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1.
Appl Immunohistochem Mol Morphol ; 28(2): 154-160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32044884

RESUMO

Nonalcoholic steatohepatitis (NASH) has the potential to progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Upregulation of sonic hedgehog (Shh) has been documented in development of NASH through sustained cell stress. At the same time, transforming growth factor-ß1 (TGF-ß1), which is a central element in fibrogenic reactions in various diseases and sites, has been reported to be associated with hepatic inflammation and fibrotic reaction. To explore crosstalk between Shh and TGF-ß1 in the development and progression of NASH, we investigated the expression of both these proteins in 135 human specimens of NASH, 35 fatty liver specimens, 35 specimens of alcoholic steatohepatitis with immunohistochemistry. Shh protein was expressed in the cytoplasm of ballooned hepatocytes with an ubiquitin-like pattern. In addition, a few scattered apoptotic hepatocytes in the inflammatory foci showed homogeneous cytoplasmic Shh expression. TGF-ß1 protein was observed mainly in the activated hepatic stellate cells (HSCs) which were located in the inflammatory foci surrounding ballooned hepatocytes. Moreover, the mRNA levels of both Shh and TGF-ß1 in the liver biopsy specimens from NASH patients was significantly increased compared with those in fatty liver patients. Statistically, there was a significant association of the expressions of Shh and TGF-ß1 proteins in NASH (r=0.6, P<0.05). In addition, increased expression of Shh protein significantly parallels the severity of hepatocellular ballooning, lobular, and portal inflammatory responses and progression of fibrosis in NASH patients. Moreover, we found that much HSCs transformed into myofibroblast-like phenotype and migrated downward to HepG2 hepatocellular carcinoma cells with overexpression of Shh by transwell assay. We also observed overexpression of proteins of Shh and TGF-ß1 in cultured activated HSCs with confocal microscopy. These findings strongly suggest there is interplay between Shh and TGF-ß1 in hepatic inflammatory reactions. Shh secreted through damaged hepatocytes may result in activation of TGF-ß1 and subsequent transformation of HSCs, which together modulate the progression of human NASH.

2.
Nat Commun ; 11(1): 184, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924767

RESUMO

Ionic substitution forms an essential pathway to manipulate the structural phase, carrier density and crystalline symmetry of materials via ion-electron-lattice coupling, leading to a rich spectrum of electronic states in strongly correlated systems. Using the ferromagnetic metal SrRuO3 as a model system, we demonstrate an efficient and reversible control of both structural and electronic phase transformations through the electric-field controlled proton evolution with ionic liquid gating. The insertion of protons results in a large structural expansion and increased carrier density, leading to an exotic ferromagnetic to paramagnetic phase transition. Importantly, we reveal a novel protonated compound of HSrRuO3 with paramagnetic metallic as ground state. We observe a topological Hall effect at the boundary of the phase transition due to the proton concentration gradient across the film-depth. We envision that electric-field controlled protonation opens up a pathway to explore novel electronic states and material functionalities in protonated material systems.

3.
Adv Mater ; 32(2): e1905548, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782566

RESUMO

Advances in the chemical and electrochemical transformation of carbon and water are vital for delivering affordable and environmentally friendly energy sources and chemicals. Central to this challenge is the performance of materials. Traditionally, noble metal particles or metal complexes have been used as catalysts for many reactions. Recently, 3d transition-metal single-site catalysts (3dTM-SSCs) have emerged as potentially transformational candidates for the next-generation high-performance noble-metal-free catalysts. Designing catalysts at the molecular level can lead to a more efficient utilization of metal atoms and at the same time enhance catalytic performance under harsh reaction conditions. Despite this promise, several fundamental issues remain, in particular the structural evolution of 3dTM-SSCs during the synthesis, the molecular-level insights into the structure of the active sites, catalytic mechanisms, and the long-term cycling stability. Here, the material chemistries that facilitate the 3dTM-SSCs generation through a controlled pyrolytic synthesis are discussed, with focus on elucidating the underlying performance descriptors that can tune the catalytic properties in various critical reactions in carbon and water cycles. The current challenges and possible solutions for improving these novel catalytic materials are also highlighted.

4.
Food Chem ; 306: 125616, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622832

RESUMO

This research aimed to explore the role of protein S-nitrosylation in regulating the tenderness of postmortem beef, from the perspective of µ-calpain autolysis and protein proteolysis. Five bovine semimembranosus muscles were incubated with three treatments including S-nitrosoglutathione (GSNO, nitric oxide donor), normal saline and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, nitric oxide synthase inhibitor). The results showed that the level of protein S-nitrosylation was improved by GSNO treatment and reduced by L-NAME treatment (p < 0.05). Compared to the control, GSNO treatment had higher shear force while L-NAME treatment presented lower shear force at 7 d postmortem (p < 0.05). In addition, µ-calpain autolysis, myofibrillar protein and desmin degradation were reduced by GSNO treatment and accelerated by L-NAME treatment (p < 0.05). Therefore, it can be speculated that protein S-nitrosylation could affect beef tenderization by regulating the autolysis of µ-calpain and the degradation of myofibrillar proteins.


Assuntos
Proteína S/metabolismo , Carne Vermelha , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Calpaína/metabolismo , Bovinos , Desmina/metabolismo , Proteína S/química , Proteólise
5.
ChemSusChem ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31802649

RESUMO

Nickel-iron layered double hydroxide (NiFe LDH) is a promising oxygen evolution reaction (OER) electrocatalyst under alkaline conditions. Much research has been performed to understand the structure-activity relationship of NiFe LDH under OER conditions. However, the specific role of the Fe species remains unclear and under debate. Herein, based on DFT calculations, it was discovered that the edge Fe sites show higher activity towards OER than either the edge Ni sites or lattice sites. Therefore, a facile acid-etching method was proposed to controllably induce the formation of edge Fe sites in NiFe LDH, and the obtained sample exhibited higher OER activity. X-ray absorption near edge structure and extended X-ray absorption fine structure analyses further revealed that the interaction of the edge Fe species with Ni is believed to contribute to the enhancement of the OER performance. This work provides a new understanding of the structure-activity relationship in NiFe LDH and offers a facile method for the design of efficient electrocatalysts in an alkaline environment.

6.
Biomed Res Int ; 2019: 4242304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886212

RESUMO

Background: Neck circumference (NC) was found to be related to the risk factors of cardiovascular disease. However, the effects of NC on cardiovascular disease are still controversial. A prospective study of Chinese patients with type 2 diabetes was performed to evaluate the relationship between NC and cardiovascular disease. Methods: A multicenter prospective study with eight-year follow-up was conducted in Beijing communities. Cardiovascular events were defined as myocardial infarction, unstable angina pectoris, hospitalization for heart failure, coronary revascularization, cardiac death, stroke, transient ischemic attack, and cerebral hemorrhage. Results: A total of 3,009 diabetic patients were recruited. Following an eight-year follow-up, 211 patients with cardiovascular events (105 in men and 106 in women) were identified. All patients were categorized into two groups according to the upper quartile of NC (43 cm in men and 39 cm in women). The prevalence of cardiovascular events in men with an NC >43 cm (16.48%) was higher than that in the group with an NC <43 cm (8.16%, p=0.007). The prevalence of cardiovascular events in women with the NC >39 cm (10.67%) was higher compared to the group with NC <39 cm (5.31%, p=0.004). The longitudinal prevalence of cardiovascular events in groups with different NC increased with the increasing duration of follow-up (p < 0.001). Cox regression analysis showed that higher NC was associated with the occurrence of cardiovascular events after adjusting for confounding variables (adjusted HR = 2.305 (1.535-3.460)). Conclusions: NC was associated with the occurrence of cardiovascular events in type 2 diabetes in Chinese communities, and greater NC may increase the risk of cardiovascular events by about 2.3-fold.

7.
PLoS Negl Trop Dis ; 13(11): e0007829, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31765414

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available. AIM: To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk. METHODS: Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors. RESULTS: During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920-0.968), 0.924 (95% CI: 0.896-0.953), and 0.924 (95% CI: 0.895-0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768). CONCLUSION: We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality.

8.
J Am Chem Soc ; 141(48): 19110-19117, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31707780

RESUMO

The tailorable structure and electronic structure of metal-organic frameworks (MOFs) greatly facilitate their modulated light harvesting, redox power, and consequently photocatalysis. Herein, a representative MOF, UiO-66, was furnished by installing Fe3+ onto the Zr-oxo clusters, to give Fe-UiO-66, which features extended visible light harvesting, based on metal-to-cluster charge transfer (MCCT). The Fe-UiO-66 with unique electronic structure and strong oxidizing power exhibits visible light-driven water oxidation, which is impossible for pristine UiO-66. More strikingly, under visible irradiation, the generated holes over Fe-UiO-66 are able to exclusively convert H2O to hydroxide radicals, initiating and driving the activation of stubborn C-H bond, such as toluene oxidation. The electrons reduce O2 to O2•- radicals that further promote the oxidation reaction. The related catalytic mechanism and the structure-activity relationship have been investigated in detail. As far as we know, this is not only an unprecedented report on activating "inert" MOFs for photocatalytic C-H activation but also the first work on extended light harvesting and enhanced photocatalysis for MOFs by introducing an MCCT process.

9.
Biomark Med ; 13(12): 1013-1023, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31385518

RESUMO

Aim: To evaluate the prognostic value of pretreatment prognostic nutritional index (PNI) in nasopharyngeal carcinoma (NPC) patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Materials & methods: We conducted a retrospective study on prognostic value of PNI in NPC patients. A new prognostic marker was explored based on risk stratification with PNI and age. Results: PNI and age were two independent prognostic factors for overall survival (OS) and progression free survival besides node stage and clinical stage. Low prognostic nutritional index and high age (LPNI-HAge) was identified as an independent prognostic factor for both OS (p < 0.001) and progression free survival (p = 0.008), which has a better predict value than sole PNI or age. Conclusion: The novel prognosis index LPNI-HAge provides prognostication of OS and progression free survival for NPC patients treated with neoadjuvant chemotherapy plus concurrent chemoradiotherapy.

10.
J Viral Hepat ; 26 Suppl 1: 32-41, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31380582

RESUMO

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)-negative CHB patients. In this prospective study, 176 HBeAg-negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3-6 months during the 48-week follow-up. The sustained functional cure was evaluated. After the 48-week follow-up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135-127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824-37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.

11.
J Viral Hepat ; 26 Suppl 1: 42-49, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31380591

RESUMO

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non-invasive index for diagnosing liver necroinflammation. This study aimed to create a non-invasive index to predict liver necroinflammation in patients who lack clear-cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)-negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609-0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723-0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg-negative patients with CHB who have normal or minimally elevated ALT levels.

12.
J Diabetes Res ; 2019: 5237371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281851

RESUMO

Background: To examine the association between morbid events and metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM). Methods: A prospective, longitudinal, multicenter study was conducted at 13 community health centers associated with Beijing Tongren Hospital. From 2008 to 2015, there have been 3,525 T2DM patients being managed based on the Chinese guideline for T2DM. The morbid events included macrovascular events, diabetic kidney disease, ophthalmologic events, cancer, and all-cause death. Results: At baseline, there were 2,708 people with MS and 817 without MS. After a seven-year management, there were 351 (12.96%) events in MS people and 74 (9.06%) events in people without MS (p = 0.003). The prevalence of macrovascular events (6.06%) was much higher in MS people than in people without MS (3.79%, p = 0.013). Cox regression analysis showed an association between MS and morbid events even after adjusting for confounding variables (adjusted hazard ratio = 1.44). MS was also associated with macrovascular events (adjusted hazard ratio = 1.96). The occurrence of morbid events and macrovascular events was increased when the numbers of metabolic abnormalities were 1, 2, 3, and 4 (p < 0.001). There was no continuously statistically significant difference in the cumulative prevalence of morbid events between patients with MS and patients without MS during the first five years. However, after six or seven years, the cumulative prevalence of morbid events in patients with MS was continuously significantly higher than that in patients without MS (11.00% vs. 8.20%, 12.96% vs. 9.06%, p < 0.05). Conclusions: T2DM with MS had higher incidence of morbid events, especially cardiovascular events, even after integrated management. The occurrence of morbid and macrovascular events increased as the number of metabolic abnormalities increased. MS was associated with increased risk of morbid events by 44% and macrovascular events by 96%. It would take at least six years to observe the association between MS and morbid events in T2DM.

13.
Sci Total Environ ; 668: 979-987, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31018476

RESUMO

The giant panda (Ailuropoda melanoleuca) is one of the most endangered animals in the world and is recognized worldwide as a symbol for conservation. The Qinling subspecies of giant panda (Ailuropoda melanoleuca qinlingensis) is highly endangered; fewer than 350 individuals still inhabit the Qinling Mountains. Last year, China announced the establishment of the first Giant Panda National Park (GPNP) with a goal of restoring and connecting fragmented habitats; the proposal ignored the environmental pollution caused by economic development in panda habitats. The spatial distribution of heavy metals (Cd, Pb, Hg, Cu, Zn, Mn, Cr, Ni and As) was analyzed in giant panda feces, soil, bamboo, and water in four of GPNP's functional areas at different altitudes and latitudes. Heavy metal pollution decreased with anthropogenic influences, from outside the park through the buffer and into the core area. Cu, Mn, Ni and Zn accumulated from natural sources; As, Hg and Cr were associated with fuel combustion; and Pb and Cd were associated with traffic and agriculture sources. The presence of heavy metals at high altitudes and latitudes in the proposed GPNP is due to emissions from Xi'an and other upwind industrial cities. We conclude that reducing emissions and heavy metal input should be included in the design of the GPNP. Policy interventions should consider functional zones planning, wind direction, reducing mining, and the abandonment of existing roads and farmland within the GPNP to reduce other direct human impacts on the Qinling panda.


Assuntos
Conservação dos Recursos Naturais , Metais Pesados/análise , Poluentes do Solo/análise , Ursidae , Animais , China , Monitoramento Ambiental , Poluição Ambiental , Fezes/química , Mineração , Análise Multivariada , Parques Recreativos
14.
Int J STD AIDS ; 30(6): 550-556, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30722749

RESUMO

Although infectious diarrhea is one of the most common complications in human immunodeficiency virus (HIV)-infected patients, robust diagnostic methods for determining potential pathogens are still limited in the clinic. Norovirus, a type of calicivirus, has been shown to be the most common cause of gastroenteritis. Here, we used multiplex polymerase chain reaction as a diagnostic tool to verify Norovirus as the diarrhea-related pathogen in HIV-infected patients with unknown etiological information. Stool specimens obtained from 81 HIV-infected patients with diarrhea were analyzed by BioFire FilmArray Gastrointestinal (GI) panel. Among 26 HIV-infected patients with unknown etiological information, we detected Norovirus in 14 stool specimens of these patients with 100% sensitivity and specificity as confirmed by reverse transcription polymerase chain reaction (RT-PCR), and one specimen showed both Norovirus and enterotoxigenic Escherichia coli infection. Among the remaining 55 patients with verified Clostridium difficile infection, nine patients also detected positive for Norovirus infection. In conclusion, using FilmArray GI panel and RT-PCR, we determined that Norovirus infection as one of the main pathogens responsible for diarrhea in HIV patients.


Assuntos
Infecções por Caliciviridae/diagnóstico , Diarreia/diagnóstico , Diarreia/virologia , Fezes/virologia , Gastroenterite/diagnóstico , Infecções por HIV/complicações , Reação em Cadeia da Polimerase Multiplex/métodos , Norovirus/isolamento & purificação , RNA Viral/metabolismo , Adulto , Idoso , Diarreia/microbiologia , Fezes/microbiologia , Feminino , Gastroenterite/virologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Norovirus/genética , Norovirus/patogenicidade , RNA Viral/genética , Sensibilidade e Especificidade
15.
Artigo em Inglês | MEDLINE | ID: mdl-30720468

RESUMO

Nonalcoholic steatohepatitis (NASH) has the potential to progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Upregulation of sonic hedgehog (Shh) has been documented in development of NASH through sustained cell stress. At the same time, transforming growth factor-ß1 (TGF-ß1), which is a central element in fibrogenic reactions in various diseases and sites, has been reported to be associated with hepatic inflammation and fibrotic reaction. To explore crosstalk between Shh and TGF-ß1 in the development and progression of NASH, we investigated the expression of both these proteins in 135 human specimens of NASH, 35 fatty liver specimens, 35 specimens of alcoholic steatohepatitis with immunohistochemistry. Shh protein was expressed in the cytoplasm of ballooned hepatocytes with an ubiquitin-like pattern. In addition, a few scattered apoptotic hepatocytes in the inflammatory foci showed homogeneous cytoplasmic Shh expression. TGF-ß1 protein was observed mainly in the activated hepatic stellate cells (HSCs) which were located in the inflammatory foci surrounding ballooned hepatocytes. Moreover, the mRNA levels of both Shh and TGF-ß1 in the liver biopsy specimens from NASH patients was significantly increased compared with those in fatty liver patients. Statistically, there was a significant association of the expressions of Shh and TGF-ß1 proteins in NASH (r=0.6, P<0.05). In addition, increased expression of Shh protein significantly parallels the severity of hepatocellular ballooning, lobular, and portal inflammatory responses and progression of fibrosis in NASH patients. Moreover, we found that much HSCs transformed into myofibroblast-like phenotype and migrated downward to HepG2 hepatocellular carcinoma cells with overexpression of Shh by transwell assay. We also observed overexpression of proteins of Shh and TGF-ß1 in cultured activated HSCs with confocal microscopy. These findings strongly suggest there is interplay between Shh and TGF-ß1 in hepatic inflammatory reactions. Shh secreted through damaged hepatocytes may result in activation of TGF-ß1 and subsequent transformation of HSCs, which together modulate the progression of human NASH.

16.
Dig Liver Dis ; 51(3): 425-433, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30241795

RESUMO

BACKGROUND: The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West. AIMS: This study aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study of the Liver (APASL). METHODS: The nomogram was based on a retrospective study of 573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan Hospital. The results were validated using a bootstrapped approach to correct for bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N = 329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N = 300). RESULTS: Multivariate analysis of the derivation cohort for survival analysis helped identify the independent factors as age, total bilirubin, albumin, international normalized ratio, and hepatic encephalopathy, which were included in the nomogram. The predictive value of nomogram was the strongest compared with CLIF-C ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better in the EASL-CLIF ACHBLF cohort. CONCLUSIONS: The proposed nomogram could accurately estimate individualized risk for the short-term mortality of patients with ACHBLF as defined by APASL.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/mortalidade , Hepatite B/diagnóstico , Hepatite B/mortalidade , Nomogramas , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
17.
BMC Gastroenterol ; 18(1): 179, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509201

RESUMO

BACKGROUND: Acute decompensation (AD) has been shown to be associated with a high mortality rate for cirrhosis patients. This study aimed to develop a prognostic nomogram to evaluating the individual prognosis for AD of cirrhosis in chronic hepatitis B (CHB). METHODS: The nomogram was developed using data from a retrospective study on 509 patients hospitalized for AD of CHB cirrhosis from October 2008 to February 2014 at the Beijing Ditan Hospital, Capital Medical University. The predictive accuracy, discriminative ability, and clinical net benefit were evaluated by concordance index (C-index), calibration curves, and decision curve analysis (DCA). The results were validated on 620 patients consecutively enrolled from January 2005 to December 2010 at the Renji Hospital, Shanghai Jiao Tong University,. RESULTS: On multivariate analysis of the derivation cohort, independent factors included in the nomogram were age, previous decompensation, bacterial infection, hepatic encephalopathy, and total bilirubin. The calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The nomogram had a C-index of 0.897, which was statistically higher than the C-index values of CTP (0.793), MELD (0.821), SOFA (0.868), or the Chronic Liver Failure Consortium AD (CLIF-C AD) (0.716) scores (p <  0.001 for all). Using DCA, the nomogram also demonstrated superior net benefits over other score models. The results were confirmed in the validation cohort. CONCLUSIONS: The proposed nomogram enables more-accurate individualized prediction of survival than MELD, CTP, SOFA, or CLIF-C AD scores for AD of CHB cirrhosis patients.


Assuntos
Hepatite B Crônica/mortalidade , Cirrose Hepática/mortalidade , Nomogramas , Adulto , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Genetics ; 210(4): 1287-1299, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30389807

RESUMO

Transgenerational epigenetic inheritance (TEI) is the inheritance of epigenetic information for two or more generations. In most cases, TEI is limited to a small number of generations (two to three). The short-term nature of TEI could be set by innate biochemical limitations to TEI or by genetically encoded systems that actively limit TEI. In Caenorhabditis elegans, double-stranded RNA (dsRNA)-mediated gene silencing [RNAi (RNA interference)] can be inherited (termed RNAi inheritance or RNA-directed TEI). To identify systems that might actively limit RNA-directed TEI, we conducted a forward genetic screen for factors whose mutation enhanced RNAi inheritance. This screen identified the gene heritable enhancer of RNAi (heri-1), whose mutation causes RNAi inheritance to last longer (> 20 generations) than normal. heri-1 encodes a protein with a chromodomain, and a kinase homology domain that is expressed in germ cells and localizes to nuclei. In C. elegans, a nuclear branch of the RNAi pathway [termed the nuclear RNAi or NRDE (nuclear RNA defective) pathway] promotes RNAi inheritance. We find that heri-1(-) animals have defects in spermatogenesis that are suppressible by mutations in the nuclear RNAi Argonaute (Ago) HRDE-1, suggesting that HERI-1 might normally act in sperm progenitor cells to limit nuclear RNAi and/or RNAi inheritance. Consistent with this idea, we find that the NRDE nuclear RNAi pathway is hyperresponsive to experimental RNAi treatments in heri-1 mutant animals. Interestingly, HERI-1 binds to genes targeted by RNAi, suggesting that HERI-1 may have a direct role in limiting nuclear RNAi and, therefore, RNAi inheritance. Finally, the recruitment of HERI-1 to chromatin depends upon the same factors that drive cotranscriptional gene silencing, suggesting that the generational perdurance of RNAi inheritance in C. elegans may be set by competing pro- and antisilencing outputs of the nuclear RNAi machinery.


Assuntos
Proteínas Argonauta/genética , Proteínas de Caenorhabditis elegans/genética , Elementos Facilitadores Genéticos/genética , Proteínas Nucleares/genética , Proteínas Quinases/genética , Interferência de RNA , Animais , Caenorhabditis elegans/genética , Núcleo Celular/genética , Cromatina/genética , Epigênese Genética , Inativação Gênica , Padrões de Herança/genética , RNA de Cadeia Dupla/genética
19.
Diabetes Res Clin Pract ; 144: 236-244, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30218743

RESUMO

OBJECTIVE: We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. METHODS: A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. RESULTS: During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. CONCLUSIONS: This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. TRIAL REGISTRATION: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.


Assuntos
Aspirina/efeitos adversos , Doenças Cardiovasculares/complicações , Transtornos Cerebrovasculares/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Idoso , Pequim , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores de Tempo
20.
Oncotarget ; 9(62): 32081-32095, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30174798

RESUMO

Background: Due to conflicting evidence regarding first-line therapies for chronic post-surgical pain (CPSP), here we comparatively evaluated the efficacy and safety of first-line therapies for the prevention of CPSP. Materials and Methods: MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for randomized, controlled trials (RCTs) of systemic drugs measuring pain three months or more post-surgery. Pairwise meta-analyses (a frequentist technique directly comparing each intervention against placebo) and network meta-analyses (a Bayesian technique simultaneously comparing several interventions via an evidence network) compared the mean differences for primary efficacy (reduction in all pain), secondary efficacy (reduction in moderate or severe pain), and primary safety (drop-out rate from treatment-related adverse effects). Ranking probabilities from the network meta-analysis were transformed using surface under the cumulative ranking analysis (SUCRA). Sensitivity analyses evaluated the impact of age, gender, surgery type, and outlier studies. Results: Twenty-four RCTs were included. Mexiletine and ketamine ranked highest in primary efficacy, while ketamine and nefopam ranked highest in secondary efficacy. Simultaneous SUCRA-based rankings of the interventions according to both efficacy and safety revealed that nefopam and mexiletine ranked highest in preventing CPSP. Through the sensitivity analyses, gabapentin and ketamine remained the most-highly-ranked in terms of efficacy, while nefopam and ketamine remained the most-highly-ranked in terms of safety. Conclusions: Nefopam and mexiletine may be considered as first-line therapies for the prevention of CPSP. On account of the paucity of evidence available on nefopam and mexiletine, gabapentin and ketamine may also be considered. Venlafaxine is not recommended for the prevention of CPSP.

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