Real world studies are essential for drug therapy in Parkinson's disease

Prospective real-world data from large patient samples, which re- port on the long-term effectiveness of the employed different drug therapies, are rare in Parkinson＇s disease （PD）. The non interven- tional ＂Transdermal Rotigotine User Surveillance Study＂ （TRUST） trial represents such a real-world study. It investigated long-term treatment with different dopamine substituting treatment regimens in 2195 PD patients （Mfiller et al., 2018）. Participation in TRUST meant that the treating neurologists were only asked to document and modify the dopaminergic drug regimen without any prior PD patient selection criteria. Thus this unique trial design reflects the real world of patient maintenance.

Drug therapy for Parkinson's disease: An update

Parkinson's disease(PD) is the most common neurodegenerative movement disorder, affecting about 1% of the population above the age of 65. PD is characterized by a selective degeneration of the dopaminergic neurons of the substantia nigra pars compacta. This results in a marked loss of striatal dopamine and the development of the characteristic features of the disease, i.e., bradykinesia, rest tremor, rigidity, gait abnormalities and postural instability. Other types of neurons/neurotransmitters are also involved in PD, including cholinergic, serotonergic, glutamatergic, adenosine, and GABAergic neurotransmission which might have relevance to the motor, non-motor, neuro-psychiatric and cognitive disturbances that occur in the course of the disease. The treatment of PD relies on replacement therapy with levodopa(L-dopa), the precursor of dopamine, in combination with a peripheral decarboxylase inhibitor(carbidopa or benserazide). The effect of L-dopa, however, declines over time together with the development of motor complications especially dyskinesia in a significant proportion of patients within 5 years of therapy. Other drugs include dopaminereceptor-agonists, catechol-O-methyltransferase inhibitors, monoamine oxidase type B(MAO-B) inhibitors, anticholinergics and adjuvant therapy with the antiviral drug and the N-methyl-D-aspartate glutamate receptor antagonist amantadine. Although, these medications can result in substantial improvements in parkinsonian symptoms, especially during the early stages of the disease, they are often not successful in advanced disease. Moreover, dopaminergic cell death continues over time, emphasizing the need for neuroprotective or neuroregenerative therapies. In recent years, research has focused on non-dopaminergic approach such as the use of A2 A receptor antagonists: istradefylline and preladenant or the calcium channel antagonist isradipine. Safinamide is a selective and reversible inhibitor of MAO-B, a glutamate receptor inhibitor as well as sodium and calcium channel blocker. Minocycline and pioglitazone are other agents which have been shown to prevent dopaminergic nigral cell loss in animal models of PD. There is also an evidence to suggest a benefit from iron chelation therapy with deferiprone and from the use of antioxidants or mitochondrial function enhancers such as creatine, alpha-lipoic acid, l-carnitine, and coenzyme Q10.

Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson's disease

Parkinson's disease(PD) is a chronic debilitating disease affecting approximately 1% of the population over the age of 60. The severity of PD is correlated to the degree of dopaminergic neuronal loss. Apomorphine has a similar chemical structure as the neurotransmitter dopamine and has been used for the treatment of advanced PD patients. In PD patients,apomorphine is normally administered subcutaneously with frequent injections because of the compound's extensive hepatic first-pass metabolism. There is, hence, a large unmet need for alternative administrative routes for apomorphine to improve patient compliance.The present review focuses on the research and development of alternative delivery of apomorphine, aiming to highlight the potential of non-invasive apomorphine therapy in PD,such as sublingual delivery and transdermal delivery.

Pharmacotherapeutics and molecular docking studies of alphasynuclein modulators as promising therapeutics for Parkinson’s disease

Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.

S4B-2 Bushen-Yizhi Formula Inhibits the NLRP3/NFκB Mediated Neuroinflammation and Improves the Motor Dysfunction in a Mouse Model of Parkinson’s Disease

Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TCM theory understanding,so we can learn from each other in the process of drug discovery.The clinical results showed that Bushen-Yizhi formula(BSYZ)could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect.Further pharmacological studies showed that BSYZ had neuroprotective effects,such as anti-inflammatory,anti-oxidation,anti-apoptosis and neurotrophic effects.In this study,the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo,and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases.Methods:C57 BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model.BSYZ(1.46,2.92,5.84 mg·kg-1)was administered for two weeks,and the positive control group was given a NSAID,piroxicam(12.5 mg·kg-1).After 1 week of pretreatment,MPTP was used to construct a PD mouse model.The mice were subjected to Rotation test on days 1,3 and 5,6th day.and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH-positive cells,Iba1 and CD68-labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP-labeled astrocytes.Western blotting was used to detect the nuclear transfer of NLRP3,Caspase-1,ASC,pro-IL-1β,IL-1βand NF-κB in the midbrain.Results:1.BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze,increase the number of neurons in SNpc region and the positive expression of TH protein.2.BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes.3.BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB.Conclusion:BSYZ can effectively relieve the motor dysfunction of PD model mice,improve the damage of dopaminergic neurons,inhibit the proliferation and activation of microglial cells and astrocytes,and have good anti-MPTPinduced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB.The results show that BSYZ has a good prospect of anti-Parkinson’s disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.

Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial

BACKGROUND： Parkinson＇s disease （PD） is a complicated disease, commonly diagnosed among the elderly, which leads to degeneration of the central nervous system. It presently lacks an effective therapy for its complex pathogenesis. Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients. Traditional Chinese medicine （TCM） has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention. Therefore, the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill （XFDCP）, a compound traditional Chinese herbal medicine, taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease. METHODS AND DESIGN： This is a multicenter, randomized controlled trial. In total, 320 patients with early- （n = 160） and middle-stage PD （n = 160） will be enrolled and divided evenly into control and trial groups. Of the 160 patients with early-stage PD, the trial group （n = 80） will be given XFDCP, and the control group （n = 80） will be given Madopar. Of the 160 patients with middle-stage PD, the trial group （n = 80） will be given XFDCP combined with Madopar and Piribedil, and the control group （n = 80） will be given Madopar and Piribedil. The Unified Parkinson＇s Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar＇s dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period. DISCUSSION： It is hypothesized that XFDCP, combined with Madopar and Piribedil, will have beneficial effects on patients with PD. The results of this study will provide evidence for developing a comprehensive therapy regimen, which can delay the progress of the disease and improve the quality of life for PD patients in different stages. TRIAL REGISTRATION： This trial has been registered in the Chinese Clinical Trial Registry with the identifer ChiCTR-TRC-12002150.

Prevalence, clinical features and treatment of depression in Parkinson's disease: An update

Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.

Clinical Experience with Generic Rasagiline (Ralago^®) in Patients with Parkinson’s Disease: An Open-Label, Multicenter, Observational Study

Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease;however, efficacy and safety of these products have been less studied. Objective: To investigate the efficacy and safety of generic rasagiline (Ralago?) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the most important motor and non-motor symptoms at baseline and 12 weeks after the initiation of Ralago?. Patients also identified symptoms which were the main sources of their disability and distress in everyday life. Results: A total of 499 patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration of disease: 3.6 ± 3.7 years). Of them, 486 patients completed the study protocol. Both motor and non-motor symptoms showed improvement during 12-week Ralago? treatment. Adverse events were rare, and the majority of them were not considered as serious. Conclusions: The generic rasagiline (Ralago?) is an effective and safe generic product.

Parkinson Disease Patient with Wheezing Manifestations: A Case Report

The dosing of anti-Parkinson drugs is considered as the optimal control of the symptoms of PD,and increasing the dose of drugs is a common method to treat the aggravate state of PD.However,this is a case of PD elderly patient who had nephritic syndrome,with an increase in the dose,the symptoms did not get improved,but a series of other adverse effects appeared.

Management of perianal fistulas in Crohn's disease:An upto-date review

Perianal disease is one of the most disabling manifestations of Crohn's disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula treatment.Available medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.

Anti-Parkinsonian Therapy:Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials

Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.

A STIR nucleic acid drug delivery system for stirring phenotypic switch of microglia in Parkinson’s disease treatments

Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.

帕金森病药物治疗研究进展

目前帕金森病(Parkinson’s disease,PD)药物治疗依然是以多巴胺替代治疗为主线的症状治疗,长期用药带来的运动并发症及神经精神症状、平衡步态障碍等问题限制了很多中晚期患者的治疗效果。近年来PD药物治疗领域也取得一些进展。在症状治疗方面,一批左旋多巴制剂新剂型和多巴胺受体激动剂新剂型,新型单胺氧化酶-B和儿茶酚胺氧位甲基转移酶抑制剂,多种非多巴胺能药物陆续进入临床或即将进入临床。目前虽然尚无疾病修饰治疗药物在临床使用,但一批针对不同PD发病机制靶点疾病修饰治疗药物正在开展早期临床试验研究,有些药物显示较好的应用前景。一些已在临床使用的药物被再开发用于PD治疗。本文对该领域新进展做一综述。

Drug therapy in patients with Parkinson’s disease

Parkinson`s disease(PD)is a progressive,disabling neurodegenerative disorder with onset of motor and non-motor features.Both reduce quality of life of PD patients and cause caregiver burden.This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other.MAO-B-Inhibitors,NMDA antagonists,dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD.This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms.These PD features predominantly result from non dopaminergic neurodegeneration.Autonomic features,such as seborrhea,hyperhidrosis,orthostatic syndrome,salivation,bladder dysfunction,gastrointestinal disturbances,and neuropsychiatric symptoms,such as depression,sleep disorders,psychosis,cognitive dysfunction with impaired execution and impulse control may appear.Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions,-side effects,and altered pharmacokinetic behaviour of applied compounds.Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms.This complicates the differentiation from the disease process itself and influences therapeutic options,which are often limited because of additional morbidity with necessary concomitant drug therapy.

帕金森病伴抑郁的治疗研究进展

帕金森病(PD)抑郁是帕金森病最常见的非运动症状之一,然而在PD早期抑郁常常被忽略,未能及时得到治疗。随着疾病的进展,抑郁症状表现更为突出,严重时患者有自杀的倾向,严重降低患者的生活质量。目前,临床针对PD伴抑郁的治疗方法虽较多,但其临床效果尚不明确,迄今仍缺乏有效的治疗干预手段。本文总结归纳了国内外较为常见的治疗手段,以期为PD伴抑郁患者制定个体化的治疗方案提供参考。

Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease

Alanine-serine-cysteine transporter 2(ASCT2)is reported to participate in the progression of tumors and metabolic diseases.It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network.However,it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson’s disease(PD).In this study,we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia.We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+or LPS/ATP challenge.Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic(DA)neuron damage in PD models in vitro and in vivo.Notably,the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasometriggered neuroinflammation.Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate.It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models.Collectively,these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD,broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis

Parkinson’s disease is the second most common neurodegenerative disease in the world.Beta-arrestin-2 has been reported to be an important protein involved in D2 dopamine receptor desensitization,which is essential to Parkinson’s disease.Moreover,the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson’s disease has recently been shown.We studied the interaction between D2 dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis.The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D2 dopamine receptor interaction among them.These compounds are promising therapies for Parkinson’s disease,and the method used in this study has great potential for application in large-scale drug screening and evaluation.

Helicobacter pylori infection and drugs malabsorption

Drug absorption represents an important factor affecting the efficacy of oral drug treatment.Gastric secretion and motility seem to be critical for drug absorption.A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori(H.pylori)infection has been proposed.Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H.pylori infection.According to the Maastricht Florence Consensus Report on the management of H.pylori infection,H.pylori treatment improves the bioavailability of both these drugs,whereas the direct clinical benefits to patients still await to be established.Less strong seems the association between H.pylori infection and other drugs malabsorption,such as delavirdine and ketoconazole.The exact mechanisms forming the basis of the relationship between H.pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated.H.pylori infection may trigger a chronic inflammation of the gastric mucosa,and impaired gastric acid secretion often follows.The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption.This minireview focuses on the evidence of H.pylori infection associated with impaired drug absorption.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

刮痧联合药物治疗原发性帕金森病的短期临床疗效研究

背景帕金森病(PD)作为常见的神经退行性疾病之一,因药物治疗不良反应明显,且长期使用疗效降低,使其成为全球医疗难题。刮痧是应用广泛的中医非药物疗法之一,在神经系统疾病治疗中具有独特优势。目前有关刮痧联合药物治疗原发性PD的研究尚少。目的 观察刮痧联合药物治疗原发性PD的短期临床疗效。方法采用目的性抽样法,选取2021年3—9月在南京市中医院和江苏省人民医院PD门诊诊治的16例原发性PD患者为观察组,按照性别、年龄、病程及Hoehn-Yahr分期相匹配的原则,选择16例原发性PD患者作为对照组。观察组采用刮痧联合西药口服治疗,4周为1个疗程,3个疗程后停止刮痧,单纯西药继续治疗1个疗程作为随访。对照组采用单纯西药口服治疗,4周为1个疗程,治疗4个疗程,最后1个疗程作为随访。治疗3个月和随访1个月,观察统一帕金森病评定量表第三部分(MDS-UPDRS Ⅲ)评分、非运动症状量表(NMSS)评分、临床疗效;治疗3个月观察血清白介素1β(IL-1β)、核转录因子κB(NF-κB)水平。结果 治疗3个月,两组患者MDS-UPDRS Ⅲ、NMSS评分及血清IL-1β、NF-κB水平均低于组内治疗前(P<0.05);随访1个月,两组患者MDS-UPDRS Ⅲ、NMSS评分均低于组内治疗前(P<0.001);随访1个月对照组患者MDS-UPDRS Ⅲ评分低于组内治疗3个月(P<0.001);随访1个月观察组患者NMSS评分高于组内治疗3个月(P=0.002)。观察组患者治疗3个月、随访1个月MDS-UPDRS Ⅲ、NMSS评分低于对照组(P<0.05)。观察组治疗后IL-1β、NF-κB水平均低于对照组(P<0.05)。治疗3个月及随访1个月,观察组患者临床疗效均优于对照组(Z值分别为-3.651、-3.468,P<0.05)。结论 刮痧联合药物治疗早、中期原发性PD安全可行,能够改善PD患者的部分运动功能障碍,减轻非运动症状,可明显提高临床疗效,其远期疗效有待开展大样本、多中心的研究进一步探索。