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OBJECTIVE: To biomechanically evaluate the stability of internal fixation methods for femoral neck fractures in small-breed dogs. Furthermore, the possibility of replacing the headed screw with fully threaded headless cannulated screws in the fixation method was assessed. METHODS: The study was conducted from December 12, 2023, to February 7, 2024. A total of 18 femurs from 9 canine cadavers were used in this study. After a simple neck fracture was created, in group A (n = 6), the fracture was stabilized with three 1.1-mm parallel Kirschner wires (K-wires). In group B (n = 6), a 3.0-mm partially threaded cannulated screw and an antirotation pin were used. In group C (n = 6), a 2.5-mm fully threaded headless cannulated screw and an antirotation pin were used. A mechanical test was conducted to apply a single axial compressive load to the femoral head. RESULTS: 9 adult small-breed dogs weighing 3.6 to 8.3 kg (mean ± SD; 5.9 ± 1.6). The mean maximum failure load was highest in group C (495 ± 81 N), followed by group B (454 ± 50.4 N), and then group A (222 ± 21.6 N). Significant differences in maximum failure load were observed between groups A and B as well as groups A and C but not between groups B and C. CONCLUSION: The use of fully threaded headless cannulated screws presents a promising method for internal fixation of canine femoral neck fractures. CLINICAL RELEVANCE: To demonstrate the potential stability and reliability of fully threaded headless cannulated screws.
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Wheels have been commonly used for locomotion in mobile robots and transportation systems because of their simple structure and energy efficiency. However, the performance of wheels in overcoming obstacles is limited compared with their advantages in driving on normal flat ground. Here, we present a variable-stiffness wheel inspired by the surface tension of a liquid droplet. In a liquid droplet, as the cohesive force of the outermost liquid molecules increases, the net force pulling the liquid molecules inward also increases. This leads to high surface tension, resulting in the liquid droplet reverting to a circular shape from its distorted shape induced by gravitational forces. Similarly, the shape and stiffness of a wheel were controlled by changing the traction force at the outermost smart chain block. As the tension of the wire spokes connected to each chain block increased, the wheel characteristics reflected those of a general circular-rigid wheel, which has an advantage in high-speed locomotion on normal flat ground. Conversely, the modulus of the wheel decreased as the tension of the wire spoke decreased, and the wheel was easily deformed according to the shape of obstacles. This makes the wheel suitable for overcoming obstacles without requiring complex control or sensing systems. On the basis of this mechanism, a wheel was applied to a two-wheeled wheelchair system weighing 120 kilograms, and the state transition between a circular high-modulus state and a deformable low-modulus state was realized in real time when the wheelchair was driven in an outdoor environment.
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PURPOSE: Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys and has proven efficacy and safety in patients with diabetic kidney disease. We aimed to evaluate the 1-year efficacy of dulaglutide in patients with diabetic kidney disease who have used the drug for more than 1 year. METHODS: This retrospective, observational study comprised 131 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 who had received dulaglutide for more than one year between June 2016 and May 2023. The primary outcome measures were changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight from baseline to the 12-month follow-up, with assessments performed at six-month intervals. Subgroup analyses were conducted based on age, sex, baseline body mass index, FPG, and HbA1c, and insulin administration at baseline and last follow-up. FINDINGS: The mean age was 60.0 ± 10.2 years, and 61.1% of the participants were males. Baseline HbA1c, FPG, and body weight were 9.1% (76.0 mmol/mol), 186.8 mg/dL, and 79.3 kg, respectively. Dulaglutide significantly reduced HbA1c, FPG, and body weight from baseline to the 12-month follow-up (mean ± standard error: -1.2 ± 0.1%, -34.8 ± 6.9 mg/dL, and -2.3 ± 0.5 kg, respectively; P < 0.001). Subgroup analysis revealed significant differences in HbA1c reduction based on baseline HbA1c. IMPLICATIONS: Dulaglutide exhibited sustained glucose-lowering and weight-reduction effects during the initial 1 year of treatment in patients with diabetic kidney disease. Altogether, dulaglutide could serve as a favorable long-term therapeutic option for patients with diabetic kidney disease in real-world clinical settings.
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We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.
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Carcinoma Hepatocelular , Estilo de Vida , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , República da Coreia/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Sistema de Registros , Fumar/efeitos adversos , AdultoRESUMO
Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.
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BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.
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Encefalopatia Hepática , Inibidores da Bomba de Prótons , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Gastrointestinal/tratamento farmacológico , Encefalopatia Hepática/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , FemininoRESUMO
The surface topography of implant tools has indicated an interfacial contact in degradation still being discovered; however, the glossy texture of a tiny magnesium wire is important for absorbable medical devices. This paper investigated the alterations of surface quality by a magnetic abrasive polishing method using a rotational magnetic field-assisted system with input parameters of revolution, abrasive media, magnetic pole, flux density, vibration, and amplitude that could noticeably enhance asperities along a sample. Furthermore, the blood flow simulation is used to analyze flow within blood vessels while maintaining the surface roughness conditions of the guide wire. The results are compared and discussed. Magnetic field simulation is employed to investigate the magnetic field strength in the polishing zone. Scanning Electron Microscopy (SEM) provides visual aids for recognizing the differences between pre-and post-workpieces of magnesium wire. The experimental results reveal that a wire diameter of 0.50 mm predominantly achieves surface morphology from the initial roughness of 0.22 µm to 0.05 µm. The results corroborate that the distribution of blood in the circulatory system was relatively stable. Hence, this study establishes a crucial benchmark for the precision polishing of ultra-thin magnesium wires, which is vital for their use as high-precision biodegradable medical devices.
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Materiais Biocompatíveis , Magnésio , Propriedades de Superfície , Microscopia Eletrônica de Varredura , CatéteresRESUMO
OBJECTIVE: We explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) risk. DESIGN: From nationwide health screening data, we identified 9 775 066 adults aged 20-79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death. RESULTS: The prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition. CONCLUSION: Over one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.
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Isquemia Encefálica , Doenças Cardiovasculares , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Acidente Vascular Cerebral , Adulto , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Pré-Escolar , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/induzido quimicamente , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Antígenos E da Hepatite B , DNA Viral , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/induzido quimicamente , Estudos de Coortes , Infecção Persistente , Antivirais/uso terapêutico , Fatores de Risco , Vírus da Hepatite B/genéticaRESUMO
BACKGROUNDS: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Prognóstico , Hepatectomia , Pontuação de PropensãoRESUMO
BACKGROUND: This study investigated the trends of nontuberculous mycobacterial (NTM) isolates and the minimal inhibitory concentrations (MIC) of antimicrobial agents in Korea. METHODS: Data from 2013 to 2019 were collected from 69 medical institutions through 12 branches of the Korean Institute of Tuberculosis. NTM identification was conducted using the Advansure Mycobacteria Genoblot assay. The MIC of antibiotics against NTM species were measured using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: Over seven years, 86,194 NTM identifications were requested, with an annual increase from 8034 in 2013-17,229 in 2019. The most frequently identified NTM species were M. intracellulare (33,467; 47.3%) and M. avium (19,818; 27.2%), followed by M. abscessus (6858; 9.4%) and M. massiliense (3156; 4.3%). Regarding the antimicrobial agents, imipenem exhibited the greatest difference in MIC between M. intracellulare and M. avium, whereas clarithromycin showed the most significant difference between M. abscessus and M. massiliense. No notable changes were observed in the annual MIC distribution of most antibacterial agents, except for clarithromycin in M. abscessus. CONCLUSIONS: The prevalence of NTM in Korea is gradually increasing, and follow-up studies on NTM isolates identified as the causative agents of infection are needed.
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Anti-Infecciosos , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Claritromicina/farmacologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , República da Coreia/epidemiologiaRESUMO
The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.
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In this study, optoelectronic synaptic transistors based on indium-gallium-zinc oxide (IGZO) with a casein electrolyte-based electric double layer (EDL) were examined. The casein electrolyte played a crucial role in modulating synaptic plasticity through an internal proton-induced EDL effect. Thus, important synaptic behaviors, such as excitatory post-synaptic current, paired-pulse facilitation, and spike rate-dependent and spike number-dependent plasticity, were successfully implemented by utilizing the persistent photoconductivity effect of the IGZO channel stimulated by light. The synergy between the light stimulation and the EDL effect allowed the effective modulation of synaptic plasticity, enabling the control of memory levels, including the conversion of short-term memory to long-term memory. Furthermore, a Modified National Institute of Standards and Technology digit recognition simulation was performed using a three-layer artificial neural network model, achieving a high recognition rate of 90.5%. These results demonstrated a high application potential of the proposed optoelectronic synaptic transistors in neuromorphic visual systems.
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Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTß, IL-22R, RANK, LTßR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.
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NF-kappa B , Timócitos , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Citoproteção , Timo , Células Epiteliais , Colágeno/metabolismo , Expressão Gênica , Proliferação de Células , Ciclofosfamida/efeitos adversosRESUMO
Purpose: The diagnostic value of preoperative hematological changes in endometrial cancer (EC) remains unclear. This study aimed to assess the role of preoperative hematologic parameters in differentiating EC from benign endometrial lesions in postmenopausal women with endometrial masses. Methods: Preoperative laboratory variables were retrospectively reviewed in patients with malignant or benign endometrial lesions, and the significance of intergroup differences was assessed. Receiver operating characteristic curves were used to analyze the optimal cut-off values for each variable. Logistic regression analysis was used to identify the variables predicting the presence of endometrial malignancy. Results: Preoperative laboratory variables of 176 patients (84 EC and 92 benign lesions) with endometrial masses were analyzed. Significant differences were observed between malignant and benign lesions in terms of WBC count, ANC, MCV, MPV, PDW, CA125, NLR, PMR, LMR, and SII (P < 0.05). Multivariate analyses showed that a high WBC count, high ANC, low MCV, low MPV, low PDW, high CA125, high NLR, high PMR, high LMR, and high SII independently predicted the presence of endometrial malignancy. Conclusion: The combination markers, MPV+PDW+NLR, had good discriminatory power for the presence of malignancy (AUC 0.797). Our results suggest that hematologic markers could be useful for the differentiation of malignant and benign endometrial lesions.
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Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered Tm4sf5 mice fed ad libitum normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and Tm4sf5-/- knockout mice, hepatocyte-specific TM4SF5-overexpressing Alb-TGTm4sf5-Flag (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal ß-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal ß-oxidation, mTOR, and autophagy.
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In this study, we enhance the synaptic behavior of artificial synaptic transistors by utilizing nanowire (NW)-type polysilicon channel structures. The high surface-to-volume ratio of the NW channels enables efficient modulation of the channel conductance, which is interpreted as the synaptic weight. As a result, NW-type synaptic transistors exhibit a larger hysteresis window compared to film-type synaptic transistors, even within the same gate voltage sweeping range. Moreover, NW-type synaptic transistors demonstrate superior short-term facilitation and long-term memory transition compared with film-type ones, as evidenced by the measured paired-pulse facilitation and excitatory post-synaptic current characteristics at varying frequencies and pulse numbers. Additionally, we observed gradual potentiation/depression characteristics, making these artificial synapses applicable to artificial neural networks. Furthermore, the NW-type synaptic transistors exhibit improved Modified National Institute of Standards and Technology pattern recognition rate of 91.2%. In conclusion, NW structure channels are expected to be a promising technology for next-generation artificial intelligence (AI) semiconductors, and the integration of NW structure channels has significant potential to advance AI semiconductor technology.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD can result in various complications. Owing to the lack of effective pharmacological therapies, lifestyle modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy. Because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR) consists of alternating phases of extreme energy restriction and regular energy intake. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice; those are a lack of appropriate assessment tools, different cutoffs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial. The trial will evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (Nonalcoholic Fatty Liver Disease-Intermittent Calorie Restriction [FLICR]). METHODS: We will include adult (19-75 years) NAFLD patients. NAFLD will be diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥ 25 kg/m2 [n = 36] and non-obese group: BMI < 25 kg/m2 [n = 36]). Participants will be followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks. DISCUSSION: This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy. TRIAL REGISTRATION: This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health. CLINICALTRIALS: gov NCT05309642. Registered on April 4, 2022.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/terapia , Restrição Calórica , Estudos Prospectivos , Padrão de Cuidado , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND/AIMS: To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. METHODS: This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. RESULTS: Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67, P<0.001; women: OR=1.59, 95% CI 1.40-1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02-1.50, P=0,028; women: OR=1.23, 95% CI 1.04-1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43-4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44-4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53-6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51-6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. CONCLUSION: In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.