非正典化的典范及启示——法默尔“后传统治理”思想评析

在西方后现代主义思潮风起云涌之际,后现代公共行政理论也作为公共行政理论的前沿而得到介绍,其中,近些年来美国公共行政学者法默尔以"后现代公共行政的知名学者"的名号颇受国内学者们的关注。但是,不同于后现代主义者惯常对传统的彻底否定与解构,法默尔以"后传统治理"思想展现了对传统公共行政理论非正典化的过程,他的行吟诗人般的写作风格及批判中的建构主义,尤其是他研究框架和方法的别树一帜,让学界在理论知识浅尝辄止的诱惑之外备受启发。本文以法默尔"后传统治理"思想为主题,分析了其"反思性公共行政语言范式"前提、基本意涵,对后传统治理思想非正典化特征带给中国行政改革实践的启示、法默尔隐喻方法中的构成主义研究路径、理论创新意识及价值倚重等作出论述,以期在兼具全球化、后工业化的背景中,在中国仍保留相当农业社会特征的工业化进程中,对中国行政学"大问题"的界定和研究有所裨益。

法默尔的后现代公共行政理论简析

后现代公共行政理论是20世纪90年代在公共行政领域提出的一种具有批判和建构意义的理论,它对传统公共行政理论进行了全面深入的批判。法默尔提出的后现代公共行政理论在批判现代主义公共行政理论局限性的基础上,对后现代公共行政概念进行了创造性的诠释,并提出了对现代公共行政进行后现代重建需要注意的方面。该理论不仅对于我国公共行政的改革具有借鉴意义,而且它所崇尚的批判思维和创新思维对于认识上的探索、创新也具有重要的启示意义。

法默尔的后现代公共行政理论析评

法默尔是一位对当代西方行政学发展具有重要理论贡献的后现代公共行政理论家,本文分别从他对公共行政理论概念的后现代诠释、对现代公共行政理论的反思与批判以及对后现代公共行政理论的探寻等方面对其后现代公共行政理论作了系统的梳理和深入的分析,并在此基础上简要地对其后现代公共行政理论进行了客观的评价。

废除官僚制:后现代公共行政理论述评

论文介绍了法默尔《杀死国王——后传统治理与官僚制》一书的理论贡献,并批判性评价后现代公共行政理论的主要观点。法默尔《公共行政的语言——官僚制、现代性与后现代性》标志着后现代公共行政语言理论的形成;《杀死国王——后传统治理与官僚制》建构了后现代治理理论总体性框架,其中"想象的游戏"的认识论、"寻求的正义"的方法论和"艺术的实践"的实践论,从理论层面为我国重塑公共行政理论提供了深刻的启迪。

Therapeutic targets and delivery challenges for Alzheimer's disease

Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.

Additive nanomanufacturing of lab-on-a-chip fluorescent peptide nanoparticle arrays for Alzheimer＇s disease diagnosis

This paper proposes an additive nanomanufacturing approach to fabricate a personalized lab-on-a-chip fluorescent peptide nanoparticles （f-PNPs） array for simultaneous multi-biomarker detection that can be used in Alzheimer＇s disease （AD） diagnosis. We will discuss optimization techniques for the additive nanomanufacturing process in terms of reliability, yield and manufacturing efficiency. One contribution of this paper lies in utilization of additive nanomanufacturing techniques to fabricate a patient-specific customize-designed lab-on-a-chip device for personalized AD diagnosis, which remains a major challenge for biomedical engineering. Through the integrated bio-design and bio-manufacturing process, doctor＇s check- up and computer-aided customized design are integrated into the lab-on-a-chip array for patient-specific AD diagnosis. In addition, f-PNPs with targeting moieties for personalized AD biomarkers will be self-assembled onto the customized lab-on-a- chip through the additive nanomanufacturing process, which has not been done before. Another contribution of this research is the personalized lab-on-a-chip f-PNPs array for AD diagnosis utilizing limited human blood. Blood-based AD assessment has been described as ＂the holy grail＂ of early AD detection. This research created the computer-aided design, fabrication through additive nanomanufacturing, and validation of the f-PNPs array for AD diagnosis. This is a highly interdisciplinary research contributing to nanotechnology, biomaterials, and biomedical engineering for neurodegenerative disease. The conceptual work is preliminary with intent to introduce novel techniques to the application. Large-scale manufacturing based on the proposed framework requires extensive validation and optimization.

Evaluation of the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease based on various mouse models

Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected according to the pathophysiological causes of AD,including senescence accelerated mouse/prone(SAMP)mice,soluble amyloid-βprotein(Aβ)injection mice/rats,amyloid precursor protein(APP)transgenic mice,and APP/PS1 double transgenic mice.Through the observation of behavioral changes and analysis of core items,the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored.Results:Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction;the major action mechanisms including increasing cerebral blood flow,improving the expressions of vital proteins in the hippocampus,preventing neuron cell apoptosis,promoting the clearance of Aβdeposition,activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor,tyrosine kinase receptor B,N-acetylaspartate and glutamic acid.Conclusion:Although the optimal mouse model is not determined,it is sure that acupuncture-moxibustion therapy can improve cognitive function.A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.

Therapeutic efficacy observation on electroacupuncture for Alzheimer's disease

Objective：To observe the effect of electroacupuncture （EA） for Alzheimer’s disease （AD）. Methods：A total of 30 eligible cases were treated by needling Shenting （GV 24）, Baihui （GV 20）, Dazhui （GV 14）, Fengfu （GV 16）, Mingmen （GV 1） and Yongquan （KI 1）. Upon arrival of qi, the G6805-II electric stimulator was connected to Shenting （GV 24） and Baihui （GV 20） （one pair）, to Dazhui （GV 14） and Fengfu （GV 16） （one pair） and to bilateral Yongquan （KI 1） （one pair） for 25 min, using continuous wave at the frequency of 2-100 Hz and voltage of 2-4 V. With a tolerable intensity, the EA was conducted once a day for 10 d （one treatment course）. There was a 3-day interval between two courses. After three courses, the therapeutic efficacies were evaluated using the mini-mental state examination （MMSE）, revised Hasegawa dementia scale （HDS-R）, activities of daily living （ADL） and neurological function defect scale （NFDS）. Results：After EA treatment, the MMSE and HDS-R scores were significantly increased （P〈0.01） and the ADL and NFDS scores were significantly decreased （P〈0.01）. Conclusion：EA is effective for AD and can improve the overall intelligence and repair neurologic deficits in AD patients.

Analysis of clinical application patterns in acupuncture-moxibustion treatment of Alzheimer disease

Objective:To summarize the clinical application patterns in acupuncture-moxibustion treatment of AD by reviewing the clinical literatures on acupuncture-moxibustion for Alzheimer disease(AD)published between January 2009 and December 2019.Methods:China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database(Wanfang),Chongqing VIP Database(CQVIP),Chinese Medicine Acupuncture-moxibustion Information Database,PubMed Medical Data Retrieval Service System,Springer Database and Ovid Technologies(OVID)were retrieved to screen clinical studies of acupuncture-moxibustion treatment of AD according to the inclusion and exclusion criteria to conduct quantitative,clustering and association analyses.Results:In acupuncture-moxibustion treatment of AD,the frequently used points were Baihui(GV 20),Zusanli(ST 36),Sishencong(EX-HN 1),Taixi(KI 3),Sanyinjiao(SP 6),and Neiguan(PC 6)in the descending order.Regarding meridians,the most frequently used one was the Governor Vessel,followed by the Stomach Meridian of Foot Yangming and Gallbladder Meridian of Foot Shaoyang.From the perspective of body regions,the points in the head-face region and the lower-limb region had the highest frequencies,followed by the upper-limb,back and chest-abdomen regions.The point group,Baihui(GV 20)and Sishencong(EX-HN 1)-Neiguan(PC 6)-Sanyinjiao(SP 6),showed the most significant association,and the group winning the second place was Baihui(GV 20)and Sishencong(EX-HN 1)-Neiguan(PC 6)-Zusanli(ST 36).The clustering analysis showed that the commonly used point pairs included Zusanli(ST 36)-Sishencong(EX-HN 1)and Taixi(KI 3)-Sanyinjiao(SP 6),which were closely associated with Baihui(GV 20).By analyzing the three commonly used acupuncture-moxibustion methods,acupuncture plus medication was found achieving the best result in the total effective rate and mini-mental state examination(MMSE)score,followed by monotherapy of electroacupuncture therapy,and these two methods were superior to acupuncture alone(P<0.05);the scores of MMSE,Alzheimer disease assessment scale-cognitive section(ADAS-cog)and activity of daily living scale(ADL)showed significant improvements after treatment(all P<0.01).Conclusion:In the acupuncture-moxibustion prescriptions for AD,the main points are Baihui(GV 20),Sishencong(EX-HN 1),Neiguan(PC 6),Zusanli(ST 36),Sanyinjiao(SP 6)and Taixi(KI 3).Monotherapy of acupuncture has the highest frequency amongst the treatment methods,but its effective rate is lower than that of acupuncture plus medication and monotherapy of electroacupuncture.

Efficacy evaluation on electroacupuncture for Alzheimer's disease

Objective： To observe the clinical efficacy of electroacupuncture（EA） on Alzheimer＇s disease（AD）.Methods： A total of 50 AD patients were randomly allocated into a Western medication（WM） group（n=25） and an acupuncture plus medication（APM） group（n=25）. Patients in the WM group took oral huperzine A capsules. In addition to huperzine A capsules, patients in the APM group also received EA at Shenting（GV 24）, Baihui（GV 20）, Dazhui（GV 14）,Fengfu（GV 16）, Mingmen（GV 4） and Yongquan（KI 1）. The needles on the above points were connected to G6805-Ⅱelectric stimulator [3 pairs： Shenting（GV 24） and Baihui（GV 20）; Dazhui（GV 14） and Fengfu（GV 16）; and bilateral Yongquan（KI 1）]. The needles were retained 25 min. The treatment was done once a day, and 10 times made up a course of treatment.The patients received a total of 3 treatment courses. There was a 3-day interval between two courses. The mini-mental state examination（MMSE） and Hasegawa dementia scale revised（HDS-R） were conducted before and after treatment. The clinical efficacies were evaluated when the treatment was completed.Results： Before treatment, there were no between-group statistical differences in MMSE and HDS-R scores（both P〈0.05）.After treatment, the MMSE and HDS-R scores in the APM group were significantly higher than those in the WM group（both P〈0.05）. The total effective rate in the APM group was 88.0%, versus 76.0% in the WM group, showing a statistical difference（P〈0.05）.Conclusion： EA is effective for AD and can improve clinical symptoms in AD patients.

Grain-sized moxibustion inhibits the progression of Alzheimer disease in 5XFAD transgenic mice

Objective To investigate whether grain-sized moxibustion at Xinshu(BL15)and Shenshu(BL23)can alleviate cognitive decline and other pathologic features in early-stage Alzheimer disease(AD)using transgenic mice with 5 familial AD mutations(5XFAD).Methods The genotype of transgenic mice was detected by polymerase chain reaction.A total of 40 transgenic mice(1.5 months old)were randomly and equally allocated to an AD model group(5XFAD group)or a grain-sized moxibustion group(5XFAD+GM group),with 20 wild-type(WT)mice(C57BL/6J)serving as the normal control group(WT group).Mice in the 5XFAD+GM group were treated by grain-sized moxibustion at bilateral Xinshu(BL15)and Shenshu(BL23).Mice in the WT group and 5XFAD group received no treatment but were restrained to ensure exposure to a similar experimental condition.Cognitive function and memory were assessed with the Morris water maze and Y-maze tests.The amyloidβ40(Aβ40)and amyloidβ42(Aβ42)levels in the brain were evaluated by enzyme-linked immunosorbent assay;amyloid plaque deposition in brain tissue sections was detected by thioflavin-S staining;the expression of glial fibrillary acidic protein(GFAP),cluster of differentiation 11b(CD11b),brain-derived neurotrophic factor(BDNF),and choline acetyltransferase(ChAT)in the hippocampus and prefrontal cortex was analyzed by immunohistochemistry.Results In the Morris water maze test,compared with the 5XFAD group,mice in the 5XFAD+GM group had a shorter escape latency and more target area crossings and spent more time in the target quadrant(P<0.05).In the Y-maze test,compared with the 5XFAD group,the number of training times of the 5XFAD+GM group was significantly decreased(P<0.05),together with more correct responses(P<0.05).Compared with the 5XFAD group,the levels of Aβ40 and Aβ42 in the brain tissue of the 5XFAD+GM group were significantly lower(P<0.05);in the hippocampus and prefrontal cortex,the total number of amyloidβplaque deposition were significantly lower(P<0.05);the expression levels of GFAP and CD11b were significantly reduced(P<0.05);and the expression levels of ChAT and BDNF were significantly increased(P<0.05).Conclusion Grain-sized moxibustion at Xinshu(BL15)and Shenshu(BL23)greatly improves learning and memory functions,decreases the levels of Aβ40 and Aβ42,inhibits amyloidβplaque deposition,decreases the expression of GFAP and CD11b,and increases the expression of ChAT and BDNF in AD mice to inhibit the progression of AD.

Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease

Objective：To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone g （SAMPg） mice models with Alzheimer disease （AD）,and to explore the possible protective mechanism of acupuncture on mitochondria.Methods：Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group,an acupuncture at non-acupoint group and a model group,20 mice in each group.The 20 male senescence-accelerated mouse/resistance 1 （SAMR1） mice of the same age were used as a normal control group.Shenshu （BL 23）,Baihui （GV 20）,Xuehai （SP 10） and Geshu （BL 17） were selected for acupuncture intervention in acupuncture at acupoint group.After an 8-week intervention,mitochondrial tissues were extracted from the hippocampus.Differentially expressed proteins were identified by subcellular organelle proteomics.Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.Results：Compared with the model group,there were 13 differentially expressed protein spots in the acupuncture at acupoint group,of which,9 were up-regulated,including neurofilament light polypeptide （NFL）,actin （cytoplasmic 1,database ID：ACTB）,tubulin beta-2A chain （TBB2A）,tropomodulin-2 （TMOD2）,pyruvate dehydrogenase E1 component subunit beta （PDHE1-β）,NADH-ubiquinone oxidoreductase 75 kDa subunit （database ID：NDUS1）,heat shock cognate 71 kDa protein （HSC71）,pyruvate dehydrogenase E1 component subunit alpha （PDHE1-α） and ATP synthase beta subunit （ATP-β）;4 were down-regulated,including glial fibrillary acidic protein （GFAP）,pyruvate dehydrogenase phosphatase 1 （PDP1）,mitochondrial-processing peptidase subunit alpha （MMP-α） and adenosine kinase （ADK）.According to the information provided in the protein database,most of the differentially expressed proteins involve the regulation of mitochondrial function and structure.The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group （P〈0.05）.ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group （P〈0.05）;there was no significant difference between the acupuncture at non-acupoint group and the model group （P〉0.05）.Conclusion：Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.