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Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.
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Conectoma , Perda Auditiva Unilateral , Humanos , Feminino , Masculino , Perda Auditiva Unilateral/diagnóstico por imagem , Perda Auditiva Unilateral/fisiopatologia , Pessoa de Meia-Idade , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/patologia , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/fisiopatologia , Neuroma Acústico/patologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Idoso , Imagem de Tensor de Difusão , Lateralidade Funcional/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologiaRESUMO
BACKGROUND: Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta-analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model. METHODS: This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta-analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random-effects model. Subgroup analyses accounted for AP severity and nutrition support initiation. RESULTS: A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n = 1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR = 0.34; 95%CI: 0.16-0.73) and nasojejunal (NJ) feeding (RR = 0.46; 95%CI: 0.25-0.84) in comparison to nil per os. Similarly, NG (RR = 0.45; 95%CI: 0.24-0.83) and NJ (RR = 0.60; 95%CI: 0.40-0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48 h, particularly in severe cases. CONCLUSION: For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24 h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP.
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Nutrição Enteral , Metanálise em Rede , Apoio Nutricional , Pancreatite , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Pancreatite/mortalidade , Pancreatite/dietoterapia , Nutrição Enteral/métodos , Apoio Nutricional/métodos , Intubação Gastrointestinal , Doença AgudaRESUMO
BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (Pâ=â0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.
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Farmacorresistência Viral , Infecções por HIV , HIV-1 , Carga Viral , Humanos , Taiwan/epidemiologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Farmacorresistência Viral/genética , Feminino , Adulto , Pessoa de Meia-Idade , Mutação , Genótipo , Inibidores de Integrase de HIV/uso terapêutico , Inibidores de Integrase de HIV/farmacologia , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Adulto Jovem , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , RNA Viral/genéticaRESUMO
BACKGROUND: Taiwan became an aged society in March 2018, and it is expected to become a super-aged society by 2025. The trend of increasing proportions of older adults continuing to work is inevitable. However, few studies have been conducted to investigate the effects of employment on the mental health of older adults. Therefore, we longitudinally explored the relationship between employment status and depressive symptoms in Taiwanese older adults. METHODS: The study included 5,131 individuals aged 50 and above, of which 55.6% were men, who had participated in the national-wide Taiwan Longitudinal Study of Aging in 1996, 1999, 2003, and 2007. Of them, 1,091 older adults had completed all four surveys. Depressive symptoms were assessed using the Center for Epidemiological Studies of Depression scale; the total score on this scale ranges from 0 to 30. Employment status was assessed during each survey wave. Logistic regression was performed using a cross-sectional design. The effects of unemployment on depressive symptoms were analyzed using a generalized estimating equation model with a repeated measures design. RESULTS: In each survey wave, employed older adults exhibited better mental health than did unemployed ones. After adjustments for potential confounders, unemployment was found to exert a significant adverse effect on depressive symptoms. The repeated measures analysis revealed that employment protected against depressive symptoms, as noted in the subsequent surveys conducted after 3 to 4 years (aOR [95% CI] = 0.679 [0.465-0.989]). CONCLUSION: Employment may reduce the risk of depressive symptoms in community-dwelling older adults in Taiwan.
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Depressão , Emprego , Humanos , Masculino , Taiwan/epidemiologia , Feminino , Idoso , Emprego/psicologia , Depressão/epidemiologia , Depressão/psicologia , Depressão/diagnóstico , Estudos Prospectivos , Pessoa de Meia-Idade , Estudos Longitudinais , Estudos Transversais , Estudos de Coortes , Idoso de 80 Anos ou maisRESUMO
This research is dedicated to developing an automatic landing system for shipborne unmanned aerial vehicles (UAVs) based on wireless precise positioning technology. The application scenario is practical for specific challenging and complex environmental conditions, such as the Global Positioning System (GPS) being disabled during wartime. The primary objective is to establish a precise and real-time dynamic wireless positioning system, ensuring that the UAV can autonomously land on the shipborne platform without relying on GPS. This work addresses several key aspects, including the implementation of an ultra-wideband (UWB) circuit module with a specific antenna design and RF front-end chip to enhance wireless signal reception. These modules play a crucial role in achieving accurate positioning, mitigating the limitations caused by GPS inaccuracy, thereby enhancing the overall performance and reception range of the system. Additionally, the study develops a wireless positioning algorithm to validate the effectiveness of automatic landing on the shipborne platform. The platform's wave vibration is considered to provide a realistic landing system for shipborne UAVs. The UWB modules are practically installed on the shipborne platform, and the UAV and the autonomous three-body vessel are tested simultaneously in the outdoor open water space to verify the functionality, precision, and adaptability of the proposed UAV landing system. Results demonstrate that the UAV can autonomously fly from 200 m, approach, and automatically land on the moving shipborne platform without relying on GPS.
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BACKGROUND: We aimed to investigate global variations in incidence and mortality and their associations to possible risk factors for prompt cancer prevention and control. METHODS: Estimates of incidence and mortality rates for six types of head and neck cancer were extracted from the GLOBOCAN 2020 database. Summary exposure values for level-two risk factors were obtained from the Global Burden of Disease. Regression models adjusting for the human development index (HDI) were constructed to analyze correlations between age-standardized rates and risk factors. RESULTS: The incidence rates of multiple types of head and neck cancer were positively associated with HDI tiers. In addition to tobacco use and alcohol consumption, high systolic blood pressure was associated with the incidence and mortality of cancers of the salivary glands, oropharynx, hypopharynx, and larynx. Dietary risks were linked to cancers of the oropharynx, nasopharynx, and hypopharynx. CONCLUSIONS: This comprehensive analysis provides valuable insights into possible risk factors for head and neck cancer.
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Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/epidemiologia , Fatores de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Uso de Tabaco , IncidênciaRESUMO
Air pollution is deemed a human carcinogen and can be linked to certain types of cancer other than lung cancer. The present study aimed to investigate the pollutant-cancer associations in a population-level cohort. We obtained the annual age-standardized incidence rates of 28 different cancer types between 2015 to 2019 from the Taiwan Cancer Registry. Outdoor concentrations of particulate matter with a diameter of 10 µm or less (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ground-level ozone (O3), and carbon monoxide (CO) between 2001 to 2010 were retrieved from the Taiwan Air Quality Monitoring Network. Weighted quantile sum (WQS) regression models were used to determine the combined effects of five air pollutants on the relationship to cancer incidence rates after controlling for sex ratio, age, average disposable income per household, overweight/obesity prevalence, current smoking rate, and drinking rate. Trend analyses showed that NO2 and CO concentrations tended to decrease, while SO2 concentrations increased in some counties. WQS regression analyses revealed significantly positive correlations between air pollutants and liver cancer, lung and tracheal cancer, colorectal cancer, thyroid cancer, kidney cancer, and small intestine cancer. Altogether, the results from this ecological study unravel that exposure to ambient air pollution is associated with the incidence of several non-lung cancer types.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias , Material Particulado , Taiwan/epidemiologia , Humanos , Neoplasias/epidemiologia , Neoplasias/induzido quimicamente , Poluentes Atmosféricos/análise , Incidência , Material Particulado/análise , Dióxido de Enxofre/análise , Masculino , Feminino , Exposição Ambiental/estatística & dados numéricos , Dióxido de Nitrogênio/análiseRESUMO
OBJECTIVE: Radiofrequency ablation is a viable option in the treatment of benign thyroid nodules. Some reports suggest that thermal ablation may also be safe for the management of low-risk thyroid cancer. In this study, we applied transient heat treatment to thyroid cancer cells to mimic clinical scenarios in which insufficient ablation leads to incomplete eradication of thyroid cancer. METHODS: Differentiated thyroid cancer cell lines B-CPAP, TPC-1, and FTC-133 were subjected to heat treatment at different temperatures for 10 min. Effects on cell growth, clonogenicity, wound healing assay, and Transwell invasion were determined. RESULTS: Heat treatment at 45°C or higher reduced cell growth, whereas viability of thyroid cancer cells was not changed after heat treatment at 37, 40, or 42°C. Heat treatment at 40°C increased the number of colony formations by 16% to 39%. Additionally, transient heat treatment at 40°C resulted in a 1.75-fold to 2.56-fold higher migratory activity than treatment at 37°C. Invasive capacity was increased after heat treatment, ranging from 115% to 126%. Expression of several epithelial-mesenchymal transition markers, including ZEB1, N-cadherin, and MMP2, was upregulated following heat treatment at 40°C. CONCLUSION: We for the first time demonstrate that sublethal thermal stress may increase clonogenicity, migration, and invasion of thyroid cancer cells.
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Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Ciclo Celular , Movimento Celular , Transição Epitelial-MesenquimalRESUMO
In primary hyperparathyroidism, postoperative hypocalcemia can be exacerbated by magnesium deficiency. However, the significance of magnesium homeostasis in surgery for secondary hyperparathyroidism is unknown. In this study, 268 consecutive adult patients on renal replacement therapy who underwent parathyroidectomy for secondary hyperparathyroidism were included for analysis. We found that about one fifth presented with hypomagnesemia (5.6%) or hypermagnesemia (14.6%). Hypomagnesemia was associated with lower calcium levels and longer postoperative hospital stays. Hypermagnesemia was associated with higher calcium-phosphorus products and lower parathyroid hormone levels. In multivariate analysis, patient age, alkaline phosphatase, and osteocalcin were independent predictors of prolonged stay after parathyroidectomy. There was a positive correlation between serum magnesium levels and severity of itching in these patients. Calcium-phosphorus products and serum magnesium levels were independently associated with pruritus. In conclusion, magnesium abnormalities play a minor role in hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism. Patients with higher serum magnesium levels had greater severity of pruritus.
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Hiperparatireoidismo Secundário , Magnésio , Paratireoidectomia , Diálise Renal , Humanos , Magnésio/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Idoso , Adulto , Prurido/etiologia , Prurido/sangue , Cálcio/sangue , Hipocalcemia/etiologia , Hipocalcemia/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Tempo de Internação , Estudos RetrospectivosRESUMO
INTRODUCTION: The cost-effectiveness of adding bevacizumab biosimilar with or without chemotherapy (CT) and drug wastage in treating platinum-resistant recurrent ovarian cancer (PRrOC) was assessed. METHODS: A three-state partitioned-survival model to compare the clinical and economic outcomes in the treatment of patients with PRrOC from a Taiwan healthcare prospective, extrapolated to two years based on data obtained from the JGOG3023 clinical trial. The primary outcomes of the model were incremental cost-effectiveness ratios (ICERs). RESULTS: In the base-case scenario, using vials of bevacizumab biosimilar (Bevbiol) plus chemotherapy, the ICER was (new Taiwan dollar) NT$ 4,555,878 per QALY gained. The incremental cost savings of an incremental 2.02 QALYs were NT$ 1,605,828 if weight-based Bevbiol plus chemotherapy were used, but the ICER remained high at the willingness-to-pay (WTP) threshold. If the cost of Bevbiol were reduced to 50% per vial, adding it to CT would be cost-effective at an acceptable WTP threshold of NTD 2,994,200, with an ICER of NT$ 2,975,484. CONCLUSIONS: Bevacizumab biosimilars in mg/kg dosage form with chemotherapy are still not cost-effective in Taiwan, but using weight-based dosing will reduce drug waste and save treatment costs.
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Medicamentos Biossimilares , Neoplasias Ovarianas , Humanos , Feminino , Bevacizumab/uso terapêutico , Análise Custo-Benefício , Estudos Prospectivos , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.
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The use of virus-neutralizing (VN) and nonstructural protein (NSP) antibody tests in a serosurveillance program for foot-and-mouth disease (FMD) can identify pig herds that are adequately vaccinated, with a high percentage of pigs with VN positive antibody titers; these tests can also help identify pigs with NSP-positivity that have previously been or are currently infected even in vaccinated herds. To identify infected herds and manage infection, the combination of VN and NSP antibody tests was used in Taiwan's serosurveillance program implemented simultaneously with the compulsory FMD vaccination program. The result was the eradication of FMD: Taiwan was recognized by the World Organization for Animal Health as an FMD-free country without vaccination in 2020. Evaluation of the compulsory vaccination program incorporated in the FMD control program in Taiwan revealed that the vaccine quality was satisfactory and the vaccination program was effective during the period of compulsory vaccination (2010-2017). Sound immunological coverage was achieved, with 89.1% of pigs having VN antibody titers exceeding 1:16 in 2016. This level of immunological coverage would be expected to substantially reduce or prevent FMD transmission, which was borne out by the results of the NSP tests. We identified farms having positive NSP reactors (very low annual prevalence) before the cessation of FMD vaccination in July 2018; however, detailed serological and clinical investigations of pigs of all ages in suspect herds demonstrated that no farms were harboring infected animals after the second half of 2013. Thus, the results revealed no evidence of FMD circulation in the field, and Taiwan regained FMD-free status.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus da Febre Aftosa , Febre Aftosa , Doenças dos Suínos , Proteínas não Estruturais Virais , Animais , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Taiwan/epidemiologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Proteínas não Estruturais Virais/imunologia , Estudos Soroepidemiológicos , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Vírus da Febre Aftosa/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinação/veterináriaRESUMO
The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death-ligand 1 (PD-L1) and hepatocyte growth factor (HGF)-engineered mesenchymal stem cell-derived exosomes (EXO-PD-L1-HGF) in enhancing neurological recovery post-stroke. EXO-PD-L1-HGF, which efficiently endocytosed into target cells, significantly diminishes the H2O2-induced neurotoxicity and increased the antiapoptotic proteins in vitro. EXO-PD-L1-HGF attenuates inflammation by inhibiting T-cell proliferation and increasing the number of CD8+CD122+IL-10+ regulatory T cells. Intravenous injection of EXO-PD-L1-HGF could target stromal cell-derived factor-1α (SDF-1α+) cells over the peri-infarcted area of the ischemic brain through CXCR4 upregulation and accumulation in neuroglial cells post-stroke. EXO-PD-L1-HGF facilitates endogenous nestin+ neural progenitor cell (NPC)-induced neurogenesis via STAT3-FOXO3 signaling cascade, which plays a pivotal role in cell survival and neuroprotection, thereby mitigating infarct size and enhancing neurological recovery in a murine stroke model. Moreover, increasing populations of the immune-regulatory CD19+IL-10+ and CD8+CD122+IL-10+ cells, together with reducing populations of proinflammatory cells, created an anti-inflammatory microenvironment in the ischemic brain. Thus, innovative approaches employing EXO-PD-L1-HGF intervention, which targets SDF-1α+ expression, modulates the immune system, and enhances the activation of resident nestin+ NPCs, might significantly alter the brain microenvironment and create a niche conducive to inducing neuroplastic regeneration post-stroke.
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BACKGROUND AND OBJECTIVES: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety. METHODS: We used a quasi-experimental design and selected 2 adult wards with similar properties as the experimental and comparison groups by convenience sampling. Data collection was from December 1, 2021, to June 30, 2022, at a teaching hospital in central Taiwan. Team members of the ward performing huddles formed the experimental group, and they participated 2 times per week in 15-minute huddles from 8:15 to 8:30 am for a total of 4 weeks. The comparison group adopted the routine team care process. Both groups completed the Safety Attitudes Questionnaire during the pre- and post-tests of the study. RESULTS: The experimental group scored significantly higher in the post-test than in the pre-test in all aspects of safety attitudes, with the exception of stress recognition. These improved aspects were teamwork climate (76.47 ± 15.90 vs 83.29 ± 13.52, P < .001), safety climate (75.94 ± 16.14 vs 82.81 ± 13.74, P < .001), job satisfaction (74.34 ± 20.22 vs 84.40 ± 17.22, P <.001), perceptions of management (78.02 ± 19.99 vs 85.51 ± 15.97, P < .001), and working conditions (78.85 ± 17.87 vs 86.81 ± 14.74, P < .001). CONCLUSION: Through the huddles, clinical team members improved their understanding of different aspects of safety attitudes. Such a study provided ward units with real-time improvement and adjustment in terms of patient safety during their medical work processes with better patient safety.
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The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1ß and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1ß, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1ß and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.
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Aminobutiratos , Compostos de Bifenilo , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamassomos , Macrófagos , Mitocôndrias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Valsartana , Animais , Camundongos , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/farmacologia , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Combinação de Medicamentos , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Valsartana/farmacologia , MasculinoRESUMO
Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P < 0.001) and longer hospitalization duration (median [IQR], 20 [14-30] days vs 3 [2-8] days; P < 0.001). After discharge, repeat revascularization, acute coronary syndrome, and repeat hospitalization all occurred more frequently in the percutaneous coronary intervention with drug-eluting stent group. Importantly, with a median follow-up of 2.8 years, coronary artery bypass grafting was significantly associated with a higher risk of all-cause overall mortality (adjusted HR, 1.19; 95% CI, 1.05-1.35; P = 0.006) in the multivariable Cox proportional hazard model. Sensitivity and subgroup analyses yielded consistent results. Limitations: This was an observational study with mainly Asian ethnicity. Conclusions: Percutaneous coronary intervention with drug-eluting stent may be associated with better survival than coronary artery bypass grafting in patients receiving dialysis. Future studies are warranted to confirm this finding.
Although coronary artery bypass grafting offers better long-term survival in the general population than percutaneous coronary intervention with drug-eluting stent, patients receiving dialysis may be too frail to tolerate the increased perioperative mortality risk of coronary artery bypass grafting. In this retrospective study in a national cohort of patients receiving dialysis from Taiwan, percutaneous coronary intervention with drug-eluting stent is associated with lower in-hospital mortality and better long-term survival when compared with coronary artery bypass grafting. Subsequent acute coronary syndrome, repeat revascularization, and rehospitalization were noted more frequently in the percutaneous coronary intervention with drug-eluting stent group. These findings may suggest percutaneous coronary intervention with drug-eluting stent as a safe revascularization strategy for patients receiving dialysis.
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Several ecological studies suggest that ambient air pollution is associated with the occurrence of thyroid cancer. In this study, we used certified diesel particulate matter as a proxy for fine particulate matter. Human thyroid cancer cell lines 8505C and TPC-1 were incubated with different concentrations of NIST1650b for 5 days and subjected to functional assays. We found that NIST1650b treatment did not affect short-term cell growth but reduced colony formation at high concentrations. Notably, NIST1650b-treated cells showed altered morphology toward cluster coalescence following treatment. Wound healing assays revealed that leading-edge cells formed protruding tips while maintaining cell-cell adhesion, and a significantly higher ratio of wound closure following treatment at 10 µg/mL was seen in both cell lines. A weak stimulatory effect on transwell cell migration was observed in 8505C cells. Taken together, our results suggest that fine particulate matter induced a coherent phenotype accompanied by augmented collective cell migration in thyroid cancer cells.