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1.
Biosci Rep ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967060

RESUMO

BACKGROUND: Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. This study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats.  Methods: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated.

 Results: The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats, however it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were upregulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003).

 Conclusions: In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis.

2.
J Clin Med ; 13(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999366

RESUMO

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

3.
Eur J Clin Invest ; : e14287, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017981

RESUMO

BACKGROUND: Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations. RESULTS: Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that Negativicutes, Selenomonadales and Lactobacillus salivarius reduced in the fructooligosaccharides-treated group. CONCLUSION: In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress.

4.
Gerontol Geriatr Med ; 10: 23337214241260147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854459

RESUMO

Care aides in long-term care (LTC) institutions care for older disabled residents at high risk for COVID-19. However, they experienced many stressors during the COVID-19 pandemic. This study aims to explore the working experiences of care aides in LTC institutions following the relaxation of COVID-19 regulations in Taiwan. This qualitative descriptive study included 20 care aides who had cared for residents with COVID-19. Data were obtained via semi-structured interviews. Caring for residents with COVID-19 and the difficulties, resources and teamwork, and impact of care aides' work on their lives were discussed. Consequently, four themes were identified. First, difficulties in care, which included physical limitations by protection, workload, and impact of work schedule on the lives of the care aides. Second, psychological impact, such as worry, social isolation, and burnout. Third, interpersonal relationships with supervisors, colleagues, residents, and their families. Fourth, infection control policy from the institution and government. When infection control policies were relaxed, care aides had difficulties in caring for residents; furthermore, their family and social lives were also affected. They were required to learn knowledge of and skills for COVID-19 management. Institutions were required to provide support in materials, care processes, environment, and management.

5.
ESC Heart Fail ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607371

RESUMO

AIMS: Left bundle branch block (LBBB) is associated with an increased risk of adverse outcomes for patients with heart failure. The prognosis of LBBB in patients with a preserved ejection fraction (EF) remains controversial. This study investigated the predictive value of T-wave discordance for the prognosis of patients with LBBB and preserved or mildly reduced EF. METHODS AND RESULTS: We enrolled 707 patients with complete LBBB and left ventricular (LV) EF ≥ 40% observed using electrocardiograms (ECGs) and echocardiograms between January 2010 and December 2018. Their serial ECGs were reviewed during the follow-up period. The T-wave pattern was classified as discordant LBBB (dLBBB) or concordant LBBB (cLBBB) according to the 12-lead ECG T-wave morphology. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure during a median follow-up period of 3.1 years. A multivariable Cox regression analysis was used to evaluate the independent predictors of the primary outcome. Patients with dLBBB had more comorbidities, a higher heart rate, a longer QRS and QTc duration, a larger LV end-systolic volume and left atrial dimension, a lower LVEF, and a higher mitral E/A ratio and E/e', compared with those with cLBBB. Older age [hazard ratio (HR) = 1.023, 95% confidence interval (CI) = 1.001-1.046, P = 0.023], history of heart failure (HR = 2.440, 95% CI = 1.524-3.905, P = 0.001), chronic kidney disease (HR = 1.917, 95% CI = 1.182-3.110, P = 0.008), larger LV end-systolic volume (HR = 1.046, 95% CI = 1.017-1.075, P = 0.002), lower LVEF (HR = 0.916, 95% CI = 0.885-0.948, P = 0.001), and presence of dLBBB (HR = 1.63, 95% CI = 1.011-2.628, P = 0.032) were independent predictors of the primary outcome in patients with LBBB and LVEF ≥ 40%. The discordant or concordant T-wave morphology of LBBB could transform from one subtype to the other in up to 23% of the study population during the follow-up period, and individuals with persistent or transformed dLBBB faced an increased risk of cardiovascular death or non-fatal heart failure hospitalization. CONCLUSIONS: In patients with LBBB and EF ≥ 40%, dLBBB serves as an independent predictor of a higher risk of cardiovascular death or non-fatal heart failure hospitalization.

6.
Heart Rhythm ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38614190

RESUMO

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

7.
Int J Cardiol Heart Vasc ; 50: 101320, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38419606

RESUMO

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p < 0.001). In the multivariate analysis, age, being a man, and BMI were significantly associated with moderate-to-severe OSA. AF burden was associated with moderate-to-severe OSA only in men (odds ratio: 1.008; 95% confidence interval: 1.001-1.014). Women and men with OSA had similar BMI (p = 0.526) and OSA severity (p = 0.754), but women were older than men (70.1 ± 1.3 vs. 63.1 ± 0.9 years, p < 0.001). Women with moderate-to-severe OSA had a lower AF burden than men did (27.6 ± 7.1 vs. 49.5 ± 3.9%, p = 0.009). Conclusions: AF burden is a sex-specific risk factor for OSA and is limited to men. In contrast, women with both AF and OSA have a lower AF burden than men, despite being older and having similar OSA severity and body habitus. Thus, AF may develop later in women with OSA than in men.

8.
J Chin Med Assoc ; 87(5): 463-470, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38380910

RESUMO

BACKGROUND: In liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats. METHODS: Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/d) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, and oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment. RESULTS: The BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia, and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry, or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL, and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like ox-LDL rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis. CONCLUSION: Ezetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats.


Assuntos
Ezetimiba , Lipoproteínas LDL , Cirrose Hepática Biliar , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Ezetimiba/farmacologia , Ezetimiba/uso terapêutico , Ratos , Lipoproteínas LDL/sangue , Cirrose Hepática Biliar/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Masculino , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/farmacologia , Azetidinas/farmacologia , Azetidinas/uso terapêutico
9.
Biomaterials ; 306: 122505, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359507

RESUMO

Atherosclerosis, a chronic inflammatory disease, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a targeted delivery system for activated and inflamed endothelium lining the plaque surface. The MoNP system is used to deliver verteporfin (VP), aimed at inhibiting YAP/TAZ specifically within arterial regions prone to atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells. When administered in mice, MoNP predominantly accumulate in intima of the atheroprone artery. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, thereby suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a lesion-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transativadores/metabolismo , Proteínas de Sinalização YAP , Células Endoteliais/metabolismo , Biomimética , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Inflamação/tratamento farmacológico
10.
Dig Dis ; 42(2): 166-177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38219719

RESUMO

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.


Assuntos
Infecções Bacterianas , Doença Hepática Terminal , Humanos , Glicosilação , Estudos Retrospectivos , Glicoproteínas de Membrana/metabolismo , Índice de Gravidade de Doença , Cirrose Hepática , Biomarcadores/metabolismo , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Albuminas/metabolismo , Antígenos de Neoplasias/metabolismo
11.
Gut ; 73(4): 682-690, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38123994

RESUMO

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.


Assuntos
Carcinoma Hepatocelular , Varizes Esofágicas e Gástricas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Ligadura/efeitos adversos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Prevenção Primária , Propranolol/uso terapêutico
12.
J Chin Med Assoc ; 87(3): 245-251, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109364

RESUMO

Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.


Assuntos
Encefalopatia Hepática , Humanos , Encefalopatia Hepática/terapia , Encefalopatia Hepática/tratamento farmacológico , Qualidade de Vida , Fármacos Gastrointestinais , Lactulose/uso terapêutico , Rifaximina/uso terapêutico
13.
JGH Open ; 7(11): 765-771, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034050

RESUMO

Background and Aim: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan. Methods: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan. Results: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic. Conclusion: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.

14.
Biomater Sci ; 11(19): 6650-6662, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37609825

RESUMO

Liver fibrosis is generally preceded by various liver injuries and often leads to chronic liver diseases and even cirrhosis. Therefore, a liver fibrosis animal model is the cornerstone for the development of therapeutic strategies for hepatic diseases. Although administration of hepatotoxic substances and/or bile duct ligation have been widely performed to construct the in vivo model over the last decades, they are seriously hindered by time-consuming protocols, high mortality, and instability, indicating that an effective and safe approach for the induction of liver fibrosis is still urgently needed nowadays. In this study, we have developed asialoglycoprotein receptor (ASGPR)-targeted lipopolysaccharide (LPS)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles named ALPNPs for establishing an animal model of liver fibrosis. The ALPNPs are characterized as having a spherical nanostructure with size of 182.9 ± 8.89 nm and surface charge of -8.3 ± 1.48 mV. An anti-ASGPR antibody bound to the surface of the nanoparticles with a crosslinking efficiency of 95.03% allows ALPNPs to have hepatocyte-binding specificity. In comparison to free LPSs, the ALPNPs can induce higher aspartate aminotransferase and total bilirubin concentrations in plasma, reduce the blood flow rate in the portal system and the kidneys, and increase vascular resistance in the liver, kidneys, and collateral shunting vasculature. Based on histological and RNA-seq analyses, the ALPNPs can provide similar capability on inducing hepatic inflammation and fibrosis compared to free LPS but possess higher liver targetability than the naked drug. In addition, the ALPNPs are less toxic in organs other than the liver in comparison to free LPS, demonstrating that the ALPNPs do not elicit off-target effects in vivo. Given the aforementioned efficacies with other merits such as biocompatibility and drug release controllability provided by PLGA, we anticipate that the developed ALPNPs are highly applicable in establishing animal models of liver fibrosis in pre-clinical studies.


Assuntos
Lipopolissacarídeos , Nanopartículas , Animais , Receptor de Asialoglicoproteína/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Modelos Animais , Nanopartículas/química
15.
J Chin Med Assoc ; 86(10): 876-884, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37537726

RESUMO

BACKGROUND: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients. METHODS: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0. RESULTS: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score. CONCLUSION: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.

16.
Artigo em Inglês | MEDLINE | ID: mdl-37553717

RESUMO

BACKGROUND: The short form of the Borderline Symptom List (BSL-23) is a self-rated instrument developed from the initial 95-item German version of the Borderline Symptom List (BSL-95). It is widely used among Chinese adults, but its applicability, factor structure and validity remain uncertain in adolescents. This study aimed to evaluate the psychometric properties of the Chinese Mandarin version of the BSL-23 in a sample of suicidal adolescents. METHODS: The Chinese Mandarin BSL-23 was given to 279 outpatient adolescents with self-injurious thoughts or behaviors. The factor structure, reliability, convergent validity, criterion-related validity and cut-off value were investigated. RESULTS: The Chinese Mandarin version of the BSL-23 demonstrated a one-factor structure and replicated the original version. The scale had high reliability and good test-retest stability. The Chinese Mandarin BSL-23 was correlated with depression, hopelessness, impulsivity, emotional dysregulation, self-esteem, loneliness, childhood trauma and parental bonding patterns evaluated with a variety of scales. The measure showed good criterion-related validity and predictive accuracy (AUC = 0.87) for self-injurious and suicidal adolescents with borderline personality disorder (BPD) at a cut-off point of 60/61 (mean score 2.60/2.65), with a sensitivity of 0.76 and specificity of 0.83. CONCLUSIONS: The Chinese Mandarin version of the BSL-23 is a reliable and valid self-reported instrument to assess BPD symptomatology among suicidal adolescents.

18.
Acta Cardiol Sin ; 39(4): 546-560, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37456947

RESUMO

Background: Radiation exposure during fluoroscopic procedures increases the risk of cancer for both patients and operators. Objectives: The aim of this study was to investigate the safety and efficacy of adopting a three-dimensional electroanatomical mapping (3D EAM) system during ablation for paroxysmal supraventricular tachycardia (PSVT), without the assistance of intracardiac echocardiography (ICE), for both right- and left-chamber cardiac procedures. Methods: We retrospectively enrolled all patients with PSVT from September 2018 to December 2020. The patients were grouped according to the use of the 3D EAM system (3D-guided group, n = 102 vs. conventional group, n = 226). Results: The acute success rates were high in both groups (100% vs. 99.1%). The fluoroscopy time was significantly lower in the 3D-guided group than in the conventional group (2.4 ± 4.4 vs. 19.0 ± 10.8 min); the procedure time was significantly increased in the 3D-guided group (104.5 ± 29.9 vs. 94.0 ± 31.9 min), and this was associated with the post-electrophysiology test diagnosis after adjustment for multiple variables [standardized B coefficient (ß) 0.188]. There was no learning curve for each electrophysiologist in terms of fluoroscopy and procedure times. Conclusions: The 3D EAM system, without the assistance of ICE, was safe and effective in guiding PSVT ablation in both left- and right-chamber ablation.

19.
Nanomaterials (Basel) ; 13(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37446439

RESUMO

Red, green, and blue light InxGa1-xN multiple quantum wells have been grown on GaN/γ-LiAlO2 microdisk substrates by plasma-assisted molecular beam epitaxy. We established a mechanism to optimize the self-assembly growth with ball-stick model for InxGa1-xN multiple quantum well microdisks by bottom-up nanotechnology. We showed that three different red, green, and blue lighting micro-LEDs can be made of one single material (InxGa1-xN) solely by tuning the indium content. We also demonstrated that one can fabricate a beautiful InxGa1-xN-QW microdisk by choosing an appropriate buffer layer for optoelectronic applications.

20.
J Chin Med Assoc ; 86(9): 786-794, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37462441

RESUMO

BACKGROUND: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. METHODS: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. RESULTS: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. CONCLUSION: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.


Assuntos
Pressão Arterial , Hipertensão Portal , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Neprilisina/farmacologia , Vasodilatação , Receptores de Angiotensina/uso terapêutico , Pressão na Veia Porta , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Hipertensão Portal/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Antivirais/uso terapêutico , Valsartana/uso terapêutico
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