Danon disease is a rare X-linked dominant disorder caused by pathogenic variants in LAMP2, typically presenting with cardiomyopathy, skeletal myopathy, and intellectual disability, and showing a severe course in males. In this study, we report the case of a 29-year-old Han Chinese male with the classic triad, plus macular degeneration and a complex neuromuscular phenotype including axonal–demyelinating sensorimotor polyneuropathy. Whole-exome sequencing identified a hemizygous splice-donor variant in LAMP2 (NM_002294.2:c.928 + 1G > A). A functional analysis in peripheral blood with matched controls experimentally confirmed markedly reduced LAMP2 mRNA levels and decreased LAMP2 protein expression, supporting the variant as a loss-of-function allele. The patient rapidly progressed to end-stage heart failure and died 18 months after diagnosis, highlighting the severe multisystem impact of this variant. This case expands the functional evidence for pathogenic LAMP2 splice-site variants and suggests peripheral nervous system involvement in severe multisystem Danon disease.

Background:Primary aldosteronism (PA) frequently coexists with obstructive sleep apnea (OSA), and this comorbidity is associated with increased cardiometabolic risk. Although both PA and OSA have been individually linked to gut microbiome alterations, it remains unclear which layer of gut microbiome-associated variation best reflects clinical heterogeneity in PA with coexisting OSA. Methods:In this prospective observational study, we performed shotgun metagenomic sequencing and untargeted fecal metabolomic profiling in 29 adults with clinically confirmed PA, who were stratified according to OSA severity (G1-G4) based on overnight polysomnography. Microbial gene richness, taxonomic composition, functional potential based on KEGG annotation, and antibiotic resistance gene profiles were analyzed using standardized bioinformatic workflows. Metabolomic variation was assessed using multivariate analysis, pathway enrichment, and additional exploratory analyses incorporating apnea-hypopnea index (AHI) as a continuous variable. Multiple-testing correction was applied to metabolite-level comparisons. Results:Global gut microbial gene richness, alpha diversity, beta diversity, and broad functional profiles did not show strong group-level separation across OSA severity strata. Additional analyses using AHI as a continuous variable similarly showed no significant association between AHI and overall gene richness or alpha diversity indices. Nevertheless, selective genera showed exploratory associations with AHI, suggesting that localized taxonomic signals may occur despite relative stability of global community structure. Antibiotic resistance gene profiles showed marked inter-individual variability without clear group-level separation, although ARO richness showed an exploratory inverse association with AHI. In contrast, fecal metabolomic profiling revealed nominal phenotype-associated differences, including trehalose-related metabolites and FAHFA species that showed inverse exploratory associations with AHI. However, no individual metabolite remained significant after global Benjamini-Hochberg false discovery rate correction. Conclusions:In PA with coexisting OSA, gut microbiome-associated heterogeneity appears to be more readily reflected by selected taxonomic and metabolic signals than by global microbial diversity or broad functional potential. However, given the small sample size, limited control of clinical and lifestyle confounders, and lack of metabolite-level significance after global FDR correction, these findings should be interpreted as exploratory and hypothesis-generating. Larger controlled cohorts incorporating PA subtype, medication exposure, dietary assessment, and longitudinal validation are needed.

Obstructive sleep apnea (OSA) is strongly associated with an increased risk of hypertension; however, the molecular mechanisms linking these two conditions remain incompletely understood. In this study, we identified phosphodiesterase 4B (PDE4B) as a key mediator in the development of OSA-related hypertension. Using integrated bioinformatics analysis and experimental validation, we found that PDE4B expression was significantly elevated in both cell and animal models of OSA combined with pulmonary hypertension. Functional studies demonstrated that PDE4B promotes pulmonary artery smooth muscle cell (PASMC) proliferation and migration, contributing to vascular remodelling. Mechanistically, we uncovered that lactate accumulation under hypoxic conditions induces histone lactylation at the PDE4B promoter, enhancing its transcriptional activity. Furthermore, PDE4B was shown to regulate the phosphorylation and nuclear translocation of FUS, which binds to the angiotensinogen (AGT) promoter and enhances AGT expression, thereby promoting pulmonary hypertension. These findings reveal a novel PDE4B-FUS-AGT signalling axis driven by epigenetic modifications in OSA-induced hypertension, offering potential therapeutic targets for patients with this comorbidity.

BACKGROUND AND OBJECTIVE:Obstructive sleep apnea syndrome (OSAS) is a common sleep breathing disorder, and nonalcoholic fatty liver disease (NAFLD) may affect OSAS. This study aimed to explore the influence of exosomes (Exos) derived from liver cells in NAFLD on the progression of OSAS and the underlying molecular mechanisms. METHODS:C57BL/6J mice were exposed to chronic intermittent hypoxia (CIH) to establish an OSAS animal model, and SH-SY5Y cells treated with CIH were used as the in vitro cellular model. THLE-2 cells treated with oleic acid (OA) were used to simulate NAFLD, and Exos were isolated from these cells. The morphological characteristics of Exos were observed by transmission electron microscopy (TEM), and their particle size distribution and concentration were determined by nanoparticle tracking analysis (NTA). Furthermore, potential binding sites between lncRNA MALAT1 and miR-579-3p, as well as between miR-579-3p and Keap1 mRNA, were predicted using the starBase database. HE staining was used to assess histopathological damage in mouse hippocampal tissues, and TUNEL staining was performed to assess neuronal apoptosis. RESULTS:Exos derived from OA-treated THLE-2 cells significantly upregulated the expression of oxidative stress markers (ROS and MDA) and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) while downregulating the activity of antioxidant factors, including SOD and GSH. These alterations exacerbated neuronal damage in both the hippocampal tissues of OSAS mice and CIH-induced SH-SY5Y cells. Mechanistically, the lncRNA MALAT1 was markedly upregulated in Exos, which promoted Keap1 expression and suppressed Nrf2 expression through MALAT1 delivery, thereby activating the Keap1/Nrf2 signaling pathway. Furthermore, MALAT1 was observed to bind and downregulate miR-579-3p expression, consequently relieving its inhibitory effect on Keap1 and ultimately aggravating neuronal injury in OSAS mice. CONCLUSION:Exosomal lncRNA MALAT1 derived from NAFLD hepatocytes exacerbates OSAS-associated neuronal injury by suppressing miR-579-3p expression and subsequently activating the Keap1/Nrf2 signaling pathway. This discovery not only reveals the molecular link between NAFLD and OSAS-induced neurological damage but also provides critical insights into the pathogenesis of OSAS and potential therapeutic strategies.

RING finger protein 4 (RNF4) acts as a SUMO-targeted ubiquitin ligase, principally regulating protein stability and playing a crucial role in liver injury, inflammatory, and cholestatic diseases. In spite of this, it is unclear how it contributes to nonalcoholic fatty liver disease (NAFLD). The rat model of NAFLD was constructed by feeding a high-fat diet (HFD), and HepG2 cells were treated with 1 mmol/L oleic acid (OA) for 24 h. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to measure the expression of associated genes and proteins. Oil red O staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and hematoxylin-eosin (HE) staining were used to assess damage to HepG2 cells and rat liver tissues. RNF4 expression is reduced in NAFLD. Overexpression of RNF4 in HepG2 cells reduced triglyceride (TG) and total cholesterol (TC) levels and increased high density lipoprotein cholesterol (HDL-C) levels. In addition, overexpression of RNF4 suppressed lipogenic genes liver X receptor alpha (LXRα), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1), and cytochrome P4A11 (Cyp4a11), inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), and cell apoptosis; it also inhibited lipid accumulation in vivo and improved liver tissue pathology, thereby mitigating NAFLD progression. Mechanistically, RNF4 promotes SUMOylation and ubiquitin-mediated degradation of hypoxia inducible factor-2 alpha (HIF-2α), thereby enhancing peroxisome proliferator-activated receptor alpha (PPARα) expression, reducing lipid accumulation, inflammation, and cell apoptosis, ultimately alleviating NAFLD development. Our research indicates that RNF4 may be a novel therapeutic target for NAFLD.

A correlation exists between obstructive sleep apnoea (OSA) and the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), OSA can induce more severe MASLD. However, the underlying regulatory mechanism between the two is unclear. To this end, this study explored the role and possible molecular mechanisms of adipocyte-derived exosomes under OSA in aggravating MASLD. Through sequencing technology, miR-455-3p was identified as a co-differentially expressed miRNA between the MASLD + OSA and Control groups and between the MASLD + OSA and MASLD groups. Upregulation of TCONS-00039830 and Smad2 and downregulation of miR-455-3p in the MASLD and MASLD + OSA groups were validated in vivo and in vitro. TCONS-00039830, as a differentially expressed LncRNA in exosomes found in the sequencing results, transfection notably downregulated miR-455-3p and upregulated Smad2 in hepatocytes. TCONS_00039830 overexpression increased fat, triglyceride and cholesterol levels, while miR-455-3p overexpression decreased these levels. Furthermore, exosome administration promoted the accumulation of fat, triglyceride and cholesterol, upregulated TCONS_00039830 and Smad2, and downregulated miR-455-3p. Overexpression of miR-455-3p reversed the increased fat accumulation and upregulated TCONS_00039830 and Smad2. In conclusion, OSA-derived exosomes promoted hepatocyte steatosis by regulating TCONS_00039830/miR-455-3p/Smad2 axis, thereby aggravating liver damage in MASLD. Exosomes from rats with obstructive sleep apnoea aggravate metabolic dysfunction-associated steatotic liver disease by delivering the lncRNA TCONS_00039830 to hepatocytes and regulating Smad2 expression through targeting miR-455-3p.

Abstract Purpose To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). Methods The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. Results OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. Conclusions OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a disease marked by apnea, hypopnea, decreased oxygen saturation, and disordered sleep structure, which is a major risk for cardiovascular disease. Recent studies have found that OSAHS patients have an increased risk of hypertension, coronary atherosclerotic heart disease, insulin resistance, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, etc. And these patients have a high prevalence of obvious glucolipid metabolism disorder (GMD) , which plays an important role in cardiovascular morbidity and mortality in OSAHS. We reviewed the latest advances in the association of GMD and OSAHS, and the potential pathogenesis of OSAHS-induced GMD and insulin resistance, aiming at providing new ideas for clinical treatment of GMD in OSAHS.

Objectives Although inter-arm blood pressure difference (IAD) and inter-ankle blood pressure difference (IAND) have been shown to be associated with cardiovascular disease, controversy remains. In this study, we investigated the prevalence of IAD and IAND as well as the correlation with arterial stiffness and systolic blood pressure in a large number of the Chinese population. Methods The four-limb blood pressure, IAD, IAND, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) of 12,176 participants have been measured. Multivariate logistic regression analysis was used to analyze the relationship of the increase in IAD/IAND with arterial stiffness and blood pressure. Reporting adheres to the STROBE guidelines. Results In 12,176 participants, 1832 (15%) subjects had an IAD >= 10 mmHg, 663 (5%) had an IAD >= 15 mmHg, and 291 (2%) had an IAD >= 20 mmHg. Correspondingly, 4548 (37%) had an IAND >= 10 mmHg, 2706 (22%) had an IAND >= 15 mmHg, and 1706 (14%) had an IAND >= 20 mmHg. baPWV was significantly higher in those with an IAD >= 10 mmHg (1881 +/- 487 cm/s vs. 1943 +/- 508 cm/s, P = 0.036) and IAND >= 10 mmHg (1850 +/- 476 cm/s vs. 1955 +/- 509 cm/s, P = 0.000). Compared to others, those with IAD or IAND >= 10 mmHg had higher systolic blood pressure (SBP), higher prevalence of hypertension, larger male gender ratio, bigger body mass index, higher pulse rate and lower ABI (P < 0.001 for all). A significant association with baPWV was observed for IAND >= 10 mmHg (OR = 1.117; 95%CI: 1.039-1.201; P = 0.003) not for IAD >= 10 mmHg (OR = 0.771; 95%CI: 0.699-0.851; P = 0.000) in multivariate logistic regression analysis. Conclusions Limb blood pressure differences were closely related to arterial stiffness and systolic blood pressure, allowing for a more comprehensive assessment of cardiovascular risk.

BackgroundThe prevalence of essential hypertension complicated with obstructive sleep apnea hypopnea syndrome (OSAHS) has been increasing year by year. However, due to the differences in medical conditions and lack of clinical understanding in different regions of China, the diagnosis of hypertension complicated with OSAHS is still insufficient. Relevant studies have shown that the pathogenesis of hypertension complicated with OSAHS is closely related to the ectopic accumulation of fat and insulin resistance.ObjectiveThis study attempted to analyze the relationship between OSAHS and abdominal visceral adipose tissue (VAT) and homeostasis model assessment of insulin resistance (HOMA-IR) , and their predictive value for hypertension complicated with OSAHS.MethodsTwo hundred and thirty-four patients with essential hypertension treated at hypertension center of Yan'an Hospital of Kunming Medical University from January 2019 to July 2020 were enrolled in the study. The HOMA-IR of the enrolled patients was calculated by polysomnography, VAT measurement, parallel glucose tolerance and insulin release experiments. According to the AHI level, 27 patients were divided into hypertension group (AHI<5 times/h) , and 207 patients were divided into hypertension complicated with OSAHS group (AHI≥5 times/h) . The levels of VAT and HOMA-IR were compared between 2 groups. The receiver operating characteristic (ROC) curve of screening hypertension patients complicated with OSAHS were determined by HOMA-IR and VAT, and the diagnosis value of area under AUC and different cut-off value were calculated. Logistic regression modeling was used to determine ROC curve with the saved probability as a separate variable to analyze the AUC of the two combined diagnosis of hypertension and OSAHS.ResultsThe VAT, HOMA-IR and BMI of hypertension complicated with OSAHS group were significantly higher than the hypertension group, while LSaO2 was significantly lower than the hypertension group. VAT, HOMA-IR and BMI were positively correlated with AHI (P<0.05) , and LSaO2 was negatively correlated with AHI (P<0.05) . The AUC of ROC curve for the diagnosis of hypertension complicated with OSAHS by VAT was 0.905 〔95%CI (0.861, 0.949) 〕, and the sensitivity and specificity were 0.763 and 0.926 when the diagnostic cut-off point was 100.5 cm2. The ROC curve AUC of HOMA-IR in the diagnosis of hypertension complicated with OSAHS was 0.813 〔95%CI (0.725, 0.900) 〕, when the diagnostic cut-off point was 2.015, the sensitivity and specificity were 0.797 and 0.778, respectively, and the AUC of ROC curve for combined factor diagnosis of hypertension complicated with OSAHS was 0.917 〔95%CI (0.871, 0.963) 〕, the diagnostic cut-off point was 2.045, the sensitivity and specificity were 0.831 and 0.963, respectively.ConclusionVAT and HOMA-IR in hypertension patients complicated with OSAHS are significantly higher than those in patients with hypertension. VAT and HOMA-IR have a certain predictive value for hypertension complicated with OSAHS, and can be applied to medical institutions that unconditionally carry out polysomnography, in order to intervene as early as possible to reduce the risk of serious complications of cardiovascular and cerebrovascular diseases.

Objective: Non-alcoholic fatty liver disease (NAFLD) is an aberrant lipid metabolism disease. Hypoxia inducible factor-1 (HIF-1 alpha) is a transcription factor which plays an important part in adapting lower oxygen condition. Here, we aimed to clarify the relationship between HIF-1 alpha and NAFLD. Methods: HepG2 cells was stimulated by oleic acid (OA) and palmitic acid (PA) to establish in vitro model of NAFLD. The expression of lipid metabolism-related genes, the binding of PPAR alpha to HIF-1 alpha promoter, the lipid deposition, and oxidative stress were detected by qRT-PCR, western blot, Chip assay, Oil Red O staining and ELISA assays, respectively. Results: HIF-1 alpha silence promoted lipid accumulation in NAFLD cells, accompanying by the significantly increased contents of TG (triglyceride) and ApoB (apolipoprotein B). In HepG2 cells treated with OA/PA, the expression of lipid metabolism-related genes and proteins, including APOE, A2m, TNFRSF11B, LDLr, and SREBP2, and the intracellular lipid deposition were up-regulated and further aggravated after silencing HIF-1 alpha. In addition, the loss of HIF-1 alpha could remarkably elevate MDA contents while inhibit the activities of beneficial antioxidant enzymes SOD and GSH-Px to activate oxidative stress, and promote the secretion of pro-inflammatory IL-6 and TNF-alpha to aggravate inflammation in NDFLD cells. PPAR alpha positively bound to HIF-1 alpha promoter. The silence of PPAR alpha aggravated lipid deposition under normal or hypoxic environment in NAFLD cells. In addition, PPAR-alpha silence could decrease the expression of HIF-1 alpha and ANGPTL4 in NAFLD cell model; moreover, the expression of APOE, A2m and TNFRSF11B and the production of TG and MDA were increased by PPAR-alpha suppression. Conclusion: HIF-1 alpha plays a crucial role in the regulation of lipid metabolism through activating PPAR-alpha/ANGPTL4 signaling pathway in NAFLD. (C) 2020 Published by Elsevier Espana, S.L.U.

目的:研究血清可溶性Klotho(sKlotho)水平与原发性高血压动脉硬化的相关性.方法:选取2017年1月-2018年12月在昆明医科大学附属延安医院就诊的196例初诊高血压患者(高血压组)和121例健康对照者(对照组),检测血清sKlotho、血脂、血糖、尿酸等常规生化指标,测定24 h尿钠排泄来计算估测摄盐量,同时检测臂踝脉搏波速度(baPWV)和颈动脉最大内膜中层厚度(IMT),研究血清sKlotho水平与高血压动脉弹性的关系.结果:高血压组血清sKlotho水平较对照组降低,而baPWV和Max IMT较对照组升高(均P＜0.05).高血压组估测摄盐量(10.51±4.19)g较对照组(8.97±3.48)g明显升高(P＜0.01).高血压组中,血清sKlotho水平与年龄、收缩压(SBP)、舒张压(DBP)、平均动脉压(MBP)、24 h尿钠呈负相关性,与估测肾小球滤过率(eG-FR)呈正相关性(均P＜0.01);高血压组baPWV和IMT与血清sKlotho水平呈负相关性(r=-0.59、-0.61,均P＜0.01).baPWV≥1400 cm/s和IMT≥1.0 mm的患者血清sKlotho显著降低(P＜0.05).多重logistic回归分析显示,年龄、吸烟、MBP、血脂异常、估测摄盐量是baPWV的危险因素,血清sKlotho是baPWV的保护因素(P=0.024,OR=0.86,95％CI:0.295～0.977).结论:高血压患者血清sKlotho水平较非高血压患者降低,与动脉硬化指标baPWV、IMT呈负相关性,是baPWV的保护因素,可作为动脉僵硬度的生物标志物.

目的:研究云南省佤族原发性高血压人群估测摄盐量与早期肾损害的关系.方法:选取2014年10月云南省临沧市耿马县四排山乡年龄≥18岁的佤族高血压患者260例(高血压组)和佤族非高血压患者286例(非高血压组).收集所有对象的年龄、性别、身高、体重、血压、腰围、臀围等基本信息.采集空腹静脉血测定空腹葡萄糖(GLU)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、肾功能、电解质等指标.收集点尿标本测定尿电解质、尿白蛋白、尿肌酐,通过点尿法估算24 h尿钠的排泄量.结果:高血压组和非高血压组间体重、BMI、腰围、臀围、收缩压、舒张压、尿酸、TG、血钠、尿钾、估测摄盐量、随机尿白蛋白/肌酐比值均差异有统计学意义(均P＜0.05).高血压组估测摄盐量较非高血压组明显升高,差异有统计学意义[(20.21±5.48) g∶(15.08±3.03)g;P＜0.05].在佤族高血压患者中,估测摄盐量和随机尿白蛋白/肌酐比值高度相关(r=0.89,P=0.000),BMI、腰臀比、收缩压、舒张压、GLU、TG、LDL-C、尿钠/尿钾与尿白蛋白/肌酐比值具有相关性(r=0.243、0.351、0.349、0.291、0.327、0.203、0.298、0.178,均P＜0.05).多元线性回归分析显示,年龄、估测摄盐量、收缩压、舒张压、BMI与尿白蛋白/肌酐比值相关,估测摄盐量是影响尿白蛋白/肌酐比值的独立危险因素.结论:佤族人群普遍估测摄盐量高,该人群估测摄盐量和随机尿白蛋白/肌酐比值高度相关,且是早期肾损害的独立危险因素.

Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and ameliorates cardiac remodeling after acute myocardial infarction (AMI), but the precise mechanisms remain obscure. Herein, we have applied CSWT to a rat model of AMI to demonstrate the arteriogenesis of coronary micrangium and protein expression changes in ischemic myocardium after CSWT. Four weeks after CSWT, the fraction shortening of rats was improved greatly and the cardiomyocyte apoptosis index was significantly lower than the AMI group (P < 0.05). Besides, the fibrotic area was markedly decreased in the CSWT group. In the infarction border zone, the thickness of smooth muscle layer was expanded apparently after CSWT. Label-free quantitative proteomic analysis and bioinformatics analysis revealed that the differentially expressed proteins were largely enriched in the focal adhesion signaling pathway. And integrin linked kinase (ILK) may be a key factor contributed to arteriogenesis of coronary micrangium during CSWT. In conclusion, non-invasive cardiac shock wave could promote arteriogenesis of coronary micrangium and alleviate myocardial apoptosis and fibrosis after AMI. Furthermore, focal adhesion signaling pathway may have a central role in the related signal network and ILK was closely related to the arteriogenesis of coronary micrangium during CSWT.

目的:探讨血管紧张素转换酶(AC E2)基因多态性与佤族原发性高血压(EH)人群的关系.方法:应用SnapShot技术检测了260例云南佤族EH患者及290名正常血压对照者ACE2基因20个多态位点基因型(rs1514283、rs1514282、rs2074192、rs233575、rs714205、rs4240157、rs4646176、rs4646174、rs879922、rs4646156、rs4646155、rs4646188、rs4646140、rs2158083、rs2285666、rs2106809、rs1978124、rs6632677、rs2301692、rs2306193),应用x2检验比较组间基因型及等位基因频率,运用Hardy-Weinberg平衡检验后,用Haploview软件进行连锁不平衡分析,并用SHEsis软件进行单倍体构建,从而探讨ACE2基因多态性与佤族人群高血压的相关关系.结果:①本次研究在20个候选位点发现5个多态位点,这5个位点均存在连锁不平衡现象,但部分位点不能在以后的研究中相互代替.②rs2285666位点、rs714205位点的CC基因型及C等位基因是佤族女性EH的保护因素(P＜0.05,OR＜1),而rs2285666位点的T等位基因、rs714205位点的G等位基因是佤族女性EH患病的致病因素(P＜0.05,OR＞1);在佤族男性群体中并没有发现具有统计学意义的基因型及等位基因(P＞0.05).③对ACE2的5个多态性位点构建单倍型,未发现具有统计学意义的单倍型,说明这5个位点组成的单倍型与佤族EH均无关联.结论:ACE2基因中rs2285666及rs714205这两个多态位点可能与佤族女性EH相关.

The purpose of our study was to identify the relative risky factors of Wa people in Genma region and provide vital recommendations for the pathogenesis, prevention and control of hypertension. The research has using cluster stratification sampling method to chose wa people over the age of 18 in

Interactions between angiotensin-converting enzyme-2 (ACE2) gene polymorphisms and high salt intake increase the risk of hypertension (HTN); however, this association is not well-established in the Chinese Wa population. In this study, we investigated the prevalence and associated factors of HTN in the Chinese Wa ethnic minority in Yunnan Province, China. In addition, we assessed the associations of single nucleotide polymorphisms (SNPs) in ACE2 with blood pressure and environmental factors. Among a total of 838 Wa individuals, the overall prevalence, awareness, treatment and control rates of HTN were 31.03%, 32.81%, 10.77%, and 0.70%, respectively. In addition, 260 hypertensive patients and 290 normotensive individuals were randomly selected for investigations of salt intake and ACE2 SNPs. The levels of e24-h salt intake in female hypertensive patients were significantly higher that those in normotensive individuals. The ACE2 rs2285666 T allele or TT genotype and rs714205 G allele or GG genotype were identified as risk factors for the development of HTN in female Wa individuals. The CGTG haplotype was a risk factor in hypertensive patients. Moreover, high salt intake increased the occurrence of hypertension among ACE2 rs2285666 TT and rs714205 GG individuals. In this study, we not only identified an association between ACE2 gene polymorphism and HTN in the Chinese Wa population, but also a possible link interaction between ACE2 polymorphism type and high salt intake in increasing the risk of HTN in this population.

Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure and hepatocellular carcinoma, which lead to poor long-term prognosis. However, the exact mechanism of development of NAFLD is not well elucidated. In order to better understand the pathogenesis of NAFLD, we have performed an integrative analysis to livers from NAFLD rat models in a global view of the transcriptome. By systemic and integrative analyses, we have found that transport, angiogenesis and cell adhesion were upregulated in response to high fat diet feeding, which may cause a large amount of free fatty acid transport, hepatic fibrosis and hepatocytes injury. GO tree analysis has shown that angiogenesis was upregulated. GO term in response to high fat diet which may cause fibrosis. The pathway interaction network has indicated that upregulated "valine, leucine, and isoleucine metabolism" may decrease the serum concentration of branched-chain amino acid (BCAA). The enhanced degradation of BCAA in NAFLD animal models may lead to inhibition of the regeneration of hepatocytes, reducing the production of albumin, attenuating the inhibition of liver cancer and decreasing immunity. Overall, high fat diet upregulated a variety of metabolism which have converged at TCA cycle. High fatty has pushed the hepatic mitochondria to a "busy state". Comprehensively, genes participated in dysregulated biological process and metabolisms may be served as indicators for evaluation of NAFLD progression and therapeutic targets.

目的 分析老年原发性高血压患者动态动脉硬化指数(AASI)与脉搏波传导速度(baPWV)、脉压指数(PPI)的关系,探讨这些指标在老年高血压患者动脉弹性评估中的意义.方法 选择昆明医科大学附属延安医院2014年5月至2015年2月门诊及住院治疗的老年原发性高血压患者89例,分别进行动态血压检测和无创动脉硬化检测,采用Spearman分析AASI与baPWV、PPI的相关性.结果 本组89例研究对象中baPWV为(1 603.41±19.84) cm/s,AASI为(0.61±0.15),PPI为(0.44±0.06).Spearman等级相关分析显示,AASI与平均舒张压呈负相关(r=-0.157,P＜O.05).baPWV、PPI、平均脉压、平均收缩压与AASI呈正相关(r=0.685、0.701、0.648、0.416,P＜O.01),且AASI与BaPWV、PPI的相关系数最高.结论 AASI可以反映动脉硬化的程度,随着AASI数值的增大,baPWV、PPI也随之增大.