Localization of PIP5Kγ selectively in proprioceptive peripheral fields and also in sensory ganglionic satellite cells as well as neuronal cell membranes and their central terminals

Based on a previous study by others reporting that PIP5Kγ (phosphatidylinositol 4-phosphate 5-kinase γ) and its product, phosphatidylinositol 4,5 bisphosphate (PIP₂), are involved in the regulation of nociception, the present immunohistochemical study examined the localization of PIP5Kγ-immunoreactivity in dorsal root ganglia (DRG) and their peripheral and central terminal fields. PIP5Kγ-immunoreactivity was localized for the first time in the muscle spindles, in which it was found in I-bands of polar regions of intrafusal muscle fibers and also in sensory nerve terminals abutting on equatorial regions of the muscle fibers. This finding indicates the involvement of PIP5Kγ in the proprioception and suggests somehow complicated mechanisms of its involvement because of its heterogeneous localization in intra-I-band structures. In DRG, on the other hand, PIP5Kγ-immunoreactivity was shown to be localized heterogeneously, but not evenly, over apposed plasma membranes of both neurons and ganglionic satellite cells in immune electron microscopy. In addition, no peripheral nerve terminals of DRG showing its distinct immunoreactivity were found in most peripheral fields of nociception and any other sensory perception except for the proprioception through muscle spindles. In contrast, numerous central terminals of DRG in the spinal posterior horn were immunoreactive for it. This finding leads us to consider the possibility that the regulation by PIP5Kγ of nociception is dominantly exerted in DRG and sensory neural tracts central, rather than peripheral, to DRG.     

tDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography

BackgroundTranscranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown.ObjectiveTo investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS.MethodThis study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [¹¹C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters.ResultsMRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [¹¹C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release.ConclusionThe present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.     

Identity crisis of Th17 cells: Many forms,many functions,many questions

Th17 cells are a subset of CD4⁺ effector T cells characterized by expression of the IL-17-family cytokines, IL-17A and IL-17F. Since their discovery nearly a decade ago, Th17 cells have been implicated in the regulation of dozens of immune-mediated inflammatory diseases and cancer. However, attempts to clarify the development and function of Th17 cells in human health and disease have generated as many questions as answers. On one hand, cytokine expression in Th17 cells appears to be remarkably dynamic and is subject to extensive regulation (both positive and negative) in tissue microenvironments. On the other hand, accumulating evidence suggests that the human Th17 subset is a heterogeneous population composed of several distinct pro- and anti-inflammatory subsets. Clearly, Th17 cells as originally conceived no longer neatly fit the long-standing paradigm of stable and irrepressible effector T cell function. Here we review current concepts surrounding human Th17 cells, with an emphasis on their plasticity, heterogeneity, and their many, tissue-specific functions. In spite of the challenges ahead, a comprehensive understanding of Th17 cells and their relationship to human disease is key to ongoing efforts to develop safer and more selective anti-inflammatory medicines.     

瑞马唑仑临床应用的研究进展

瑞马唑仑是一种新型的超短效苯二氮?类药,它具有像瑞芬太尼一样器官独立的新陈代谢作用,并能像咪达唑仑一样作用于γ氨基丁酸（GABA）受体。其起效快,恢复迅速,对肝肾功能及血流动力学影响较轻,且能够被氟马西尼快速逆转,这些药理作用使瑞马唑仑在理论上成为较理想的镇静药物。本文主要就瑞马唑仑的作用机制、药代动力学、对器官功能的影响、临床应用研究进展进行综述,为其临床应用提供理论依据。     

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin-α3γ2, integrin-α6β4, CD151, collagen α-1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642-phosphorylation at the basement membrane, and deposits of laminin-α3 and laminin-γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.     

日本血吸虫感染兔Ⅰ型和Ⅲ型胶原动态变化及干扰素-γ对其的作用

目的　观察感染日本血吸虫的新西兰兔肝脏Ⅰ型和Ⅲ型胶原的动态变化以及γ 干扰素 (IFN γ)对Ⅰ型和Ⅲ型胶原的降解作用。方法　日本血吸虫感染兔在感染后不同时期取 8只病兔肝脏 ,作常规石蜡切片 ,分别进行免疫组织化学α SMA染色、伊红染色和天狼红染色 ,并在偏光显微镜下观察Ⅰ型和Ⅲ型胶原分布情况 ,计算机图像分析计算胶原含量。感染 16wk后 ,给予吡喹酮治疗 ,IFN γ治疗 8wk ,停药观察 4wk。观察IFN γ对Ⅰ型和Ⅲ型胶原沉积的降解作用。结果　感染日本血吸虫的病兔Ⅰ型胶原在第 8周时占总面积百分比的 5 73± 3 40 ,至第2 8周时达总面积百分比的 40 14± 17 0 0 ,约增加了 7倍 ;Ⅲ型胶原则由第 8周时总面积百分比的 1 15± 1 34增加到6 80± 5 19。α SMA阳性细胞表达数则由 2 8± 1 0增加至 7 3± 1 5。自血吸虫感染 16wk开始采用IFN γ治疗 ,8wk后 ,IFN γ治疗组的Ⅰ型和Ⅲ型胶原所占面积百分比分别由原来的 18 5 1± 7 5 2和 4 63± 3 64下降为 2 4wk时的3 0 9± 1 5 4和 0 40± 0 37(P <0 0 1) ,模型对照组和吡喹酮治疗组比较差异具有显著性 (P <0 0 1)。停药 4wk后IFN γ治疗组的Ⅰ型和Ⅲ型胶原所占面积百分比均有所回升 (P <0 0 5 )。结论　IFN γ对日本血吸虫感染的新西兰兔肝纤     

The prevalence of nonalcoholic fatty liver disease in Chinese adults screened by vibration controlled transient elastography and its diagnostic discrepancy compared with ultrasound

BackgroundThe prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques.MethodsWe collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound.ResultsAmong the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P < 0.001), were obese (45.09% vs. 1.79%, P < 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter.ConclusionsMore than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.     

芪柴煎剂对变应性鼻炎大鼠血清IL-4,IFN-γ影响的实验研究

目的:研究芪柴煎剂(自拟方)对变应性鼻炎大鼠模型血清IL-4、IFN-γ的影响,探讨其对变应性鼻炎大鼠的作用疗效。方法:应用卵清蛋白将实验大鼠制作成变应性鼻炎模型,随机分为正常对照组(A组)、芪柴煎剂低剂量组(B组)、高剂量组(C组)、地氯雷他定组(D组)、模型对照组(E组)各8只。连续14 d分别给予对应的药物,A组、E组以蒸馏水替代。用双抗体夹心ELISA法检测血清IL-4、IFN-γ的含量。结果:各实验组血清IL-4含量较模型对照组明显偏低,差异均有统计学意义(P<0.05);芪柴煎剂低剂量组IL-4含量高于芪柴煎剂高剂量组,差异有统计学意义(P<0.05)。各实验组血清IFN-γ含量高于模型对照组,差异均有统计学意义(P<0.05);芪柴煎剂低剂量组、地氯雷他定组IFN-γ含量低于高剂量组,差异有统计学意义(P<0.05)。结论:芪柴煎剂能够下调变应性鼻炎大鼠血清IL-4水平;上调IFN-γ水平。     

甘草干姜汤治疗变应性鼻炎大鼠的实验研究

目的:观察甘草干姜汤对变应性鼻炎大鼠外周血中γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)的表达及鼻黏膜组织的影响。方法:120只大鼠随机分为正常组、甘草干姜汤组、模型组及西药组4组,后3组用卵清蛋白(AVO)制作变应性鼻炎动物模型,分别给予甘草干姜汤2~2.5 m L/只、西替利嗪溶液2~2.5 m L/只、生理盐水2~2.5 m L/只灌胃(模型组及对照组),每天1次;每组大鼠分别在灌胃10、20及30 d时处死10只,检测大鼠血清中IFN-γ和IL-4水平,同时观察各组大鼠各时点的行为学和鼻黏膜组织学变化。结果:灌胃10 d,甘草干姜汤组和西药组与模型组大鼠行为学表现无明显差异(P>0.05),但与正常组存在明显差异(P<0.01);灌胃20 d,甘草干姜汤组和西药组大鼠与模型组和正常组均有明显的差异(P<0.01);灌胃30 d,甘草干姜汤组和西药组行为学变化接近正常组(P>0.05);甘草干姜汤组和西药组灌胃10和20 d时,血清中IFN-γ、IL-4水平与正常组、模型组均有明显差异(P<0.01);灌胃30 d,甘草干姜汤组、西药组IFN-γ和IL-4与模型组比较,分别有明显升高和下降(P<0.01),但与正常组无明显差异(P>0.05);HE染色示甘草干姜汤组与西药组灌胃30 d,鼻黏膜结构逐渐修复,嗜酸细胞显著减少,而正常组与模型组未见明显改变。结论:甘草干姜汤能改善变应性鼻炎大鼠的症状,对鼻黏膜有一定修复作用,其机制可能与调节IFN-γ-及IL-4水平有关。