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1.
Small ; : e2406448, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279302

RESUMEN

Designing nano-electrocatalysts rich in surface defects is critical to improve their catalytic performance. However, prevailing synthesis techniques rely heavily on complex procedures that compromise defect extensiveness and uniformity, casting a high demand for methods capable of synthesizing large-scale crystalline defects. An innovative design strategy is herein proposed that induces ample strain/dislocation defects during the growth of palladium (Pd), which is well-known as a good oxygen reduction reaction (ORR) catalyst. The controlled defect engineering on Pd core is achieved by the tensile stress exerted from an intentionally applied Fe3O4 skin layer during synthesis, which changes the surface free energy of Pd to stabilize the defect presence. With such large-scale crystalline defects, this Pd catalyst exhibits significantly higher ORR activity than commercial Pt/C, enabling its promising future in zinc-air battery catalysis. Additionally, the protective Fe3O4 skin covering the catalyst also enhances its catalytic stability. Theoretical calculations show that the superior catalytic property of such defect-engineered Pd is associated with the correspondingly modified adsorption energy of *O intermediates onto its surface, which further improves the reaction rate and thus boosts ORR kinetics. Findings here are expected to provide a paradigm for designing efficient and stable metal catalysts with plentiful large-scale strain defects.

2.
Heliyon ; 10(17): e36770, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39290260

RESUMEN

Background and aim: Accurately predicting microvascular invasion (MVI) before surgery is beneficial for surgical decision-making, and some high-risk hepatocellular carcinoma (HCC) patients may benefit from postoperative adjuvant transarterial chemoembolization (PA-TACE). The purpose of this study was to develop and validate a novel nomogram for predicting MVI and assessing the survival benefits of selectively receiving PA-TACE in HCC patients. Methods: The 1372 HCC patients who underwent hepatectomy at four medical institutions were randomly divided into training and validation datasets according to a 7:3 ratio. We developed and validated a nomogram for predicting MVI using preoperative clinical data and further evaluated the survival benefits of selective PA-TACE in different risk subgroups. Results: The nomogram for predicting MVI integrated alpha-fetoprotein, tumor diameter, tumor number, and tumor margin, with an area under the curve of 0.724, which was greater than that of any single predictive factor. The calibration curve, decision curve, and clinical impact curve demonstrated that the nomogram had strong predictive performance. Risk stratification based on the nomogram revealed that patients in the low-risk group did not achieve better DFS and OS with PA-TACE (all p > 0.05), while patients in the medium-to-high risk groups could benefit from higher DFS (Medium-risk, p = 0.039; High-risk, p = 0.027) and OS (Medium-risk, p = 0.001; High-risk, p = 0.019) with PA-TACE. Conclusions: The nomogram predicting MVI demonstrated strong predictive performance, and its risk stratification aided in identifying different subgroups of HCC patients who may benefit from PA-TACE with improved survival outcomes.

3.
Sci China Life Sci ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39327392

RESUMEN

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39255183

RESUMEN

Differentiable architecture search (DARTS) has attracted much attention due to its simplicity and significant improvement in efficiency. However, the excessive accumulation of the skip connection, when training epochs become large, makes it suffer from weak stability and low robustness, thus limiting its practical applications. Many works have attempted to restrict the accumulation of skip connections by indicators or manual design. These methods, however, are susceptible to human priors and hyperparameters. In this work, we suggest a more subtle and direct approach that no longer explicitly searches for skip connections in the search stage, based on the paradox that skip connections were proposed to guarantee the performance of very deep networks, but the networks in the search stage of DARTS are actually very shallow. Instead, by introducing channel importance ranking and channel allocation strategy, the skip connections are implicitly searched and automatically refilled unimportant channels in the evaluation stage. Our method, dubbed adaptive channel allocation (ACA) strategy, is a general-purpose approach for DARTS, which universally works in DARTS variants without introducing human priors, indicators, or hyperparameters. Extensive experiments on various datasets and DARTS variants verify that the ACA strategy is the most effective one among the existing methods in improving robustness and dealing with the collapse issue when training epochs become large.

5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(10): 1249-1254, 2024 Oct 10.
Artículo en Chino | MEDLINE | ID: mdl-39344622

RESUMEN

OBJECTIVE: To explore the clinical characteristics and pathogenic variant in a child with Cantú syndrome (CS). METHODS: A male who was admitted to the Children's Hospital Affiliated to Zhengzhou University on February 23, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole-exome sequencing (WES). Candidate variant was verified by Sanger sequencing. This study was approved by the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-087). RESULTS: The child, a 3-year-and-2-month-old male, was born with hirsutism, with heavy hair all over the body and peculiar facial features. Routine echocardiography 1 month before had discovered atrial septal defect. Sequencing revealed that the child has harbored a heterozygous c.2438G>C (p.S813T) variant of the ABCC9 gene, which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2438G>C variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3). CONCLUSION: The heterozygous c.2438G>C variant of the ABCC9 gene probably underlay the pathogenesis of CS in this child.


Asunto(s)
Hirsutismo , Receptores de Sulfonilureas , Humanos , Masculino , Receptores de Sulfonilureas/genética , Preescolar , Hirsutismo/genética , Mutación , Secuenciación del Exoma , Osteocondrodisplasias/genética , Pruebas Genéticas , Cardiomegalia , Hipertricosis
6.
Transl Cancer Res ; 13(8): 4062-4084, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39262488

RESUMEN

Background: The diphthamide (DPH) gene family is a group of genes that encode a set of enzymes that specifically modify eukaryotic elongation factor 2 (eEF2). Although previous studies have shown a link between the DPH genes (DPHs) and carcinogenesis, it is still unknown how the DPHs affect hepatocellular carcinoma (HCC). This study aimed to describe the expression, clinical significance, and potential mechanisms of DPHs in HCC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR), Genotype-Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) databases were utilized to research the expression of DPHs in HCC. The relationship between the expression of DPHs and the clinicopathological characteristics of HCC patients was investigated using TCGA data, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves and their prognostic value was analyzed using Kaplan-Meier curves and univariate and multivariate Cox regression analyses. Potential reasons for the upregulation of DPH2 and DPH3 (DPH2,3) expression in HCC were analyzed using multiple databases. Additionally, this study also explored the potential biological functions of DPH2,3 in HCC via gene sets enrichment analysis (GSEA). Correlation analysis of DPH2,3 expression with immune-related genes and immune checkpoints was performed using Spearman's correlation analysis, and single-sample GSEA was used to assess the distribution of tumor-infiltrating immune cell types. Results: DPH1,7 expression was downregulated in tumor tissues while DPH2,3,5,6 expression was upregulated and showed a similar expression pattern in HCC. The results of the ROC analysis suggested that DPHs had valuable diagnostic properties in HCC. Kaplan-Meier analysis demonstrated that DPH2,3,7 had prognostic predictive value in HCC. Furthermore, univariate and multivariate Cox regression suggested that DPH2,3 was an independent predictive factor for HCC. GSEA analysis revealed that DPH2,3 might be tightly associated with Pathways in cancer, cell cycles, Fc gamma R mediated phagocytosis, etc. Additionally, DPH2,3 expression and numerous immune-related genes showed a positive connection, including chemokines receptor genes, immunosuppressive genes, chemokines genes, human leukocyte antigen (HLA) genes, and immunostimulatory genes. Further analysis of the association between 24 immune infiltrating cells and DPH2,3 revealed the greatest negative correlation between natural killer (NK) cells and Th17 cells, but the greatest positive correlation with Th2 cells. Conclusions: DPHs significantly influence the development and progression of HCC. DPH2,3 has significant diagnostic and prognostic potential and may be a promising target for immunotherapy.

7.
Sci Total Environ ; 951: 175320, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39111429

RESUMEN

Tolfenpyrad (TFP) is an extensively used pesticide that inevitably leads to human exposure to both TFP and its transformation product residues. However, the biotransformation of TFP in humans has not been elucidated, and the toxicity of TFP along with its biotransformation products remains largely unknown. In this study, the biotransformation process of TFP was investigated using human liver microsomes and human hepatic cells. Endogenous metabolic changes in the cells were studied to investigate the hepatocytotoxicity of TFP at environmentally relevant concentrations. Fourteen phase I biotransformation products and four phase II TFP products were characterized, among which twelve products were identified for the first time. The oxidative product tolfenpyrad-benzoic acid (PT-CA) was particularly abundant and stable. Further hepatotoxicity assessments and metabolic studies demonstrated comparable metabolic profiles for TFP and PT-CA in HepG2 cells, with both significantly disrupting purine and glutathione metabolism. These processes are closely associated with oxidative stress, mitochondrial damage, and cell death. Our results provide novel perspectives on the biotransformation, metabolism, and hepatotoxicity of TFP, thereby highlighting the non-negligible toxicity of its crucial biotransformation product PT-CA in environmental risk assessments.


Asunto(s)
Biotransformación , Metabolómica , Microsomas Hepáticos , Humanos , Microsomas Hepáticos/metabolismo , Células Hep G2 , Estrés Oxidativo , Hígado/metabolismo , Hígado/efectos de los fármacos
8.
World J Gastrointest Surg ; 16(7): 2106-2118, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087126

RESUMEN

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a common consequence of radical partial hepatectomy in hepatocellular carcinoma (HCC). AIMS: To investigate the relationship between preoperative antiviral therapy and PHLF, as well as assess the potential efficacy of hepatitis B virus (HBV) DNA level in predicting PHLF. METHODS: A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy. Receiver operating characteristic (ROC) analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses. Logistic regression analyses were performed to assess the independent risk factors of PHLF. The increase in the area under the ROC curve, categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to quantify the efficacy of HBV DNA level for predicting PHLF. The P < 0.05 was considered statistically significant. RESULTS: Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF (P < 0.05). HBV DNA level with an optimal cutoff value of 269 IU/mL (P < 0.001) was an independent risk factor of PHLF. All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve, categorical NRI, and IDI, particularly for the fibrosis-4 model, with values of 0.729 (95%CI: 0.705-0.754), 1.382 (95%CI: 1.341-1.423), and 0.112 (95%CI: 0.110-0.114), respectively. All the above findings were statistically significant. CONCLUSION: In summary, preoperative antiviral treatment can reduce the incidence of PHLF, whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

9.
Drug Dev Res ; 85(6): e22242, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39161064

RESUMEN

Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 µM and 2.16 µM, and by propofol with a IC50 value of 42.51 µM and 48.37 µM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway.


Asunto(s)
Ferroptosis , Ratones Desnudos , Propofol , Triterpenos , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Animales , Triterpenos/farmacología , Humanos , Propofol/farmacología , Ferroptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Invasividad Neoplásica , Escape del Tumor/efectos de los fármacos , Sinergismo Farmacológico , Transducción de Señal/efectos de los fármacos
11.
Clin Transl Oncol ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965191

RESUMEN

BACKGROUND: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. METHODS: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. RESULTS: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. CONCLUSION: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

12.
Clin Transl Gastroenterol ; 15(9): e1, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38920294

RESUMEN

INTRODUCTION: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis. METHODS: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes. RESULTS: Both cohorts showed strong parameter similarity ( P > 0.05). High AG was associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (hazard ratio: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable with established scoring systems. DISCUSSION: Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.


Asunto(s)
Equilibrio Ácido-Base , Enfermedad Crítica , Mortalidad Hospitalaria , Cirrosis Hepática , Humanos , Enfermedad Crítica/mortalidad , Masculino , Femenino , Cirrosis Hepática/sangre , Cirrosis Hepática/mortalidad , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Pronóstico , Factores de Riesgo , Medición de Riesgo/métodos , Estimación de Kaplan-Meier , Admisión del Paciente/estadística & datos numéricos , Valor Predictivo de las Pruebas
13.
Neurosurg Focus ; 56(6): E18, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38823051

RESUMEN

OBJECTIVE: This study aimed to investigate the differences in clinical features, diagnostic examination, treatment, and pathological results between adult-onset and pediatric-onset tethered cord syndrome (TCS). METHODS: The authors searched the PubMed, Embase, and Cochrane Library databases through January 2023 for reports on TCS, extracting information on clinical features, imaging data, treatment modalities, prognosis, and pathological research results. A total of 6135 cases from 246 articles were included in the analysis. This review was conducted in accordance with the 2020 PRISMA guidelines and registered on PROSPERO. RESULTS: The most common adult clinical manifestations were pain, urinary symptoms, and numbness; in children, they were urinary symptoms, skin lesions, bowel symptoms, and unspecific motor deficits. Surgical treatment was the primary approach for both adults and children, with a higher clinical improvement rate observed in adults. However, adults also had a higher rate of surgical complications than children. TCS pathological studies have not yet identified the differences between adults and children, and the pathogenesis of adult-onset TCS requires further investigation. CONCLUSIONS: Adult-onset and pediatric-onset TCS exhibit certain differences in clinical characteristics, diagnostic examinations, and treatments. However, significant differences have not been found in current pathological studies between adults and children. Systematic review registration no.: CRD42023479450 (www.crd.york.ac.uk/prospero).


Asunto(s)
Defectos del Tubo Neural , Humanos , Defectos del Tubo Neural/cirugía , Defectos del Tubo Neural/diagnóstico , Niño , Adulto , Edad de Inicio
14.
Environ Sci Technol ; 58(25): 11118-11127, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38864774

RESUMEN

Intermediate volatility organic compounds (IVOCs) are important precursors to secondary organic aerosols (SOAs), but they are often neglected in studies concerning SOA formation. This study addresses the significant issue of IVOCs emissions in the Qinghai-Tibetan plateau (QTP), where solid fuels are extensively used under incomplete combustion conditions for residential heating and cooking. Our field measurement data revealed an emission factor of the total IVOCs (EFIVOCs) ranging from 1.56 ± 0.03 to 9.97 ± 3.22 g/kg from various combustion scenarios in QTP. The markedly higher EFIVOCs in QTP than in plain regions can be attributed to oxygen-deficient conditions. IVOCs were dominated by gaseous phase emissions, and the primary contributors of gaseous and particulate phase IVOCs are the unresolved complex mixture and alkanes, respectively. Total IVOCs emissions during the heating and nonheating seasons in QTP were estimated to be 31.7 ± 13.8 and 6.87 ± 0.45 Gg, respectively. The estimated SOA production resulting from combined emissions of IVOCs and VOCs is nearly five times higher than that derived from VOCs alone. Results from this study emphasized the pivotal role of IVOCs emissions in air pollution and provided a foundation for compiling emission inventories related to solid fuel combustion and developing pollution prevention strategies.


Asunto(s)
Aerosoles , Contaminantes Atmosféricos , Carbón Mineral , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Contaminantes Atmosféricos/análisis , China , Animales , Tibet , Monitoreo del Ambiente
16.
Nano Lett ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842926

RESUMEN

Two-dimensional (2D) Fe3Sn2, which is a room-temperature ferromagnetic kagome metal, has potential applications in spintronic devices. However, the systematic synthesis and magnetic study of 2D Fe3Sn2 single crystals have rarely been reported. Here we have synthesized 2D hexagonal and triangular Fe3Sn2 nanosheets by controlling the amount of FeCl2 precursors in the chemical vapor deposition (CVD) method. It is found that the hexagonal Fe3Sn2 nanosheets exist with Fe vacancy defects and show no obvious coercivity. While the triangular Fe3Sn2 nanosheet has obvious hysteresis loops at room temperature, its coercivity first increases and then remains stable with an increase in temperature, which should result from the competition of the thermal activation mechanism and spin direction rotation mechanism. A first-principles calculation study shows that the Fe vacancy defects in Fe3Sn2 can increase the distances between Fe atoms and weaken the ferromagnetism of Fe3Sn2. The resulting 2D Fe3Sn2 nanosheets provide a new choice for spintronic devices.

17.
BMJ Paediatr Open ; 8(1)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38823802

RESUMEN

OBJECTIVES: This study aimed to describe the genetic and clinical characteristics of paediatric cardiomyopathy in a cohort of Chinese patients. METHODS: We retrospectively reviewed the clinical history and mutation spectrum of 75 unrelated Chinese paediatric patients who were diagnosed with cardiomyopathy and referred to our hospital between January 2016 and December 2022. RESULTS: Seventy-five children with cardiomyopathy were enrolled, including 32 (42.7%) boys and 43 (57.3%) girls. Dilated cardiomyopathy was the most prevalent cardiomyopathy (61.3%) in the patients, followed by hypertrophic cardiomyopathy (17.3%), ventricular non-compaction (14.7%), restrictive cardiomyopathy (5.3%) and arrhythmogenic right ventricular cardiomyopathy (1.3%). Whole-exome sequencing and targeted next-generation sequencing identified 34 pathogenic/likely pathogenic variants and 1 copy number variant in 14 genes related to cardiomyopathy in 30 children, accounting for 40% of all patients. TNNC1 p.Asp65Asn and MYH7 p.Glu500Lys have not been reported previously. The follow-up time ranged from 2 months to 6 years. Twenty-two children died (mortality rate 29%). CONCLUSIONS: Comprehensive genetic testing was associated with a 40% yield of causal genetic mutations in Chinese cardiomyopathy cases. We found diversity in the mutation profile in different patients, which suggests that the mutational background of cardiomyopathy in China is heterogeneous, and the findings may be helpful to those counselling patients and families.


Asunto(s)
Cardiomiopatías , Pruebas Genéticas , Mutación , Humanos , Masculino , Femenino , Estudios Retrospectivos , Niño , Lactante , Cardiomiopatías/genética , Preescolar , China/epidemiología , Secuenciación del Exoma , Adolescente
18.
Pharmgenomics Pers Med ; 17: 271-288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827182

RESUMEN

Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38706659

RESUMEN

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

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