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BACKGROUND: Early palliative care (EPC) benefits some cancers, but its clinical outcomes differ depending on patients' racial and ethnic disparities, and customs. To determine whether EPC improves symptoms, emotional distress, and quality of life among Taiwanese patients with early or advanced-stage head and neck cancer (HNC). METHODS: Based on participants' pathological stages, they were categorized as having early and advanced-stage HNC. Those willing and unwilling to undergo EPC were assigned to the EPC and standard groups, respectively. Their daily cancer-related symptoms were assessed using the Distress Thermometer (DT) and MD Anderson Symptom Inventory (MDASI), whose scores' concurrent validity was evaluated using the European Organization for Research and Treatment of Core Quality of Life (EORTC-QLQ-C30) and Head and Neck 35 (EORTC-QLQ-H&N35) questionnaires. RESULTS: Patients (n = 93) diagnosed with HNC at Taiwan's Chia-Yi Christian Hospital from November 2020 to October 2022 were recruited. The patients voluntarily split into two groups: EPC groups and standard groups (23 and 11 in early-stage; 46 and 13 in advanced-stage, respectively). DT assessment showed significant emotional distress improvements for all patients with HNC who received EPC. The EORTC-QLQ-C30 questionnaire indicated that, compared to standard interventions, EPC groups significantly improved the quality of life and some symptoms for both early and advanced-stage HNC patients. However, the EORTC-QLQ-H&N35 questionnaire found no significant difference between the two groups. Furthermore, advanced-stage patients' anticancer treatment completion rates with EPC and standard interventions were 95.35% and 75%, respectively. CONCLUSION: EPC improves symptoms, emotional distress, quality of life, and treatment completion rates in Taiwanese patients with early or advanced-stage HNC. Nonetheless, further extensive clinical studies are required for validation.
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Neoplasias de Cabeza y Cuello , Cuidados Paliativos , Calidad de Vida , Humanos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/psicología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Taiwán , Adulto , Encuestas y CuestionariosRESUMEN
The early detection of esophageal cancer presents a substantial difficulty, which contributes to its status as a primary cause of cancer-related fatalities. This study used You Only Look Once (YOLO) frameworks, specifically YOLOv5 and YOLOv8, to predict and detect early-stage EC by using a dataset sourced from the Division of Gastroenterology and Hepatology, Ditmanson Medical Foundation, Chia-Yi Christian Hospital. The dataset comprised 2741 white-light images (WLI) and 2741 hyperspectral narrowband images (HSI-NBI). They were divided into 60% training, 20% validation, and 20% test sets to facilitate robust detection. The images were produced using a conversion method called the spectrum-aided vision enhancer (SAVE). This algorithm can transform a WLI into an NBI without requiring a spectrometer or spectral head. The main goal was to identify dysplasia and squamous cell carcinoma (SCC). The model's performance was evaluated using five essential metrics: precision, recall, F1-score, mAP, and the confusion matrix. The experimental results demonstrated that the HSI model exhibited improved learning capabilities for SCC characteristics compared with the original RGB images. Within the YOLO framework, YOLOv5 outperformed YOLOv8, indicating that YOLOv5's design possessed superior feature-learning skills. The YOLOv5 model, when used in conjunction with HSI-NBI, demonstrated the best performance. It achieved a precision rate of 85.1% (CI95: 83.2-87.0%, p < 0.01) in diagnosing SCC and an F1-score of 52.5% (CI95: 50.1-54.9%, p < 0.01) in detecting dysplasia. The results of these figures were much better than those of YOLOv8. YOLOv8 achieved a precision rate of 81.7% (CI95: 79.6-83.8%, p < 0.01) and an F1-score of 49.4% (CI95: 47.0-51.8%, p < 0.05). The YOLOv5 model with HSI demonstrated greater performance than other models in multiple scenarios. This difference was statistically significant, suggesting that the YOLOv5 model with HSI significantly improved detection capabilities.
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Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which are harmful to cells at high levels. Oxidative stress caused by ROS accumulation has been associated with an increased risk of cancer, and cardiovascular and liver diseases. Glutathione (GSH) is an abundant cellular antioxidant that is primarily synthesized in the cytoplasm and delivered to the mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within the mitochondria. A long-term imbalance in the ratio of mitochondrial ROS to mGSH can cause cell dysfunction, apoptosis, necroptosis, and ferroptosis, which may lead to disease. This study aimed to review the physiological functions, anabolism, variations in organ tissue accumulation, and delivery of GSH to the mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide (GSSG) ratio, programmed cell death, and ferroptosis. We also discuss diseases caused by mGSH deficiency and related therapeutics.
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Glutatión , Mitocondrias , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Homeostasis , Oxidación-ReducciónAsunto(s)
Adenoma , Apéndice , Resección Endoscópica de la Mucosa , Humanos , Tracción , Endoscopios , Adenoma/cirugía , Resultado del TratamientoRESUMEN
Early detection of esophageal cancer through endoscopic imaging is pivotal for effective treatment. However, the intricacies of endoscopic diagnosis, contingent on the physician's expertise, pose challenges. Esophageal cancer features often manifest ambiguously, leading to potential confusions with other inflammatory esophageal conditions, thereby complicating diagnostic accuracy. In recent times, computer-aided diagnosis has emerged as a promising solution in medical imaging, particularly within the domain of endoscopy. Nonetheless, contemporary AI-based diagnostic models heavily rely on voluminous data sources, limiting their applicability, especially in scenarios with scarce datasets. To address this limitation, our study introduces novel data training strategies based on transfer learning, tailored to optimize performance with limited data. Additionally, we propose a hybrid model integrating EfficientNet and Vision Transformer networks to enhance prediction accuracy. Conducting rigorous evaluations on a carefully curated dataset comprising 1002 endoscopic images (comprising 650 white-light images and 352 narrow-band images), our model achieved exceptional outcomes. Our combined model achieved an accuracy of 96.32%, precision of 96.44%, recall of 95.70%, and f1-score of 96.04%, surpassing state-of-the-art models and individual components, substantiating its potential for precise medical image classification. The AI-based medical image prediction platform presents several advantageous characteristics, encompassing superior prediction accuracy, a compact model size, and adaptability to low-data scenarios. This research heralds a significant stride in the advancement of computer-aided endoscopic imaging for improved esophageal cancer diagnosis.
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Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.
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COVID-19 , Enfermedades Mitocondriales , Humanos , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , InflamaciónRESUMEN
Heavy metal pollution of water is a burning issue of today's world. Among several strategies involved for heavy metal remediation purpose, biomineralization has shown great potential. Of late, research has been focused on developing effective mineral adsorbents with reduced time and cost consumption. In this present paper, the Biologically-Induced Synthetic Manganese Carbonate Precipitate (BISMCP) was produced based on the biologically-induced mineralization method, employing Sporosarcina pasteurii in aqueous solutions containing urea and MnCl2. The prepared adsorbent was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), SEM-energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD) and BET surface area analyzer. EDX analysis showed the elements in the crystal BISMCP were Mn, C, and O. XRD result of BISMCP determined the crystal structure, which is close to rhodochrosite (MnCO3). Spectral peaks of FTIR at 1641.79 cm-1 confirmed the appearance of C[bond, double bond]O binding, with strong stretching of CO32- in Amide I. From the six kinds of BISMCP produced, sample MCP-6 has the higher specific surface area by BET analysis at 109.01 m2/g, with pore size at 8.76 nm and higher pore volume at 0.178 cm3/g. These specifications will be suitable as an adsorbent for heavy metal removal by adsorption process. This study presents a preliminary analysis of the possibility of BISMCP for heavy metals adsorption using ICP multi-element standard solution XIII (As, Cr, Cd, Cu, Ni, and Zn). BISMCP formed from 0.1 MnCl2 and 30 ml of bacteria volume (MCP-6) produced a better adsorbent material than others concentrations, with the adsorption efficiency of total As at 98.9%, Cr at 97.0%, Cu at 94.7%, Cd at 88.3%, Zn at 48.6%, and Ni at 29.5%. Future work could be examined its efficiency adsorbing individual heavy metals.
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Polimetil Metacrilato , Trombosis de la Vena , Humanos , Polimetil Metacrilato/efectos adversos , Tomografía Computarizada Multidetector , Vena Cava Inferior/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Cementos para Huesos/efectos adversos , Ultrasonografía IntervencionalRESUMEN
Mitochondria are an important energy source in skeletal muscle. A main function of mitochondria is the generation of ATP for energy through oxidative phosphorylation (OXPHOS). Mitochondrial defects or abnormalities can lead to muscle disease or multisystem disease. Mitochondrial dysfunction can be caused by defective mitochondrial OXPHOS, mtDNA mutations, Ca2+ imbalances, mitochondrial-related proteins, mitochondrial chaperone proteins, and ultrastructural defects. In addition, an imbalance between mitochondrial fusion and fission, lysosomal dysfunction due to insufficient biosynthesis, and/or defects in mitophagy can result in mitochondrial damage. In this review, we explore the association between impaired mitochondrial function and skeletal muscle disorders. Furthermore, we emphasize the need for more research to determine the specific clinical benefits of mitochondrial therapy in the treatment of skeletal muscle disorders.
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Mitocondrias , Enfermedades Musculares , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Fosforilación Oxidativa , Mitofagia , Dinámicas Mitocondriales , Enfermedades Musculares/metabolismo , Músculo Esquelético/metabolismo , Proteínas Mitocondriales/metabolismo , ADN Mitocondrial/genéticaRESUMEN
In this study, the combination of hyperspectral imaging (HSI) technology and band selection was coupled with color reproduction. The white-light images (WLIs) were simulated as narrow-band endoscopic images (NBIs). As a result, the blood vessel features in the endoscopic image became more noticeable, and the prediction performance was improved. In addition, a single-shot multi-box detector model for predicting the stage and location of esophageal cancer was developed to evaluate the results. A total of 1780 esophageal cancer images, including 845 WLIs and 935 NBIs, were used in this study. The images were divided into three stages based on the pathological features of esophageal cancer: normal, dysplasia, and squamous cell carcinoma. The results showed that the mean average precision (mAP) reached 80% in WLIs, 85% in NBIs, and 84% in HSI images. This study's results showed that HSI has more spectral features than white-light imagery, and it improves accuracy by about 5% and matches the results of NBI predictions.
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Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-ß1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice.
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Benzazepinas , Diabetes Mellitus Experimental , Nefropatías Diabéticas , Histona Demetilasas , Péptidos y Proteínas de Señalización Intercelular , Pirimidinas , Animales , Benzazepinas/farmacología , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrosis , Histona Demetilasas/antagonistas & inhibidores , Inflamación/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Riñón/metabolismo , Ratones , Pirimidinas/farmacología , ARN Mensajero/metabolismoRESUMEN
SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal-lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis.
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COVID-19 , Enfermedades Gastrointestinales , Microbioma Gastrointestinal , COVID-19/complicaciones , Vacunas contra la COVID-19 , Enfermedades Gastrointestinales/etiología , Tracto Gastrointestinal , Humanos , SARS-CoV-2RESUMEN
Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepacivirus , Virus de la Hepatitis B , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , TaiwánRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm with high metastatic potential and poor clinical outcome. Like other solid tumors, PDAC in the early stages is often asymptomatic, and grows very slowly under a distinct acidic pHe (extracellular pH) microenvironment. However, most previous studies have only reported the fate of cancerous cells upon cursory exposure to acidic pHe conditions. Little is known about how solid tumors-such as the lethal PDAC originating within the pancreatic duct-acinar system that secretes alkaline fluids-evolve to withstand and adapt to the prolonged acidotic microenvironmental stress. METHODS: Representative PDAC cells were exposed to various biologically relevant periods of extracellular acidity. The time effects of acidic pHe stress were determined with respect to tumor cell proliferation, phenotypic regulation, autophagic control, metabolic plasticity, mitochondrial network dynamics, and metastatic potentials. RESULTS: Unlike previous short-term analyses, we found that the acidosis-mediated autophagy occurred mainly as an early stress response but not for later adaptation to microenvironmental acidification. Rather, PDAC cells use a distinct and lengthy process of reversible adaptive plasticity centered on the early fast and later slow mitochondrial network dynamics and metabolic adjustment. This regulates their acute responses and chronic adaptations to the acidic pHe microenvironment. A more malignant state with increased migratory and invasive potentials in long-term acidosis-adapted PDAC cells was obtained with key regulatory molecules being closely related to overall patient survival. Finally, the identification of 34 acidic pHe-related genes could be potential targets for the development of diagnosis and treatment against PDAC. CONCLUSIONS: Our study offers a novel mechanism of early rapid response and late reversible adaptation of PDAC cells to the stress of extracellular acidosis. The presence of this distinctive yet slow mode of machinery fills an important knowledge gap in how solid tumor cells sense, respond, reprogram, and ultimately adapt to the persistent microenvironmental acidification.
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Acidosis , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adaptación Fisiológica , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Concentración de Iones de Hidrógeno , Conductos Pancreáticos/metabolismo , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMEN
To identify whether urolithiasis with or without hydronephrosis has an impact on acute kidney injury (AKI) in patients with urinary tract infection (UTI). This study aimed to identify whether urolithiasis with or without hydronephrosis has an impact on AKI in patients with UTI. This retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to April 2019. Of the 1113 participants enrolled, 191 (17.2%) had urolithiasis and 76 (6.8%) had ureteral stone complicated with hydronephrosis. Multivariate logistic regression analysis showed that in UTI patients with urolithiasis, the presence of ureteral stone with concomitant hydronephrosis was an independent risk factor for AKI (odds ratio [OR] 2.299, 95% confidence interval [CI] 1.112-4.755, P = 0.025). In addition, urolithiasis was associated with an increased risk for AKI (OR 2.451, 95% CI 1.369-4.389, P = 0.003) in UTI patients without hydronephrosis. The presence of ureteral stone with hydronephrosis increases the risk for AKI of UTI patients with urolithiasis, and urolithiasis remains a risk factor of AKI in UTI patients without hydronephrosis.
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Lesión Renal Aguda/patología , Hidronefrosis/complicaciones , Cálculos Ureterales/complicaciones , Infecciones Urinarias/fisiopatología , Urolitiasis/complicaciones , Lesión Renal Aguda/etiología , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized data are currently available on MGO levels in colorectal precancerous and cancerous lesions. We collected 40 matched colorectal tumor and peritumor tissues from patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer (IC). MGO levels increased between LGD, HGD, and IC tumor tissues (215.25 ± 39.69, 267.45 ± 100.61, and 587.36 ± 123.19 µg/g protein, respectively; p = 0.014). The MGO levels in peritumor tissue increased and were significantly higher than MGO levels in tumor tissue (197.99 ± 49.40, 738.09 ± 247.87, 933.41 ± 164.83 µg/g protein, respectively; p = 0.002). Tumor tissue MGO levels did not correlate with age, sex, underlying disease, or smoking status. These results suggest that MGO levels fluctuate in progression of CRC and warrants further research into its underlying mechanisms and function in tumor biology.
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses. CASE PRESENTATION: A 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far. CONCLUSIONS: This is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed.
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Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94-0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25-0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15-3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04-2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20-2.45, p = 0.003).
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Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease. The natural history of DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated glomerular filtration rate, and, ultimately, kidney failure. It is known that DKD is associated with metabolic changes caused by hyperglycemia, resulting in glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Hyperglycemia is also known to cause programmed epigenetic modification. However, the detailed mechanisms involved in the onset and progression of DKD remain elusive. In this review, we discuss recent advances regarding the pathogenic mechanisms involved in DKD.
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Nefropatías Diabéticas/fisiopatología , Redes Reguladoras de Genes , Fallo Renal Crónico/etiología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/genética , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/genética , Fallo Renal Crónico/fisiopatologíaRESUMEN
The role of the epithelial-mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-ß1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-ß1 treatment. CSE or TGF-ß1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.