Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

脑白质病变MRI视觉分级方法的比较

目的:比较7种常用的脑白质病变(WMLs)MRI视觉分级方法,评价各分级之间的相关性和一致性,并计算两两间相互转化的参数.方法:随机选取50例MRI T2-FLAIR显示有不同程度WMLs患者,由两名医师分别用7种分级方法对其WMLs进行评分. 视觉分级间的相关性评价采用Spearman 等级相关分析,不同评估者之间的一致性分析采用Kappa检验,通过回归分析计算各分级间相互转化的参数.结果:不同视觉分级在WMLs评分上均有较强的相关性(相关系数rs: 0.579～0.917, P＜0.05). 除Schelten(modilified)分级和Ylikoski分级外,其它分级在不同观察者间的一致性好(κ＞0.585). 除Aharon-Peretz J分级和De Groot JC分级外,通过回归分析得出了其它5个分级间相互转化的参数,其确定系数R2的范围为0.5856～0.8892.结论:7种不同白质病变的MRI视觉分级间有较好的相关性,而不同评估者间Aharon-Peretz J分级的一致性最好.     

Drug D,a Diosgenin Derive,Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD^-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.     

Associations of Nutritional,Environmental, and Metabolic Biomarkers with Diabetes-Related Mortality in U.S. Adults: The Third National Health and Nutrition Examination Surveys between 1988–1994 and 2016

Background: Nutritional, environmental, and metabolic status may play a role in affecting the progression and prognosis of type 2 diabetes. However, results in identifying prognostic biomarkers among diabetic patients have been inconsistent and inconclusive. We aimed to evaluate the associations of nutritional, environmental, and metabolic status with disease progression and prognosis among diabetic patients. Methods: In a nationally representative sample in the NHANES III (The Third National Health and Nutrition Examination Survey, 1988–1994), we analyzed available data on 44 biomarkers among 2113 diabetic patients aged 20 to 90 years (mean age: 58.2 years) with mortality data followed up through 2016. A panel of 44 biomarkers from blood and urine specimens available from NHANES III were included in this study and the main outcomes as well as the measures are mortalities from all-causes. We performed weighted logistic regression analyses after controlling potential confounders. To assess incremental prognostic values of promising biomarkers beyond traditional risk factors, we compared c-statistics of the adjusted models with and without biomarkers, separately. Results: In total, 1387 (65.2%) deaths were documented between 1988 and 2016. We observed an increased risk of all-cause mortality associated with higher levels of serum C-reactive protein (p for trend = 0.0004), thyroid stimulating hormone (p for trend = 0.04), lactate dehydrogenase (p for trend = 0.02), gamma glutamyl transferase (p for trend = 0.02), and plasma fibrinogen (p for trend = 0.03), and urine albumin (p for trend < 0.0001). In contrast, higher levels of serum sodium (p for trend = 0.005), alpha carotene (p for trend = 0.006), and albumin (p for trend = 0.005) were associated with a decreased risk of all-cause mortality. In addition, these significant associations were not modified by age, sex, or race. Inclusion of thyroid stimulating hormone (p = 0.03), fibrinogen (p = 0.01), and urine albumin (p < 0.0001), separately, modestly improved the discriminatory ability for predicting all-cause mortality among diabetic patients. Conclusions: Our nationwide study findings provide strong evidence that some nutritional, environmental, and metabolic biomarkers were significant predictors of all-cause mortality among diabetic patients and may have potential clinical value for improving stratification of mortality risk.     

Size-Dependent Persistent Luminescence of YAGG:Cr3+ Nanophosphors

In the current work, YAGG:Cr³⁺ nanophosphors were synthesized by the Pechini method and then annealed at different temperatures in the range 800–1300 °C. The structure and morphology of the samples were characterized by X-ray Powder Diffraction (XRPD). The lattice parameters and average crystalline sizes as site occupation by Al³⁺ and Ga³⁺ ions were calculated from the Rietveld refinement data. To investigate the effect of crystalline size of the materials on their optical properties: excitation and emission spectra were recorded and analyzed. Finally, the effect of crystalline size on the probability of carrier recombination leading to PersL was determined experimentally with thermoluminescence analyses. The T_max-T_stop method was applied to determine the trap type and particle size (calcination temperature) effect on their redistribution. A correlation between structural changes and trap redistribution was found. In particular, the extinction of high-temperature TL maximum with increasing annealing temperatures is observed, while low-temperature TL maximum increases and reaches a maximum when the lattice parameter reaches saturation.     

Microstructure and Friction Properties of CoCrFeMnNiTix High-Entropy Alloy Coating by Laser Cladding

To enhance the friction and wear properties of 40Cr steel’s surface, CoCrFeMnNi high-entropy alloy (HEA) coatings with various Ti contents were prepared using laser cladding. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) were used to characterize the phase composition, microstructure, and chemical composition of the samples. The findings demonstrated that the CoCrFeMnNiTi_x HEA coatings formed a single FCC phase. Fe₂Ti, Ni₃Ti, and Co₂Ti intermetallic compounds were discovered in the coatings when the molar ratio of Ti content was greater than 0.5. The EDS findings indicated that Cr and Co/Ni/Ti were primarily enriched in the dendrite and interdendrite, respectively. Ti addition can effectively enhance the coating’s mechanical properties. The hardness test findings showed that when the molar ratio of Ti was 0.75, the coating’s microhardness was 511 HV0.5, which was 1.9 times the hardness of the 40Cr (256 HV0.5) substrate and 1.46 times the hardness of the CrCrFeMnNi HEA coating (348 HV0.5). The friction and wear findings demonstrated that the addition of Ti can substantially reduce the coating’s friction coefficient and wear rate. The coating’s wear resistance was the best when the molar ratio of Ti was 0.75, the friction coefficient was 0.296, and the wear amount was 0.001 g. SEM and 3D morphology test results demonstrated that the coating’s wear mechanism changed from adhesive wear and abrasive wear to fatigue wear and abrasive wear with the increase in Ti content.     

蛋氨酸限制提高内源性H2S活性延缓衰老的机制研究进展

蛋氨酸限制(Methionine restriction,MetR)作为饮食限制的方法之一,能够改善多种无脊椎动物、啮齿类动物及包括人类灵长类动物的衰老及其相关疾病.但MetR对衰老的具体调节作用机制尚未完全明确,目前除了与饮食限制的共有机制以外,越来越多的研究表明内源性硫化氢(Endogenous hydrogen ...     

Prior statin and short‐term outcomes of primary intracerebral hemorrhage: From a large‐scale nationwide longitudinal registry

IntroductionThe relationship between statins and intracerebral hemorrhage outcomes is unclear.AimWe aimed to compare the in‐hospital mortality and evacuation of intracranial hematoma rates in patients with primary intracerebral hemorrhage between prior statin users and nonusers.ResultsThe final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in‐hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61–1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61–0.82). Propensity score matching analyses yielded similar results.ConclusionPrior statin use was not associated with in‐hospital mortality but did reduce evacuation of intracranial hematoma rates.     

脂联素在骨代谢中的研究进展

脂联素是由脂肪组织分泌的一种内源性细胞因子,与受体结合后,参与机体的代谢调节.因此脂联素及脂联素受体也成为治疗代谢性疾病的重要分子靶标.脂联素信号传导的研究对指导临床上骨代谢相关疾病的治疗有着积极的作用.本文就脂联素的生物学特性及其信号传导、脂联素对骨代谢的影响作一综述,为脂联素在骨代谢疾病中的治疗提供参考.     

如何正确使用信韦林(利巴韦林气雾剂)

信韦林（利巴韦林气雾剂）由于疗效确切,在病毒性上呼吸道感染的防治中得到不少医生和患者的认可。然而,由于尚有一些患者、医生不熟悉该剂型,在使用中经常会遇到各种问题。本文以问答形式,向有关患者和医生介绍该品的正确使用方法。