico por imagem , Sinusite/etiologia , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/radioterapia
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