Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 510
Filtrar
1.
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.

2.
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
3.
Sci Total Environ ; 951: 175320, 2024 Aug 05.
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.

4.
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.

6.
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.

8.
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
9.
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.

10.
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.

11.
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
12.
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
13.
Aliment Pharmacol Ther ; 60(2): 112-123, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38818831

RESUMEN

BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (UGIB) is challenging in patients at high risk of re-bleeding in whom standard endoscopic treatment (ST) has limited effectiveness. Over-the-scope clips (OTSC) have shown promise in these patients although their precise role remains uncertain. AIMS: To confirm the role of OTSC in patients with UGIB at high risk of re-bleeding. METHODS: We systematically searched CENTRAL, MEDLINE and Embase from January 1st, 1970 to April 24, 2024 for randomised controlled trials (RCTs) comparing OTSC and ST in acute non-variceal UGIB with high re-bleeding risk. The GRADE framework assessed evidence certainty, while trial sequential analysis (TSA) controlled random errors and evaluated conclusion validity. RESULTS: We analysed four RCTs (319 patients); pooled risk ratio (RR) for clinical success at initial endoscopy favoured OTSC (RR = 1.30, 95% CI = 1.08-1.56, p = 0.006, I2 = 58%, moderate certainty of evidence). TSA showed the desired sample size was 410 and the cumulative Z curve crossing the trial sequential monitoring boundary. The pooled RR for re-bleeding within 30 days favoured OTSC (RR = 0.53, 95% CI = 0.30-0.94, p = 0.03, I2 = 0%, moderate certainty of evidence). There was no significant difference in 30-day mortality, or length of hospital or ICU stay. CONCLUSIONS: Moderate certainty evidence supports OTSC as a superior initial treatment for acute non-variceal UGIB with high re-bleeding risk. Further large-scale studies are needed to confirm OTSCs' role by exploring other prognostic outcomes and assessing cost-effectiveness and potential complications.


Asunto(s)
Hemorragia Gastrointestinal , Instrumentos Quirúrgicos , Humanos , Hemorragia Gastrointestinal/etiología , Instrumentos Quirúrgicos/efectos adversos , Recurrencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Endoscopía Gastrointestinal/métodos , Hemostasis Endoscópica/instrumentación , Hemostasis Endoscópica/métodos , Resultado del Tratamiento , Tracto Gastrointestinal Superior
14.
Sci Rep ; 14(1): 10069, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697990

RESUMEN

Helicobacter pylori infection, a worldwide health issue, is typically treated with standard antibiotic therapies. However, these treatments often face resistance and non-compliance due to side effects. In this umbrella review, we aimed to comprehensively assess the impact of probiotics supplementation in different preparations on Helicobacter pylori standard treatment. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials in the Cochrane Library from inception to June 1, 2023, to identify systematic reviews with meta-analyses that focused on eradication rates, total side effects and other outcomes of interest. The most comprehensive meta-analysis was selected for data extraction. AMSTAR 2 was used to assess quality of meta-analyses. Overall, 28 unique meta-analyses based on 534 RCTs were included. The results suggests that probiotics supplementation with pooled probiotic strains was significantly associated with improved eradication rates (RR 1.10, 95% CI 1.06-1.14) and reduced risk of total side effects (RR 0.54, 95% CI 0.42-0.70) compared with standard therapy alone. Single-strained or multi-strained preparation of probiotics supplementation showed similar results. Despite Bifidobacterium spp. showing the highest potential for eradication, the study quality was critically low for most meta-analyses, necessitating further high-quality research to explore the optimal probiotic strains or their combinations for Helicobacter pylori treatment.aq_start?>Kindly check and confirm the edit made in article title.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Probióticos , Revisiones Sistemáticas como Asunto , Probióticos/uso terapéutico , Helicobacter pylori/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/terapia , Infecciones por Helicobacter/microbiología , Humanos , Metaanálisis como Asunto , Suplementos Dietéticos , Antibacterianos/uso terapéutico , Resultado del Tratamiento
15.
Artículo en Inglés | MEDLINE | ID: mdl-38776207

RESUMEN

In convolutional neural networks (CNNs), the convolutions are conventionally performed using a square kernel with a fixed N × N receptive field (RF). However, what matters most to the network is the effective receptive field (ERF), which indicates the extent to which input pixels contribute to an output pixel. Inspired by the property that ERFs typically exhibit a Gaussian distribution, we propose a Gaussian Mask convolutional kernel (GMConv). Specifically, GMConv utilizes the Gaussian function to generate a concentric symmetry mask that is placed over the kernel to refine the RF. We analyze the RFs of CNN kernels in different CNN layers and evaluate our approach through extensive experiments on image classification and object detection tasks. Over several tasks and standard base models, our approach compares favorably against the standard convolution. For instance, using GMConv for AlexNet and ResNet-50, the top-1 accuracy on ImageNet classification is boosted by 0.98% and 0.85% , respectively.

16.
Talanta ; 275: 126134, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38692044

RESUMEN

Phosphoenolpyruvate (PEP) is an essential intermediate metabolite that is involved in various vital biochemical reactions. However, achieving the direct and accurate quantification of PEP in plasma or serum poses a significant challenge owing to its strong polarity and metal affinity. In this study, a sensitive method for the direct determination of PEP in plasma and serum based on ethylenediaminetetraacetic acid (EDTA)-facilitated hydrophilic interaction liquid chromatography-tandem mass spectrometry was developed. Superior chromatographic retention and peak shapes were achieved using a zwitterionic stationary-phase HILIC column with a metal-inert inner surface. Efficient dechelation of PEP-metal complexes in serum/plasma samples was achieved through the introduction of EDTA, resulting in a significant enhancement of the PEP signal. A PEP isotopically labelled standard was employed as a surrogate analyte for the determination of endogenous PEP, and validation assessments proved the sensitivity, selectivity, and reproducibility of this method. The method was applied to the comparative quantification of PEP in plasma and serum samples from mice and rats, as well as in HepG2 cells, HEK293T cells, and erythrocytes; the results confirmed its applicability in PEP-related biomedical research. The developed method can quantify PEP in diverse biological matrices, providing a feasible opportunity to investigate the role of PEP in relevant biomedical research.


Asunto(s)
Ácido Edético , Interacciones Hidrofóbicas e Hidrofílicas , Fosfoenolpiruvato , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Animales , Humanos , Ácido Edético/química , Ratones , Cromatografía Liquida/métodos , Ratas , Fosfoenolpiruvato/química , Fosfoenolpiruvato/sangre , Fosfoenolpiruvato/metabolismo , Células HEK293 , Células Hep G2 , Ratas Sprague-Dawley , Masculino
17.
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.

18.
Therap Adv Gastroenterol ; 17: 17562848241255295, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812707

RESUMEN

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment. Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs). Design: Meta-analysis of RCTs. Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions. Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66-3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary. Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design. Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621).

20.
Int Immunopharmacol ; 134: 112139, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38739978

RESUMEN

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.


Asunto(s)
Proliferación Celular , Neoplasias Hepáticas , Serina-Treonina Quinasas TOR , Proteínas de Motivos Tripartitos , Proteína p53 Supresora de Tumor , Animales , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Transducción de Señal , Sorafenib/farmacología , Sorafenib/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA