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Gas sensors are essential for ensuring public safety and improving quality of life. Room-temperature gas sensors are notable for their potential economic benefits and low energy consumption, and their expected integration with wearable electronics, making them a focal point of contemporary research. Advances in nanomaterials and low-dimensional semiconductors have significantly contributed to the enhancement of room-temperature gas sensors. These advancements have focused on improving sensitivity, selectivity, and response/recovery times, with nanocomposites offering distinct advantages. The discussion here focuses on the use of semiconductor nanocomposites for gas sensing at room temperature, and provides a review of the latest synthesis techniques for these materials. This involves the precise adjustment of chemical compositions, microstructures, and morphologies. In addition, the design principles and potential functional mechanisms are examined. This is crucial for deepening the understanding and enhancing the operational capabilities of sensors. We also highlight the challenges faced in scaling up the production of nanocomposite materials. Looking ahead, semiconductor nanocomposites are expected to drive innovation in gas sensor technology due to their carefully crafted design and construction, paving the way for their extensive use in various sectors.
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Tubal pregnancy is a common cause of maternal mortality in early pregnancy. Transumbilical laparoendoscopic single-site surgery (TU-LESS) has gained popularity due to its safety and aesthetic advantages. However, the lack of affordable disposable entry platforms hinders its widespread adoption. This study aimed to investigate the learning curve of tubal pregnancy removal using single-incision multiport (SIMP) laparoscopy and provide guidance for novice gynecologists. A retrospective analysis was conducted on cases of ectopic pregnancy (EP) diagnosed at Dongguan Songshan Lake Central Hospital from June 2020 to June 2022. The analysis included 50 cases, with 25 undergoing single-port laparoscopy and 25 undergoing conventional laparoscopy (CL). Various indicators, including body mass index (BMI), previous pregnancies, mass size, hemoglobin levels, surgical duration, and complications, were collected. Learning curve analysis using the cumulative sum (CUSUM) technique was performed to assess procedural proficiency. There were no significant differences in patient characteristics or complications between the 2 groups. However, the single-port laparoscopy group exhibited a statistically significant longer average surgical time (41.60â ±â 13.38 minutes) compared to the conventional laparotomy group (32.96â ±â 7.32 minutes). The CUSUM analysis demonstrated a decline in surgical time after the completion of approximately 11 cases, indicating an improvement in SIMP laparoscopy surgical proficiency. SIMP laparoscopy for tubal pregnancy removal achieved similar safety outcomes as CL. Notably, the CUSUM analysis revealed that proficiency in single-port laparoscopy could be achieved after approximately 11 cases, leading to stable surgical times. These findings serve as valuable guidance for novice gynecologists interested in adopting single-incision laparoscopy.
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Laparoscopía , Curva de Aprendizaje , Tempo Operativo , Salpingectomía , Humanos , Femenino , Estudios Retrospectivos , Laparoscopía/métodos , Laparoscopía/educación , Salpingectomía/métodos , Salpingectomía/educación , Adulto , Embarazo , Embarazo Tubario/cirugía , Competencia ClínicaRESUMEN
Multi-frame super-resolution (MFSR) leverages complementary information between image sequences of the same scene to increase the resolution of the reconstructed image. As a branch of MFSR, burst super-resolution aims to restore image details by leveraging the complementary information between noisy sequences. In this paper, we propose an efficient burst-enhanced super-resolution network (BESR). Specifically, we introduce Geformer, a gate-enhanced transformer, and construct an enhanced CNN-Transformer block (ECTB) by combining convolutions to enhance local perception. ECTB efficiently aggregates intra-frame context and inter-frame correlation information, yielding an enhanced feature representation. Additionally, we leverage reference features to facilitate inter-frame communication, enhancing spatiotemporal coherence among multiple frames. To address the critical processes of inter-frame alignment and feature fusion, we propose optimized pyramid alignment (OPA) and hybrid feature fusion (HFF) modules to capture and utilize complementary information between multiple frames to recover more high-frequency details. Extensive experiments demonstrate that, compared to state-of-the-art methods, BESR achieves higher efficiency and competitively superior reconstruction results. On the synthetic dataset and real-world dataset of BurstSR, our BESR achieves PSNR values of 42.79 dB and 48.86 dB, respectively, outperforming other MFSR models significantly.
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BACKGROUND & AIMS: The role of solute carrier family 25 member 15 (SLC25A15), a critical component of the urea cycle, in hepatocellular carcinoma (HCC) progression remains poorly understood. This study investigated the impact of SLC25A15 on HCC progression and its mechanisms. METHODS: We systematically investigated the function of SLC25A15 in HCC progression using large-scale data mining and cell, animal, and organoid models. Furthermore, we analyzed its involvement in reprogramming glutamine metabolism. RESULTS: SLC25A15 expression was significantly decreased in HCC tissues, and patients with low SLC25A15 levels had a poorer prognosis. Hypoxia-exposed HCC cells or tissues had lower SLC25A15 expression. A positive correlation between HNF4A, a transcription factor suppressed by hypoxia, and SLC25A15 was observed in both HCC tissues and cells. Modulating HNF4A levels altered SLC25A15 mRNA levels. SLC25A15 upregulated SLC1A5, increasing glutamine uptake. The reactive metabolic pathway of glutamine was increased in SLC25A15-deficient HCC cells, providing energy for HCC progression through additional lipid synthesis. Ammonia accumulation due to low SLC25A15 levels suppressed the expression of OGDHL (oxoglutarate dehydrogenase L), a switch gene that mediates SLC25A15 deficiency-induced reprogramming of glutamine metabolism. SLC25A15-deficient HCC cells were more susceptible to glutamine deprivation and glutaminase inhibitors. Intervening in glutamine metabolism increased SLC25A15-deficient HCC cells' response to anti-PD-L1 treatment. CONCLUSION: SLC25A15 is hypoxia-responsive in HCC, and low SLC25A15 levels result in glutamine reprogramming through SLC1A5 and OGDHL regulation, promoting HCC progression and regulating cell sensitivity to anti-PD-L1. Interrupting the glutamine-derived energy supply is a potential therapeutic strategy for treating SLC25A15-deficient HCC. IMPACT AND IMPLICATIONS: We first demonstrated the tumor suppressor role of solute carrier family 25 member 15 (SLC25A15) in hepatocellular carcinoma (HCC) and showed that its deficiency leads to reprogramming of glutamine metabolism to promote HCC development. SLC25A15 can serve as a potential biomarker to guide the development of precision therapeutic strategies aimed at targeting glutamine deprivation. Furthermore, we highlight that the use of an inhibitor of glutamine utilization can enhance the sensitivity of low SLC25A15 HCC to anti-PD-L1 therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Humanos , Carcinoma Hepatocelular/genética , Glutamina , Neoplasias Hepáticas/genética , Hipoxia/genética , Transporte Biológico , Antígenos de Histocompatibilidad Menor , Sistema de Transporte de Aminoácidos ASC/genéticaRESUMEN
Background: Hepatocellular carcinoma (HCC) patients have a poor prognosis after radio-frequency ablation (RFA), and investigating the risk factors affecting RFA and establishing predictive models are important for improving the prognosis of HCC patients. Methods: Patients with HCC undergoing RFA in Shenzhen People's Hospital between January 2011 and December 2021 were included in this study. Using the screened independent influences on recurrence and survival, predictive models were constructed and validated, and the predictive models were then used to classify patients into different risk categories and assess the prognosis of different categories. Results: Cox regression model indicated that cirrhosis (hazard ratio [HR] = 1.65), alpha-fetoprotein (AFP) ⩾400 ng/mL (HR = 2.03), tumor number (multiple) (HR = 2.11), tumor diameter ⩾20 mm (HR = 2.30), and platelets (PLT) ⩾ 244 (109/L) (HR = 2.37) were independent influences for recurrence of patients after RFA. On the contrary, AFP ⩾400 ng/mL (HR = 2.48), tumor number (multiple) (HR = 2.52), tumor diameter ⩾20 mm (HR = 2.25), PLT ⩾244 (109/L) (HR = 2.36), and hemoglobin (HGB) ⩾120 (g/L) (HR = 0.34) were regarded as independent influences for survival. The concordance index (C-index) of the nomograms for predicting disease-free survival (DFS) and overall survival (OS) was 0.727 (95% confidence interval [CI] = 0.770-0.684) and 0.770 (95% CI = 0.821-7.190), respectively. The prognostic performance of the nomograms was significantly better than other staging systems by analysis of the time-dependent C-index and decision curves. Each patient was scored using nomograms and influencing factors, and patients were categorized into low-, intermediate-, and high-risk groups based on their scores. In the Kaplan-Meier survival curve, DFS and OS were significantly better in the low-risk group than in the intermediate- and high-risk groups. Conclusions: The 2 prediction models created in this work can effectively predict the recurrence and survival rates of HCC patients following RFA.
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OBJECTIVE: To investigate the influencing factors affecting the occurrence of microvascular invasion (MVI) and the prognosis of hepatocellular carcinoma (HCC) patients treated with hepatectomy, and to explore how MVI affects prognosis in subgroups with different prognostic factors. METHODS: Clinical data of a total of 1633 patients treated surgically for HCC in four treatment centers were included, including 754 patients with MVI. By using the Cox risk regression model and the Mann-Whitney U-test, the common independent influences on prognosis and MVI were made clear. The incidence of MVI in various subgroups was then examined, as well as the relationship between MVI in various subgroups and prognosis. RESULTS: The Cox risk regression model showed that MVI, Child-Pugh classification, alpha-fetoprotein (AFP), hepatocirrhosis, tumor diameter, lymphocyte-to-monocyte ratio (LMR), and, Barcelona clinic liver cancer (BCLC) grade were independent determinants of overall survival (OS), and MVI, AFP, hepatocirrhosis, tumor diameter, and LMR were influencing determinants for disease-free survival (DFS). The receiver operating characteristic (ROC) curve showed that MVI was most closely associated with patient prognosis compared to other prognostic factors. AFP, hepatocirrhosis, tumor diameter, and LMR were discovered to be common influences on the prognosis of patients with HCC and MVI when combined with the results of the intergroup comparison of MVI. After grouping, it was showed that patients with hepatocirrhosis, positive AFP (AFP ≥ 20 ng/mL), tumor diameter >50 mm, and LMR ≤3.4 had a significantly higher incidence of MVI than patients in other subgroups, and all four subgroups of MVI-positive patients had higher rates of early recurrence and mortality (p < 0.05). CONCLUSIONS: MVI was found to be substantially linked with four subgroups of HCC patients with hepatocirrhosis, positive AFP, tumor diameter >50 mm, and LMR ≤3.4, and the prognosis of MVI-positive patients in all four subgroups tended to be worse.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , alfa-Fetoproteínas , Estudios Retrospectivos , Hepatectomía/efectos adversos , Pronóstico , Invasividad Neoplásica/patologíaRESUMEN
A temperature-insensitive high-sensitivity refractive index sensor is proposed and experimentally demonstrated, which is based on utilization of a thinned helical fiber grating but with an intermediate period (THFGIP). Attributed to the reduced diameter and an intermediate period of the grating, the proposed sensor has a high surrounding refractive-index (SRI) sensitivity and a low temperature sensitivity. The average SRI sensitivity of the proposed sensor is up to 829.9â nm/RIU in the range of 1.3410-1.4480 RIU. Moreover, unlike the traditional sensitivity-enhancement method by increasing the waveguide dispersion factor, here the waveguide dispersion factor at the resonant wavelength was decreased by reducing the diameter of the fiber grating and as a result, the crosstalk effect due to the temperature change can be further suppressed. The proposed temperature-insensitive SRI sensor has the superiorities of simple structure, ease fabrication, and low cost, which could be found more potential applications in the SRI sensing fields.
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BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Nomogramas , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Factores de Riesgo , Recurrencia , PronósticoRESUMEN
OBJECTIVE: To simulate hysteroscopic suturing in vitro and analyze the learning curve of gynecologists with different experience levels. METHODS: Three gynecologists were trained on uterine models in a circulating water box. The posterior uterine wall was sutured 10 times under hysteroscopy for 5 consecutive days, and the time of each suture procedure was recorded. RESULTS: Doctors A, B, and C completed 50 posterior uterine sutures. After Dr. C completed 50 sutures on the posterior wall, he added 50 sutures on the anterior wall (Group D). The mean suturing time was 71.54 ± 68.158 s in Group A, 50.10 ± 28.060 s in Group B, 34.04 ± 10.457 s in Group C, and 30.38 ± 8.734 s in Group D. The difference between Groups C and B and between Groups B and A was statistically significant. There was no statistically significant difference between Groups C and D. Simulation curves were created using the number of features as the abscissa and cumulative sum as the coordinate, with peak curves of 19, 27, and 18 cases for Group A, B, and C, respectively. CONCLUSION: Doctors with experience in single-hole laparoscopic surgery or hysteroscopic suture surgery can significantly shorten the hysteroscopic suturing time.
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Levonorgestrel , Entrenamiento Simulado , Masculino , Femenino , Embarazo , Humanos , Curva de Aprendizaje , Histeroscopía , SuturasRESUMEN
RATIONALE: Endometrial vascular dystrophy refers to abnormal vessels that are very tortuous, dilated, and sometimes thrombosed. Endometrial vascular dystrophy is rare under hysteroscopy. PATIENT: All three patients had a history of abnormal uterine bleeding. The duration of vaginal bleeding ranged from 1 month to 2 years. There was no history of unusual diseases, alcohol or drug abuse, or genetic history. DIAGNOSES: Endometrial vascular dystrophy. INTERVENTION: Three patients underwent hysteroscopy and curettage under intravenous general anesthesia. Pathological examination showed secretory endometrium, with one case coexisting with endometrial polyps. OUTCOMES: No recurrence was found during postoperative follow-up at 12 months. LESSONS: Endometrial vascular dystrophy is a rare hysteroscopy phenomenon shown in the secretory endometrium. We believe that it was a capillary loop with different manifestations.
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Enfermedades Uterinas , Neoplasias Uterinas , Embarazo , Femenino , Humanos , Endometrio/patología , Enfermedades Uterinas/diagnóstico , Enfermedades Uterinas/cirugía , Hemorragia Uterina/etiología , Hemorragia Uterina/diagnóstico , Histeroscopía/efectos adversos , Neoplasias Uterinas/patologíaRESUMEN
Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer-related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)-assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.
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Gardner syndrome has head and neck manifestations that may be recognized during dental visits. Features such as multiple gnathic osteomas, impacted supernumerary teeth, and multiple foci of idiopathic osteosclerosis can be easily identified on dental radiographs, prompting the clinician to refer the patient for further investigation. A dental examination and routine radiographs play a vital role in revealing the extracolonic presentation of Gardner syndrome, which facilitates timely screening and detection of colorectal cancer and other malignancies associated with this condition. This report discusses the case of a 50-year-old Caucasian man who presented with a hard swelling of the left angle of the mandible and was diagnosed with Gardner syndrome based on abnormal findings from an oral examination, dental imaging, and medical and family history.
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Production of mesoporous silica films with vertically oriented pores has been a challenge since interest in such systems developed in the 1990s. Vertical orientation can be achieved by the electrochemically assisted surfactant assembly (EASA) method using cationic surfactants such as cetyltrimethylammonium bromide (C16TAB). The synthesis of porous silicas using a series of surfactants with increasing head sizes is described, from octadecyltrimethylammonium bromide (C18TAB) to octadecyltriethylammonium bromide (C18TEAB). These increase pore size, but the degree of hexagonal order in the vertically aligned pores reduces as the number of ethyl groups increases. Pore accessibility is also reduced with the larger head groups.
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Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619-22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619-22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619-22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC. SIGNIFICANCE: A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Animales , Apolipoproteínas B , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Hipoxia , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Humanos , MicropéptidosRESUMEN
BACKGROUND: The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS: 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS: A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS: Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hepatectomía , Recurrencia Local de Neoplasia/patología , Puntaje de Propensión , Estudios Retrospectivos , Quimioembolización Terapéutica/métodos , Pronóstico , Adyuvantes Inmunológicos , Resultado del TratamientoRESUMEN
BACKGROUND: We aimed to investigate the efficacy of postoperative adjuvant transarterial chemoembolisation (PA-TACE) in patients with hepatocellular carcinoma (HCC) complicated by microvascular invasion (MVI). METHODS: A retrospective analysis of 1505 patients with HCC who underwent hepatectomy at four medical centers, including 782 patients who received PA-TACE and 723 patients who did not receive adjuvant PA-TACE, has been conducted. Propensity score matching (PSM) (1:1) was performed on the data to minimise selection bias, which resulted in a balanced clinical profile between groups. RESULTS: After PSM, 620 patients who received PA-TACE and 620 patients who did not receive PA-TACE were included. Disease-free survival (DFS, 1-, 2-, and 3-year: 88%-68%-61% vs. 70%-58%-51%, p < 0.001) and overall survival (OS, 1-, 2-, and 3-year: 96%-89%-82% vs. 89%-77%-67%, p < 0.001) were significantly higher in patients who received PA-TACE than in those who did not. Patients with MVI who received PA-TACE had significantly higher DFS (1-, 2-, and 3-year: 68%-57%-48% vs. 46%-31%-27%, p < 0.001) and OS (1-, 2-, and 3-year: 96%-84%-77% vs. 79%-58%-40%, p < 0.001) than those who did not receive PA-TACE. Among the six different liver cancer stages, MVI-negative patients did not have significant survival outcomes from PA-TACE (p > 0.05), whereas MVI-positive patients achieved higher DFS and OS from it (p < 0.05). Liver dysfunction, fever, and nausea/vomiting were the most common adverse events in patients receiving PA-TACE. There was no significant difference in grade 3 or 4 adverse events between the groups (p > 0.05). CONCLUSIONS: Postoperative adjuvant transarterial chemoembolisation has a good safety profile and may be a potentially beneficial treatment modality for survival outcomes in patients with HCC, especially those with concomitant MVI.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Resultado del Tratamiento , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodosRESUMEN
Emerging evidence has indicated that peroxisome proliferator-activated receptor-gamma coactivator-1α (PPARGC1A) is involved in hepatocellular carcinoma (HCC). However, its detailed function and up- and downstream mechanisms are incompletely understood. In this study, we confirmed that PPAGC1A is lowly expressed in HCC and is associated with poor prognosis using large-scale public datasets and in-house cohorts. PPAGC1A was found to impair the progression and sensitivity of HCC to lenvatinib. Mechanistically, PPAGC1A repressed bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) by inhibiting WNT/ß-catenin signaling. BAMBI mediated the function of PPARGC1A and regulated ACSL5 through TGF-ß/SMAD signaling. PPARGC1A/BAMBI regulated ROS production and ferroptosis-related cell death by controlling ACSL5. PPARGC1A/BAMBI/ACSL5 axis was hypoxia-responsive. METTL3 and WTAP silenced PPARGC1A in an m6A-YTHDF2-dependent way under normoxia and hypoxia, respectively. Metformin restored PPARGC1A expression by reducing its m6A modification via inhibiting METTL3. In animal models and patient-derived organoids, consistent functional data of PPARGC1A/BAMBI/ACSL5 were observed. Conclusions: These findings provide new insights into the role of the aberrant PPARGC1A/BAMBI/ACSL5 axis in HCC. And the mechanism of PPARGC1A dysregulation was explained by m6A modification. Metformin may benefit HCC patients with PPARGC1A dysregulation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Metformina , Animales , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , PPAR gammaRESUMEN
BACKGROUND: Cyclin-dependent kinase 12 (CDK12) mutation has been shown to be associated with the prognosis and clinicopathological characteristics of various tumors. The aim of this meta-analysis was to investigate the role of mutations in prostate cancer (PCa). RESEARCH DESIGN AND METHODS: PubMed/Medline, EMBASE, Cochrane Library, and Web of Science database were searched for relevant articles. Meta-analysis was performed by using RevMan5.3 software, and the quality of the included literature was evaluated according to the Newcastle-Ottawa scale (NOS). RESULTS: A total of 13 studies comprising 5182 participants were enrolled in this meta-analysis. The frequency of CDK12 mutation in PCa was 7.26%. CDK12 mutation was significantly correlated with poor OS/PFS and had a shorter time to progress to CRPC. CDK12 mutant was associated with high-grade Gleason scores, while no relationships were found among CDK12 mutant, age, and the PSA level at diagnosis. CONCLUSION: This meta-analysis indicates that patients with CDK12 mutation have poor prognosis in PCa. CDK12 may be used as a biomarker for molecular subtype and a potential therapeutic target of PCa.
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Neoplasias de la Próstata , Masculino , Humanos , Pronóstico , Neoplasias de la Próstata/patología , Quinasas Ciclina-Dependientes , Biomarcadores , MutaciónRESUMEN
As one of the commonly used folk psychological concepts, self-deception has been intensively discussed yet is short of solid ground from cognitive neuroscience. Self-deception is a biased cognitive process of information to obtain or maintain a false belief that could be both self-enhancing or self-diminishing. Study 1 (N = 152) captured self-deception by adopting a modified numerical discrimination task that provided cheating opportunities, quantifying errors in predicting future performance (via item-response theory model), and measuring the belief of how good they are at solving the task (i.e., self-efficacy belief). By examining whether self-efficacy belief is based upon actual ability (true belief) or prediction errors (false belief), Study 1 showed that self-deception occurred in the effortless (easier access to answer cues) rather than effortful (harder access to answer cues) cheating opportunity conditions, suggesting high ambiguity in attributions facilitates self-deception. Studies 2 and 3 probed the neural source of self-deception, linking self-deception with the metacognitive process. Both studies replicated behavioral results from Study 1. Study 2 (ERP study; N = 55) found that the amplitude of frontal slow wave significantly differed between participants with positive/self-enhancing and negative/self-diminishing self-deceiving tendencies in incorrect predictions while remaining similar in correct predictions. Study 3 (functional magnetic resonance imaging study; N = 33) identified self-deceiving associated activity in the anterior medial prefrontal cortex and showed that effortless cheating context increased cheating behaviors that further facilitated self-deception. Our findings suggest self-deception is a false belief associated with a distorted metacognitive mental process that requires ambiguity in attributions of behaviors.
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Metacognición , Humanos , Decepción , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Señales (Psicología)RESUMEN
The demand for the ubiquitous detection of gases in complex environments is driving the design of highly specific gas sensors for the development of the Internet of Things, such as indoor air quality testing, human exhaled disease detection, monitoring gas emissions, etc. The interaction between analytes and bioreceptors can described as a "lock-and-key", in which the specific catalysis between enzymes and gas molecules provides a new paradigm for the construction of high-sensitivity and -specificity gas sensors. The electrochemical method has been widely used in gas detection and in the design and construction of enzyme-based electrochemical gas sensors, in which the specificity of an enzyme to a substrate is determined by a specific functional domain or recognition interface, which is the active site of the enzyme that can specifically catalyze the gas reaction, and the electrode-solution interface, where the chemical reaction occurs, respectively. As a result, the engineering design of the enzyme electrode interface is crucial in the process of designing and constructing enzyme-based electrochemical gas sensors. In this review, we summarize the design of enzyme-based electrochemical gas sensors. We particularly focus on the main concepts of enzyme electrodes and the selection and design of materials, as well as the immobilization of enzymes and construction methods. Furthermore, we discuss the fundamental factors that affect electron transfer at the enzyme electrode interface for electrochemical gas sensors and the challenges and opportunities related to the design and construction of these sensors.