Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.

Yizhi Xingnao prescription improves the cognitive function of patients after a transient ischemic attack

Patients with mild cognitive impairment after a transient ischemic attack were included in this study. They were treated with Yizhi Xingnao prescription, ergoloid mesylates or aspirin for 60 days. Evaluation using the Montreal Cognitive Assessment Scale showed that cognitive function was significantly improved in all patients, especially after the combined treatment of Yizhi Xingnao and aspirin. The scores from the Montreal Cognitive Assessment Scale were improved overall and the effective treatment rate was as high as 79%, which was higher than patients treated with a combination of ergoloid mesylates and aspirin, or aspirin alone. Our experimental findings indicate that YizhiXingnao prescription can improve mild cognitive impairment after a transient ischemic attack, and that it is more effective than ergoloid mesylates.

Intervention of Bushen Yizhi formula on cognitive disorder rat and the related mechanism of the protective function on neural network

OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.

复方苁蓉益智胶囊治疗轻中度血管性痴呆

目的探讨复方苁蓉益智胶囊治疗轻中度血管性痴呆的临床疗效及对患者各临床检测指标的影响。方法选择2022年9月-2023年5月收治的轻中度血管性痴呆患者140例,随机分为对照与治疗组,各70例。对照组给予银杏叶提取物注射液治疗,治疗组在对照组基础上联合复方苁蓉益智胶囊治疗。比较2组临床疗效结果,治疗前后认知、神经功能、精神行为症状、血液流变学、血流动力学、应激反应指标、血清血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)水平变化,比较2组不良反应发生情况。结果治疗组治疗6个月后临床疗效总有效率(95.71%,67/70)高于对照组(78.57%,55/70)(P<0.05)。2组治疗6个月后MMSE评分、大脑前动脉平均血流速度、中动脉平均血流速度及血清SOD、VEGF、BDNF水平高于治疗前(P<0.05),治疗组高于对照组(P<0.05);2组治疗6个月后NIHSS、NPI-Q评分、全血低切黏度、全血高切黏度、血浆黏度及血清MDA、Caspase-12、CRP78、MMP-9、MMP-2水平代于治疗前(P<0.05),治疗组低于对照组(P<0.05)。治疗组治疗不良反应总发生率低于对照组(P<0.05)。结论复方苁蓉益智胶囊治疗轻中度血管性痴呆患者临床疗效较好,安全性较高。

方以智与晦山戒显的青原之会

康熙五年(1666),晦山在青原山净居寺拜会了方以智。方以智非常兴奋,给予了极其热情的接待。晦山戒显对此感动不已,遂赋诗一首,记录下了自己的兴奋之情。方以智与晦山谈及自己的著作《药地炮庄》,晦山为之作序,给予高度评价。可以说,晦山戒显与药地愚者方以智青原之会具有多方面的文化意蕴。

“必震六兆”溯源与举证

“必震六兆”出自1935年《重修隆德县志》的《震灾》篇,它源于龙华民《地震解》中的“地震六兆”;《地震解》是龙华民译自科英布拉《〈天象学〉疏注》。古今许多震例证明“必震六兆”是基本可信的,但也有其局限性。《震灾》篇作者总结出“必震六兆”,是有胆有识,贡献卓著的创新之举,值得后人学习、传承、发扬光大。

基于网络药理学探讨复方苁蓉益智胶囊治疗轻度认知障碍的作用机制

目的基于网络药理学对复方苁蓉益智胶囊(fufang congrong yizhi capsule,FCYC)治疗轻度认知障碍(mild cognitive impairment,MCI)的作用机制进行预测和细胞实验验证。方法利用TCMSP、GeneCards、OMIM和TTD数据库、《中国药典》以及文献筛选FCYC的活性成分及治疗MCI的作用靶点,构建中药-化合物-靶点-疾病网络图以及交集靶点的蛋白相互作用图,通过易汉博生物信息平台进行GO和KEGG分析。利用Aβ25-35诱导神经细胞PC12损伤建立MCI细胞模型,FCYC预处理探究药效及机制:CCK-8法和LDH试剂盒测定细胞活力,JC-1检测细胞线粒体膜电位,ELISA法检测IL-1β、IL-6和TNF-α表达,免疫荧光法及Western blot法检测Bcl2、Bax和PI3K/AKT信号通路相关蛋白的表达。结果FCYC共有57个活性成分可能通过66个潜在靶点治疗MCI,GO富集分析结果显示这些靶点涉及339个生物过程、39个细胞组成以及65个分子功能;KEGG通路主要涉及PI3K-AKT、TNF信号通路等。实验结果表明,FCYC可明显提高Aβ25-35诱导损伤的PC-12细胞活力,降低PC-12细胞中IL-1β、IL-6和TNF-α的分泌,上调Bcl2/Bax的比例,并增加p-PI3K/PI3K和p-AKT/AKT的表达。结论FCYC通过多成分-多靶点-多通路治疗MCI,其可抑制神经炎症和神经细胞凋亡,其可能机制为通过调控PI3K/AKT信号治疗MCI。

杞参益智方改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的效应评价研究

目的评价杞参益智方对D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的改善效应。方法小鼠皮下注射D-半乳糖构建亚急性衰老动物模型,分别给予阳性药多奈哌齐(2 mg·kg^(-1)·d^(-1))、杞参益智方低剂量组(1.33 g·kg^(-1)·d^(-1))、高剂量组(2.67 g·kg^(-1)·d^(-1)),连续给药30 d。通过水迷宫和Y迷宫实验评价模型小鼠学习与记忆行为;采用HE染色考察模型小鼠海马损伤情况;采用TUNEL法检测小鼠海马组织凋亡情况;采用ELISA法检测小鼠海马组织中氧化应激因子与炎症因子表达水平;采用Western blot法检测小鼠海马凋亡、氧化应激与炎性应激相关信号通路蛋白表达。结果杞参益智方水提取物显著缩短模型小鼠水迷宫测试中潜伏期和上台前路程(P<0.01),增加穿越平台次数(P<0.01);增加模型小鼠Y迷宫新臂探索时间和次数(P<0.05);抑制模型小鼠海马TUNEL荧光表达(P<0.01);上调氧化应激因子超氧化物歧化酶(SOD)活力(P<0.05)与谷胱甘肽(GSH)含量(P<0.05),下调丙二醛(MDA)含量(P<0.05);下调白细胞介素(IL)-1β、IL-6与肿瘤坏死因子(TNF-α)表达水平(P<0.05,P<0.01);下调凋亡信号通路蛋白Cleaved Caspase-3与Caspase-3表达(P<0.05),上调氧化应激信号通路蛋白Nrf2与HO-1表达(P<0.05),下调炎性应激信号通路蛋白p-NF-κB与NF-κB表达(P<0.05)。结论杞参益智方具有改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的作用,可能与其抑制海马氧化应激与炎性应激作用相关。

生慧益智汤联合盐酸多奈哌齐对轻中度阿尔茨海默病患者精神行为症状的影响

目的基于“神志病”视角,探究生慧益智汤联合盐酸多奈哌齐对轻中度阿尔茨海默病(Alzheimer,s disease,AD)患者精神行为症状(behavioral and psychological symptoms of dementia,BPSD)的临床疗效。方法选取符合纳入标准的AD患者70例,随机分为治疗组和对照组,每组35例。对照组患者给予盐酸多奈哌齐,治疗组患者给予生慧益智汤联合盐酸多奈哌齐治疗,疗程6个月。治疗前后采用AD认知评定量表(Alzheimer's disease assessment scale-cognitive subscale,ADAS-cog)和神经精神症状问卷(neuropsychiatric inventory,NPI)评分,评估患者认知功能及精神行为异常表现,并观察治疗期间药物不良反应。结果治疗后2组患者ADAS-cog、NPI评分较治疗前均显著降低(P<0.05),治疗组明显低于对照组(P<0.05)。NPI在抑郁、焦虑、情感淡漠领域,2组患者治疗后评分均低于治疗前(P<0.05),且治疗组明显低于对照组(P<0.05);此外治疗组患者治疗后妄想、易激惹、睡眠/夜间行为异常评分低于治疗前(P<0.05),且评分低于对照组(P<0.05)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论轻中度AD患者BPSD以抑郁、淡漠、易激惹、焦虑、睡眠/夜间行为异常、妄想为主,生慧益智汤联合多奈哌齐能整体改善认知功能、减轻上述BPSD症状。中西医结合疗效优于单用多奈哌齐,值得临床推广应用。

益智清心方单次给药毒性试验研究

目的:观察24 h内益智清心方经口灌胃后的急性毒性反应和死亡情况,评价益智清心方的安全性,为进一步的重复给药毒性试验以及临床用药提供参考。方法:选取24~33 g ICR小鼠,雌雄各半,随机分为益智清心方组和空白对照组,采用最大给药量法,以最大灌胃体积40 mL/kg计,分别给予等体积的益智清心方药液和纯水,2次/d,给药期间定期监测小鼠一般状况和体质量,14 d后,收集血、尿样本,并进行大体解剖,评价益智清心方对脏器系数、血常规、尿常规等安全性指标的影响。结果:ICR小鼠按40 mL/kg经口灌胃给予最大可配制浓度为0.36 g干浸膏/mL的益智清心方药液,当日2次,累积剂量为98.6 g生药/kg体质量,约相当于成人临床拟用剂量的298倍(按公斤体质量计算)和38倍(按体表面积计算)。各组小鼠均未发现毒性相关的症状和死亡,益智清心方组小鼠在体质量、脏器系数、血常规、尿常规指标方面与对照组小鼠比较差异均无统计学意义(均P>0.05)。结论:本试验条件下,益智清心方的单次给药毒性试验中未见明显的急性毒性反应及死亡,提示其最大耐受量(MTD)>98.6 g生药/kg体质量。

侯外庐的方以智思想研究及其典范意义

全面评介方以智思想,是侯外庐后期学术研究的焦点。经过他与其学术团队的持续努力,方以智被遮蔽近三百年的思想全貌得以公之于世,恢复了其在中华民族文化史上的哲学地位。侯外庐的方以智思想研究,既具有《中国思想通史》理论与方法的一般特征,又存在自身特色。不仅以社会史研究为前提,深刻剖析方以智生平悲剧的矛盾根源及内在思想张力,而且以宏通的世界历史眼光,在中西启蒙思想的对比评价中,赋予方以智思想以世界性哲学意义。侯外庐的方以智思想研究业已成为历史,固然需要“批判地对待”,但他在研究中贯彻的史学理论、方法与目标,即以马克思主义历史科学的民族化来建立比较完整的马克思主义中国思想史体系,具有深远的典范意义,在今天仍能予人有益的启发。

基于网络药理学和分子对接技术探讨复方菖蒲益智汤治疗轻度认知功能障碍的作用机制

目的:基于网络药理学和分子对接技术探究复方菖蒲益智汤治疗轻度认知功能障碍(MCI)的药理学作用机制。方法:通过TCMSP平台和PubChem、Swiss Target Prediction数据库获取复方菖蒲益智汤主要的6味中药的活性成分和作用靶点,从GeneCards、DisGeNet、OMIM、TTD数据库获取MCI的相关基因。利用Venny 2.1.0平台将药物的成分靶点与MCI相关的靶基因取交集,利用Cytoscape 3.7.2进行“药物-成分-靶点-疾病”网络图的构建,并利用STRING平台构建蛋白-蛋白相互作用(PPI)网络图,然后利用Metascape平台进行KEGG通路富集分析与GO功能富集分析。最后利用Autodock vina V1.2.0对核心作用靶点及主要药效成分进行分子对接,验证它们之间的紧密联系程度。结果:复方菖蒲益智汤治疗MCI的潜在靶基因共178种。PPI网络图筛选出AKT1、TNF、EGFR、CASP3、IL1B、VEGFA 6个关键核心靶点,涉及7NH5、6Q00、8A27等关键核心靶蛋白;KEGG通路富集分析结果表明,AKT1、TNF、IL1B、VEGFA 4个关键核心靶点在AGE-RAGE信号通路中。分子对接结果显示,复方菖蒲益智汤的有效成分与上述6个关键核心靶点的结合活性良好。结论:复方菖蒲益智汤中主要的6味中药的活性成分可作用于AKT1、TNF、IL1B等多个靶点,通过调控AGE-RAGE通路发挥治疗MCI的作用。

益智清心方对记忆功能障碍小鼠的保护作用研究

目的:评价益智清心方对小鼠记忆功能障碍的影响。方法:在益智清心方给药15 d后,分别于训练前、训练后以及测试前选取96只ICR小鼠分别采用东莨菪碱、亚硝酸钠和乙醇建立记忆获得障碍、记忆巩固障碍和记忆再现障碍小鼠模型,各32只。按随机数字表法分对照组、模型组、益智清心方低剂量组和益智清心方高剂量组,每组8只。采用旷场实验、新物体识别实验和跳台实验评估各组小鼠运动能力,以及益智清心方对记忆获得障碍、记忆巩固障碍和记忆再现障碍的影响。此外,运用苏木精-伊红(HE)染色观察益智清心方对学习记忆障碍小鼠脑组织病理形态影响。结果:旷场实验未发现各组小鼠运动能力的差异。新物体识别实验表明,益智清心方低、高剂量组小鼠较模型组对新物体的偏好指数和识别系数均明显升高。跳台实验显示,益智清心方低、高剂量组较模型组小鼠的错误次数减少,逃避潜伏期延长。海马区HE染色显示.与模型组比较,益智清心方低、高剂量组锥体细胞层细胞带结构较完整,分层明显,细胞排列紧密,神经元体积较大,形态较规则,结构清晰,胞浆透明。结论:益智清心方可以改善记忆损伤模型动物的学习记忆能力。

Protective effect of Shouwu Yizhi decoction against vascular dementia by promoting angiogenesis

Shouwu is a traditional Chinese medicine(TCM)with neuroprotective effect.Shouwu Yizhi decoction(SYD)was designed based on TCM theory.However,little is known about the roles of SYD in Vascular dementia(Va D).The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion(I/R)rat model to induce Va D.SYD administration(54 mg·kg^(-1))for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion(MCAO)rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test.Moreover,SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats,thereby alleviating Va D.Mechanistically,SYD caused increases in the expression of vascular endothelial growth factor(VEGF),CD34 and CD31,compared with the MCAO rats in coronal hippocampus.Simultaneously,the expression level of mi R-210 was elevated significantly after SYD administration,compared with the vehicle rats(P<0.01).The expression of Notch 4 at both m RNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats(P<0.05).Overall,the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced mi R210 expression to activate Notch pathway,and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats,ultimately enhancing the cognition and memory of MCAO rats.Therefore,our findings preliminarily identified the effect and the mechanism of action for SYD on Va D in rats.SYD could be a potential candidate in treatment of Va D.

Clinical Experience in Treatment of Alzheimer’s Disease with Jiannao Yizhi Formula (健脑益智方) and Routine Western Medicine

Objective:To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula(健脑益智方,JYF)in the treatment of Alzheimer’s disease(AD).Methods:Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment(30 with JYF)and the control groups(30 with donepezil)for 6 months with the random numbers.The primary outcomes were scores of Alzheimer’s Disease Rating Scale-Cognitive(ADAS-Cog)and Chinese Medicine Symptom Scale(CM-SS).The secondary outcomes were scores of Mini Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA),and Activities of Daily Living(ADL).Safety assessments were conducted at baseline and the 6 th month of treatment.Serum levels of acetylcholine(Ach),amyloid-β protein 42(Aβ42),and the microtubule-associated protein tau(Tau)were also determined by enzyme-liked immunosorbent assay.Results:Fifty-one participants were included in the final analyses(JYF n=27;donepezil n=24).Compared with baseline,both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores(P<0.05 or P<0.01).Both drugs increased the serum levels of Ach and decreased the serum levels of Aβ42 and Tau(all P<0.05).There was no significant difference in these variables between the two groups,which showed that JYF was not inferior to donepezil.No obviously significant changes were observed in the ADL.No severe adverse events were observed in both groups.Conclusion:The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.

涤痰益智汤对血管性痴呆大鼠海马神经元形态及FAM134B蛋白表达的影响

目的观察涤痰益智汤对血管性痴呆大鼠学习记忆能力、海马组织结构、海马神经元形态及海马组织内质网自噬相关蛋白FAM134B表达的影响,探讨其治疗血管性痴呆的作用机制。方法32只SD大鼠随机分为假手术组、模型组、多奈哌齐组和涤痰益智汤组,每组8只。模型组、多奈哌齐组和涤痰益智汤组采用改良双侧颈总动脉永久性结扎法制备血管性痴呆大鼠模型,假手术组仅分离颈总动脉、不结扎。造模结束后,多奈哌齐组予盐酸多奈哌齐溶液灌胃,涤痰益智汤组予涤痰益智汤药液灌胃,假手术组和模型组予等体积蒸馏水灌胃,连续4周。Morris水迷宫实验评估大鼠学习记忆能力,HE染色及尼氏染色观察海马组织形态,透射电镜观察海马神经元超微结构,Western blot检测海马组织FAM134B、p-FAM134B蛋白表达。结果与假手术组比较,模型组大鼠逃避潜伏期延长,穿越原平台次数和目标象限停留时间减少(P<0.01),海马CA1区神经元间隙增大,细胞形态不规则,边界模糊,神经元固缩,尼氏体溶解破碎、数量减少,内质网排列散乱,线粒体肿胀、变形,海马组织FAM134B、p-FAM134B蛋白表达升高(P<0.01);与模型组比较,多奈哌齐组和涤痰益智汤组大鼠逃避潜伏期缩短,穿越原平台次数和目标象限停留时间增加(P<0.01),海马CA1区神经元形态较规则、数量增多,神经元固缩减少,尼氏体数量增多、溶解破碎减轻,内质网肿胀变形恢复,海马组织FAM134B、p-FAM134B蛋白表达升高(P<0.01),且涤痰益智汤组效果优于多奈哌齐组(P<0.01)。结论涤痰益智汤可改善血管性痴呆大鼠学习记忆能力及神经元形态,其机制与上调FAM134B蛋白表达及磷酸化水平,进而促进内质网自噬有关。

补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆临床研究

目的:观察补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆的临床疗效。方法:选取124例老年髓海不足型阿尔茨海默病痴呆进行研究,按照随机数字表法分为治疗组与对照组各62例。治疗组给予补肾生髓益智汤联合甘露特钠胶囊治疗,对照组给予甘露特钠胶囊治疗。比较2组临床疗效,以及治疗前后简易精神状态量表(MMSE)、阿尔茨海默病评定量表-认知部分(ADAS-cog)、长谷川痴呆量表(HDS)、痴呆行为量表(BEHAVE-AD)评分。结果:治疗后,治疗组总有效率为90.32%,对照组为75.81%。2组比较,差异有统计学意义(P<0.05)。治疗后,2组MMSE评分均较治疗前上升(P<0.05),且治疗组MMSE评分高于对照组(P<0.05);2组ADAS-cog评分均较治疗前下降(P<0.05),且治疗组ADAS-cog评分低于对照组(P<0.05)。治疗后,2组HDS评分均较治疗前上升(P<0.05),且治疗组HDS评分高于对照组(P<0.05);2组BEHAVE-AD评分均较治疗前下降(P<0.05),且治疗组BEHAVE-AD评分低于对照组(P<0.05)。结论:补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆临床疗效良好,可改善患者认知功能及痴呆症状。

基于“命门学说”探析王素梅教授应用附桂益智汤辨治小儿自闭症经验

小儿自闭症是发病于婴幼儿时期的广泛发育障碍性疾病,本文梳理总结命门学说的历史演变,探讨命门作为原始动力对于心、脾、肾的推动作用,基于命门学说分析王素梅教授注重脾肾、固护心脑、采用附桂益智汤辨治小儿自闭症的经验,为临床辨治该病提供新的治疗思路。

Anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方)in hypoxia/reoxygenation primary cortical neurons through the promotion of synaptic plasticity by modulating the NogoA-Nogo receptor/Rho-Rho kinase signaling pathway

OBJECTIVE:To evaluate the anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方,QNYZ)in cultured cerebral cortical neuronal cells(CNCs)and the regulation of the NogoA-Nogo receptor(NgR)/Rho-Rho kinase(ROCK)signaling pathway.METHODS:Primary cultured CNCs were randomly divided into the following groups:normal control group(N-C),hypoxia-reoxygenation group(H/R),high-dose QNYZ group(Q-H),low-dose QNYZ group(Q-L)butylphthalide(NBP)group,and Y-27632(a selective ROCK transduction pathway inhibiter)group.Except those in the N-C group,CNCs were placed in hypoxic conditions for 24 h and then in reoxygenation conditions for 24 h.Cell media was changed every 48 h,and various assays were performed on the 7 th day.Cell viability was evaluated by measuring mitochondrial dehydrogenase activity,using a CCK-8 assay,in triplicate.Synapsin(SYN)protein concentrations were evaluated by enzyme-linked immunosorbent assay.NogoA and RhoA protein expression were evaluated through Western blotting.The gene expression of NogoA,NgR,RhoA,and ROCK was evaluated by reverse transcription-polymerase chain reaction.Cell apoptosis was measured using a terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling assay.RESULTS:Compared with the N-C group,the cell viability of the H/R group decreased significantly(P<0.05).The cell viability values for the Q-H and Q-L groups increased compared with that for the H/R group,and the difference was significant for the Q-H group(P<0.05).The NogoA and RhoA protein levels and the NogoA,NgR,RhoA,and ROCK m RNA expression levels increased in the H/R group,compared with the N-C group,and decreased significantly in the Q-H and Q-L groups(P<0.05)and in the Y-27632 group(P<0.05)compared with the H/R group.The SYN levels in the Q-H,Q-L,and NBP groups significantly increased compared with that in the H/R group(P<0.05).Compared with the H/R group,the numbers of apoptotic cells in the Q-H,Q-L,and NBP groups significantly decreased(P<0.05).CONCLUSION:The presented study demonstrated that QNYZ exerted anti-apoptotic effects on H/R-induced CNCs,possibly through the modulation of the NogoA-NgR/Rho-ROCK signaling pathway and the promotion of synaptic plasticity in H/R CNCs.

益智开窍十三针疗法结合康复训练在孤独症患儿中的应用效果

目的观察益智开窍十三针疗法配合康复训练在治疗小儿孤独症中的临床效果。方法选取2021年7月至2023年1月菏泽医学专科学校附属医院收治的120例孤独症患儿作为研究对象,按照随机数字表法分为观察组(n=60)和对照组(n=60)。对照组采用康复训练,观察组在对照组的基础上配合针刺治疗,采用益智开窍十三针疗法。比较两组患儿治疗前后的儿童孤独症评定量表(CARS)、孤独症行为评定量表(ABC)和Gesell发育量表(包括社会适应、语言和个人社交)评分。结果治疗前,两组患儿CARS评分、ABC评分及Gesell发育量表中社会适应、语言、个人社交能区各评分的比较,差异无统计学意义(P>0.05)。治疗后,两组患儿CARS、ABC评分及Gesell发育量表中社会适应、语言和个人社交的评分均高于治疗前,差异有统计学意义(P<0.05)。治疗后,观察组CARS评分、ABC评分及Gesell发育量表中社会适应、语言、个人社交的评分均高于对照组,差异有统计学意义(P<0.05)。结论益智开窍十三针疗法配合康复治疗小儿孤独症效果确切,有助于改善小儿孤独症患儿病情,改善孤独症患儿社会适应、语言、个人社交能力,可临床推广。