RESUMO
BACKGROUND: Intraoperative intravenous fluid administration proves to be associated with surgical patients' postoperative outcomes. Few studies reported the relationship between intraoperative crystalloid-colloid infusion ratio and early surgical complications after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). METHODS: Data on patients with underwent IPAA from January 2008 to March 2022 at our three inflammatory bowel disease (IBD) surgery centers were retrospectively collected. Intraoperative anesthetic data were recorded and later evaluated by our team anesthesiologist. RESULTS: A total of 140 eligible patients with a median follow-up time of 6.0 years [interquartile range (IQR): 2.0-8.0] were enrolled. Among all enrolled patients, 34 (24.3%) developed early surgical complications after IPAA. Greater blood loss and lower crystalloid-colloid infusion ratio were observed in patients with early surgical complications. Crystalloid-colloid infusion ratio < 2 and blood loss ≥ 200 ml had the most significant area under the receiver-operating characteristic curve (AUC) of 0.664 and 0.674 in predicting early surgical complications. Crystalloid-colloid infusion ratio < 2 [odds ratio (OR), 2.571; 95% confidence intervals (CI), 1.067-6.195, p = 0.035] and blood loss ≥ 200 ml (OR, 3.165; 95% CI, 1.288-7.777, p = 0.012) were independent risk factors for the development of early post-IPAA complications. CONCLUSION: Intraoperative crystalloid-colloid infusion ratio < 2 and blood loss volume over 200 ml during IPAA contribute to the occurrence of early surgical complications. Early attentions and necessary interventions are warranted to avoid these risk factors during the IPAA surgery in order to prevent the development of early surgical complications.
Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Seguimentos , Estudos Retrospectivos , Soluções Cristaloides , Proctocolectomia Restauradora/efeitos adversos , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Bolsas Cólicas/efeitos adversos , Resultado do TratamentoRESUMO
The persistent bioavailability of toxic metal(oids) (TM) is undeniably the leading source of serious environmental problems. Through the transfer of these contaminants into food networks, sediments and the aquatic environmental pollution by TM serve as key routes for potential risks to soil and human health. The formation of iron oxyhydroxide plaque (IP) on the root surface of hydrophytes, particularly rice, has been linked to the impact of various abiotic and biotic factors. Radial oxygen loss has been identified as a key driver for the oxidation of rhizosphere ferrous iron (Fe2+) and its subsequent precipitation as low-to-high crystalline and/or amorphous Fe minerals on root surfaces as IP. Considering that each plant species has its unique capability of creating an oxidised rhizosphere under anaerobic conditions, the abundance of rhizosphere Fe2+, functional groups from organic matter decomposition and variations in binding capacities of Fe oxides, thus, impacting the mobility and interaction of several contaminants as well as toxic/non-toxic metals on the specific surface areas of the IP. More insight from wet extraction and advanced synchrotron-based analytical techniques has provided further evidence on how IP formation could significantly affect the fate of plant physiology and biomass production, particularly in contaminated settings. Collectively, this information sets the stage for the possible implementation of IP and related analytical protocols as a strategic framework for the management of rice and other hydrophytes, particularly in contaminated sceneries. Other confounding variables involved in IP formation, as well as operational issues related to some advanced analytical processes, should be considered.
Assuntos
Oryza , Poluentes do Solo , Humanos , Ferro/análise , Oryza/química , Cádmio/análise , Poluentes do Solo/análise , Minerais/metabolismoRESUMO
BACKGROUND AND AIM: Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilation (EPBD), and endoscopic sphincterotomy plus balloon dilation (ESBD) are all techniques used to manage choledocholithiasis. We aim to analyze the efficacy and safety of these techniques for treating choledocholithiasis in patients undergoing hemodialysis (HD). METHODS: We performed a retrospective study of 80 patients with end-stage renal disease (ESRD) on HD who underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis management between August 1st, 2012, and December 31st, 2020, at a medical center in southern Taiwan. These patients were divided into three groups: EST (n = 21), EPBD (n = 28), and ESBD (n = 31). Post-ERCP complications, including pancreatitis, bleeding, cholangitis, and perforation, were reviewed for analysis. RESULTS: There were no significant among-group differences in the rate of complete stone clearance and hospitalization day after ERCP. Patients in the EST group had a higher post-ERCP complication rate than was the case in the other groups (p = 0.016). ESBD significantly reduced post-ERCP bleeding, compared with that occurring with EST (OR 0.07; 95% CI, 0.01-0.72, p = 0.026). There were no significant among-group differences in the rates of pancreatitis and cholangitis. There were no ERCP-related perforations or deaths in this study. CONCLUSIONS: EST, EPBD, and ESBD are efficient methods for treating choledocholithiasis in ESRD patients. ESBD was found to lead to a lower risk of bleeding than EST, and the rate of pancreatitis or cholangitis was comparable for EST and EPBD. Our results suggest that ESBD is the best choice of treatment of choledocholithiasis in patients with ESRD undergoing HD.
Assuntos
Colangite , Coledocolitíase , Falência Renal Crônica , Pancreatite , Humanos , Coledocolitíase/cirurgia , Estudos Retrospectivos , Esfinterotomia Endoscópica/efeitos adversos , Esfinterotomia Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Dilatação/efeitos adversos , Dilatação/métodos , Colangite/etiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Pancreatite/etiologia , Hemorragia , Resultado do TratamentoRESUMO
BACKGROUND: The coronavirus disease 2019 infection (COVID-19) pandemic is a new global outbreak disease. According to the Taiwan Centers for Diseases Control statement, hospitals had to change their corresponding measures to prevent the spread of COVID-19. The frequency of parental visits to the special care nursery was reduced from three times to once daily. Visiting was not permitted from April 4 to May 10, 2020, and rooming-in with healthy neonates was discontinued, which could increase maternal postpartum distress. Therefore, this study was conducted to determine whether COVID-19 prevention increased maternal psychological distress. METHODS: This prospective study used convenience sampling to enroll healthy mothers who had just delivered via normal spontaneous delivery. Based on the neonates' status and visiting times, mothers were grouped into no-rooming-in, rooming-in, no-visiting, and one-visit/day groups. Mothers' baseline characteristics were compared using the Chi-square or Fisher's exact test and t-test. Salivary cortisol levels and scores of Chinese versions of the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory were evaluated on postpartum days 1 and 3 and analyzed by one-way analysis of variance and a paired t-test. RESULTS: There were 16, 58, 28, and 47 women categorized as no-rooming-in, rooming-in, no-visit, and one-visit/day groups, respectively. No significant differences were found between groups in mothers' baseline characteristics and postpartum salivary cortisol levels. The PSS on day 3 was significantly higher than on day 1 in every group (p < 0.001). The PSS increasing trend in the no-rooming-in group was significantly greater than that in the no-visit group (p = 0.02) and significantly greater in the rooming-in group than that in the one-visit/day group (p = 0.001). CONCLUSION: Postpartum stress increased for all mothers and was an even more significant response to the COVID-19 pandemic than the stress associated with neonates' hospitalization.
Assuntos
COVID-19 , Angústia Psicológica , Recém-Nascido , Feminino , Humanos , Pandemias , COVID-19/epidemiologia , Projetos Piloto , Hidrocortisona/análise , Estudos Prospectivos , Período Pós-Parto/psicologia , Mães/psicologiaRESUMO
Tumor brain metastasis is a severe threat to patients' neurological function, in which microglia may be involved in the process of tumor cell metastasis among nerve cells. Our study focused on the interaction between microglia and breast and lung cancer cells. Changes in the proliferation and migration ability of cocultured tumor cells were examined; synchrotron radiation-based fourier transform infrared microspectroscopy (SR-FTIR) was used to detect changes in the structures and contents of biomolecules within the tumor cells. The experimental results showed that the proliferation and migration ability of tumor cells increased after coculture, and the structures and contents of biological macromolecules in tumor cells changed. The absorption peak positions of the amide â ¡ and amide â bands observed for the four kinds of tumor cells changed, and the absorption intensities were significantly enhanced, indicating changes in the secondary structures and contents of proteins in tumor cells, which may be the root cause of the change in tumor cell characteristics. Therefore, the metabolites of microglia may be involved in the progression of tumor cells in the nervous system. In this study, we focused on the interaction between microglia and tumor cells by using SR-FTIR and provided a new understanding of the mechanism of brain metastasis.
Assuntos
Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Microglia/patologia , Células A549 , Neoplasias da Mama/química , Linhagem Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/química , Células MCF-7 , Microglia/química , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Fruits are reproductive organs in flowering plants and the harvested products of many agricultural crops. They play an increasingly important role in the human diet due to their nutritional values. Water is the most abundant component of most fleshy fruits, and it is essential for fruit growth and quality formation. Water is transported to the fruit via the vascular system (xylem and phloem) and lost to the air through the fruit surface due to transpiration. This minireview presents a framework for understanding water transport in fleshy fruits along with brief introductions of key methodologies used in this research field. We summarize the advances in the research on the patterns of water flow into and out of the fruit over development and under different environmental conditions and cultural practices. We review the key findings on fruit transpiration, xylem transport, phloem transport, and the coordination of water flows in maintaining fruit water balance. We also summarize research on post-vascular water transport mediated by aquaporins in fruits. More efforts are needed to elucidate the mechanisms by which different environmental conditions impact fruit water transport at the micro-level and to better understand the physiological implications of the coordination of water flows. Incorporating fruit water transport into the research area of plant hydraulics will provide new insights into water transport in the soil-plant-atmosphere continuum.
Assuntos
Frutas , Transpiração Vegetal , Floema , Água , XilemaRESUMO
BACKGROUND: In a previous study, persistent pain was suggested to be a risk factor for tumor patients. However, the mechanism underlying this phenomenon is still unclear. Substance P (SP), a pain-related neuropeptide secreted by the neural system and the immune system, plays an important role in the induction and maintenance of persistent pain. METHODS: In this study, in order to explore whether SP participates in the influence of pain on tumor progression, the serum samples of lung cancer and breast cancer patients were collected and tested. An elevated expression of SP was found in patients with pain. RESULTS: Cell pharmacological experiments revealed that SP can upregulate the expression of Toll-like receptor-4 (TLR-4) in tumor cells and increase the proliferation, migration, and invasive activity of tumor cells. As high expression of TLR-4 has the ability to enhance the biological activity of tumor cells, TLR-4 is thought to be involved in SP-induced tumor proliferation, migration, and invasion. Treatment of tumor cells with Aprepitant, a specific blocker of the NK-1 receptor, could reduce the expression of TLR-4 and reduce the proliferation, invasion, and migration activities of tumor cells; further proof of the influence of SP on TLR-4 expression depends on the NK-1 receptor located in tumor cells. CONCLUSIONS: Based on the results above, we proposed a possible mechanism underlying pain affecting tumor progression: The presence of pain increases the content of SP in patients' blood, and elevated SP increases the expression of tumor TLR-4 by acting on the NK-1 receptor, which ultimately affects the biological activity of the tumor.
Assuntos
Neoplasias , Substância P , Humanos , Dor , Receptores da Neurocinina-1 , Receptor 4 Toll-LikeRESUMO
BACKGROUND/AIMS: MicroRNAs play regulatory role in cardiovascular disease. MicroRNA-223 (miR-223) was found to be expressed abundantly in myocardium. TNNI3K, a novel cardiac troponin I (cTnI)-interacting and cardiac hypertrophy related kinase, is computationally predicted as a potential target of miR-223. This study was designed to investigate the cellular and molecular effects of miR-223 on cardiomyoctye hypertrophy, focusing on the role of TNNI3K. METHODS: Neonatal rat cardiomyocytes (CMs) were cultured, and CMs hypertrophy was induced by endothelin-1 (ET-1). In vivo cardiac hypertrophy was induced by transverse aorta constriction (TAC) in rats. Expression of miR-223 in CMs and myocardium was detected by real-time PCR (RT-PCR). MiR-223 and TNNI3K were overexpressed in CMs via chemically modifed sense RNA (miR-223 mimic) transfection or recombinant adenovirus infection, respectively. Cell size was measured by surface area calculation using fluorescence microscopy after anti-α-actinin staining. Expression of hypertrophy-related genes was detected by RT-PCR. The protein expression of TNNI3K and cTnI was determined by Western blots. Luciferase assay was employed to confirm the direct binding of miR-223 to the 3'UTR of TNNI3K mRNA. Intracellular calcium was measured by sensitive fluorescent indicator (Furo-2). Video-based edge detection system was employed to measure cardiomyocyte contractility. RESULTS: MiR-223 was downregulated in ET-1 induced hypertrophic CMs and in hypertrophic myocardium compared with respective controls. MiR-223 overexpression in CMs alleviated ET-1 induced hypertrophy, evidenced by smaller cell surface area and downregulated ANP, α-actinin, Myh6 and Myh7 expression. Luciferase reporter gene assay showed that TNNI3K serves as a direct target gene of miR-223. In miR-223-overexpressed CMs, the protein expression of TNNI3K was significantly downregulated. MiR-223 overexpression also rescued the upregulated TNNI3K expression in hypertrophic CMs. Furthermore, cTnI phosphorylation was downregulated post miR-223 overexpression. Ad.rTNNI3K increased intracellular Ca(2+) concentrations and cell shortening in CMs, while miR-223 overexpression significantly rescued these hypertrophic effects. CONCLUSION: By direct targeting TNNI3K, miR-223 could suppress CMs hypertrophy via downregulating cTnI phosphorylation, reducing intracellular Ca(2+) and contractility of CMs. miR-223 / TNNI3K axis may thus be major players of CMs hypertrophy.
Assuntos
Cardiomegalia/enzimologia , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Troponina I/metabolismo , Regiões 3' não Traduzidas , Actinina/genética , Actinina/metabolismo , Animais , Sequência de Bases , Cálcio/metabolismo , Cardiomegalia/genética , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Endotelina-1/farmacologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Contração Muscular , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Oligonucleotídeos Antissenso/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de SequênciaRESUMO
Following a myocardial infarction (MI), fibroblasts differentiate to myofibroblasts, which possess some of the characteristics of smooth muscle cells (SMCs) and contribute to wound healing. Previous studies suggested that the miR-143/-145 cluster plays a critical role in SMC differentiation. Therefore, we determined whether miR-145 promoted differentiation of cardiac fibroblasts to myofibroblasts. Following coronary occlusion in mice, myocardial miR-145 expression was downregulated at 3 days but was restored at 7 days. In vitro studies showed that hypoxia also downregulated miR-145 in cardiac fibroblasts. The number of α-smooth muscle actin (α-SMA) positive cells in fibroblast cultures was employed to determine their transdifferentiation to cardiac myofibroblasts and was increased by 73.5% after transient transfection with miR-145. Ultrastructural analysis of α-SMA stress fibers revealed that ~95% of the α-SMA(+) cells treated with miR-145 organized their actin-filament bundles with a specific orientation compared to only 15% in the scrambled control group. This orientation of the SMA bundles and their integration with the filamentous actin fibers of the cytoskeleton permit infarct wound contraction. Structural and functional studies showed that miR-145 induced a myofibroblast phenotype, and miR-145 also potentiated the production of mature collagen by myofibroblasts. Repression of KLF5, a target of miR-145, was validated by a chimeric luciferase construct tagged with the full-length 3'-UTR of KLF5. A dramatic decrease in KLF5 and a corresponding increase in myocardin expression were observed after transfecting cultured fibroblasts with miR-145. Similar results were found in vivo: the transient decrease in miR-145 expression 3 days post-MI was associated with an increase in KLF5 and a decrease in myocardin. In addition, in vivo delivery of a miR-145 antagomir 1 day prior to and 2 and 6 days after MI decreased myofibroblast formation and increased scar size. The antagomir also reversed the suppressed expression of KLF5 protein in the scar region at day 7 after MI. In summary, we describe a novel association between miR-145 and fibroblast differentiation toward myofibroblasts. These observations provide a new approach to promote endogenous scar healing and contracture by stimulating the transdifferentiation of cardiac fibroblasts to myofibroblasts.
Assuntos
Fibroblastos/metabolismo , MicroRNAs/genética , Miocárdio/metabolismo , Reepitelização/fisiologia , Actinas/genética , Actinas/metabolismo , Animais , Diferenciação Celular , Transdiferenciação Celular , Colágeno/genética , Colágeno/metabolismo , Oclusão Coronária/patologia , Vasos Coronários/cirurgia , Feminino , Fibroblastos/patologia , Expressão Gênica , Genes Reporter , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Luciferases/genética , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Miocárdio/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oligonucleotídeos Antissenso/genética , Transativadores/genética , Transativadores/metabolismoRESUMO
Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.
Assuntos
Pressão Sanguínea , Frequência Cardíaca , Estimulação Luminosa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Adulto , Hipertensão/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/terapia , Idoso , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial/métodosRESUMO
BACKGROUND & AIMS: Perianal fistulising Crohn's disease (PFCD) is different from the characteristics and outcomes of traditional non-inflammatory bowel disease (IBD) anal fistulas. The presence of perianal disease was a poor prognostic indicator for Crohn's disease (CD) patients and PFCD patients were more likely to bear an increased risk of recurrence. However, the effective and accurate diagnosis methods to early distinguish PFCD from simple perianal fistula were still scarce. The purpose of this study is to develop a non-invasive detecting approach to predict CD in patients with perianal fistulas. METHODS: Data on patients with anal fistulizing disease were collected from July 2020 to September 2020 in two IBD centers. Urine samples from PFCD and simple perianal fistula patients were investigated by surface-enhanced Raman spectroscopy (SERS). Principal component analysis (PCA)-support vector machine (SVM) was utilized to establish classification models to distinguish PFCD from simple perianal fistula. RESULTS: After a case-matched 1:1 selection by age and gender, 110 patients were included in the study. By analyzing the average SERS spectra of PFCD and simple perianal fistula patients, it revealed that there were significant differences in intensities at 11 Raman peaks. The established PCA-SVM model distinguished PFCD from simple perianal fistula with a sensitivity of 71.43%, specificity 80.00% and accuracy 75.71% in the leave-one-patient-out cross-validation. The accuracy of the model in validation cohort was 77.5%. CONCLUSIONS: Investigation of urine samples by SERS helps clinicians to predict Crohn's disease from perianal fistulas, which make patients achieve benefit from a more individualized treatment strategy.
Assuntos
Doenças do Ânus , Doença de Crohn , Fístula Cutânea , Fístula Retal , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Análise Espectral Raman , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Prognóstico , Doenças do Ânus/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Various extracellular matrix (ECM) reshaping events are involved in inflammatory bowel disease (IBD). LAMB3 is a vital subunit of laminin-332, an important ECM component. Data on the biological function of LAMB3 in intestinal inflammation are lacking. Our aim is to discuss the effect of LAMB3 in IBD. METHODS: LAMB3 expression was assessed in cultured intestinal epithelial cells, inflamed mucosal tissues of patients and mouse colitis models. RNA sequencing, quantitative real-time polymerase chain reaction and Western blotting were used to detect the LAMB3 expression distribution and potential downstream target genes. Dual-luciferase assays and chromatin immunoprecipitation-quantitative polymerase chain reaction were used to determine whether P65 could transcriptionally activate LAMB3 under tumor necrosis factor α stimulation. RESULTS: LAMB3 expression was increased in inflammatory states in intestinal epithelial cells and colonoids and was associated with adverse clinical outcomes in Crohn's disease. Knockdown of LAMB3 inhibited the expression of proinflammatory cytokines. Mechanistically, LAMB3 expression was directly transcriptionally activated by P65 and was inhibited by nuclear factor kappa B inhibitors under tumor necrosis factor α stimulation. Furthermore, RNA sequencing and replenishment experiments revealed that LAMB3 upregulated SERPINA3 to promote intestinal inflammation via the integrin α3ß1/FAK pathway. CONCLUSION: We propose that LAMB3 could serve as a potential therapeutic target of IBD and a predictor of intestinal stenosis of Crohn's disease. Our findings demonstrate the important role of ECM in the progression of IBD and offer an experimental basis for the treatment and prognosis of IBD.
Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Serpinas , Animais , Humanos , Camundongos , Doença de Crohn/patologia , Inflamação/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Serpinas/metabolismo , Serpinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Background/Aims: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Methods: Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. Results: A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). Conclusions: The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.
Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Bolsas Cólicas/efeitos adversos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Qualidade de Vida , Resultado do Tratamento , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
IκB kinase (IKK) complex is central regulators of the NF-κB pathway, and dysregulation of IKK phosphorylation leads to hyperactivation of proinflammatory response in various chronic inflammatory diseases, including inflammatory bowel disease (IBD). However, the dynamic modulation of IKK phosphorylation and dephosphorylation in intestinal inflammation remains uncharacterized. Here, we found that autophagy/beclin-1 regulator 1 (AMBRA1) was highly expressed in inflamed colons in a colitis mouse model and in clinical IBD samples. Importantly, AMBRA1 deletion significantly decreased proinflammatory cytokine expression and enhanced the therapeutic effect of infliximab on intestinal inflammation. Mechanistically, the N-term F1 domain of AMBRA1 was required for AMBRA1 to competitively interact with protein phosphatase 4 regulatory subunit 1 (PP4R1) and catalytic protein phosphatase 4 (PP4c) to suppress their interactions with IKK, promote the dissociation of the PP4R1/PP4c complex, and antagonize the dephosphorylation activity of this complex towards the IKK complex. In response to TNF-α stimulation, IKKα phosphorylates AMBRA1 at S1043 to stabilize AMBRA1 expression by impairing its binding to Cullin4A (CUL4A) to decrease its CUL4A-mediated K48-linked ubiquitination. Overall, our study identifies an autophagy-independent function of AMBRA1 as a positive modulator of IKK phosphorylation to promote intestinal inflammation, thus providing a new targeted therapeutic strategy for patients with refractory IBD.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Autofagia , Quinase I-kappa B , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autofagia/efeitos dos fármacos , Colite/metabolismo , Colite/patologia , Colite/induzido quimicamente , Células HEK293 , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Camundongos Endogâmicos C57BL , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/genética , FosforilaçãoRESUMO
Increasing evidence suggests that PCSK9 inhibition protects cardiomyocytes against ischemia-reperfusion injury after myocardial infarction. However, it is not clear whether PCSK9 inhibitor (PCSK9i) affects cardiac fibroblasts (CFs) activation after MI. In this study we used SBC-115076, an antagonist of PCSK9, to investigate the role of PCSK9i in the conversion of CFs to cardiac myofibroblasts (CMFs) after MI and provided a basic for its clinical application in cardiac fibrosis after MI. In vivo study, PCSK9i was injected into mice 4 days after MI. Cardiac function and degree of fibrosis were evaluated by echocardiographic and tissue staining after treatment. Western blot showed that PCSK9i treatment decreases expression of α-SMA, collagen and increases expression of Notch1 in border infarct area. Vitro studies showed that PCSK9i decreased the degree of fibrosis, migration, and collagen fiber deposition in CFs. Confocal microscopy imaging also showed that hypoxia contributes to the formation of α-SMA stress filaments, and PCSK9i alleviated this state. Moreover, overexpression of Notch1 further suppress the activation of CFs under hypoxia. These results revealed that SBC-115076 ameliorates cardiac fibrosis and ventricular dysfunction post-myocardial infarction through inhibition of the differentiation of cardiac fibroblasts to myofibroblasts via Notch1/Hes1 signaling.
Assuntos
Infarto do Miocárdio , Miofibroblastos , Animais , Camundongos , Transdiferenciação Celular , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibrose , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/uso terapêuticoRESUMO
BACKGROUND: Pouchitis is a common late complication in patients with ulcerative colitis (UC) who undergo ileal pouch-anal anastomosis (IPAA). The heterogeneous nature of the clinical and endoscopic presentations could affect the evaluation of therapeutic interventions for pouchitis. Thus, identifying the risk factors and clinical outcomes of pouch inflammation at different sites and severity is becoming increasingly important for colorectal surgeons. METHODS: Data on patients who underwent IPAA January from 2008 to June 2022 in our three pouch centers affiliated with the China UC Pouch Center Union were retrospectively collected. Pouchitis was categorized as a different phenotype according to the Chicago Classification. J pouches were classified into short (14 ± 2 cm) and long pouches (22 ± 2 cm) according to the distribution of ileal pouch length in our institute. RESULTS: Altogether, 143 patients with a median follow-up time of 5.0 years (interquartile range: 2.0-8.0) were enrolled. Among them, 41 patients (28.7%) developed pouchitis and 32 patients (78%) had diffuse inflammation of the pouch. Patients with diffuse pouchitis had a higher pouchitis disease activity index and more seriously impaired improvement of long-term quality of life than those with pouch phenotypes. A short J pouch, recurrent UC, and preoperative high white blood cell count were independent risk factors for diffuse pouchitis. Furthermore, a short J pouch could effectively predict the occurrence of diffuse pouchitis with an area under the receiver-operating characteristic curve of 0.614, a sensitivity of 62.5%, and a specificity of 60.4% (p = 0.049) and significantly decreased the overall diffuse pouchitis-free survival compared to a long J pouch (p = 0.0002). CONCLUSION: Diffuse pouchitis is a common phenotype of pouchitis that seriously impairs long-term prognosis. For colorectal surgeons, decision-making regarding pouch construction with an appropriate length should be considered to prevent the development of diffuse pouchitis.
Assuntos
Colite Ulcerativa , Bolsas Cólicas , Neoplasias Colorretais , Pouchite , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Bolsas Cólicas/efeitos adversos , Estudos Retrospectivos , Qualidade de Vida , Estudos de Coortes , Pouchite/etiologia , Pouchite/epidemiologia , Pouchite/cirurgia , Colite Ulcerativa/cirurgia , Anastomose Cirúrgica/efeitos adversos , Fatores de Risco , Inflamação/etiologia , Neoplasias Colorretais/cirurgiaRESUMO
Background and study aims Submucosal injection solution is essential for successful endoscopic resection of the early gastrointestinal tumor. We evaluated a new endoscopic hydrogel for submucosal injection and its clinical feasibility. Patients and methods A hydrogel (AceGel) containing 0.4% sodium alginate and 2% calcium lactate was developed for ex vivo and animal studies. Subsequently, a prospective, single-arm study was conducted to assess its feasibility and safety in humans. Patients with gastrointestinal neoplasms undergoing endoscopic resection were enrolled. All patients underwent endoscopic surveillance after 4 weeks and outpatient follow-up at week 6. Afterward, they received endoscopic follow-up according to the medical routine. Results In the ex vivo experiments, the submucosal elevation height of AceGel was equivalent to sodium hyaluronate and superior to saline or glycerol. Animal studies showed that the excised wounds healed well without surrounding tissue damage. Twelve patients participated in the clinical trial, including three, two, and seven patients with esophageal, gastric, and colonic lesions, respectively. The mean neoplasm size and submucosal injection volumes were 24.0±8.6 mm and 22.8±19.9 mL, respectively. All patients had adequate wound healing on 4-week surveillance endoscopy, and none had serious adverse events during 6-week follow-up. Moreover, endoscopic follow-up showed complete wound healing after 6 to 46 months without local mucosal inflammation in all patients. Conclusions AceGel is good for endoscopic submucosal injection and demonstrated its usefulness in durable mucosal elevation for endoscopic therapy in preclinical tests. This clinical trial shows its safety and feasibility in all participating patients.
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Background: Candida parapsilosis is the most common non-albicans candida species that causes invasive candidiasis, but little is known about its impacts on the outcomes of pediatric patients. We aimed to characterize the clinical characteristics, risk factors and outcomes of C. parapsilosis bloodstream infections (BSIs) in children. Methods: All pediatric patients with Candida parapsilosis BSIs between 2005 and 2020 from a medical center in Taiwan were enrolled and analyzed. The antifungal susceptibility, clinical manifestations, management and outcomes were investigated. Cases of Candida parapsilosis BSIs were compared between patients with C. albicans BSIs and other Candida spp. BSIs. Results: During the study period, 95 episodes (26.0% of total cases) of Candida parapsilosis BSIs were identified and analyzed. No significant difference was found between pediatric patients with C. parapsilosis BSIs and those with C. albicans BSIs in terms of patients' demographics, most chronic comorbidities or risk factors. Pediatric patients with C. parapsilosis BSIs were significantly more likely to have previous azole exposure and be on total parenteral nutrition than those with C. albicans BSIs (17.9 vs. 7.6% and 76.8 vs. 63.7%, p = 0.015 and 0.029, respectively). The duration of C. parapsilosis candidemia was relatively longer, and therefore patients often required a longer duration of antifungal treatment when compared with those of C. albicans candidemia, although the candidemia-attributable mortality rates were comparable. Of the C. parapsilosis isolates, 93.7% were susceptible to all antifungal agents, and delayed appropriate antifungal treatment was an independent factor in treatment failure. Conclusions: Pediatric patients with C. parapsilosis BSIs were more likely to have previous azole exposure and be on total parenteral nutrition, and the clinical significances included a longer duration of candidemia and patients often required a longer duration of antifungal treatment.
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Comparative effects of partial root-zone irrigation (PRI) and deficit irrigation (DI) on xylem pH, ABA, and ionic concentrations of tomato (Lycopersicon esculentum L.) plants were investigated in two split-root pot experiments. Results showed that PRI plants had similar or significantly higher xylem pH, which was increased by 0.2 units relative to DI plants. Nitrate and total ionic concentrations (cations+anions), and the proportion of cations influenced xylem pH such that xylem pH increases as nitrate and total ionic concentrations decrease, and the proportion of cations increases. In most cases, the xylem ABA concentration was similar for PRI and DI plants, and a clear association between increases in xylem pH with increasing xylem ABA concentration was only found when the soil water content was relatively low. The concentrations of anions, cations, and the sum of anions and cations in PRI were higher than in the DI treatment when soil water content was relatively high in the wetted soil compartment. However, when water content in both soil compartments of the PRI pots were very low before the next irrigation, the acquisition of nutrients by roots was reduced, resulting in lower concentrations of anions and cations in the PRI than in the DI treatment. It is therefore essential that the soil water content in the wet zone should be maintained relatively high while that in the drying soil zone should not be very low, both conditions are crucial to maintain high soil and plant water status while sustaining ABA signalling of the plants.
Assuntos
Ácido Abscísico/metabolismo , Irrigação Agrícola/métodos , Solanum lycopersicum/fisiologia , Água/fisiologia , Xilema/metabolismo , Ácido Abscísico/análise , Ânions/análise , Transporte Biológico/fisiologia , Biomassa , Desidratação , Concentração de Íons de Hidrogênio , Folhas de Planta/fisiologia , Raízes de Plantas/fisiologia , Brotos de Planta/fisiologia , Estômatos de Plantas/fisiologia , Transpiração Vegetal/fisiologia , Transdução de Sinais/fisiologia , Solo/químicaRESUMO
It remains unknown whether and to what extend the angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can play a role in the development of atrial fibrillation (AF) after pacemaker implantation in very old patients. Therefore, we aimed to investigate the association between oral ACEIs or ARBs and the risk of developing AF in very old patients after pacemaker implantation. Patients above 80 years old with pacemaker implantation and without baseline history of AF were included and their real-world information about ACEIs or ARBs use was extracted from electronic medical records. New AF cases were confirmed via the records of outpatient visits. The multivariable Cox proportional-hazards model was used to evaluate the associations between oral ACEIs or ARBs and risk of AF after pacemaker implantation. Among a total of 388 identified patients aged 80 to 98 years, 118 used ACEIs, 174 had ARBs therapy, and 115 AF were identified after pacemaker implantation during a median follow-up time of 3.1 years. After adjustment for potential confounders, patients with daily use of ARBs had a relatively lower risk of AF after pacemaker implantation (HR: 0.627, 95% CI: 0.425, 0.926; P = 0.019) compared with those non-users, whereas ACEIs therapy didn't show a significant relation with AF risk (HR: 1.335, 95% CI: 0.894, 1.995; P = 0.157). In conclusion, for very old patients with a permanent pacemaker, daily use of oral ARBs was associated with a relative lower risk of AF after pacemaker implantation, however, daily use of ACEIs was not related with AF risk.