RESUMO
Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or ß (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.
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Acidemia Propiônica , Propionil-Coenzima A Carboxilase , RNA Mensageiro , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , Administração Intravenosa , Relação Dose-Resposta a Droga , Acidemia Propiônica/genética , Acidemia Propiônica/terapia , Propionil-Coenzima A Carboxilase/genética , Propionil-Coenzima A Carboxilase/metabolismo , RNA Mensageiro/administração & dosagem , RNA Mensageiro/efeitos adversos , RNA Mensageiro/genética , RNA Mensageiro/uso terapêuticoRESUMO
Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Proteínas de Transporte , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas dos Microfilamentos , Sirtuínas , Humanos , Acetilação , Actinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Histona Acetiltransferases/metabolismo , Metástase Linfática , Sirtuínas/metabolismoRESUMO
Alveolar epithelial cell (AEC) necroptosis is critical to disrupt the alveolar barrier and provoke acute lung injury (ALI). Here, we define calcitonin gene-related peptide (CGRP), the most abundant endogenous neuropeptide in the lung, as a novel modulator of AEC necroptosis in lipopolysaccharide (LPS)-induced ALI. Upon LPS-induced ALI, overexpression of Cgrp significantly mitigates the inflammatory response, alleviates lung tissue damage, and decreases AEC necroptosis. Similarly, CGRP alleviated AEC necroptosis under the LPS challenge in vitro. Previously, we identified that long optic atrophy 1 (L-OPA1) deficiency mediates mitochondrial fragmentation, leading to AEC necroptosis. In this study, we discovered that CGRP positively regulated mitochondrial fusion through stabilizing L-OPA1. Mechanistically, we elucidate that CGRP activates AMP-activated protein kinase (AMPK). Furthermore, the blockade of AMPK compromised the protective effect of CGRP against AEC necroptosis following the LPS challenge. Our study suggests that CRGP-mediated activation of the AMPK/L-OPA1 axis may have potent therapeutic benefits for patients with ALI or other diseases with necroptosis.
Assuntos
Lesão Pulmonar Aguda , Animais , Masculino , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/tratamento farmacológico , Células Epiteliais Alveolares/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Linhagem Celular , GTP Fosfo-Hidrolases/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Necroptose , Transdução de SinaisRESUMO
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity, mortality, and health care use worldwide with heterogeneous pathogenesis. Mitochondria, the powerhouses of cells responsible for oxidative phosphorylation and energy production, play essential roles in intracellular material metabolism, natural immunity, and cell death regulation. Therefore, it is crucial to address the urgent need for fine-tuning the regulation of mitochondrial quality to combat COPD effectively. Mitochondrial quality control (MQC) mainly refers to the selective removal of damaged or aging mitochondria and the generation of new mitochondria, which involves mitochondrial biogenesis, mitochondrial dynamics, mitophagy, etc. Mounting evidence suggests that mitochondrial dysfunction is a crucial contributor to the development and progression of COPD. This article mainly reviews the effects of MQC on COPD as well as their specific regulatory mechanisms. Finally, the therapeutic approaches of COPD via MQC are also illustrated.
Assuntos
Mitocôndrias , Doença Pulmonar Obstrutiva Crônica , Humanos , Mitocôndrias/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Envelhecimento , MitofagiaRESUMO
BACKGROUND: The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. METHODS: Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway. RESULTS: Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. CONCLUSION: This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.
Assuntos
Asma , Autofagia , Células Epiteliais , Transição Epitelial-Mesenquimal , Proteína Wnt-5a , Humanos , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Asma/metabolismo , Asma/patologia , Asma/genética , Células Epiteliais/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Brônquios/metabolismo , Brônquios/patologia , Masculino , Linhagem Celular , Feminino , Pessoa de Meia-Idade , Transdução de Sinais , AdultoRESUMO
Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.
Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Animais , Humanos , Camundongos , DNA Viral , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Metiltransferases , Proteínas Repressoras/genética , Replicação ViralRESUMO
Antibiotic resistance genes (ARGs) have moved into focus as a critically important response variable in global change biology, given the increasing environmental and human health threat posed by these genes. However, we propose that elevated levels of ARGs should also be considered a factor of global change, not just a response. We provide evidence that elevated levels of ARGs are a global change factor, since this phenomenon is linked to human activity, occurs globally, and affects biota. We explain why ARGs could be considered the global change factor, rather than the organisms containing them; and we highlight the difference between ARGs and the presence of antibiotics, which are not necessarily linked since elevated levels of ARGs are caused by multiple factors. Importantly, shifting the perspective to elevated levels of ARGs as a factor of global change opens new avenues of research, where ARGs can be the experimental treatment. This includes asking questions about how elevated ARG levels interact with other global change factors, or how ARGs influence ecosystem processes, biodiversity or trophic relationships. Global change biology stands to profit from this new framing in terms of capturing more completely the real extent of human impacts on this planet.
Assuntos
Resistência Microbiana a Medicamentos , Humanos , Resistência Microbiana a Medicamentos/genética , Antibacterianos/farmacologia , Mudança Climática , Ecossistema , Atividades HumanasRESUMO
Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor ß (TGF-ß)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-ß/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-ß/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.
Assuntos
Células-Tronco Mesenquimais , Hiperplasia Prostática , Fator de Crescimento Transformador beta , Quinases Associadas a rho , Quinases Associadas a rho/metabolismo , Masculino , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular , Próstata/patologia , Próstata/metabolismo , Movimento Celular , Camundongos , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4â³,4â´-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.
Assuntos
Antibacterianos , Complexos de Coordenação , Cobre , Nitrofuranos , Polímeros , Antibacterianos/química , Antibacterianos/análise , Ligantes , Nitrofuranos/análise , Nitrofuranos/química , Cobre/química , Cobre/análise , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Polímeros/química , Molibdênio/química , Piridinas/química , Estrutura Molecular , Técnicas Eletroquímicas , Modelos MolecularesRESUMO
Herein, SnO2QDs (<10 nm) with small size instead of conventional nanoparticles was employed to modify ZnFe2O4to synthesize porous and heterogeneous SnO2/ZnFe2O4(ZFSQ) composites for gas sensing. By an immersion process combined with calcination treatment, the resultant porous ZFSQ composites with different contents of SnO2QDs were obtained, and their sensing properties were investigated. Compared with bare ZnFe2O4and SnO2QDs, porous ZFSQ composites based-sensors showed much improved sensor response to acetone. For contrast, the sensor performance of ZFSQ composites was also compared with that of ZnFe2O4sphere modified by SnO2nanoparticles with different size. The porous ZFSQ composite with 5 wt% SnO2QDs (ZFSQ-5) showed a better acetone sensing response than that of other ZFSQ composites, and it exhibited a high response value of 110-100 ppm of acetone and a low detection limit of 0.3 ppm at 240 °C. In addition to the rich heterojunctions and porous structure, the size effect of SnO2QDs was other indispensable reasons for the improved sensor performance. Finally, the ZFSQ-5 composite sensor was attempted to be applied for acetone sensing in exhaled breath, suggesting its great potential in monitoring acetone.
RESUMO
Fluorinated liquid crystal monomers (FLCMs) have been suggested as emerging contaminants, raising global concern due to their frequent occurrence, potential toxic effects, and endurance capacity in the environment. However, the environmental fate of the FLCMs remains unknown. To fill this knowledge gap, we investigated the aerobic microbial transformation mechanisms of an important FLCM, 4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3, 5-difluoro-4'-propylbiphenyl (DTMDPB), using an enrichment culture termed as BG1. Our findings revealed that 67.5 ± 2.1% of the initially added DTMDPB was transformed in 10 days under optimal conditions. A total of 14 microbial transformation products obtained due to a series of reactions (e.g., reductive defluorination, ether bond cleavage, demethylation, oxidative hydroxylation and aromatic ring opening, sulfonation, glucuronidation, O-methylation, and thiolation) were identified. Consortium BG1 harbored essential genes that could transform DTMDPB, such as dehalogenation-related genes [e.g., glutathione S-transferase gene (GST), 2-haloacid dehalogenase gene (2-HAD), nrdB, nuoC, and nuoD]; hydroxylating-related genes hcaC, ubiH, and COQ7; aromatic ring opening-related genes ligB and catE; and methyltransferase genes ubiE and ubiG. Two DTMDPB-degrading strains were isolated, which are affiliated with the genus Sphingopyxis and Agromyces. This study provides a novel insight into the microbial transformation of FLCMs. The findings of this study have important implications for the development of bioremediation strategies aimed at addressing sites contaminated with FLCMs.
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Cristais Líquidos , Biodegradação Ambiental , HidroxilaçãoRESUMO
Microplastic pollution, an emerging pollution issue, has become a significant environmental concern globally due to its ubiquitous, persistent, complex, toxic, and ever-increasing nature. As a multifaceted and diverse suite of small plastic particles with different physicochemical properties and associated matters such as absorbed chemicals and microbes, future research on microplastics will need to comprehensively consider their multidimensional attributes. Here, we introduce a novel, conceptual framework of the "microplastome", defined as the entirety of various plastic particles (<5 mm), and their associated matters such as chemicals and microbes, found within a sample and its overall environmental and toxicological impacts. As a novel concept, this paper aims to emphasize and call for a collective quantification and characterization of microplastics and for a more holistic understanding regarding the differences, connections, and effects of microplastics in different biotic and abiotic ecosystem compartments. Deriving from this lens, we present our insights and prospective trajectories for characterization, risk assessment, and source apportionment of microplastics. We hope this new paradigm can guide and propel microplastic research toward a more holistic era and contribute to an informed strategy for combating this globally important environmental pollution issue.
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Microplásticos , Poluentes Químicos da Água , Plásticos/toxicidade , Ecossistema , Estudos Prospectivos , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidadeRESUMO
Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.
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Fungos , Lipopolissacarídeos , Estrutura Molecular , Lipopolissacarídeos/farmacologia , Cristalografia por Raios X , Dicroísmo CircularRESUMO
Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1â³-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.
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Aspergillus , Imunossupressores , Aspergillus/química , Humanos , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Estrutura Molecular , Cristalografia por Raios X , Interleucina-6/metabolismo , Antraquinonas/farmacologia , Antraquinonas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Linfócitos T/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacosRESUMO
Ship ballast water promoting the long-range migration of antibiotic resistance genes (ARGs) has raised a great concern. This study attempted to reveal ARGs profile in ballast water and decipher their hosts and potential risk using metagenomic approaches. In total, 710 subtypes across 26 ARG types were identified among the ballast water samples from 13 ships of 11 countries and regions, and multidrug resistance genes were the most dominant ARGs. The composition of ARGs were obviously different across samples, and only 5% of the ARG subtypes were shared by all samples. Procrustes analysis showed the bacterial community contributed more than the mobile genetic elements (MGEs) in shaping the antibiotic resistome. Further, 79 metagenome-assembled genomes (46 genera belong to four phyla) were identified as ARG hosts, with predominantly affiliated with the Proteobacteria. Notably, potential human pathogens (Alcaligenes, Mycolicibacterium, Rhodococcus and Pseudomonas) were also recognized as the ARG hosts. Above 30% of the ARGs hosts contained the MGEs simultaneously, supporting a pronounced horizontal gene transfer capability. A total of 43 subtypes (six percent of overall ARGs) of ARGs were assessed with high-risk, of which 23 subtypes belonged to risk Rank I (including rsmA, ugd, etc.) and 20 subtypes to the risk Rank II (including aac(6)-I, sul1, etc.). In addition, antibiotic resistance risk index indicated the risk of ARGs in ballast water from choke points of maritime trade routes was significantly higher than that from other regions. Overall, this study offers insights for risk evaluation and management of antibiotic resistance in ballast water.
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Bactérias , Navios , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Metagenômica , Microbiologia da Água , Antibacterianos/farmacologia , Metagenoma , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Resistência Microbiana a Medicamentos/genéticaRESUMO
OBJECTIVE: Endovascular stent therapy (EST) for spontaneous isolated superior mesenteric artery dissection (SISMAD) is gaining popularity, yet the treatment strategy - BMT or EST - remains debatable. METHODS: A meta-analysis examined all randomized trials and observational studies exploring the relative merits and potential risks of EST vs. BMT in treating SISMAD patients. Key outcomes included early and long-term adverse effects, with odds ratios (ORs) and 95% confidence intervals (CI) calculated. A random- or fixed-effects model was selected according to a 50% heterogeneity threshold. RESULTS: 9 observational studies involving a total of 672 SISMAD patients (303 EST), met our selection criteria. We discovered no noteworthy distinctions between the EST group and the BMT group in terms of early symptoms' alleviation, reinterventions, or all-cause mortality. However, patients receiving EST management will be hospitalized longer than those receiving BMT (EST: 13.2 ± 5.1 months vs. BMT: 7.0 ± 2.2 months, P < 0.01). In the long run, EST was found to significantly contribute to a higher rate of complete remodeling (OR: 4.53, CI: 3.01 ~ 6.81, P < 0.01; heterogeneity, I2 = 50%) and a lower incidence of aneurysm formation (OR: 0.19, CI: 0.06 ~ 0.6, P < 0.01; heterogeneity, I2 = 0%) than BMT. However, there are no significant differences between ESTand BMTin terms of all-cause mortality, recurrent syndrome, reintervention, and SMA stenosis or occlusion. CONCLUSION: EST can effectively prevent the formation of aneurysmal dissection and improve SISMAD remodeling. Both EST and BMT are similar in reducing long-term mortality, recurrent symptoms, severe SMA stenosis or occlusion, and the need for reintervention in patients with SISMAD.
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Dissecção de Vasos Sanguíneos , Procedimentos Endovasculares , Artéria Mesentérica Superior , Stents , Humanos , Procedimentos Endovasculares/métodos , Artéria Mesentérica Superior/cirurgia , Resultado do Tratamento , Dissecção de Vasos Sanguíneos/diagnóstico por imagem , Dissecção de Vasos Sanguíneos/mortalidade , Dissecção de Vasos Sanguíneos/cirurgiaRESUMO
BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.
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Hipertensão Pulmonar , Hipóxia , Embolia Pulmonar , Síndromes da Apneia do Sono , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Hipóxia/etiologia , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Idoso , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Doença Crônica , China/epidemiologia , PolissonografiaRESUMO
INTRODUCTION: This study investigated the clinical characteristics of and risk factors for microcystic macular edema (MME) in patients with chronic primary angle-closure glaucoma (CPACG) and primary open-angle glaucoma (POAG). METHODS: This retrospective observational study included 1,588 eyes from 926 glaucoma inpatients and analyzed the patients' basic demographic information, visual field parameters, macular scans, and peripapillary retinal nerve fiber layer thickness. RESULTS: Our findings were that the incidence rate of MME was 3.97% (34/857) in CPACG and 5.88% (43/731) in POAG. MME was predominantly diagnosed at an advanced stage in CPACG (almost 100%) compared to POAG (93.02%). MME was most frequently involved in the inferior (83.12%) quadrant of the peri-macular region in both CPACG and POAG. Risk factors for MME occurrence in CPACG and POAG included lower visual field mean deviation (OR = 1.14, 95%: CI 1.05-1.24, p = 0.003; OR = 1.14, 95% CI: 1.06-1.21, p < 0.001) and younger age (OR = 0.92, 95% CI: 0.88-0.96, p < 0.001; OR = 0.96, 95% CI: 0.93-0.99, p = 0.003), while female sex (OR = 0.30, 95% CI: 0.11-0.84, p = 0.022) reduced the MME occurrence in POAG. CONCLUSION: MME could develop in both CPACG and POAG patients, occurring earlier in POAG. The inferior peri-macular region is commonly affected. Younger age and poorer visual field are risk factors for MME in glaucoma patients.