Effect of Non-Alcoholic Fatty Liver Disease on Estimated Glomerular Filtration Rate Could Be Dependent on Age

There is a gap between the association of non-alcoholic fatty liver disease (NAFLD) and renal function in an apparently healthy population. This study aims to assess whether NAFLD is associated with estimated glomerular filtration rate (eGFR) levels and to understand early changes of eGFR in NAFLD. A cross-sectional study was performed among apparently healthy persons who underwent general health screening including laboratory assessments and hepatic ultrasonography from January 2013 to December 2013 at the First Affiliated Hospital of Zhejiang University, College of Medicine, China. This study included 1,193 subjects with a mean age of 48 years. Prevalence of NAFLD was 31.3%. Mean eGFR was significantly lower in NAFLD than in controls (107 ± 19 mL/min/1.73 m²vs. 113 ± 23 mL/min/1.73 m², P<0.001). Correlation analysis between eGFR and NAFLD related risk factors revealed an inverse correlation between eGFR levels and some NAFLD risk factors (all P<0.01). All subjects were classified into five phases according to age. Average eGFR levels of NAFLD were lower than controls in three phases for subjects with ≤ 50 years of age (all P<0.05), while there were no significant differences on average eGFR levels between NAFLD and controls in two phases for subjects with >50 years of age (Both P>0.05). The eGFR level is significantly associated with NAFLD and its risk factors in an apparently healthy population. Effects of NAFLD on eGFR could be dependent on age.     

Assessment of Heart Autonomic Control on the Basis of Spectral Analysis of Heart Rate Variability

An orthostatic test with frequency-controlled breathing (with a respiration period of 10 s) or spontaneous breathing was used to analyze frequency estimates of the heart rate variability (HRV) in the low-frequency (LF) and high-frequency (HF) ranges in young men and women. It was demonstrated that the spectral components of HRV bear no signs of sex differentiation, suggesting a uniform structural organization of the system of autonomic nervous control of the heart (SANCH) in humans. The LF component of the HRV spectrum is a marker of the functional state of the SANCH; it should be studied under conditions of controlled breathing at a frequency of 0.1 Hz. The HF and LF components of the HRV characterize the state of the SANCH at a given moment and do not reflect directly its adaptation reserve. The HF component of the HRV is interesting as a parameter that may be used for estimating the changes in the adaptation reserve of heart autonomic control. It is preferable to analyze this component in the absence of external disturbances in the LF range of the spectrum.     

Ceramide as a Mediator of Non-Alcoholic Fatty Liver Disease and Associated Atherosclerosis

Cardiovascular disease (CVD) is a serious comorbidity in nonalcoholic fatty liver disease (NAFLD). Since plasma ceramides are increased in NAFLD and sphingomyelin, a ceramide metabolite, is an independent risk factor for CVD, the role of ceramides in dyslipidemia was assessed using LDLR-/- mice, a diet-induced model of NAFLD and atherosclerosis. Mice were fed a standard or Western diet (WD), with or without myriocin, an inhibitor of ceramide synthesis. Hepatic and plasma ceramides were profiled and lipid and lipoprotein kinetics were quantified. Hepatic and intestinal expression of genes and proteins involved in insulin, lipid and lipoprotein metabolism were also determined. WD caused hepatic oxidative stress, inflammation, apoptosis, increased hepatic long-chain ceramides associated with apoptosis (C16 and C18) and decreased very-long-chain ceramide C24 involved in insulin signaling. The plasma ratio of ApoB/ApoA1 (proteins of VLDL/LDL and HDL) was increased 2-fold due to increased ApoB production. Myriocin reduced hepatic and plasma ceramides and sphingomyelin, and decreased atherosclerosis, hepatic steatosis, fibrosis, and apoptosis without any effect on oxidative stress. These changes were associated with decreased lipogenesis, ApoB production and increased HDL turnover. Thus, modulation of ceramide synthesis may lead to the development of novel strategies for the treatment of both NAFLD and its associated atherosclerosis.     

Vitamin E Attenuates the Progression of Non-Alcoholic Fatty Liver Disease Caused by Partial Hepatectomy in Mice

Background and Aim

The progression of non-alcoholic fatty liver disease (NAFLD) likely involves a ‘multiple hit’ mechanism. We hypothesized that partial hepatectomy, a procedure performed frequently in patients with NAFLD, would accelerate the progression of disease.

Methods

C57BL/6JolaHsd mice were fed a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA). Part of the mice in the CD-AA group received a diet enriched in vitamin E (~20 mg /day). Two weeks after the start of the diet, mice underwent a partial hepatectomy or a sham operation.

Results

In the CD-AA group, NAFLD activity scores were significantly higher at 7 days after partial hepatectomy compared to the sham operated mice (3.7 ± 1.3 vs. 1.8 ± 0.7; P<0.05). In addition, TBARS, a measure for oxidative stress, in liver tissue of the CD-AA group were significantly higher at day 1, 3 and 7 after partial hepatectomy compared to the sham operated mice (P<0.05). Vitamin E therapy significantly reduced TBARS level at day 7 after partial hepatectomy compared to the CD-AA diet group (P< 0.05). Vitamin E suppletion reduced NAFLD activity score at day 7 after partial hepatectomy compared to the CD-AA group (2.3 ± 0.8 vs. 3.8 ± 1.0; P<0.05).

Conclusion

Partial hepatectomy accelerates the progression of NAFLD. Disease progression induced by partial hepatectomy is substantially attenuated by vitamin E.     

2型糖尿病并发非酒精性脂肪性肝病发病机制的研究进展

随着2型糖尿病(type 2 diabetes,T2DM)患者人数的不断增加,T2DM已成为现代社会影响人们生活质量的沉重负担.T2DM的主要危害为其慢性并发症,除已知的心脑血管、肾脏、视网膜等病变外,非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)也是其常见并发症之一.T2DM与NAFLD密切相关,非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是T2DM患者终末期肝病的最主要原因,并且促进心血管疾病的发生.T2DM和NAFLD相互影响,产生严重后果,因此对二者发病机制的研究也越来越受到重视.本文将就2型糖尿病并发非酒精性脂肪性肝病发病机制的研究进展做一综述.     

2型糖尿病患者心率变异性时域及频域参数与颈动脉粥样硬化的相关性分析

摘要 目的：探讨2型糖尿病患者心率变异性（HRV）时域及频域参数与颈动脉粥样硬化（CAS）患病风险的相关性。方法：根据纳入与排除标准共收集2019年7月至2021年8月上海交通大学医学院附属第九人民医院内分泌代谢科住院的377例2型糖尿病患者的临床资料,并通过3分钟的心电图记录HRV时域[R-R间隔的标准差（SDNN）、相邻R-R间隔差值的均方根（RMSSD）、相邻R-R间隔差值>50 ms的数目占所有R-R间隔总数百分比（PNN50）]和频域[低频功率（LF）、高频功率（HF）、LF/HF、总功率（TP）]参数。根据颈动脉超声有无斑块形成分为无CAS组和CAS组,分析其与HRV各参数的关系。结果：与无CAS组相比,CAS组年龄、心血管疾病、体质量指数（BMI）、糖化血红蛋白A1c（HbA1C）、甘油三酯（TG）水平明显升高,舒张压（DBP）、空腹血糖（FPG）水平降低,差异具有统计学意义（P＜0.05）。CAS组大多数HRV参数低于无CAS组,包括SDNN、RMSSD、PNN50、LF、LF/HF、TP,差异有统计学意义（P＜0.05或P＜0.01）。SDNN与年龄、病程、心血管疾病、饮酒呈负相关（P＜0.05或P＜0.01）;RMSSD与病程、饮酒呈负相关（P＜0.05或P＜0.01）;PNN50与病程呈负相关（P＜0.05）;LF与年龄、病程、心血管疾病呈负相关,与DBP、低密度脂蛋白（LDL）呈正相关（P＜0.05或P＜0.01）;HF与年龄、病程呈负相关,与LDL呈正相关（P＜0.05或P＜0.01）;LF/HF与年龄、心血管疾病、TG呈负相关（P＜0.05或P＜0.01）;TP与年龄、病程、心血管疾病呈负相关,与DBP、LDL呈正相关（P＜0.05或P＜0.01）。使用多因素logistic回归对部分可能的混杂因素进行校正后,SDNN、RMSSD、LF、LF/HF、TP降低仍然与CAS发生的风险增加相关（均P＜0.05）。进一步按糖化血红蛋白（≤7.0%、＞7.0%）分层后分析,糖化血红蛋白＞7.0%组的患者SDNN、RMSSD、LF、TP的降低与CAS发生的风险增加相关（P＜0.05）,而在糖化血红蛋白≤7.0%组,仅RMSSD、PNN50有统计学意义（P＜0.05）。结论：2型糖尿病患者HRV参数SDNN、RMSSD、LF、TP降低与CAS发生的风险增加有关,且糖化血红蛋白＞7.0%的患者有更多的HRV参数（SDNN、RMSSD、LF、TP）与CAS相关。     

OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease

OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance—ROS and PKCε activity—were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD⁺ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD⁺]/[NADH] ratio, indicating respiration-mediated control of the [NAD⁺]/[NADH] ratio. Supporting a prominent role for NAD⁺, increasing the concentration of NAD⁺ stimulated complete oxidation of fatty acids. Importantly, NAD⁺ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD⁺, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.     

Effect of Bombyx mori on the Liver Protection of Non-Alcoholic Fatty Liver Disease Based on In Vitro and In Vivo Models

Edible insects, Bombyx mori (silkworm; SW), which feed on mulberry leaves, have been consumed by humans for a long time as supplements or traditional medication. Non-alcoholic fatty liver disease (NAFLD) is a liver metabolic disorder that affects many people worldwide. We examined the hepatoprotective effects of SW using in vitro and high-fat and high-fructose (HFHF) diet-induced obese in vivo model mice by real-time PCR, immunoblot analysis, and fecal microbiota analysis. SW significantly reduced lipid accumulation and expression of the lipogenic genes in HepG2 cells and the livers of HFHF-induced mice. SW caused significant reductions in triglycerides, and total cholesterol in serum and upregulation of fatty acid oxidation markers compared to the HFHF group. Besides, SW significantly induced phosphorylation of AMPK and ACC in both models, suggesting roles in AMPK activation and the ACC signaling pathway. Furthermore, the gut microbiota analysis demonstrated that SW treatment reduced Firmicutes to Bacteroidetes ratios and the relative abundance of the Lachnospiraceae family compared to HFHF-induced obese mice. These results provide a novel therapeutic agent of hepatoprotective effects of SW for non-alcoholic hepatic steatosis that targets hepatic AMPK and ACC-mediated lipid metabolism.     

Regulation of Inflammation by IL-17A and IL-17F Modulates Non-Alcoholic Fatty Liver Disease Pathogenesis

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. While it is well-accepted that inflammation is central to NAFLD pathogenesis, the immune pathway(s) orchestrating disease progression are poorly defined. Notably, IL-17RA signaling, via IL-17A, plays an important role in obesity-driven NAFLD pathogenesis. However, the role of the IL-17F, another IL-17RA ligand, in NAFLD pathogenesis has not been examined. Further, the cell types expressing IL-17RA and producing IL-17RA ligands in the pathogenesis of NAFLD have not been defined. Here, IL-17RA^-/-, IL-17A^-/-, IL-17F^-/- and wild-type (WT) mice were fed either standard chow diet or methionine and choline deficient diet (MCDD)—a diet known to induce steatosis and hepatic inflammation through beta-oxidation dysfunction—and hepatic inflammation and NAFLD progression were subsequently quantified. MCDD feeding augmented hepatic IL-17RA expression and significantly increased hepatic infiltration of macrophages and IL-17A and IL-17F producing CD4⁺ and CD8⁺ T cells in WT mice. In contrast, IL-17RA^-/-, IL-17A^-/-, and IL-17F^-/- mice, despite increased steatosis, exhibited significant protection from hepatocellular damage compared to WT controls. Protection from hepatocellular damage correlated with decreased levels of hepatic T-cell and macrophage infiltration and decreased expression of inflammatory mediators associated with NAFLD. In sum, our results indicate that the IL-17 axis also plays a role in a MCDD-induced model of NAFLD pathogenesis. Further, we show for the first time that IL-17F, and not only IL-17A, plays an important role in NAFLD driven inflammation.     

Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease

One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.     

S100A9: A Potential Biomarker for the Progression of Non-Alcoholic Fatty Liver Disease and the Diagnosis of Non-Alcoholic Steatohepatitis

Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. Additionally, there are no definite noninvasive methods for NASH diagnosis currently. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with non-alcoholic fatty liver disease (NAFLD) and its progression. Histologic features of rat livers were scored according to criteria established by the Nonalcoholic Steatohepatitis Clinical Research Network. Microarray was performed to assess gene expression changes in rat livers. We find that gene expression of s100a9 was higher in NAFL group compared with control, and was increased in NASH groups and decreased in NAFL + T2DM group compared with NAFL. In contrast, srebf1, tbx21, and gimap4 only showed limited discriminating abilities in different groups. There is a significant positive correlation between serum levels of S100A9 and NAFLD Activity Score (NAS), the severity of hepatic steatosis, and lobular inflammation (r = 0.80, 0.64 and 0.86, P < 0.001). These findings suggest that S100A9 may be extremely useful in the diagnosis of NASH (AUROC: 0.947, CI: 0.845-1.049). Additionally, serum S100A9 levels displayed a strong correlation with ALT, AST and TBil (r = 0.81, 0.89 and 0.91, P < 0.001) but a weak correlation with FBG, HOMA-IR, TG, and TC (r = -0.41, -0.40, 0.47 and 0.49, P < 0.05). Conclusions: The results we provide here suggest that S100A9 may be useful as a biomarker for the hepatic and metabolic progression of NAFLD and the non-invasive diagnosis of NASH.     

Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus

Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more “rigid”), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves.     

Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease

Myeloid-derived suppressor cells (MDSCs) are potent suppressors of T cell immunity in tumors and inflammatory diseases. They are identified by surface expression of CD11b⁺Gr1⁺ in mice, and CD11b⁺Gr1⁺ cells accumulate in the livers of obese mice. However, many myeloid cells share these CD11b⁺Gr1⁺ markers. Accordingly, the aim of this study was to identify the authentic phenotype of MDSCs and investigate their functions in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were divided into 2 diet groups: a normal control group and high-fat group to induce NAFLD. We demonstrated that monocytic CD11b⁺Gr1^dim cells could be further divided into 2 populations based on side scatter (SSC) during flow cytometry. We found that SSC^lowCD11b⁺Gr1^dim cells accumulated in the livers of NAFLD mice over time, and that these cells were recruited by the chemokine CCL2 and its receptor CCR2 and might expand in the liver via macrophage colony-stimulating factor stimulation. Furthermore, SSC^lowCD11b⁺Gr1^dim cells had a strong suppressive ability on T cells; this effect was not observed for SSC^highCD11b⁺Gr1^dim cells, and was dependent on nitric oxide production by inducible nitric oxide synthase. Our findings demonstrate that SSC^lowCD11b⁺Gr1^dim cells represent authentic MDSCs in NAFLD livers, and might serve an important negative feedback function in liver inflammation.     

Preterm Birth Has Sex-Specific Effects on Autonomic Modulation of Heart Rate Variability in Adult Sheep

Introduction

Globally, 11% of infants are born preterm. In adulthood, individuals born preterm are at increased risk of cardiovascular morbidity and mortality, but the mechanistic basis of this remains unknown. Clinically overt cardiovascular disease may be preceded by altered cardiac autonomic activity characterised by increased sympathetic activity and/or reduced parasympathetic activity. Thus, altered cardiac autonomic activity in survivors of preterm birth may underlie later cardiovascular risk.

Objective

To investigate the impact of gestational age on cardiac autonomic activity in juvenile and adult sheep.

Methods and Results

Singleton-bearing ewes were randomised antenatally to spontaneous term birth (TC; n=73) or corticosteroid induced preterm birth (PT; n=60). Cardiac autonomic modulation was assessed using heart rate variability analysis in juvenile and adult offspring. Preterm birth in adult males was associated with altered sympatho-vagal modulation (LFnu: PT 64±4 vs. TC 49±4, p<0.05; LogLF/HF: PT 1.8±0.1 vs. TC 1.5±0.1, p<0.05) and reduced parasympathetic modulation (LogRMSSD: PT 2.9±0.2 vs. TC 3.4±0.1, p<0.05; LogNN50: PT 0.3±0.4 vs. TC 1.6±0.4, p<0.05). Within the range of term birth, each one-day increment in gestational age was associated with a decrement in LFnu in juvenile females and with a decrement in LFnu and LF/HF ratio, but an increment in RMSSD and NN50 in adult females.

Conclusions

Cardiac autonomic function in adult sheep is affected in a sex-specific manner by gestational age at birth, even within the term range. Altered cardiac autonomic function may contribute to increased later cardiovascular morbidity in those born preterm.     

Phenotype,Body Composition,and Prediction Equations (Indian Fatty Liver Index) for Non-Alcoholic Fatty Liver Disease in Non-Diabetic Asian Indians: A Case-Control Study

Objective

In this study, we have attempted comparison of detailed body composition phenotype of Asian Indians with non-alcoholic fatty liver disease (NAFLD) vs. those without, in a case controlled manner. We also aim to analyse prediction equations for NAFLD for non-diabetic Asian Indians, and compare performance of these with published prediction equations researched from other populations.

Methods

In this case-control study, 162 cases and 173 age-and sex-matched controls were recruited. Clinical, anthropometric, metabolic, and body composition profiles, and liver ultrasound were done. Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR), and serum high sensitive C-reactive protein (hs-CRP) levels were evaluated. Multivariate logistic and linear regression analyses were used to arrive at prediction equations for fatty liver [Indian fatty liver index (IFLI)].

Results

As compared to those without fatty liver, those with fatty liver exhibited the following; Excess dorsocervical fat (‘Buffalo hump’), skin tags, xanthelasma, ‘double chin’, arcus; excess total, abdominal and subcutaneous adiposity, and high blood pressure, blood glucose, measures of insulin resistance (fasting insulin and HOMA-IR values), lipids and hs-CRP levels. Two prediction equations were developed; Clinical [Indian Fatty Liver Index-Clinical; IFLI-C]: 1(double chin) +15.5 (systolic blood pressure) +13.8 (buffalo hump); and IFLI-Clinical and Biochemical (CB): serum triglycerides+12 (insulin)+1(systolic blood pressure) +18 (buffalo hump). On ROC Curve analysis, IFLI performed better than all published prediction equations, except one.

Conclusion

Non-diabetic Asian Indians with NAFLD researched by us were overweight/obese, had excess abdominal and subcutaneous fat, multiple other phenotypic markers, had higher insulin resistance, glycemia, dyslipidemia and subclinical inflammation than those without. Prediction score developed by us for NAFLD; IFLI-C and IFLI-CB, should be useful for clinicians and researchers.     

The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis

MethodsWe conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1–19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study.ResultsThe pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3%) and 34.2% (95% CI: 27.8% to 41.2%) in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I² = 98%). There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT) was used to assess NAFLD compared with biopsies, ultrasound scan (USS) or magnetic resonance imaging (MRI).ConclusionsOur review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.     

不稳定型心绞痛心率变异性特点及美托洛尔对其的影响

目的:了解心率变异性(heart rate variability,HRV)在不稳定型心绞痛(unstable angina pectoris,UAP)发病中的作用及其用于病情严重程度判断的价值;了解美托洛尔对UAP患者HRV的影响。方法:选择年龄、性别相匹配的UAP患者、SAP患者和健康人各60例做动态心电图检查,经Holter软件分析进行HRV时域指标的比较。UAP组动态心电图检查后加用美托洛尔25-50 mg/d(分两次口服),20天后重复动态心电图检查。结果:1UAP组与正常组比较各项指标均降低(P0.01)。2正常人HRV具有昼夜节律变化的特点,UAP组HRV昼夜节律变化性降低。3UAP病人服用美托洛尔后,心肌缺血、心律失常得到改善。结论:1.UAP患者心脏自主神经活性主要是副交感神经活性受损,交感神经活性相对占优势。2.无合并症的UAP病人HRV呈昼夜节律性降低。3.美托洛尔可改善UAP患者HRV。     

微粒体甘油三酯转移蛋白基因-164T/C基因多态性与非酒精性脂肪肝的关联性研究

目的:探讨微粒体甘油三酯转移蛋白(Microsomal triglyceride transfer protein,MTP)MTP基因启动子区164T/C单核苷酸多态性与(Single nucleotide polymorphism,SNP)与非酒精性脂肪肝(Non-alcoholic fatty liver disease,NAFLD)的相关性.方法:严格按照诊断标准收集NAFLD患者156例,随机选择健康体检者125例作为对照组,应用聚合酶链反应-限制性酶切片段长度多态性(Polymerase chain reaction restriction fragment length polymorphism,PCR-RFLP)技术对受试者进行基因分型.采用SPSS11.5软件分析各位点基因型、等位基因频率及组间差异.结果:病例组和对照组均检测到MTP基因-164T/C位点TT、TC和CC 3种基因型;MTP基因-164T/C位点的基因型及等位基因频率分布在病例和对照组中差别有统计学意义(P<0.05),NAFLD组等位基因C频率显著高于对照组(P<0.01).结论:MTP基因启动子区164T/C位点多态性可能与非酒精性脂肪肝有关.携带有等位基因C的个体可能更容易患非酒精性脂肪肝.     

Genetic Variants in PNPLA3 and Risk of Non-Alcoholic Fatty Liver Disease in a Han Chinese Population

We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (PNPLA3) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population. We evaluated twelve tagging single-nucleotide polymorphisms (tSNPs) of the PNPLA3 gene in a frequency matched case–control study from Fuzhou city of China (553 cases, 553 controls). In the multivariate logistic regression analysis, the rs738409 GG or GC, and rs139051 TT genotypes were found to be associated with increased risk of NAFLD, and a significant trend of increased risk with increasing numbers of risk genotype was observed in the cumulative effect analysis of these single nucleotide polymorphisms. Furthermore, haplotype association analysis showed that, compared with the most common haplotype, the CAAGAATGCGTG and CGAAGGTGTCCG haplotypes conferred a statistically significant increased risk for NAFLD, while the CGGGAACCCGCG haplotype decreased the risk of NAFLD. Moreover, rs738409 C>G appeared to have a multiplicative joint effect with tea drinking (P<0.005) and an additive joint effect with obesity (Interaction contrast ratio (ICR) = 2.31, 95% CI: 0.7–8.86), hypertriglyceridemia (ICR = 3.07, 95% CI: 0.98–5.09) or hypertension (ICR = 1.74, 95% CI: 0.52–3.12). Our data suggests that PNPLA3 genetic polymorphisms might influence the susceptibility to NAFLD development independently or jointly in Han Chinese.     

冠心病合并脑梗死患者心率变异性及心律失常的变化分析

目的：研究冠心病合并脑梗死患者的心率变异性情况,和心律失常的发生率,分析它们的变化规律,为患者疾病的治疗及预后提供更好的治疗指导。方法：研究对象为2012年2月~2012年12月我院心内科及神经内科的患者,其中Ⅰ组：冠心病合并脑梗死患者40例、Ⅱ组：单纯冠心病患者40例、Ⅲ组：单纯脑梗死患者40例、以及Ⅳ组：健康成人50例,统计全部患24 h心率变异性及心律失常发生情况,并进行对比分析。结果：Ⅰ组患者的心率变异性和心律失常发生明显高于其它组患者,差异均具有统计学意义（P〈0.05）。且心率变异性时域参数下降,心律失常发生率升高。结论：冠心病合并脑梗死患者的心率变异性和心律失常发生率增高,为避免冠心病合并脑梗死的患者突然心律失常及猝死,应积极改变治疗措施。