血清TXNIP在非酒精性脂肪性肝病中的临床意义

目的检测非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)患者血清硫氧还蛋白结合蛋白(thioredoxin-interacting protein,TXNIP)浓度水平,探讨TXNIP在NAFLD中的临床意义。方法用酶联免疫吸附法(ELISA)检测134例NAFLD患者及100名健康对照者血清TXNIP水平,同时收集血糖、血脂等一般资料。结果 NAFLD组血清TXNIP浓度明显高于对照组[(423.94±63.46)pg/ml vs(246.74±83.63)pg/ml,P=0.000];脂肪肝炎组血清TXNIP浓度明显高于单纯性脂肪肝组[(473.30±54.48)pg/ml vs(396.84±65.15)pg/ml,P=0.000]。相关分析表明TXNIP与MDA(r=0.257,P=0.006)、hs-CRP(r=0.178,P=0.018)、TNF-α(r=0.245,P=0.005)、HOMA-IR(r=0.214,P=0.001)呈正相关,但与HDL-c(r=-0.184,P=0.027)、GSH(r=-0.358,P=0.000)呈负相关。多重线性回归分析提示MDA、HOMA-IR是影响TXNIP水平的独立相关因素,血清TXNIP诊断NAFLD和脂肪肝炎ROC曲线下面积为0.957(0.933~0.980)和0.832(0.755~0.909)。结论血清TXNIP与胰岛素抵抗、氧化应激密切相关,有助于NAFLD诊断及病情检测。     

角蛋白18片段与炎症相关因子在脂肪性肝病诊断中的作用

目的 探讨非酒精性脂肪性肝病(NAFLD)伴代谢综合征(MS)的患者细胞角蛋白18片段、炎症相关因子的表达水平,为临床早期预防NAFLD伴有MS的患者向严重肝病进展提供依据.方法 采用横断面调查研究,成组设计.入组85例脂肪肝患者及20例正常对照者.根据是否伴MS分为三组:NAFLD +MS组、NAFLD组、NC组.采用酶联免疫吸附法(ELISA)检测各组血清中细胞角蛋白18片段、炎症相关因子肿瘤坏死因子(TNF)α、白细胞介素6(IL-6)表达水平.通过速率散射比浊法检测血清超敏C-反应蛋白(hs -CRP)表达水平.结果 (1)血清细胞角蛋白18片段(M30)在NAFLD+MS组中高表达[(143±38.7)ng/L],与NAFLD组[(125±36.05)ng/L]、NC组[(118±30.40) ng/L]比较差异有统计学意义(P＜0.05).(2)炎症相关因子TNF α在NAFLD+ MS组[(316±74.5)ng/L]和NAFLD组[(308.6±87.5) ng/L]升高、与NC组[(241.7±75.8)ng/L]比较差异有统计学意义(P＜0.05),在NAFLD组与NAFLD+ MS组间无统计学差异(P =0.677).(3)hs-CRP和IL -6表达水平在MS+ NAFLD组高表达,分别为1.63(1.01,2.42 ) mg/L和(2.18 +0.87)pg/L,与NAFLD、NC组间均具有统计学差异.结论 细胞角蛋白18片段和炎症相关因子在NAFLD伴MS患者中明显增高,提示可能向严重肝病发展,临床工作中应注意对该类患者严密监测.     

硫氧还蛋白相互作用蛋白和炎症小体在慢性心力衰竭中的应用价值

目的:分析硫氧还蛋白相互作用蛋白(TXNIP)、炎症小体3(NLRP3)与心力衰竭(心衰)患者再住院率、活动耐量间的关系。方法:入选患者分为对照组(60例)、射血分数保留组(50例)、射血分数中间组(50例)和射血分数降低组患者(40例)。检测各组患者血浆中TXNIP、NLRP3、BNP的表达水平;记录患者心脏彩超、6 min步行试验结果。分析血清中TXNIP、NLRP3的表达水平是否和心脏功能、患者活动耐力和心衰的再入院率相关。结果:各组年龄和基础病史间无明显差异。随访期间随着射血分数的减低和患者活动耐力降低,血清中TXNIP和NLRP3的表达水平明显升高(P<0.001)。回归分析显示TXNIP和NLRP3是心衰患者再发住院的独立危险因素(P<0.001)。TXNIP和NLRP3预测心衰患者再住院曲线下面积分别为0.815、0.882。结论:TXNIP和NLRP3的表达水平随射血分数和活动耐量的减低逐渐增加,TXNIP和NLRP3是可用于心衰患者再入院的预测因素。     

血清尿酸水平对新诊断2型糖尿病患者非酒精性脂肪性肝病的影响

目的探讨血清尿酸(SUA)水平对新诊断T2DM患者非酒精性脂肪性肝病(NAFLD)的影响。方法选取新诊断T2DM住院患者523例,其中不伴NAFLD患者(Non-NAFLD组)131例,伴NAFLD患者(NAFLD组)392例;按SUA水平分为SUA360μmol/L(N-SUA组)436例,SUA≥360μmol/L(H-SUA组)87例。分别比较两组一般临床指标、SUA、肝功、血脂、血糖、C-P、胰岛素抵抗指数(HOMA-IR)并行相关性分析。结果与Non-NAFLD组比较,NAFLD组SUA水平、SBP、WC、臀围、WHR、体重、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转肽酶(GGT)、TC、TG、LDL-C、FC-P、2hC-P、HOMA-IR升高(P0.05或P0.01)。在男性新诊断T2DM患者中,H-SUA组和N-SUA组NAFLD的发生率分别为87.9%、71.3%(P0.05);在女性新诊断T2DM患者中,H-SUA组和N-SUA组NAFLD的发生率分别为87.4%、75.5%(P0.05);Logistic回归分析显示,高SUA水平是新诊断T2DM患者伴NAFLD的独立危险因素(OR=1.003,95%CI:1.000~1.007,P0.05)。SUA水平预测新诊断T2DM合并NAFLD的受试者工作特征(ROC)曲线下面积为0.646(95%CI:0.594~0.697),当SUA水平≥276.55μmol/L时有最大敏感性(52%)和特异性(69.5%)。结论新诊断T2DM患者NAFLD的发生与SUA水平有相关性,高SUA是新诊断T2DM患者发生NAFLD的独立危险因素。     

血尿酸水平与非酒精性脂肪性肝病的相关性分析

目的观察非酒精性脂肪性肝病(NAFLD)在不同血尿酸(SUA)水平人群中的分布,探讨SUA与NAFLD的相关性。方法选取NAFLD患者(NAFLD组)298例及健康对照者(NC)286名,进一步按SUA水平的四分位数进行分组,比较各组NAFLD的患病率,并进行Logistic回归分析。结果与NC组比较,NAFLD组发病年龄更小,BMI、FPG、SUA、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、TC、TG、LDL-C、SBP、DBP、胰岛素抵抗指数(HOMA-IR)均升高,仅HDL-C降低,差异有统计学意义(P0.05)。Logistic回归分析显示,随着SUA水平的升高,发生NAFLD的风险性增大,趋势差异有统计学意义。结论 SUA水平与NAFLD密切相关。     

MS组分与非酒精性脂肪性肝病相关性分析

目的研究代谢综合征组分与非酒精性脂肪性肝病的关系。方法采用二分类组间比较与多分类趋势分析,比较MS组与非MS组之间、MS组分分组之间样本特征;对符合MS组分标准的患者发生NAFLD的影响因素进行二项Logistic回归分析,并拟合预测方程。结果 MS组的BMI、TC、DBP、SBP、TG、SUA水平值和NAFLD的患病率显著高于非MS组(P0.05);HDL-C与MAU水平值显著低于非MS组(P0.05)。MS组分分组中,随着代谢异常组分的增加,BMI、FPG、DBP、SBP、TG、MAU、SUA水平与NAFLD患病率升高。年龄、BMI、TC、FPG和TG是MS患者发生NAFLD的独立影响因素(P0.05);拟合方程为:Logit(P)=-19.476+0.08年龄+0.457 BMI-1.326 TC+0.918 FPG+2.679 TG。结论 MS组分与NAFLD关系密切;年龄、BMI、TC、FPG和TG是MS患者发生NAFLD的独立影响因素;拟合方程可用于NAFLD的预测判断,为临床筛查识别高风险患者。     

高血压病人非酒精性脂肪肝与血清尿酸的相关性分析

目的探讨高血压病人非酒精性脂肪肝(NAFLD)与血清尿酸(SUA)水平的相关性。方法采用回顾性横断面研究方法分析经腹部B超证实有或无脂肪肝且监测血清尿酸的高血压病人397例,探讨高血压人群中NAFLD与SUA水平的关系。结果腹部B超结果显示,NAFLD189例(47.6%),非脂肪肝208例(52.4%),NAFLD的高血压人群SUA水平较无NAFLD的高血压人群明显升高(321.65μmol/L±83.72μmol/L和288.38μmol/L±73.78μmol/L,P0.01),NAFLD与SUA呈正相关(r=0.218,P0.05);397例高血压病人中SUA360μmol/L 89例(22.4%,高SUA组),SUA≤360μmol/L 308例(77.6%,低SUA组)。高SUA水平组NAFLD发病率64.0%,低SUA组NAFLD发病率为42.8%,两组比较差异有统计学意义(P0.01)。多元Logistic回归分析进一步发现,在校正性别、年龄、体重指数等因素后,高SUA组的NAFLD患病风险较低SUA组明显增加[OR=2.375,95%CI(1.458,3.870),P0.01]。结论高血压病人中NAFLD与SUA呈正相关,SUA是NAFLD的独立危险因素。     

非酒精性脂肪性肝病与动脉粥样硬化关联性的研究进展

非酒精性脂肪性肝病(NAFLD)是与遗传易感性和胰岛素抵抗(IR)密切相关的代谢应激性肝病,目前亦认为是代谢综合征(MS)的肝脏表现,常常与肥胖、2型糖尿病、高血压病、高脂血症以及MS等合并存在。近年来,NAFLD的患病率逐年增高,并且在2型糖尿病、肥胖患者中其患病率更高。动脉粥样硬化(AS)是心血管疾病(CVD)的基础,而目前研究发现NAFLD与CVD关系密切,NAFLD患者主要死亡原因是CVD和恶性肿瘤,NAFLD与AS关系亦密切,其机制目前仍不明确,可能涉及到胰岛素抵抗、血脂代谢紊乱、氧化应激、炎症反应、脂肪激素水平变化和肝功能等方面。本文就NAFLD和AS间的相关性及可能机制进行综述。     

糖耐量减低合并高甘油三酯血症患者硫氧还原蛋白相互作用蛋白与胰岛功能的相关性研究

目的观察IGT伴或不伴高甘油三酯血症(HTG)患者硫氧还原蛋白相互作用蛋白(TXNIP)与胰岛功能的关系。方法选取IGT患者90例(IGT组),IGT合并HTG患者87例(IGT+HTG组)以及正常对照组(NGT组)90名。检测各组血浆TXNIP水平,静脉葡萄糖耐量试验(IVGTT)评价第一时相胰岛素分泌(FPIR),HOMA-β用于评价基础胰岛功能。结果IGT组血TXNIP水平高于NGT组(P0.05),而IGT+HTG组TXNIP水平进一步升高,与IGT组比较,差异有统计学意义(P0.05)。胰岛β细胞功能指数(HOMA-β)和FPIR在NGT组、IGT组、IGT+HTG组逐渐下降,各组间两两比较,差异有统计学意义(P0.05)。相关分析显示,HOMA-β和FPIR与TXNIP呈负相关(P0.05)。结论 IGT患者血浆TXNIP升高,合并HTG患者升高更明显;基础胰岛功能及早时相胰岛素分泌功能均与血浆TXNIP相关。     

正常血清尿酸与非酒精性脂肪性肝病的相关性研究

目的研究普通人群中正常SUA与非酒精性脂肪性肝病(NAFLD)的关系。方法收集22209例正常SUA体检者的临床和生化资料并通过腹部B超诊断NAFLD。按照是否存在NAFLD分为非NAFLD(Non-NAFLD)组和NAFLD组,按照性别特异的SUA四分位数分为4组(Q1~Q4)。结果本研究人群中NAFLD的患病率为20.9%。随着SUA水平升高,各组年龄、BMI、SBP、DBP、TG、TC、LDL-C、Scr、谷丙转氨酶(ALT)和谷草转氨酶(AST)均升高,而HDL-C降低(P0.001);Q1组至Q4组,NAFLD患病率逐渐升高(分别为12.3%、16.0%、23.0%和32.6%,P0.001);校正性别、年龄、BMI、血压、血脂后,多元Logistic回归分析显示,Q2~Q4组NAFLD患病风险较Q1组分别增加24%、43%和94%(P0.001)。结论普通人群正常范围内SUA的升高与NAFLD密切相关,可能是其发生的独立危险因素。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.