Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Sclerosing angiomatoid nodular transformation of the spleen, a rare cause for splenectomy: Two case reports

BACKGROUND Sclerosing angiomatoid nodular transformation(SANT)is a rare benign disease of the spleen with unknown origin.Clinical symptoms are inhomogeneous,and suspicious splenic lesion often found incidentally,leading to splenectomy,as malignancy cannot securely be ruled out.Diagnosis is made histologically after resection.CASE SUMMARY Two cases of German,white,non-smoking,and non-drinking patients of normal weight are presented.The first one is a 26-year-old man without medical history who was exhibiting an undesired weight loss of 10 kg and recurring vomiting for about 18 mo.The second one is a 65-year-old woman with hypertension who had previously undergone gynecological surgery,suffering from a lasting feeling of abdominal fullness.Both showed radiologically an inhomogeneous splenic lesion leading to splenectomy approximately 6 and 9 wk after surgical presentation.Both diagnoses of SANT were made histologically.Follow-up went well,and both were treated according to the recommendation for asplenic patients.CONCLUSION SANT is a rare cause of splenectomy and an incidental histological finding.Further research should focus on clinical and radiological diagnosis of SANT as well as on treatment of patients with asymptomatic and small findings.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

Nie-pinching the spine,puncturing Sifeng(EX-UE 10)plus Chinese herbs for pediatric anorexia due to dysfunction of spleen in transportation:a randomized controlled trial

Objective:To observe the clinical efficacy of Nie-pinching the spine,puncturing Sifeng(EX-UE 10)plus Chinese herbs in treating pediatric anorexia due to dysfunction of spleen in transportation.Methods:A total of 64 kids were randomized into an observation group and a control group by the random number table method,with 32 cases in each group.Patients in both groups received Jian Pi Kai Wei(strengthening spleen and stomach)powder according to pattern differentiation of traditional Chinese medicine(TCM).In addition,patients in the observation group received Nie-pinching the spine and puncturing Sifeng(EX-UE 10).Nie-pinching the spine was applied twice a week,and puncturing Sifeng(EX-UE 10)was performed once a week,with 2 weeks counted as 1 course of treatment.After 2 courses of treatment,the body mass index(BMI),peripheral blood leptin level and the microelements Zn,Fe and Se were compared at different time points(before treatment,after the first and second courses of treatment),as well as the therapeutic efficacy and onset time.Results:After 2 courses of treatment,31 cases in each group were evaluated.After the 1st course and the 2nd course,the BMI and serum Zn,Fe and Se levels in the observation group increased significantly(all P<0.05),the leptin level decreased substantially(both P<0.05);the BMI in the control group showed a substantial rise(P<0.05),while the Zn,Fe and Se levels slightly increased showing no statistical significance(all P>0.05),and the leptin level decreased but the difference showed no statistical significance(P>0.05).After the 1st and the 2nd courses of treatment,the BMI,serum Zn,Fe and Se levels increased more significantly(all P<0.05),and the serum leptin level decreased more significantly(both P<0.05)in the observation group than in the control group.After the 2nd course,the total effective rate and recovery rate in the observation group were both higher than those in the control group(both P<0.05),together with a quicker onset time(P<0.05).Conclusion:Nie-pinching the spine,puncturing Sifeng(EX-UE 10)plus Chinese herbs is effective for pediatric anorexia due to dysfunction of spleen in transportation.It can decrease leptin,increase Zn,Fe and Se levels,alleviate apositic symptoms and increase BMI in the kids.

Mitochondrial dysfunction, mitophagy and tissue fibrosis therapy

Current pharmacological therapies used in clinical practice for individuals with cardiac, hepatic, renal or pulmonary fibrosis do not show desirable effects; therefore, new targets of therapy are urgently required. Mitochon- dria play pivotal role in energy production, metabolism, serving as storage tanks of calcium ions and cell fate deter- mination. Recent results of our experiments and other authors＇ studies suggest that the electron transport chain dys- function, electron leakage increasing, the accumulation of fragmented mitochondria, and the impairment in the mi- tophagy system contribute to pathogenesis of tissue fibrosis. Mitochondria targeting compounds exert promise in trea- ring and attenuating the progress of these diseases, indicating potential strategies to target mitochondria in the treat- ment of tissue fibrosis.

Neuronal PPARαdeficiency-induced axonal mitochondrial transport defects underly isch⁃emic stroke pathology

OBJECTIVE Peroxisome proliferator activated receptor alpha(PPARα)is an important protective factor in neurovascular diseases such as ischemic stroke.Although PPARαexpression is higher in neurons than astrocytes and microglia,the pathophysiological functions of neuronal specific-PPARαin isch⁃emic stroke remains unknown.Here,we report that neuronal PPARαdeficiency is a key factor of neuronal injury.PPARαexpression markedly decreased in neurons after ischemic stroke.METHODS AND RESULTS Neuronal-specific PPARαknockout(NCKO)exacerbates neuronal damage and brain ischemic injury.PPARαdefi⁃ciency disrupts axonal microtubule organization and mitochondrial transport by decreasing the expression of dynein light chain Tctex-type 1(Dynlt1),which is implicated in cytoprotective role with damaged neurons.Furthermore,resto⁃ration of Dynlt1 expression in neurons of NCKO mice rescue mitochondrial transport disorder,cognitive deficits and brain ischemic injury asso⁃ciated with PPARαdeletion.CONCLUSION These results reveal a critical role for neuronal PPARαin ischemic brain injury by modulating axonal mitochondrial transportation.

中医脾虚本质科学内涵研究之探讨

脾虚是中医理论体系的重要组成部分,其在不同的历史时期经历了起源、规范、成熟、完善、发展的过程。中医脾的生理功能涉及“脾主运化、升清、统血”;从脾本脏功能将“脾主运化”分解为“脾主运”和“脾主化”两部分进行研究,更有利于阐释脾主运化科学内涵。脾主运化是脾主升清的基础,脾主升清又是脾主运化的深化,脾主统血则是脾主升清的转归,三者存在递进的逻辑层次关系。随着蛋白质组学、代谢组学和肠道菌群研究的兴起,为脾虚的研究提供了技术支撑;另外,基于中医脾与内质网功能之间的关联性,从内质网应激角度探讨脾虚本质物质基础,为脾虚研究提供了新的方向。

健脾祛痰法治疗血脂异常研究概况

血脂异常在我国普遍存在,中医药干预血脂异常越来越得到人们的重视。中医学认为脾主运化水谷精微,脂质亦需要脾的运化功能布散周身。脾气虚则脾失健运,清气不升,浊阴独留,生湿生痰;痰湿进一步阻碍气机,影响脾胃运化,使脾虚更甚,加重脂浊,浸润血脉。近年来健脾祛痰法被越来越多地应用于血脂异常的防治中,且在临床中收到不错的疗效。

从“脾主运化”理论探讨微塑料在体内的运输和蓄积

微塑料作为新型污染物具有生物危害性,其体内过程尚未阐明。阐明微塑料在体内的运输、蓄积机制是认识其危害的前提和防治其危害的关键环节,但该机制目前尚不清楚。脂质借助载脂蛋白转运与“脾主运化”功能关系密切,作为与脂质具有相似性的微塑料是否也受脾功能调控有待阐明。通过阐明微塑料与载脂蛋白的关系探讨其运输机制,通过脾虚膏脂转输障碍时微塑料蓄积的时空特征探讨其蓄积机制,将有助于认识微塑料体内生理过程和蓄积条件,并深化现代知识背景下中医脾脏象理论新内涵。

基于“脾主运化,在体合肌”理论探析T2DM肌少症骨骼肌细胞铁死亡发病机制及辨证论治

2型糖尿病(Type 2 diabetes mellitus,T2DM)伴随的衰老性疾病是目前糖尿病领域研究热点,肌少症现已成为T2DM继微血管和大血管病变之外的第三大类并发症,能够导致骨折、失能、活动障碍等多种不良事件的发生发展。脾属土,居中焦,主运化,在体合肌。脾之健运、精气得布、肌肉充养,方可发挥正常生理功能。近年研究表明,骨骼肌细胞铁死亡在T2DM肌少症发病机制中具有重要作用。基于“脾主运化,在体合肌”理论,从中医学“脾失运化、精气亏虚、湿浊困阻、肌肉失养”病机观及现代医学“骨骼肌细胞铁死亡”病理机制的角度对T2DM肌少症发病机制进行探讨,归纳T2DM肌少症从脾论治的中医防治原则,为丰富脾藏象理论内涵以及中医药防治T2DM肌少症基础研究和临床试验提供理论支撑。

基于“脾失运化”探讨运脾法调节多囊卵巢综合征内质网应激作用

多囊卵巢综合征(PCOS)是临床常见的异质性疾病,生殖障碍和代谢异常为本病两大病理特征。内质网应激指的是由于多种因素导致未折叠和(或)蛋白质聚集,通过恢复蛋白质正确的折叠方式的一种真核细胞的适应性反应。通过对脾主运化理论的古籍文献梳理发现,脾脏运化水谷,将精微物质布散周身的功能与现代医学中内质网在细胞中的重要作用有着类似之处,即通过承担蛋白质折叠和钙储存等多项任务,保证细胞能够正常发挥生理功能。若脾失运化,痰湿阻滞是本病的核心病机,现代研究认为内质网应激能够较好地阐释脾失运化的发生学原理,这与中医学的病机认识相同。因本病的发病机制与内质网应激存在相似之处,即其发生发展均与炎症、氧化应激、雄激素过多和胰岛素合成及分泌异常等相关。内质网应激的发生可能在PCOS的疾病进展中扮演着重要角色。运脾法能够延缓内质网应激的发生,同时也可有效缓解PCOS的肥胖、胰岛素代偿性增高等相关特征。因此,缓解内质网应激有望成为治疗本病的新思路。健运脾气,补益脾阳为本病治疗大法,从恢复脾运的角度调控内质网应激,以期为改善PCOS相关临床症状提供不同的治疗角度。

滋阴运脾法治疗干燥综合征

目的观察滋阴运脾法联合西医治疗干燥综合征的临床疗效与对患者炎症因子及免疫功能的影响。方法选择干燥综合征患者80例,采用随机数表法分为对照组与观察组,各40例。对照组给予西医治疗,观察组在西医基础上联合滋阴运脾方中药治疗。检测2组外分泌腺指标、免疫球蛋白、补体及红细胞沉降率(ESR)、干扰素-α(IFN-α)、B细胞刺激因子(BAFF)蛋白水平,评估2组干燥综合征疾病自我感受(ESSPRI)评分、中医证候积分、干燥综合征疾病活动指数(ESSDAI)评分变化。结果与治疗前比较,2组治疗12周后唾液流量、自然唾液流率及左侧/右侧泪液分泌明显升高,观察组治疗12周后相关外分泌腺指标均高于对照组(P<0.05)。IgA、IgM、IgG及ESR、IFN-α、BAFF蛋白明显下降,观察组治疗12周后除IgM外其他指标均低于对照组(P<0.05)。2组治疗12周后C3、C4明显升高,观察组治疗12周后C3高于对照组(P<0.05)。2组治疗12周后ESSPRI评分、中医证候积分、ESSDAI评分明显下降,且观察组低于对照组(P<0.05)。结论滋阴运脾法联合西医治疗干燥综合征,可减轻患者症状,抑制炎症因子表达,改善免疫功能和外分泌腺功能。

基于“脾失藏意”从菌群-肠-脑轴探讨认知功能障碍病因病机

认知功能障碍指由大脑功能和结构异常引起的个体感知觉、记忆、理解、学习、创造等功能失调。本文基于脾之运化失常、统血无权和清气不升,结合菌群-肠-脑轴,对肠道菌群失调影响认知功能障碍的中医病因病机展开探讨。中医脾与肠道菌群在生理、病理上相通:脾藏意主认知,脾失健运,运化、统血、升清无能,均可导致脑神失养;肠道菌群与中医脾密切相关,通过神经系统、内分泌、免疫及代谢等机制影响大脑机能。本文可为认知功能障碍的中西医临床研究和治疗提供思路。

益气蠲痹方治疗脾失健运型膝骨关节炎性滑膜炎临床研究

目的:观察益气蠲痹方治疗脾失健运型膝骨关节炎性滑膜炎(knee synovitis,KS)的临床疗效。方法:将70例患者随机分为试验组(35例,后脱落3例,纳入32例)和对照组(35例,后脱落5例,纳入30例)。对照组给予塞来昔布胶囊口服,试验组予以益气蠲痹方口服,两组连续治疗3周。评价治疗前后症状评分、视觉模拟评分法(visual analogue scale,VAS)、西安大略和麦克马斯特大学骨关节炎指数(Western Ontario and McMaster Universities Osteoarthritis Index,WOMAC)评分、膝关节肿胀程度评分等情况,评估不良反应发生情况。结果:治疗后试验组总有效率[93.75%(30/32)]高于对照组[83.33%(25/30)](P<0.01);两组治疗后VAS评分、WOMAC评分及关节肿胀程度评分相比治疗前均降低(P<0.05),且试验组下降幅度大于对照组(P<0.05)。治疗后对照组症状总评分及关节肿胀、关节疼痛、关节活动不利及乏力等症状评分较治疗前降低(P<0.05),但腹胀纳呆、便溏、面黄肌瘦症状评分变化不明显(P>0.05);试验组症状总评分及各症状评分均较治疗前降低(P<0.05);两组在关节活动不利症状评分的改善方面效果相当(P>0.05),但试验组在关节肿胀、关节疼痛、腹胀纳呆、便溏、面黄肌瘦、乏力症状评分的改善方面优于对照组(P<0.01)。结论:益气蠲痹方治疗脾失健运型KS患者,在改善患者腹胀纳呆、便溏、面黄肌瘦等伴随症状上优势明显,并且在治疗期间未出现明显不良反应。

脾不藏意不寐论治刍议

脾不藏意不寐以思虑纷纭所致的迟寐或不寐为主要症状特征,核心病机为脾意失养或脾受邪扰致脾意不安于舍而生不寐,治疗当以安脾意为法。补中益气汤、归脾汤、附子理中汤、参苓白术散、连朴饮、沙参麦冬汤等均具有安脾意的作用,其中,补中益气汤补脾益气升阳以安脾意,归脾汤益气补血健脾以安脾意,附子理中汤温脾阳以安脾意,参苓白术散运脾湿以安脾意,连朴饮化脾热以安脾意,沙参麦冬汤滋脾阴以安脾意,最终达到治疗脾不藏意不寐的目的。

钙离子转运ATP酶B2杂合突变导致小鼠渐进性前庭功能障碍

目的·研究不同月龄钙离子转运ATP酶B2(ATPase plasma membrane Ca^(2+)transporting 2,ATP2B2)Oblivion杂合突变小鼠前庭毛细胞结构和前庭功能的变化。方法·选取2月龄及8月龄Atp2b2 Oblivion杂合突变雄性小鼠各10只,以同龄C57BL/6J野生型雄性小鼠作为对照。通过免疫荧光实验观察不同月龄2组小鼠前庭毛细胞ATP2B2表达情况,并对微纹区及纹外区毛细胞数量进行统计;通过扫描电子显微镜(电镜)观察小鼠前庭毛细胞纤毛形态;通过透射电镜观察小鼠前庭毛细胞带状突触和线粒体;采用前庭诱发电位(vestibular evoked potential,VsEP)、前庭肌源性诱发电位(vestibular evoked myogenic potential,VEMP),及转棒、平衡木实验检测小鼠的前庭功能。结果·2组小鼠ATP2B2均主要表达于前庭毛细胞纤毛,2月龄及8月龄Atp2b2 Oblivion杂合突变小鼠微纹区及纹外区毛细胞数量与野生型小鼠均无明显差异。扫描电镜下,2月龄及8月龄杂合突变小鼠椭圆囊毛细胞纤毛无明显结构异常。透射电镜下,2月龄杂合突变小鼠前庭毛细胞表皮板与神经连接部位附近的线粒体结构无异常,突触结构无异常;8月龄杂合突变小鼠前庭毛细胞表皮板附近线粒体出现空泡样变性,神经连接部位附近的线粒体及突触结构无异常。2月龄及8月龄杂合突变小鼠VsEP及VEMP阈值均较野生型小鼠显著上升,VsEP波形分析显示杂合突变小鼠P1潜伏期延长,P1N1波幅降低(均P<0.05)。2月龄杂合突变小鼠转棒、平衡木实验结果未见明显改变,但8月龄杂合突变小鼠完成转棒、平衡木能力较野生型小鼠显著下降(均P<0.05)。结论·Atp2b2 Oblivion杂合突变小鼠2月龄时前庭电生理功能下降,8月龄时出现前庭相关行为学异常,Atp2b2 Oblivion杂合突变小鼠呈渐进性前庭功能障碍。

从脾论治脂肪组织参与肥胖型胰岛素抵抗

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