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OBJECTIVES: To develop and validate a prediction model utilizing clinical and ultrasound (US) data for preoperative assessment of efficacy following US-guided thermal ablation (TA) in patients with benign thyroid nodules (BTNs) ≥ 2 cm. MATERIALS AND METHODS: We retrospectively assessed 962 patients with 1011 BTNs who underwent TA at four tertiary centers between May 2018 and July 2022. Ablation efficacy was categorized into therapeutic success (volume reduction rate [VRR] > 50%) and non-therapeutic success (VRR ≤ 50%). We identified independent factors influencing the ablation efficacy of BTNs ≥ 2 cm in the training set using multivariate logistic regression. On this basis, a prediction model was established. The performance of model was further evaluated by discrimination (area under the curve [AUC]) in the validation set. RESULTS: Of the 1011 nodules included, 952 (94.2%) achieved therapeutic success at the 12-month follow-up after TA. Independent factors influencing VRR > 50% included sex, nodular composition, calcification, volume, and largest diameter (all p < 0.05). The prediction equation was established as follows: p = 1/1 + Exp∑[8.113 -2.720 × (if predominantly solid) -2.790 × (if solid) -1.275 × (if 10 mL < volume ≤ 30mL) -1.743 × (if volume > 30 mL) -1.268 × (if with calcification) -2.859 × (if largest diameter > 3 cm) +1.143 × (if female)]. This model showed great discrimination, with AUC of 0.908 (95% confidence interval [CI]: 0.868-0.947) and 0.850 (95% CI: 0.748-0.952) in the training and validation sets, respectively. CONCLUSIONS: A clinical prediction model was successfully developed to preoperatively predict the therapeutic success of BTNs larger than 2 cm in size following US-guided TA. This model aids physicians in evaluating treatment efficacy and devising personalized prognostic plans.
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OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .
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The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.
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Ubiquitination is a type of post-translational modification that covalently links ubiquitin to a target protein, which plays a critical role in modulating protein activity, stability, and localization. In contrast, this process is reversed by deubiquitinases (DUBs), which remove ubiquitin from ubiquitinated substrates. Dysregulation of DUBs is associated with several human diseases, such as cancer, inflammation, neurodegenerative disorders, and autoimmune diseases. Thus, DUBs have become promising targets for drug development. Although the physiological and pathological effects of DUBs are increasingly well understood, the clinical drug discovery of selective DUB inhibitors has been challenging. Herein, we summarize the structures and functions of main classes of DUBs and discuss the recent progress in developing selective small-molecule DUB inhibitors as antitumor agents.
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Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Ubiquitina/metabolismo , Proteínas/metabolismo , Ubiquitinação , Enzimas Desubiquitinantes/químicaRESUMO
Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.
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Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.
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Neoplasias Gástricas , Humanos , Processamento Alternativo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/genética , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
PURPOSE: To explore the feasibility of a 5G-based telerobotic ultrasound (US) system for providing qualified abdominal US services on a rural island. METHODS: This prospective study involved two medical centers (the tele-radiologist site's hospital and the patient site's hospital) separated by 72 km. Patients underwent 5G-based telerobotic US by tele-radiologists and conventional US by on-site radiologists from September 2020 to March 2021. The clinical feasibility and diagnostic performance of the 5G-based telerobotic abdominal US examination were assessed based on safety, duration, image quality, diagnostic findings, and questionnaires. RESULTS: A total of 401 patients (217 women and 184 men; mean age, 54.96 ± 15.43 years) were enrolled. A total of 90.1% of patients indicated no discomfort with the telerobotic US examination. For the examination duration, telerobotic US took longer than conventional US (12.54 ± 3.20 min vs. 7.23 ± 2.10 min, p = 0.001). For image quality scores, the results of the two methods were similar (4.54 ± 0.63 vs. 4.57 ± 0.61, p = 0.112). No significant differences were found between the two methods in measurements for the aorta, portal vein, gallbladder, kidney (longitudinal diameter), prostate, and uterus; however, telerobotic US underestimated the transverse diameter of the kidney (p < 0.05). A total of 504 positive results, including 31 different diseases, were detected. Among them, 455 cases were identified by the two methods; 17 cases were identified by telerobotic US only; and 32 cases were identified by conventional US only. There was good consistency in the diagnosis of 29 types of disease between the two methods (κ = 0.773-1.000). Furthermore, more than 90% of patients accepted the telerobotic US examination and agreed to pay additional fees in future. CONCLUSION: The 5G-based telerobotic US system can expand access to abdominal US services for patients in rural areas, thereby reducing health care disparities.
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Robótica , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Robótica/métodos , Ultrassonografia , Abdome/diagnóstico por imagem , RimRESUMO
Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD â¼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.
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Imunoconjugados , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Linhagem Celular Tumoral , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias PancreáticasRESUMO
BACKGROUND: Rural general practitioners (GPs) have insufficient diagnostic information to deal with complex clinical scenarios due to the inequality in medical imaging resources in rural and remote communities. The objective of this study is to explore the value of a tele-mentored handheld ultrasound (tele-HHUS) system, allowing GPs to provide ultrasound (US) services in rural and remote communities. METHODS: Overall, 708 patients underwent tele-HHUS examination between March and October 2021 and March and April 2022 across thirteen primary hospitals and two tertiary-care general hospitals. All US examinations were guided and supervised remotely in real time by US experts more than 300 km away using the tele-HHUS system. The following details were recorded: location of tele-HHUS scanning, primary complaints, clinical diagnosis, and US findings. The recommendations (referral or follow-up) based on clinical experience alone were compared with those based on clinical experience with tele-HHUS information. RESULTS: Tele-HHUS examinations were performed both in hospital settings (90.6%, 642/708) and out of hospital settings (9.4%, 66/708). Leaving aside routine physical examinations, flank pain (14.2%, 91/642) was the most common complaint in inpatients, while chest distress (12.1%, 8/66) and flank discomfort (12.1%, 8/66) were the most common complaints in out-of-hospital settings. Additionally, the referral rate increased from 5.9% to 8.3% (kappa = 0.202; p = 0.000). CONCLUSIONS: The tele-HHUS system can help rural GPs perform HHUS successfully in remote and rural communities. This novel mobile telemedicine model is valuable in resource-limited areas.
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OBJECTIVE: To investigate the factors affecting the efficacy of ultrasound (US)-guided percutaneous microwave ablation (PMWA) for adenomyosis with abnormal uterine bleeding (AUB-A). METHODS: Baseline data of patients with AUB-A who underwent US-guided PMWA treatment between October 2020 and October 2021, including demography characteristics, laboratory and imaging examination results were retrospectively analyzed. 3D reconstruction of magnetic resonance imaging (MRI) was applied to quantitatively assess the local treatment responses, including ratio of non-perfusion volume to adenomyosis volume (NPVr), ablation rate of the endometrial-myometrial junction (EMJ), and surface area (SA) of the ablated part of the EMJ. Patients were followed up at 3, 6, and 12 months after treatment, and divided into two groups: group with complete relief (CR), and group with partial relief (PR) or no relief (NR). Data were compared between them. RESULTS: Thirty-one patients were analyzed with a mean age of 38.7 ± 6.8 years (range: 24-48): 48.4% (15/31), 63.3% (19/30), and 65.5% (19/29) achieved CR at 3, 6, and 12 months, respectively. In univariate analysis, compared with the PR/NR group, serum CA125 levels were significantly lower in CR group at 3 months, while ablation rates of EMJ and SA of the ablated part of the EMJ were significantly higher at the three time points. Other baseline characteristics and NPVr did not differ between the two groups. CONCLUSION: Baseline CA125 and ablation rate of the EMJ and SA of the ablated part of the EMJ are associated with the outcome of AUB-A patients after US-guided PMWA treatment.
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Adenomiose , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adenomiose/complicações , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Ultrassonografia de Intervenção , Hemorragia UterinaRESUMO
Trophoblast cell surface antigen 2 (Trop2) has emerged as a potential target for effective cancer therapy. In this study, we report a novel anti-Trop2 antibody IMB1636, developed using hybridoma technology. It exhibited high affinity and specificity (KD = 0.483 nM) in binding both antigens and cancer cells, as well as human tumor tissues. hIMB1636 could induce endocytosis, and enabled targeted delivery to the tumor site with an in vivo retention time of 264 h. The humanized antibody hIMB1636, acquired using CDR grafting, exhibited the potential to directly inhibit cancer cell proliferation and migration, and to induce ADCC effects. Moreover, hIMB1636 significantly inhibited the growth of MDA-MB-468 xenograft tumors in vivo. Mechanistically, hIMB1636 induced cell cycle arrest and apoptosis by regulating cyclin-related proteins and the caspase cascade. In comparison to commercialized sacituzumab, hIMB1636 recognized a conformational epitope instead of a linear one, bound to antigen and cancer cells with similar binding affinity, induced significantly more potent ADCC effects against cancer cells, and displayed superior antitumor activities both in vitro and in vivo. The data presented in this study highlights the potential of hIMB1636 as a carrier for the formulation of antibody-based conjugates, or as a promising candidate for anticancer therapy.
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Imunoconjugados , Neoplasias , Humanos , Moléculas de Adesão Celular , Anticorpos Monoclonais , Neoplasias/tratamento farmacológico , Imunoconjugados/farmacologia , Proliferação de Células , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A Gram-negative, aerobic, motile by flagellum, and rod-shaped bacterium, designated ASW11-7T, was isolated from coastal surface seawater sample collected from the Yellow Sea, PR China. Strain ASW11-7T grew optimally at 37â, 4.0% (w/v) NaCl and pH 7.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain ASW11-7T belongs to the genus Alteromonas and most closely related to Alteromonas ponticola MYP5T (99.6% similarity), followed by Alteromonas confluentis DSSK2-12T (98.2%), Alteromonas lipolytica JW12T (98.2%), and Alteromonas hispanica F-32T (98.0%). The draft genome of strain ASW11-7T had a length of 3,530,922 bp with a G + C content of 44.9%, predicting 3108 coding sequences, 5 rRNA, 4 ncRNAs, 49 tRNAs genes, and 18 pseudogenes. The average nucleotide identity and digital DNA-DNA hybridization values between genomic sequences of strain ASW11-7T and closely related species of Alteromonas were in ranges of 66.9-77.8% and 18.3-27.5%, respectively. The major fatty acids of strain ASW11-7T were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), and summed feature 8 (C18:1ω7c/C18:1ω6c). The predominant respiratory quinone was Q-8 and the major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Based on the phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain ASW11-7T is considered to represent a novel Alteromonas species, for which the name Alteromonas aquimaris sp. nov. is proposed. The type strain is ASW11-7T (= KCTC 92853T = MCCC 1K07240T).
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Alteromonas , Alteromonas/genética , Filogenia , RNA Ribossômico 16S/genética , China , DNARESUMO
OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: ⢠The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. ⢠The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. ⢠The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.
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Carcinoma , Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Humanos , Estudos Prospectivos , Meios de Contraste , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Aprendizado de Máquina , Medição de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia. However, an alternative treatment approach is needed for patients who cannot tolerate general anesthesia. We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia. CASE SUMMARY: A 46-year-old female suffered from abnormal uterine bleeding, severe anemia, and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma. She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency. A new individualized combined treatment, consisting uterine artery embolization (UAE), percutaneous microwave ablation (PMWA) of the pedicle and the endometrium, and transvaginal removal of the leiomyoma by twisting, was performed. The lesion was completely removed successfully under local anesthesia without any major complications. The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life. CONCLUSION: UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.
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Aberrant FGF19/FGFR4 signaling has been demonstrated to be an oncogenic driver of growth and survival in human hepatocellular carcinoma (HCC). At present, the development of FGFR4-specific drugs has become a hotspot in tumor-targeted therapy research. However, no selective FGFR4 inhibitors have been approved by FDA so far. Currently, most of the reported FGFR4 inhibitors that use a covalent targeting strategy to be selective are typical type I inhibitors with a single type. Here, based on Ponatinib, we designed and synthesized a series of arylurea derivatives as novel type II irreversible covalent inhibitors of FGFR4. Among them, the representative compound 6v exhibited an IC50 value of 74 nM against FGFR4 and antiproliferative potency of 0.25 µM and 0.22 µM against Huh7 and Hep3B cell lines. Western blotting results showed that compound 6v significantly inhibited the phosphorylation of FGFR4 and its downstream signaling factors AKT and ERK in a dose-dependent manner in Hep3B cell. These results showed that this series of compounds, as type II irreversible FGFR4 inhibitors, are worthy of further research and structural optimization.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- and anti-angiogenic molecules, which plays a crucial role in tumor growth, invasion, and metastasis. With the advances in molecular and cellular biology, various biomolecules such as growth factors, chemokines, and adhesion factors involved in tumor angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules has driven anti-angiogenic treatment to become a promising strategy in anti-tumor therapy. The most widely used anti-angiogenic agents include monoclonal antibodies and tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) pathway. However, the clinical benefit of this modality has still been limited due to several defects such as adverse events, acquired drug resistance, tumor recurrence, and lack of validated biomarkers, which impel further research on mechanisms of tumor angiogenesis, the development of multiple drugs and the combination therapy to figure out how to improve the therapeutic efficacy. Here, we broadly summarize various signaling pathways in tumor angiogenesis and discuss the development and current challenges of anti-angiogenic therapy. We also propose several new promising approaches to improve anti-angiogenic efficacy and provide a perspective for the development and research of anti-angiogenic therapy.
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Neoplasias , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate the efficacy and safety of percutaneous microwave ablation (PMWA) for treating adenomyosis in the posterior uterine wall. METHODS: Thirty-six patients with symptomatic adenomyosis in the posterior uterine wall who had been subjected to PMWA were retrospectively enrolled in this study. 20 patients who had no ideal transabdominal puncture path due to the retroverted or retroflexed uterine position were treated with PMWA combined with Yu's uteropexy (Group 1). The other 16 patients were treated with PMWA only (Group 2). The non-perfused volume (NPV) ratio, symptomatic relief rate, recurrence rate, changes in clinical symptom scores, economic cost, and complications were compared. RESULTS: The mean NPV ratio for the 36 patients was 90.2±18.3%, and the percentage of patients who obtained complete relief of dysmenorrhea and menorrhagia was 81.3% (26/32), and 69.6% (16/23) respectively. The recurrence rate was 11.1% (4/36). No major complication was observed. Minor complications included lower abdominal pain, fever, vaginal discharge, nausea, and/or vomiting after ablation, with incidences of 55.6%, 41.7%, 47.2%, and 19.4% respectively. Subgroup analysis showed no significant difference in the median value of NPV ratio, symptomatic relief rate of dysmenorrhea and menorrhagia, changes in clinical symptom scores, recurrence rate and economic cost between the two groups (all p > 0.05). CONCLUSION: PMWA is an effective and safe treatment for adenomyosis in the posterior uterine wall. ADVANCES IN KNOWLEDGE: This study focused on the ultrasound-guided PMWA treatment for adenomyosis in the posterior uterine wall. Yu's uteropexy, a new ancillary technique allowing safe PMWA for deep posterior uterine wall lesions in retroverted uterus, expanded the indications of PMWA for symptomatic adenomyosis.
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Adenomiose , Menorragia , Feminino , Humanos , Adenomiose/cirurgia , Adenomiose/patologia , Dismenorreia , Estudos Retrospectivos , Micro-Ondas/uso terapêutico , Resultado do TratamentoRESUMO
Sclerosing angiomatoid nodular transformation (SANT) is an uncommon non-tumorous disease of the spleen. The low morbidity and non-specific clinical symptoms of SANT might cause a misdiagnosis. The present study reported a case of a 31-year-old female with a SANT of the spleen. Findings on clinical manifestations and examinations, especially on contrast-enhanced ultrasound (CEUS), were carefully analyzed, and relevant literatures have also been reviewed.
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Baço , Feminino , Humanos , Adulto , Baço/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVES: This study was aimed to evaluate the diagnostic performance of ultrasound (US) in differentiating trichilemmal cysts (TCs) from epidermoid cysts (ECs). METHODS: Based on clinical and ultrasound features, a prediction model was established and validated. 164 cysts in the pilot cohort and another 69 in the validation cohort diagnosed with TCs or ECs histopathologically were evaluated. The same radiologist performed all ultrasound examinations. RESULTS: For clinic features, TCs tended to occur in females compared with ECs (66.7 vs 28.5%; P < .001). In addition, TCs were prone to occur in the hairy area compared with ECs (77.8 vs 13.1%; P < .001). For ultrasound features, the internal hyperechogenicity and cystic change were more likely to appear in TCs in comparison with ECs (92.6 vs 25.5%; P < .001; 70.4 vs 23.4%; P < .001, respectively). Upon the features mentioned above, a prediction model was established with the areas under the receiver operating characteristic curves of 0.936 and 0.864 in the pilot and validation cohorts, respectively. CONCLUSIONS: US is promising for differentiating TCs from ECs and is valuable for their clinical management.