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BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.
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BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.
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Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct zyg-type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H2O2). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H2O2 synthesis rate of 3324 µmol g-1 h-1, which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.
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Transparent soil (TS) presents immense potential for root phenotyping due to its ability to facilitate high-resolution imaging. However, challenges related to transparency, mechanical properties, and cost hinder its development. Herein, we introduce super-transparent soil (s-TS) prepared via the droplet method using low acyl gellan gum and hydroxyethyl cellulose crosslinked with magnesium ions. The refractive index of the hydroxyethyl cellulose solution (1.345) closely aligns with that of water (1.333) and the low acyl gellan gum solution (1.340), thereby significantly enhancing the transmittance of hydrogel-based transparent soil. Optimal transmittance (98.45%) is achieved with polymer concentrations ranging from 0.8 to 1.6 wt.% and ion concentrations between 0.01 and 0.09 mol·L-1. After 60 days of plant cultivation, s-TS maintains a transmittance exceeding 89.5%, enabling the detailed visualization of root growth dynamics. Furthermore, s-TS exhibits remarkable mechanical properties, withstanding a maximum compressive stress of 477 kPa and supporting a maximum load-bearing depth of 186 cm. This innovative approach holds promising implications for advanced root phenotyping studies, fostering the investigation of root heterogeneity and the development of selective expression under controlled conditions.
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Fenotipo , Raíces de Plantas , Suelo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/química , Suelo/química , Polisacáridos Bacterianos/químicaRESUMEN
Atrial fibrillation (AF) is a common arrhythmia, and out-of-hospital, wearable, long-term electrocardiogram (ECG) monitoring can help with the early detection of AF. The presence of a motion artifact (MA) in ECG can significantly affect the characteristics of the ECG signal and hinder early detection of AF. Studies have shown that (a) using reference signals with a strong correlation with MAs in adaptive filtering (ADF) can eliminate MAs from the ECG, and (b) artificial intelligence (AI) algorithms can recognize AF when there is no presence of MAs. However, no literature has been reported on whether ADF can improve the accuracy of AI for recognizing AF in the presence of MAs. Therefore, this paper investigates the accuracy of AI recognition for AF when ECGs are artificially introduced with MAs and processed by ADF. In this study, 13 types of MA signals with different signal-to-noise ratios ranging from +8 dB to -16 dB were artificially added to the AF ECG dataset. Firstly, the accuracy of AF recognition using AI was obtained for a signal with MAs. Secondly, after removing the MAs by ADF, the signal was further identified using AI to obtain the accuracy of the AF recognition. We found that after undergoing ADF, the accuracy of AI recognition for AF improved under all MA intensities, with a maximum improvement of 60%.
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Algoritmos , Artefactos , Inteligencia Artificial , Fibrilación Atrial , Electrocardiografía , Procesamiento de Señales Asistido por Computador , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Electrocardiografía/métodos , Humanos , Relación Señal-RuidoRESUMEN
BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.
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Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.
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Contactinas , Epilepsia Generalizada , Epistasis Genética , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Estudios de Casos y Controles , Contactinas/genética , Epilepsia Generalizada/genética , Secuenciación del Exoma , Frecuencia de los GenesRESUMEN
Retrograde signaling between plastids and the nucleus is vital for chloroplast biogenesis and environmental responses. GENOMES UNCOUPLED1 (GUN1) was proposed to be a central integrator of multiple retrograde signaling pathways in the model plant Arabidopsis thaliana (Arabidopsis). However, the function of GUN1 orthologs in other plant species has not been well studied. Here, we found that many GUN1 orthologs from the Solanaceae family have a short N-terminus before the first pentatricopeptide repeat (PPR) motif which is predicted as intrinsically disordered regions (IDRs). Functional analyses of tomato (Solanum lycopersicum L.) GUN1 (SlGUN1), which does not contain N-terminal IDRs, show that it can complement the GUN phenotype of the Arabidopsis gun1 mutant (Atgun1). However, in contrast to the AtGUN1 protein, which does contain the N-terminal IDRs, the SlGUN1 protein is highly accumulated even after chloroplast biogenesis is completed, suggesting that the N-terminal IDRs may determine the stability of the GUN1 protein. Furthermore, we generated tomato Slgun1 genome-edited mutants via the CRISPR-Cas9 system. The Slgun1 mutants exhibited a typical GUN phenotype under lincomycin (Lin) or norflurazon (NF) treatment. Moreover, Slgun1 mutants are hypersensitive to low concentrations of Lin or NF. Taken together, our results suggest that, although lacking the N-terminal IDRs, SlGUN1 plays conserved roles in plastid retrograde signaling in tomato plants.
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Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Solanum lycopersicum/genética , Proteínas de Unión al ADN/genética , Plastidios/genética , Plastidios/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Autoimmune hepatitis (AIH) is an autoimmune disease characterized by chronic liver inflammation, with a gradually increasing incidence rate, and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years, it has been believed that changes in intestinal microecology can cause changes in autoimmune state, microbial metabolites, and intestinal barrier, which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients, elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH, and briefly describes related treatment regimens from the perspective of intestinal microecology, so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis, diagnosis, and treatment of AIH.
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ObjectiveTo investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells (HSC). MethodsPathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis (S1-S4) and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy, and immunohistochemistry was used to measure the protein expression levels of PERK, eIF2α, and C/EBP homologous protein (CHOP). Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin (0, 125, 250, 500, and 1 000 nmol/L), and qRT-PCR was used to measure the mRNA expression level of PERK, while Western blot was used to measure the protein expression levels of PERK, inositol requiring protein 1 (IRE1), activating transcription factor 6 (ATF6), CHOP, and α-smooth muscle actin (α-SMA). The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group; qRT-PCR was used to measure the mRNA expression levels of PERK, eIF2α, and α-SMA, Western blot was used to measure the protein expression levels of PERK, phosphorylated eIF2α (p-eIF2α), and α-SMA, and immunofluorescence assay was used to measure the expression of collagen type I alpha 1 (COL1A1). The independent samples t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with normal liver tissue, the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK, eIF2α, and CHOP (Z=-3.56, t=-5.75, Z=-3.52, all P<0.001). Compared with the solvent group, the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK, CHOP, IRE1, ATF6, and α-SMA (all P<0.05). Compared with the control group, the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK, eIF2α, and α-SMA and the protein expression levels of PERK, p-eIF2α, and α-SMA (all P<0.05), and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group (P<0.05). ConclusionPERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells, suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.
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Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66â¯000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.
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BACKGROUND: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy. METHODS: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups. RESULTS: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery. CONCLUSION: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia.
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Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Neoplasias de la Mama/patología , Mastectomía/métodos , Músculos Pectorales/cirugía , Puntaje de Propensión , Recurrencia Local de Neoplasia/patología , Mamoplastia/métodos , Fascia , Estudios RetrospectivosRESUMEN
Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.
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Epilepsia Generalizada , Epilepsia , Humanos , Epilepsia Generalizada/genética , Frecuencia de los Genes , FenotipoRESUMEN
As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli.
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Corynebacterium glutamicum , Proteínas de Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Ingeniería Metabólica/métodos , Arginina/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , FermentaciónRESUMEN
Protein homeostasis (proteostasis) is a dynamic balance of protein synthesis and degradation. Because of the endosymbiotic origin of chloroplasts and the massive transfer of their genetic information to the nucleus of the host cell, many protein complexes in the chloroplasts are constituted from subunits encoded by both genomes. Hence, the proper function of chloroplasts relies on the coordinated expression of chloroplast- and nucleus-encoded genes. The biogenesis and maintenance of chloroplast proteostasis are dependent on synthesis of chloroplast-encoded proteins, import of nucleus-encoded chloroplast proteins from the cytosol, and clearance of damaged or otherwise undesired "old" proteins. This review focuses on the regulation of chloroplast proteostasis, its interaction with proteostasis of the cytosol, and its retrograde control over nuclear gene expression. We also discuss significant issues and perspectives for future studies and potential applications for improving the photosynthetic performance and stress tolerance of crops.
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Cloroplastos , Proteostasis , Cloroplastos/genética , Cloroplastos/metabolismo , Fotosíntesis , Núcleo Celular/genética , Citosol/metabolismoRESUMEN
BACKGROUND: Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. METHODS: HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias. RESULTS: A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group (P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate (n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification (P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05). After PSM, alpha-fetoprotein (AFP) ≥ 400 µg/L [hazard ratio (HR) = 4.71, 95% confidence interval (CI): 2.69-8.25], ascites (HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. CONCLUSIONS: LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.
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Carcinoma Hepatocelular , Hipertensión Portal , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , alfa-Fetoproteínas , Ascitis , Puntaje de Propensión , Estudios Retrospectivos , Hepatectomía/métodos , Análisis de Supervivencia , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/cirugía , Tiempo de InternaciónRESUMEN
OBJECTIVES: To construct and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram to predict Ki-67 expression level in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 217 patients with HNSCC who underwent CECT scans and immunohistochemical examination of their Ki-67 index were enrolled in this study. The patients were divided into a training set (n = 140; Ki-67: ≥ 50% [n = 72] and < 50% [n = 68]) and an external test set (n = 77; Ki-67: ≥ 50% [n = 38] and < 50% [n = 39]). The least absolute shrinkage and selection operator method was used to select key features for a CECT-image-based radiomics signature and a radiomics score (Rad-score) was calculated. A clinical model was established using clinical data and CT findings. The independent clinical factors and Rad-score were then combined to construct a radiomics nomogram. The performance characteristics of the Rad-score, clinical model, and nomogram were assessed using ROCs and decision curve analysis. RESULTS: Twenty features were finally selected to construct the Rad-score. The radiomics nomogram incorporating the Rad-score, low histological grade, and lymphatic spread showed higher predictive value for the Ki-67 index (≥ 50% vs. < 50%) than the clinical model on both the training (AUC, 0.919 vs. 0.648, p < 0.001) and test (AUC, 0.832 vs. 0.685, p = 0.030) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed to predict the expression of Ki-67 in HNSCC. This model showed favorable predictive efficacy and might be useful for prognostic evaluation and clinical decision-making in patients with HNSCC. KEY POINTS: ⢠Accurate pre-treatment prediction of Ki-67 index in HNSCC is crucial. ⢠A CECT-based radiomics nomogram showed favorable predictive efficacy in estimation of Ki-67 expression status in HNSCC patients.
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Neoplasias de Cabeza y Cuello , Nomogramas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Antígeno Ki-67 , Tomografía Computarizada por Rayos X/métodos , Neoplasias de Cabeza y Cuello/diagnóstico por imagenRESUMEN
OBJECTIVE@#To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells.@*METHOD@#Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with LipofectamineTM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein.@*RESULTS@#Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells.@*CONCLUSION@#MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .
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Humanos , Niño , MicroARNs/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proliferación Celular , Apoptosis , Trastornos Mieloproliferativos , Movimiento Celular , Hemoglobinas , Línea Celular Tumoral , ForminasRESUMEN
Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.
Asunto(s)
Inteligencia Artificial , Inhibidores Enzimáticos/farmacología , Ensayos Analíticos de Alto Rendimiento , Simulación del Acoplamiento MolecularRESUMEN
OBJECTIVE@#To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.@*METHODS@#This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.@*RESULTS@#Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.@*CONCLUSION@#Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.