脂质比值与代谢综合征的关联及预测价值评价：基于多阶段横断面研究

背景 随着代谢性疾病发病率的上升,代谢综合征(MS)的预防与控制引起广泛的关注。而脂质比值是重要的筛查指标之一,与MS之间的关系成为热点研究话题。目的 基于贵州省多阶段横断面研究人群分析三酰甘油/高密度脂蛋白胆固醇(TG/HDL-C)、总胆固醇/HDL-C(TC/HDL-C)、低密度脂蛋白胆固醇/HDL-C(LDL-C/HDL-C)及非高密度脂蛋白胆固醇(non-HDL-C)与MS发病风险的关联及预测价值评价。方法 回顾性选取贵州省参与2010年全国疾病监测地区慢性病及危险因素调查、2013年中国慢性病及其危险因素监测、2015年中国成人慢性病与营养监测和2018年中国成人慢性病与营养监测的21 727例自然人群为研究对象,收集研究对象的基线资料,根据是否患有MS将研究对象分为MS组(n=4 981)和非MS组(n=16 746)。绘制受试者工作特征曲线(ROC曲线)分别评价男性和女性TG/HDL-C、TC/HDL-C、LDL-C/HDL-C和non-HDL-C对MS的预测价值。通过Delong检验比较脂质比值预测MS发生的ROC曲线下面积(AUC)的差异。采用多因素Logistic回...     

于阴阳与基因调控关系辨治胃黏膜上皮内瘤变

胃黏膜上皮内瘤变是胃癌前病变,具有发展为胃癌的危险。阳主动,阴主静,文章基于阴阳理论,衷中参西,微观辨证与宏观辨证结合,以阴阳消长失调和基因调控紊乱的关系为出发点,认为胃黏膜上皮内瘤变发生时胃黏膜细胞凋亡周期紊乱和细胞异常增殖分化是阴阳消长失衡在细胞基因调控水平上的体现,进而探讨胃黏膜上皮内瘤变的病因病机以及辨证论治过程,为中医药治疗胃黏膜上皮内瘤变提供更多的理论依据,丰富治疗该病的临床手段。     

糖尿病肾病患者血清TRPM7、Sirtuin-1与钙磷代谢、颈动脉钙化的相关性

目的 探讨糖尿病肾病（DN）患者血清瞬时受体电位通道7(TRPM7)、沉默调节蛋白-1(Sirtuin-1)与钙磷代谢、颈动脉钙化的相关性。方法 选取2020年12月—2022年11月成都大学附属医院收治的97例DN患者作为DN组,另取同期在该院就诊的120例2型糖尿病患者作为对照组。采用实时荧光定量聚合酶链反应检测血清TRPM7的表达,酶联免疫吸附试验检测血清Sirtuin-1水平。采用Pearson法分析DN患者血清TRPM7、Sirtuin-1水平与钙磷代谢的相关性,并通过多因素Logistic逐步回归模型分析DN患者颈动脉钙化的危险因素。结果 DN组血肌酐、尿素氮、血清TRPM7、血磷、颈动脉钙化率高于对照组（P <0.05）。DN组Sirtuin-1、血钙低于对照组（P <0.05）。Pearson相关性分析结果显示,DN患者血清TRPM7与血钙呈负相关（r=-0.247,P=0.000）,与血磷呈正相关（r=0.415,P=0.000）;DN患者血清Sirtuin-1与血钙呈正相关（r=0.367,P=0.000）,与血磷呈负相关（r=-0.505,P=0.00...     

Anion channels in a leaky epithelium

We have used the patch-clamp technique to characterize three anion channels in the ventricular membrane of the choroid plexus epithelium from Necturus. The most frequently occurring channel had a nonlinear IV-curve. The conductance in excised patches with 112 mM chloride at both sides was 28 pS at 0 mV, increasing towards positive membrane potentials. The selectivity ratios were P _NaP _Cl 0.1 and . SITS and furosemide (1 mM) on the inside reduces chloride flux to 0.15 and 0.37 times the control value. In attached patches, the most commonly observed channel had a conductance of 7.5 pS. The single-channel current for this channel reversed direction at 15 mV hyperpolarization, indicating accumulation of chloride to a factor of 1.8 above equilibrium. External stimulation of the tissue by theophylline, IBMX and dbcAMP, or by hypotonic shock did not increase the activity of this channel. In very few excised patches, we have observed a chloride channel with a conductance of 7 pS with 112 mM chloride at both sides. The 7 pS channel appears to be identical to a 2 pS channel found in attached patches. The 2 pS channel was not normally active in attached patches but was activated in 28% of the patches by external stimulation. Finally, in few excised patches we have found a 375 pS channel which inactivates within seconds when membrane potential is stepped from 0 mV to a value that differs more than 10–20 mV from zero. The channel did not conduct gluconate but and P _NaP _Cl 0.1. Internal SITS and furosemide (1 mM) reduced chloride flux to 0.3 and 0.5 times the control value. The channel was never seen in attached patches. The current carried through these channels can not account for the transepithelial steady state Cl^–-flux measured by microelectrodes. KCl exit from the cell is suggested to be carried by KCl-cotransport or by channels that are too small to be seen in patch-clamp experiments.     

Pulmonary and haemodynamic effects of extracorporeal circulation in the cat and the beneficial effects of prostacyclin

Side-effects of a veno-venous extracorporeal system and possible beneficial effects of prostacyclin (epoprostenol) are analyzed on the cat. Three groups were studied; one control group without extracorporeal circulation and two groups with an extracorporeal flow of 10–12 ml/kg/min, one of which was given prostacyclin (70–110 ng/kg/min). The extracorporeal circulation triggered a decrease in arterial saturation (from 99 to 91 %) and carbon dioxide elimination (increase in arterial to end-tidal PCO₂ by about 1 kpa) a metabolic acidosis (pH7.20), a platelet consumption (50%) and shortened survival time, side-effects reduced by prostacyclin. Further, there was a marked increase in haemoglobin concentration indicating hypovolemia via capillary fluid filtration. None of these side-effects were seen in the control group. Extracorporeal circulation as a trigger for pulmonary dysfunction and for impaired tissue nutrition with possible beneficial effects of prostacyclin is discussed, and also from a clinical point of view (i.e. extracorporeal lung assistance, ECLA), on the basis of the results.     

“Reducing body”-like inclusions in skeletal muscle in childhood-onset acid maltase deficiency

Summary Unusual inclusions with some of the features of reducing bodies were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhoodonset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appeared dark blue with the menadione-nitroblue tetrazolium reaction. The significance of the association of inclusions with reducing properties in the setting of acid maltase deficiency is discussed.     

Reciprocal interactions between α2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat

Summary Interactions between a ₂-adrenoreceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (³H-PAC; ₂-adrenoceptor agonist), idazoxan (³H-IDA; ₂-adrenoceptor antagonist) and iodinated neuropeptide Y (¹²⁵I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10^–8M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10nM) increased the K_D value of³H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25nmol) did not change the³H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10^–4 lowered the affinity of³H-PAC binding. NPY (10 nM) had no additional effect, nor did NPYinfluence the GTP induced shift in potency of clonidine to displace³H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10nM) significantly reduced³H-PAC binding (2nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75nmol) or in vitro (10 nM) the binding of¹²⁵I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 g i.e. 24h)¹²⁵I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the ₂-adrenoreceptor antagonist idazoxan.These results provide support for a direct intramembrane interaction between the ₂-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation.     

Role of histamine receptor in mesencephalic nucleus dorsalis raphe in cardiovascular regulation

Summary The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 g) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H₂-receptor blocker, cimetidine (10 g) resulted in hypertension and tachycardia while H₁-receptor antagonist, mepyramine (10 g) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H₁ and H₂ receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 g) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones. These adrenoceptors appear to be of ₁ type (Saxena et al. 1985, 1987) since phenylephrine microinjection evoked excitatory cardiovascular responses could be blocked by piperoxan. Send offprint requests to K. K. Tangri at the above address     

Plateau potentials evoked by climbing-fibre stimulation are restricted to the Purkinje cell dendrites of the cat

The present study investigated the duration of afterdepolarizations in Purkinje cell somata following climbing-fibre activation. Intracellular recordings revealed that, in cells with membrane potentials more negative than -50 mV and with normal spike-generating capabilities, climbing-fibre activation resulted in somatic responses with short afterdepolarizations. As the cell deteriorated and the resting membrane potential became more positive, the duration and form of the climbing-fibre response resembled the plateau potentials recorded from proximal dendrites. The absence of plateau potentials in undamaged Purkinje cell somata was confirmed by extracellular recording of test spike amplitudes following evoked climbing-fibre responses.     

Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-gamma production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies.