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Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.
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ADN Glicosilasas , Cardiomiopatías Diabéticas , Resistencia a la Insulina , Animales , ADN Glicosilasas/metabolismo , ADN Glicosilasas/genética , ADN Glicosilasas/deficiencia , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/patología , Ratones , Masculino , PPAR gamma/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Miocardio/patología , Modelos Animales de Enfermedad , Glucólisis , Humanos , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.
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Teorema de Bayes , Comorbilidad , Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Persona de Mediana Edad , Femenino , Masculino , Enfermedad Coronaria/epidemiología , Estudios de Casos y Controles , Anciano , Adulto , Factores de RiesgoRESUMEN
This study investigated the optimal proportion of biochar derived from pinewood pellets (PW) and coke as reducing agents for the carbothermal reduction of iron ore at high temperatures. Thermogravimetric analysis, elemental analysis, X-ray fluorescence, and scanning electron microscopy were used to characterize the raw materials. To determine the effect of biochar proportion on reduction efficiency, presented as metallization, metallized pellets were subjected to chemical analysis, including total iron (T.Fe) analysis, metallic iron (M.Fe) analysis, and residual Fe2O3 and FeO analysis. The results indicated that the addition of biochar derived from PW, with coke as a reducing agent, considerably increased the efficiency of carbothermal reduction. Optimal reduction conditions were established at a reduction temperature of 1300 °C and a holding time of 20 min, with 20% coke and 80% pinewood char. In summary, biochar derived from PW can be used as an alternative to coke as a reducing agent in the iron reduction process. In addition, biomass can be used as a reducing agent to mitigate carbon consumption by reducing the amount of coke required in iron production.
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Cellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-ß-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1ß, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in vivo in OGG1-deficient mice. Overall, we provide direct evidence in vivo and in vitro that OGG1 plays an important role in protecting tissue cells against aging associated with the p53 pathway.
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ADN Glicosilasas , Guanina/análogos & derivados , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Pulmón/metabolismo , Senescencia Celular , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismoRESUMEN
Introduction: Recent developments in artificial intelligence large language models (LLMs), such as ChatGPT, have allowed for the understanding and generation of human-like text. Studies have found LLMs abilities to perform well in various examinations including law, business and medicine. This study aims to evaluate the performance of ChatGPT in the United Kingdom Medical Licensing Assessment (UKMLA). Methods: Two publicly available UKMLA papers consisting of 200 single-best-answer (SBA) questions were screened. Nine SBAs were omitted as they contained images that were not suitable for input. Each question was assigned a specialty based on the UKMLA content map published by the General Medical Council. A total of 191 SBAs were inputted in ChatGPT-4 through three attempts over the course of 3 weeks (once per week). Results: ChatGPT scored 74.9% (143/191), 78.0% (149/191) and 75.6% (145/191) on three attempts, respectively. The average of all three attempts was 76.3% (437/573) with a 95% confidence interval of (74.46% and 78.08%). ChatGPT answered 129 SBAs correctly and 32 SBAs incorrectly on all three attempts. On three attempts, ChatGPT performed well in mental health (8/9 SBAs), cancer (11/14 SBAs) and cardiovascular (10/13 SBAs). On three attempts, ChatGPT did not perform well in clinical haematology (3/7 SBAs), endocrine and metabolic (2/5 SBAs) and gastrointestinal including liver (3/10 SBAs). Regarding to response consistency, ChatGPT provided correct answers consistently in 67.5% (129/191) of SBAs but provided incorrect answers consistently in 12.6% (24/191) and inconsistent response in 19.9% (38/191) of SBAs, respectively. Discussion and conclusion: This study suggests ChatGPT performs well in the UKMLA. There may be a potential correlation between specialty performance. LLMs ability to correctly answer SBAs suggests that it could be utilised as a supplementary learning tool in medical education with appropriate medical educator supervision.
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Cardiomyocyte apoptosis caused by fat metabolism disorder plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Apurinic/apyrimidinic endonuclease 1 (APE1) has multiple functions, including regulating redox and DNA repair. However, the role of APE1 in the pathogenesis of DCM remains unclear. To investigate the mechanism of APE1 on high-fat induced apoptosis in H9C2 cells, we treated H9C2 cells with palmitic acid (PA) as an apoptosis model caused by hyperlipidemia. We found that PA reduced the viability and increased apoptosis of H9C2 cells by inducing up-regulation of APE1 protein and endoplasmic reticulum (ER) stress. APE1 knockdown enhanced PA-induced apoptosis, and ER stress and overexpression of APE1 demonstrated the opposite effect. Furthermore, APE1 regulated PA-induced apoptosis via ER stress. The APE1 mutant (C65A, lack of redox regulation) loses its protective effect against ER stress and apoptosis. These findings indicate that APE1 protects PA-induced H9C2 cardiomyocyte apoptosis through ER stress via its redox-regulated function. This study provided new insights into the therapy for DCM.
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ADN-(Sitio Apurínico o Apirimidínico) Liasa , Miocitos Cardíacos , Ácido Palmítico , Apoptosis , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Endonucleasas/metabolismo , Estrés del Retículo Endoplásmico , Miocitos Cardíacos/metabolismo , Ácido Palmítico/farmacología , Ratas , AnimalesRESUMEN
BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.
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Colitis Ulcerosa , Enfermedad de Crohn , Hepatitis B , Enfermedades Inflamatorias del Intestino , Humanos , Taiwán , Inducción de Remisión , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Recurrencia , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
The diagnostic value and optimal cutoff level of cardiac troponin I in patients with sepsis have not been studied. In this single hospital retrospective study, we assessed the optimal cutoff value of troponin I for diagnosing non-ST-segment elevation myocardial infarction (NSTEMI) with type 1 myocardial infarction (MI) in patients with sepsis who had undergone a percutaneous coronary intervention from 2009 to 2019. In total, 5,341 patients (excluding patients with chronic kidney disease) were included, of whom 277 had sepsis or septic shock. Of the 123 patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and sepsis, 77 (62.6%) were diagnosed with NSTEMI with type 1 MI. The receiver-operating characteristic curve showed an area under the curve (AUC) of 0.705 for diagnosis of NSTEMI with type 1 MI with a troponin I cutoff of >300 ng/L (sensitivity: 68.4%, specificity: 70.2%, Youden index: 0.386). Multiple linear regression showed no significant predictors of NSTEMI with type 1 MI. Troponin level and the Global Registry of Acute Coronary Events (GRACE) scores were correlated (R 2 = 0.0625, p = 0.032) and showed comparable predictive value for 6-month mortality (AUC: 0.637 and 0.611, respectively, p = 0.7651). The optimal troponin I cutoff to effectively diagnose NSTEMI with type 1 MI in patients with sepsis was 300 ng/L.
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Síndrome Coronario Agudo , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Sepsis , Síndrome Coronario Agudo/diagnóstico , Electrocardiografía , Humanos , Infarto del Miocardio sin Elevación del ST/diagnóstico , Estudios Retrospectivos , Sepsis/diagnóstico , Troponina IRESUMEN
With recent increases in environmental awareness, the circular economy concept, which involves turning waste into usable products, has gradually become widely accepted. Spent mushroom substrate (SMS) is an agricultural waste that lacks recycling channels in Taiwan. This study explored the feasibility of simultaneously recycling two completely different types of waste: spent mushroom substrate (SMS), an agricultural waste, and electric-arc furnace dust (EAFD), an industrial waste. Specifically, SMS was used to replace metallurgical coke as a reducing agent for EAFD, which underwent carbothermic reduction to recycle valuable metallic Zn. The results showed that if SMS and EAFD were mixed at a C/O ratio of 0.8, the degree of Zn removal achieved 95% at 1100 °C, which is 150 °C lower than the reduction temperature of the EAFD-coke mixture (due to volatile matter (VM) in SMS). For the reduction of ZnO in EAFD, with the assistance of VM in SMS, the C/O ratio can be decreased from 0.8 to 0.16 at 1300 °C, achieving a high degree of Zn removal over 95%. In addition, the torrefaction of SMS increased the fixed carbon content and improved the Zn productivity at the same C/O ratio, reaching almost the same productivity as the coke sample (SMS torrefaction = 500 °C, C/O = 0.8, reduction = 1200 °C, Zn removal~99%). Finally, CO2 emission reductions from the use of SMS were also estimated.
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BACKGROUND: Liver cirrhosis is a well-known risk factor of sepsis after emergent gastrointestinal (GI) endoscopy. Elective GI endoscopy before living donor liver transplantation (LDLT), however, may also carry the septic risk among these patients. METHODS: This retrospective study reviewed the medical records of 642 cirrhotic recipients who underwent GI endoscopy from 2008 to 2016. We analyzed the incidence and risk factors of post-endoscopy sepsis during 2008-2012 (experience cohort). Our protocol changed after 2013 (validation cohort) to include antibiotic prophylaxis. RESULTS: In experience cohort, 36 cases (10.5%) of the 342 LDLT candidates experienced sepsis within 48 h after endoscopy. The sepsis rate was significantly higher in patients with hepatic decompensation than patients without (22.2% vs. 9.6% vs. 2.6% in Child C/B/A groups respectively; ×2 = 20.97, P < 0.001). Using multivariate logistic regression analysis, the factors related to post-endoscopy sepsis were the Child score (OR 1.46; 95% CI 1.24-1.71), Child classes B and C (OR 3.80 and 14.13; 95% CI 1.04-13.95 and 3.97-50.23, respectively), hepatic hydrothorax (OR 4.85; 95% CI 1.37-17.20), and use of antibiotic prophylaxis (OR 0.08; 95% CI 0.01-0.64). In validation cohort, antibiotics were given routinely, and all cases of hepatic hydrothorax (n = 10) were drained. Consequently, 4 (1.3%) episodes of sepsis occurred among 300 LDLT candidates, and the incidence was significantly lower than before (1.3% vs. 10.5%, P < 0.001). CONCLUSIONS: Patients with decompensated cirrhosis and hepatic hydrothorax have higher risk of sepsis following endoscopy. In advanced cirrhotic patients, antibiotic prophylaxis and drainage of hydrothorax may be required to prevent sepsis before elective GI endoscopy.
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Trasplante de Hígado , Sepsis , Niño , Endoscopía Gastrointestinal , Extremidades , Humanos , Cirrosis Hepática/complicaciones , Donadores Vivos , Estudios Retrospectivos , Factores de Riesgo , Sepsis/epidemiología , Sepsis/etiologíaRESUMEN
BACKGROUND: The use of biologic agents has become the cornerstone of therapy for moderate to severe IBD. Few studies have investigated the efficacy of vedolizumab (VDZ) induction for ulcerative colitis (UC) in Asian patients in a real practice setting. AIMS: To evaluate the efficacy and safety of VDZ induction therapy for moderate to severe UC in Taiwan. METHODS: This was a retrospective and observational study. Selected moderate to severe UC patients received VZD 300 mg i.v. at weeks 0, 2, and 6 as induction therapy. Mayo scores were calculated to evaluate the efficacy. RESULTS: A total of 37 patients with UC who received VDZ and completed the induction therapy at Chang Gung Memorial Hospital (2017/10-2021/5) were included. The mean age was 46.5 year-old and the male to female ratio was 1:1 (19/18). 81.8% of the patients were biologic-naive. At weeks 8-10, a clinical response, clinical remission and endoscopic remission with VDZ induction therapy were achieved in 56.8% (21/37), 32.4% (12/37) and 58.3% (7/12) of the patients, respectively. 54.1% (20/37) were able to taper off at week 8. Overall, only 10.8% (4/37) of the patients were primary non-responders during induction therapy. No obvious VDZ-related severe adverse events were noted. Overall, 58.9% (11/19) of the patients relapsed after stopping VDZ, and the relapse rate after VDZ discontinuation was 42.1% (8/19) within first 6 months and 52.6% (10/19) within the first year. CONCLUSION: In real-world experience, induction therapy with VDZ showed promising clinical benefits and safety profile for patients with UC.
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Colitis Ulcerosa , Anticuerpos Monoclonales Humanizados , Femenino , Fármacos Gastrointestinales , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the efficacy of aggressive hydration compared with general hydration for contrast-induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). METHODS: The Aggressive hydraTion in patients with STEMI undergoing pPCI to prevenT Contrast-Induced Acute Kidney Injury study is an open-label, randomised controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 min, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/hour for 6 hours after randomisation. The primary end point is CI-AKI, defined as a >25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48-72 hours after primary angioplasty. The safety end point is acute heart failure. RESULTS: From July 2014 to May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs 31.1%; risk ratio (RR) 0.70, 95% CI 0.52 to 0.96). Acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (8.1% vs 6.4%, RR 1.13, 95% CI 0.66 to 2.44). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants. CONCLUSIONS: Comparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Medios de Contraste/efectos adversos , Insuficiencia Cardíaca/etiología , Humanos , Riñón , Masculino , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The Taiwan Society of Cardiology (TSOC) has established multicenter registries for coronary artery disease (CAD) to investigate clinical characteristics, management and risks for mortality. However, the impacts of newly-emerged evidence-based therapies, including the use of drug-eluting stents (DESs), on patients with CAD in Taiwan remain unclear. METHODS: The Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry is a single-center, prospective, longitudinal registry in Taiwan containing data from 2014-2016. Individuals who were admitted for coronary angiography were enrolled. Patient profiles, management and in-hospital outcome data were collected. RESULTS: We included 3352 patients: 2349 with stable angina and 1003 with acute coronary syndrome (ACS). In the stable angina group, both patients receiving stenting and those receiving medical treatment had a 0.7% mortality rate; DESs were used in 70.4% of the patients receiving stenting. In the ACS group, the patients receiving stenting and those receiving medical treatment had a 4.9% and 10.7% mortality rate, respectively; DESs were used in 63.1% of the patients receiving stenting. In the 2008-2010 Taiwan ACS registry, DESs were used in only 28% of all stenting procedures, and the estimated hospital mortality rate was 1.8%. Multivariate analysis indicated that older age, prior stroke, and cardiogenic shock on admission were associated with an increased risk of in-hospital mortality in the ACS group. CONCLUSIONS: Compared with the Taiwan ACS cohort, the TSGH-CHD registry revealed increased DES use and increased disease complexity and severity after 2010. Although unlikely to significantly improve survival, interventionists seemed to perform high-risk procedures for complex CAD more often in the new DES era.
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Naringin, a natural bioflavonoid, has been shown to exert protective effects in multiple cardiovascular diseases; however, the protective effects of naringin against hypoxic/ischemiainduced myocardial are not yet fully understood. Autophagy is a vital factor involved in the pathogenesis of myocardial injury. The aim of the present study was to investigate the protective effects of naringin on H9c2 cells against chemical hypoxia [cobalt chloride (CoCl2)]induced injury. The role of autophagy and the hypoxiainducible factor1α (HIF1α)/Bcl2/BCL2 interacting protein 3 (BNIP3) signaling pathway in the protective effects of naringin were also assessed. The results revealed that naringin pretreatment significantly attenuated the CoCl2induced cytotoxicity and apoptosis, and also decreased caspase3 activity, which had been increased by CoCl2. In addition, CoCl2 increased Beclin1 expression, enhanced the IL3BII/IL3BI ratio and increased p62 expression in the H9C2 cells. Treatment with 3methyladenine (3MA), a selective inhibitor of autophagy, also blocked CoCl2induced cytotoxicity and apoptosis. Notably, treatment with bafilomycin A1 (Baf A1), an inhibitor of the vacuolar H+ ATPase of lysosomes, resulted in an increase in the upregulation of the LC3BII/LC3BI ratio, but did not further increase the LC3BII/LC3BI ratio compared with CoCl2 treatment. These results suggested that CoCl2 inhibited the autophagic flux, which resulted in myocardial cell damage. Furthermore, naringin pretreatment exacerbated Beclin 1 expression and the increased IL3BII/IL3BI ratio, and reduced p62 expression in CoCl2treated H9C2 cells. 3MA and Baf A1 both reversed the protective effects of naringin against CoCl2induced injury, indicating that naringin attenuated CoCl2induced myocardial cell injury by the increasing autophagic flux. Moreover, naringin treatment resulted in upregulated expression levels of HIF1α and BNIP3 in the CoCl2treated H9C2 cells. The inhibition of the HIF1α/BNIP3 signaling pathway using 3(5'hydroxymethyl2'furyl)1benzylindazole (an inhibitor of HIF1α) prevented the effects of naringin on the autophagic flux and reversed its protective effects against CoCl2induced injury. Taken together, these results suggest that naringin protects the H9C2 cells against CoCl2induced injury by enhancing the autophagic flux via the activation of the HIF1α/BNIP3 signaling pathway.
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Autofagia , Citoprotección , Flavanonas/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Transducción de Señal , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/farmacología , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Cobalto/toxicidad , Citoprotección/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , RatasRESUMEN
PURPOSE: Non-bismuth concomitant quadruple therapy is commonly administered in Taiwan, achieving an acceptable efficacy as a first-line anti-Helicobacter pylori treatment. This study compared the eradication rates between esomeprazole- and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line anti-H. pylori treatment. PATIENTS AND METHODS: This study included 206 H. pylori-infected naïve patients between July 2016 and February 2019. The patients were prescribed with either a 7-day non-bismuth containing quadruple therapy (esomeprazole, 40 mg twice daily; amoxicillin, 1 g twice daily; and metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily for 7 days [EACM group]; lansoprazole, 30 mg twice daily; amoxicillin, 1 g twice daily; metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily [LACM group]). Then, the patients were asked to perform urea breath tests 8 weeks later. RESULTS: The eradication rates in the EACM group were 86.1% (95% confidence interval [CI], 77.8%-92.2%) and 90.6% (95% CI, 82.9%-95.6%) in the intention-to-treat (ITT) and the per-protocol (PP) analyses, respectively. Moreover, the eradication rates in the LACM group were 90.1% (95% CI, 82.6%-95.2%) and 92.6% (95% CI, 85.5%-96.9%) in the ITT and the PP analyses, respectively. Consequently, the LACM group exhibited more diarrhea patients than the EACM group (7.1% versus 1.0%, p = 0.029), but all symptoms were mild. Univariate analysis in this study showed that metronidazole-resistant strains were the clinical factor affecting the eradications (95.3% versus 78.9%, p = 0.044). Moreover, a trend was observed in dual clarithromycin- and metronidazole-resistant strains (91.5% versus 66.7%, p = 0.155). CONCLUSION: The eradication rates between esomeprazole and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line H. pylori treatment were similar in this study. Both could achieve a > 90% report card in the PP analysis.
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INTRODUCTION: Automated text messaging programs have been studied as a treatment tool, but have not been studied as an outreach tool to increase the reach of smoking cessation treatment. AIMS AND METHODS: Two distinct text messaging programs were developed. One was aimed at connecting smokers to quitline phone counseling via text message (Text4Coach [T4C]) and the other was aimed at connecting smokers to a smoking cessation text messaging program (Text&Quit [T&Q]). Adult daily smokers with Medicaid insurance (N = 80) were recruited from the Emergency Department at an urban hospital and randomized to T4C or T&Q. The primary outcome was program reach. RESULTS: Outreach text messages were found to have moderately high uptake, with the majority of participants (63.8%) opting into their assigned tobacco treatment program and younger and female participants more likely to opt in (p < .01). Receipt of the treatment portion of the program differed among the programs with 67.5% of T&Q receiving the treatment program and 27.5% of T4C receiving the program (p < .001). Most participants across both groups replied to at least one message (71.3%) and very few unsubscribed from the service over the 3-week trial. The majority of participants reported overall satisfaction with their program (63.8%), found it helpful for quitting smoking (60.0%) and would recommend the program to a friend (62.5%). Overall, 11 (13.8%) participants reported being abstinent from smoking for the past 7 days at follow-up, with no differences between groups. CONCLUSIONS: Outreach text messages were found to have moderately high reach among Medicaid smokers. Larger trials are needed to evaluate the impact of such programs on helping low-income smokers quit. IMPLICATIONS: Automated text messaging programs have been tested as a treatment tool, but have not been tested as an outreach tool to increase the reach of smoking cessation treatment. This study tests a new way of conducting outreach to smokers in a health system through text messages. It tests the effect of outreach on (1) rates of opting in and (2) successful treatment delivery. Results may inform new models of providing outreach for tobacco treatment in health systems.
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Cese del Hábito de Fumar , Envío de Mensajes de Texto , Adulto , Servicio de Urgencia en Hospital , Humanos , Proyectos Piloto , NicotianaRESUMEN
BACKGROUND: Peripheral neuropathy is not an uncommon manifestation in patients with chronic hepatitis. The role of cryoglobulin (CG) in neuropathy in patients with chronic hepatitis remains controversial. There is limited information about the autonomic neuropathy in chronic hepatitis. This study aimed to evaluate autonomic function in treatment-naive patients with chronic hepatitis B or hepatitis C infection and to elucidate the association between autonomic neuropathy and CG in these patients. METHODS: A total of 29 treatment-naive patients with chronic, yet mild degrees of hepatitis B or C infection were evaluated for autonomic function, including those in the sympathetic sudomotor, cardiovagal, and adrenergic domains, to compare with the control subjects. The autonomic impairment was graded using the Composite Autonomic Scoring Scale. Then, association analyses between autonomic parameters/scores and CG were performed. RESULTS: Patients with chronic hepatitis B or C infection had significantly worse autonomic function than control subjects, especially in the sudomotor and cardiovagal domains. The autonomic manifestations in cases with and without CG were similar. There was no significant difference in autonomic dysfunction between patients with hepatitis B and C infections. CONCLUSION: The study demonstrated that autonomic neuropathy was not uncommon in patients with chronic hepatitis B or C infection. There was no association between autonomic neuropathy and CG.
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BACKGROUND: Non-bismuth containing quadruple therapy (concomitant therapy) is an alternative treatment for Helicobacter pylori (H. pylori) eradication with increasing clarithromycin-resistant strains over times. This study compared the efficacies of non-bismuth containing quadruple therapy (concomitant therapy) in the treatment of first-line anti-Helicobacter Pylori between two time intervals (January 2013 to June 2014 and June 2016 to December 2017). METHODS: H. pylori-infected patients were recruited in the intention-to-treat (ITT analysis) and divided into EACM-A group (enrolled from January 2013 to June 2014, N = 98) and EACM-B group (enrolled from June 2016 to December 2017, N = 99). Patients were prescribed with 7-day esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. Ninety patients and 93 patients were analyzed in the per protocol (PP) analysis (8 and 6 patients lost follow-up in each group). Urea breath tests were performed 4-8 weeks thereafter. RESULTS: The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.7%-93.5%) and 84.8% (95% CI = 76.2%-91.2%) (p = 0.55) in intention-to-treat (ITT) analysis; 95.6% (95% CI = 89.1%-98.8%) and 90.3% (95% CI = 82.4%-95.5%) (p = 0.17) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. 0.24). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.46); metronidazole (32.4% vs. 33.3%, p = 0.93) and levofloxacin (14.7% vs. 37.8%, p = 0.02). CONCLUSION: The success rate of 7-days concomitant therapy encountered an approximately 5% decrease across 4-year time interval (2013-2017) with the changes of clarithromycin resistance from 11.8% to 17.8% in Taiwan.
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Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Farmacorresistencia Microbiana , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Metronidazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Clopidogrel is widely prescribed for patients with of aspirin-related upper gastrointestinal bleeding (UGIB) history. This study aimed to compare the risk of a major adverse cardiovascular event (MACE), UGIB, and mortality between aspirin and clopidogrel in patients at risk of bleeding. METHODS: We analyzed adult patients at high risk of UGIB following aspirin-related bleeding for secondary MACE prevention between 2000 and 2012. Secondary prevention was for those patients who had ever been hospitalized for cardiovascular disease and reused aspirin or changed to clopidogrel after discharge. Study endpoints were recurrence of MACE, UGIB, and death in 90 days of follow-up. The associations between study outcomes and the use of clopidogrel (vs aspirin) were analyzed. RESULTS: Among 947 eligible patients, 653 reused aspirin (in combination with a proton-pump inhibitor), and 294 were treated with clopidogrel (in combination with a proton-pump inhibitor) after discharge for UGIB. Compared with aspirin treatment, clopidogrel showed an increased risk of MACE (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.87-3.12) and UGIB (aHR 1.25; 95% CI 0.66-2.36), but without statistical significance in 90 days' follow-up. Clopidogrel use was associated with greater than four times the risk of any cause of mortality (aHR 4.84; 95% CI 1.59-14.75), but the significance did not hold in propensity score-matched cohort analysis (P = 0.06). CONCLUSIONS: A nonsignificant difference between clopidogrel and aspirin for short-term MACE prevention as well as UGIB recurrence was found in the present study. Further research to assess 90-day mortality would assist clinical decision making.
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Aspirina/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Clopidogrel/efectos adversos , Úlcera Péptica Hemorrágica/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Clopidogrel/uso terapéutico , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/complicaciones , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica Hemorrágica/etiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Medición de Riesgo , Factores de Riesgo , Prevención SecundariaRESUMEN
OBJECTIVE: Several studies evaluating the preventive effect of N-acetylcysteine (NAC) on contrast-associated acute kidney injury (CA-AKI) among patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) have suggested inconsistent results and that a systematic review and meta-analysis should be performed. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, MEDLINE, EMBASE, ClinicalTrials.gov and the Cochrane Central databases were searched from inception to 15 November 2019. ELIGIBILITY CRITERIA: Randomised controlled trials assessing use of NAC compared with non-use of NAC (eg, placebo) in preventing CA-AKI in patients with STEMI following PPCI were included. DATA SYNTHESIS: Relative risks with 95% CIs were pooled using a random-effects model. Evidence level of conclusions was assessed by Cochrane GRADE measure. RESULTS: Seven trials including 1710 patients were identified. Compared with non-use of NAC, use of NAC significantly reduced the incidence of CA-AKI by 49% (risk ratio (RR) 0.51, 95% CI 0.31 to 0.82, p<0.01) and all-cause in-hospital mortality by 63% (RR 0.37, 95% CI 0.17 to 0.79, p=0.01). The estimated effects on the requirement for dialysis (RR 0.61, 95% CI 0.11 to 3.38, p=0.24) were not statistically significant. Trial sequential analysis conï¬rmed the true positive of NAC in reducing risk of CA-AKI. Subgroup analyses suggested that the administration of NAC had greater benefits in patients with renal dysfunction and in those receiving oral administration and higher dosage of NAC. CONCLUSIONS: NAC intake reduces the risk of CA-AKI and all-cause in-hospital mortality in patients with STEMI undergoing PPCI. The estimated potential benefit of NAC in preventing dialysis was ambiguous, and further high-quality studies are needed. PROSPERO REGISTRATION NUMBER: CRD42020155265.