Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 133
Filtrar
1.
J Clin Transl Hepatol ; 9(5): 607-614, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722175

RESUMO

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. Methods: A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. Results: Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%). Conclusions: Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

2.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34633921

RESUMO

A Gram-stain-negative, non-motile, rod-shaped bacterial strain, named SJ-16T, was isolated from desert soil collected in Inner Mongolia, northern PR China. Strain SJ-16T grew at pH 6.0-11.0 (optimum, pH 8.0-9.0), 4-40 °C (optimum, 30-35 °C) and in the presence of 0-8 % (w/v) NaCl (optimum, 0-2 %). The strain was negative for catalase and positive for oxidase. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain SJ-16T clustered with Luteimonas chenhongjianii 100111T and Luteimonas terrae THG-MD21T, and had 98.8, 98.6, 98.3 and <97.9 % of 16S rRNA gene sequence similarity to strains L. chenhongjianii 100111T, L. terrae THG-MD21T, L. aestuarii B9T and all other type strains of the genus Luteimonas, respectively. The major cellular fatty acids were iso-C15 : 0, iso-C16 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1 ω9c). Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were the major polar lipids, and ubiquinone-8 was the only respiratory quinone. The genomic DNA G+C content was 69.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values of strain SJ-16T to L. chenhongjianii 100111T, L. terrae THG-MD21T, L. rhizosphaerae 4-12T and L. aestuarii B9T were 36.9, 37.5, 24.0 and 21.1 %, and 80.9, 80.6, 80.7 and 76.3 %, respectively. Based on phenotypic, physiological and phylogenetic results, strain SJ-16T represents a novel species of the genus Luteimonas, for which the name Luteimonas deserti is proposed. The type strain is SJ-16T (=CGMCC 1.17694T=KCTC 82207T).


Assuntos
Ácidos Graxos , Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Xanthomonadaceae
3.
Oxid Med Cell Longev ; 2021: 5093216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650663

RESUMO

Ischemia-reperfusion (I/R) injury often occurred in some pathologies and surgeries. I/R injury not only harmed to physiological functions of corresponding organ and tissue but also induced multiple tissue or organ dysfunctions (even these in distant locations). Although the reperfusion of blood attenuated I/R injury to a certain degree, the risk of secondary damages was difficult to be controlled and it even caused failures of these tissues and organs. Lipoic acid (LA), as an endogenous active substance and a functional agent in food, owns better safety and effects in our body (e.g., enhancing antioxidant activity, improving cognition and dementia, controlling weight, and preventing multiple sclerosis, diabetes complication, and cancer). The literature searching was conducted in PubMed, Embase, Cochrane Library, Web of Science, and SCOPUS from inception to 20 May 2021. It had showed that endogenous LA was exhausted in the process of I/R, which further aggravated I/R injury. Thus, supplements with LA timely (especially pretreatments) may be the prospective way to prevent I/R injury. Recently, studies had demonstrated that LA supplements significantly attenuated I/R injuries of many organs, though clinic investigations were short at present. Hence, it was urgent to summarize these progresses about the effects of LA on different I/R organs as well as the potential mechanisms, which would enlighten further investigations and prepare for clinic applications in the future.

4.
Exp Ther Med ; 22(5): 1238, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34539834

RESUMO

The incidence of acute myocardial infarction (AMI) is currently increasing. Early detection is important for the treatment and prognosis of patients with AMI. Heart-type fatty acid-binding protein (H-FABP) may be used as an early marker of AMI due to its high sensitivity, specificity and prognostic value. Therefore, in the present study, H-FABP was used as a biomarker in a double-antibody sandwich method and colloidal gold-based lateral flow immunoassay to develop a rapid detection kit for H-FABP with a processing time of only 5 min. The sensitivity of the kit in plasma and whole blood was 1 ng/ml and this method had good specificity, exhibiting no cross-reaction with cardiac troponin I, myoglobin or creatine kinase-Mb. The kits had good shelf life and stability, as they were able to be stored at 40˚C for 30 days. A total of 12 clinical samples were collected for detection and the coincidence rate with the ELISA method was up to 91.67%. Therefore, the present study provided a simple, rapid and economical early-detection in-home testing kit.

5.
Clin Infect Dis ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487151

RESUMO

OBJECTIVES: Pradefovir is a liver-targeted prodrug of adefovir, a nucleotide analog with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30mg, 45mg, 60mg, and 75mg) versus tenofovir disoproxil fumarate (TDF; 300mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were HBeAg positive and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/ml with pradefovir doses of 30mg, 45mg, 60mg, and 75mg, respectively, compared to 5.12 log10 IU/ml with TDF. However, HBeAg loss was attained by more participants who received 45mg, 60mg or 75mg pradefovir than those receiving TDF (12%, 6%, 9% vs. 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30mg or 45mg groups, and serum phosphate levels were comparable among all groups. Most adverse events were mild (grade 1). No treatment-related severe adverse events were reported. Overall, adverse events and laboratory abnormalities were comparable to the TDF group. CONCLUSIONS: Pradefovir exhibited comparable reductions in HBV DNA levels to TDF. All treatments were safe and well tolerated.

6.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4089-4095, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467718

RESUMO

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Animais , Mucosa Gástrica , Metilnitronitrosoguanidina/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/tratamento farmacológico
7.
J Pharmacol Sci ; 147(3): 234-244, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34507632

RESUMO

The incidence of diabetes-associated cognitive dysfunction is increasing. However, few clinical interventions are available to prevent the disorder. Several researches have shown that liraglutide, as a glucagon-like peptide-1 analog, has protective effects on various neurodegenerative diseases, but its roles in diabetic cognitive dysfunction are rarely reported. This study aims to investigate the protective effects of liraglutide on diabetic cognitive dysfunction and its underlying mechanisms. In vivo, the effects of liraglutide treatment were investigated in a mouse model of type 2 diabetes mellitus (T2DM). In vitro, we investigated the effects of liraglutide on the high-glucose-induced rat primary neurons. The results showed that liraglutide reduced the escape latency and increased the time in effective area in the Morris water maze test, improved the damage of hippocampal and synaptic ultrastructure, and decreased the accumulation of amyloid ß protein in hippocampus of T2DM mice. Furthermore, liraglutide increased the ratio of microtubule-associated protein light 1 chain Ⅱ/Ⅰ, the expression of Beclin1 protein and Lysosome-associated membrane protein 2 in vivo and vitro. Additionally, Bafilomycin A1 which can inhibit the fusion of autophagosome and lysosome partially abolished the effects of liraglutide. These findings indicate liraglutide ameliorates diabetes-associated cognitive dysfunction by rescuing autophagic flux.

8.
Aliment Pharmacol Ther ; 54(9): 1134-1149, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34587302

RESUMO

BACKGROUND: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).


Assuntos
Hepatite B Crônica , Antivirais/efeitos adversos , DNA Viral , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Tenofovir/efeitos adversos , Resultado do Tratamento , Carga Viral
9.
Hum Vaccin Immunother ; : 1-6, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344258

RESUMO

The impact of Coronavirus disease 2019 (COVID-19) on children aged 3-6 can be severe. Vaccination for COVID-19 is one of the most important primary preventative measures to reduce disease transmission. Parents are hesitant to vaccinate their children against COVID-19 because it was reported in the news that some adults have had adverse reactions to the vaccine. This study aims to investigate the willingness of Chinese parents of 3-6 year old children to vaccinate them with the COVID-19 vaccine and identify what factors influence their decisions. A survey was conducted using a two-stage stratified random sampling method from December 2020 to February 2021. We used univariate analysis and multivariate binary logistic analysis to explore potential factors that may determine the acceptance of the COVID-19 vaccine. Of the 468 parents who participated, 86.75% were willing to vaccinate their children with the COVID-19 vaccine. Parents who were female (OR = 2.591; 95% CI: 0.432-4.689), recognized their children in the high-risk category (OR = 2.494; 95% CI:1.244-5.002), often followed-up with COVID-19 vaccine-related information (OR = 9.065; 95% CI: 3.220-28.654), believed in the safety of the COVID-19 vaccine (OR = 3.068; 95% CI: 1.313-7.168), or thought the COVID-19 vaccine could prevent COVID-19 (OR = 13.750; 95% CI: 2.516-75.140) were more willing to vaccinate their children. To ease parents' hesitation about vaccines, the authority organization should release updated information on the safety and reliability of vaccines, target gender-specific health education for parents, and ask the media to report scientifically support information.

10.
Front Med (Lausanne) ; 8: 709884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409052

RESUMO

Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. Design: We conducted a cohort study of two multicenter prospective cohorts. Setting: China. Participants: Acute-on-chronic liver disease patients with various etiologies. Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Conclusions and Relevance: Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.

11.
Ann Palliat Med ; 10(9): 9342-9353, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412498

RESUMO

BACKGROUND: Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD). METHODS: A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation). RESULTS: In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P<0.001). From univariate and multivariate analyses, platelet count was inversely associated with the incidence of 90-day adverse outcomes in patients (P for trend <0.001). The group with platelet count <20×109/L had the highest risk (odds ratio, 3.15; 95% confidence interval, 1.59-6.25), with 21 (36.8%) of these patients having adverse outcomes within 90 days. The risk of a 90-day adverse outcome in patients increased by 5% for every 10×109/L decrease in platelet count below 210×109/L. CONCLUSIONS: Lower platelet count was associated with a higher incidence of 90-day adverse outcomes in patients with AoCLD. Even within the normal platelet count range, the risk of a 90-day adverse outcome in patients increased with decreases in platelet count. TRIAL REGISTRATION: NCT02457637, NCT03641872.


Assuntos
Hepatopatias , Transplante de Fígado , Humanos , Hepatopatias/etiologia , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos
12.
World J Clin Cases ; 9(18): 4690-4699, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34222435

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China. AIM: To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients. METHODS: This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A (n = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96th week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates. RESULTS: For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 vs 5.73 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% vs 77.97%, 31.00% vs 27.27%, and 20.22% vs 15.79%, respectively, in Group A vs Group B; P > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 vs 4.70 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% vs 94.12% in Group A vs Group B, respectively; P > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% vs 84.57% in Group A vs Group B, respectively; P > 0.05), and similar incidences of adverse events were observed (106 vs 104 in Group A vs Group B, respectively; P > 0.05). CONCLUSION: Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.

13.
Front Med (Lausanne) ; 8: 704452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249983

RESUMO

Introduction: Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality via evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Methods: Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Results: Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. Conclusion: This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.

14.
Hepatobiliary Pancreat Dis Int ; 20(5): 426-432, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

15.
J Hepatol ; 75(2): 454-461, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34019941

RESUMO

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

16.
Acta Pharmacol Sin ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040166

RESUMO

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular settings. Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death. Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide, particularly in the aging population. Dysregulated systemic inflammation is a classic characteristic of sepsis, and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes. Here, we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury, the ways by which HMGB1 are released, and the signaling pathways and therapeutics associated with HMGB1. This review highlights recent advances related to HMGB1: the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.

18.
J Int Med Res ; 49(4): 3000605211005945, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33853430

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database. METHODS: We retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified. RESULTS: The analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups. CONCLUSIONS: Bicyclol is a potential candidate for DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Pacientes Internados , Alanina Transaminase , Compostos de Bifenilo/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Fígado , Pontuação de Propensão , Estudos Retrospectivos
19.
Cancer Cell Int ; 21(1): 179, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752668

RESUMO

BACKGROUND: Studies have discussed long noncoding RNA DDX11-AS1 (DDX11-AS1)-mediated downstream mechanism in hepatocellular carcinoma (HCC). The goal of this study was to investigate the regulatory mechanism of DDX11-AS1-mediated microRNA-34a-3p (miR-34a-3p)/tumor necrosis factor receptor-associated factor 5 (TRAF5) axis on HCC cells. METHODS: DDX11-AS1, miR-34a-3p and TRAF5 expression levels in HCC were detected. The correlation of DDX11-AS1, miR-34a-3p and TRAF5 in HCC patients was analyzed by Pearson test. HCC cells were transfected with corresponding plasmid/oligonucleotide, and cell proliferation, migration, invasion, apoptosis and tumor formation ability were detected. Bioinformatics software, dual luciferase report experiment and RNA-pull down experiment analysis were applied to verify the targeting relationship between DDX11-AS1, miR-34a-3p and TRAF5. RESULTS: Elevated DDX11-AS1 and TRAF5 and reduced miR-34a-3p exhibited in HCC. Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibited the proliferation, migration, invasion, promoted apoptosis of HCC cells and repressed the tumor growth in nude mice. In addition, DDX11-AS1 bound to miR-34a-3p to target TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated up-regulated DDX11-AS1-mediated promotion of tumor growth. CONCLUSION: Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibits HCC cell growth via elevation of TRAF5, which could be of great benefit to find early diagnostic markers for HCC patients.

20.
Life Sci ; 270: 119144, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545201

RESUMO

Activation of hepatic stellate cells (HSCs) is an important event during the progress of liver fibrosis. MicroRNA (miR)-15b and miR-16 have been found to be involved in activation of HSCs. However, the roles of miR-15b/16 in liver fibrosis remain unclear. The expression of miR-15b/16 was decreased in TGF-ß1-stimulated LX-2 cells. Overexpression of miR-15b/16 in LX-2 cells suppressed TGF-ß1-induced cell proliferation and the expression levels of tissue inhibitor of metalloproteinase type 1, collagen type I, and α-smooth muscle actin. The activation of Smad2/3 caused by TGF-ß1 was repressed by miR-15b/16 overexpression. The two miRNAs directly bound to the 3'-UTR of lysyl oxidase-like 1 (LOXL1) and suppressed the LOXL1 expression. Furthermore, knockdown of LOXL1 attenuated miR-15b/16 downregulation-induced cell proliferation, fibrogenic response and phosphorylation of Smad2/3. Collectively, miR-15b/16 exhibited anti-fibrotic activity through regulation of Smad2/3 pathway.


Assuntos
Aminoácido Oxirredutases/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Aminoácido Oxirredutases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Colágeno Tipo I/metabolismo , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , MicroRNAs/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...