Deep brain stimulation of dorsal and ventral borders of the subthalamic nucleus in patients with Parkinson's disease: a systematic review

Parkinson's disease patients experience motor signs and non-motor symptoms caused by the disease. Deep brain stimulation of the Subthalamic Nucleus (STN) itself or its ventral or dorsal borders is one of the treatment options indicated to treat the refractory symptoms of this disease. However, it is still unknown which edge, when stimulated, generates more beneficial effects for these patients, which is the objective of this systematic review. To answer this question, electronic and manual searches were conducted in five databases and gray literature to identify studies that answered the question in this review. The selection of studies, data extraction, and analysis of the risk of bias of the included studies were performed. In total, seven studies were included in this systematic review. Most studies presented a minimal risk of bias, and their main methodological limitation was related to the sample inclusion criteria. Stimulation of the dorsal or ventral borders of the STN resulted in improved motor signs of Parkinson's disease, with some of the studies tending towards the choice of dorsal border stimulation for better motor effects, while the improvement in non-motor symptoms and inhibitory control was due to stimulation of the ventral border. The findings of this systematic review suggest that the improvement in the motor signs of Parkinson's disease can be brought about by stimulating the dorsal or ventral borders of the subthalamic nucleus, whereas non-motor symptoms such as anxiety improve with stimulation of the ventral border.

The effect of dyskinesia on postural control, balance, gait, and fall risk in people with Parkinson's disease: a systematic review protocol

Dyskinesia affects the limbs, trunk, and head and is more prevalent in people with Parkinson's disease (PD) and a history of falls. More evidence about the effects of dyskinesia on postural control, balance, gait, and fall risk could help improve the quality of life of individuals with PD. This review aims to examine associations between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Such information could lead to new approaches to quality of life improvement among individuals with PD. PubMed, CINAHL, PsycInfo, Scopus, and SciELO will be searched for longitudinal, cohort, and case-control studies published in English or Portuguese in any year that investigated the association between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Two reviewers will independently evaluate the titles, abstracts, and full texts according to PRISMA guidelines to select eligible studies for the review. Data on participants, dyskinesia, postural control, balance, gait, and fall risk will be extracted and summarized in tables. Two reviewers will independently assess the methodological quality of each study using the Newcastle Ottawa quality assessment scale. Meta-analysis will not be performed. The results of this systematic review will offer insight into the effects of dyskinesia on postural control, balance, gait, and fall risk. Such information could significantly contribute to informed decisions about early motor intervention in individuals with PD. (AU)

FNDC5/Irisin in dementia and cognitive impairment: update and novel perspective

Epidemiological surveys show that the incidence of age-related dementia and cognitive impairment is increasing and it has been a heavy burden for society, families, and healthcare systems, making the preservation of cognitive function in an increasingly aging population a major challenge. Exercise is beneficial for brain health, and FDNC5/irisin, a new exercise-induced myokine, is thought to be a beneficial mediator to cognitive function and plays an important role in the crosstalk between skeletal muscle and brain. This review provides a critical assessment of the recent progress in both fundamental and clinical research of FDNC5/irisin in dementia and cognitive impairment-related disorders. Furthermore, we present a novel perspective on the therapeutic effectiveness of FDNC5/irisin in alleviating these conditions.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Juvenile Parkinson's disease caused by PRKN gene compound heterozygous mutation:A case report and literature review / 吉林大学学报(医学版)

Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.

Research progress in pathogenesis and treatment of gastrointestinal motility disorders in Parkinson's disease / 吉林大学学报(医学版)

The gastrointestinal motility disorder of the patients with Parkinson's disease(PD)occurs in the early stages of this disease,even before the onset of motor symptoms.The gastrointestinal motility disorder is one type of gastrointestinal dysfunction,not only affect the absorption of medication,exacerbating the progression of PD,but also severely impact the quality of life of the patients.Therefore,it is essential to find new therapeutic targets to alleviate PD-induced gastrointestinal dysmotility in order to improve the progression of the disease and the quality of life of the patients.The gastrointestinal motility function is highly dependent on the health of the gut and central nervous regulating the gastrointestinal movements.A healthy gut is closely related to the integrity of the intestinal barrier,gut microbiota,neuroinflammation,and the normal function of enteric neurons responsible for the contraction and relaxation of the gastrointestinal tract.The gut function of the PD patients is compromised to some extent.This review summarizes the effects of the enteric nervous system,central nervous system,and gut microbiota on the development of gastrointestinal motility disorder of the PD patients;it also outlines the current therapeutic methods available and their limitations,with the aim of providing the new insights into the treatment of gastrointestinal motility disorder of the PD patients.

Correlation analysis of serum dopamine,5-hydroxytryptamine,homovanillic acid levels and cognitive dysfunction in patients with Parkinson's disease / 国际检验医学杂志

Objective To explore the relationship between the levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and cognitive dysfunction in patients with Parkinson's disease.Methods A total of 118 Parkinson's disease patients admitted to Bazhong Central Hospital from February 2020 to February 2022 were selected as the disease group,and 106 healthy patients who underwent physical examination in the hospital during the same period were selected as the control group.The levels of serum do-pamine,5-hydroxytryptamine and homovanillic acid were measured in all subjects,and the cognitive function was evaluated with Montreal Cognitive Assessment Scale(MoCA).Parkinson's disease patients were divided into cognitive impairment group and non cognitive impairment group according to MoCA score.The serum do-pamine,5-hydroxytryptamine,homovanillic acid levels of the cognitive impairment group and the non cogni-tive impairment group were compared.Pearson correlation analysis was used to analyze the correlation be-tween serum dopamine,5-hydroxytryptamine and homovanillic acid levels and cognitive function of Parkinson's disease patients,and the receiver operating characteristic curve was drawn to analyze the evaluation value of serum dopamine,5-hydroxytryptamine and homovanillic acid levels on cognitive dysfunction of Parkinson's disease patients.Results The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in the disease group were lower than those in the control group,with statistical significance(P＜0.05).The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in advanced patients were lower than those in early patients,and the difference was statistically significant(P＜0.05).The levels of serum dopamine,serotonin and homovanillic acid in the cognitive dysfunction group were lower than those in the non-cognitive dysfunction group,and the difference was statistically significant(P＜0.05).The results of Pearson analysis showed that the levels of serum dopamine,5-hydroxytryptamine and homovanillic acid in Parkinson's disease patients were positively correlated with MoCA score(P＜0.05).The sensitivity of the combined assessment of serum dopamine,serotonin and homovanillic acid in Parkinson's disease patients was higher than that in Parkinson's disease patients alone(x2=7.413,P=0.006;x2=9.714,P=0.002;x2=8.541,P=0.003),the area under the curve(AUC)was higher than the AUC for assessing cognitive impair-ment in Parkinson's disease alone(Z=2.479,P=0.013;Z=2.271,P=0.023;Z=2.451,P=0.014).Conclusion There are differences in serum levels of dopamine,5-hydroxytryptamine,homovanillic acid and cognitive function among different stages of Parkinson's disease patients.Serum levels of dopamine,5-hydroxytryptamine,and homovanillic acid are closely related to cognitive function in Parkinson's disease pa-tients,all of which have evaluation value for the occurrence of cognitive dysfunction in Parkinson's disease pa-tients.However,the combination of the three serum indicators is more helpful for clinical evaluation and diag-nosis.

Propofol Regulates MPP+-induced Mitochondrial Oxidative Stress and Apoptosis in SH-SY5Y Cells / 昆明医科大学学报

Objective To investigate the effects of different concentrations of PPF on oxidative stress and apoptosis of PD model cells induced by MPP+.Methods The human neuroblastoma cell SH-SY5Y was induced by 1 mM MPP+ to establish PD cell model.In PPF treatment group,SH-SY5Y cells were stimulated with 10,20,40 and 80 μM PPF for 4 h before MPP+ induction.Cell counting kit-8(CCK-8)was performed to evaluate cell proliferation activity.H2DCF-DA fluorescent probe was used to detect ROS in cells.The levels of MDA and NADPH oxidase were analyzed by the kit.Western blot examined the protein expression of cytochrome c in mitochondria and cytoplasm,as well as the relative expression of Bcl-2,Bax and cleaved caspase-3 in SH-SY5Y cells.Apoptosis rate was analyzed by flow cytometry.Results MPP+ significantly inhibited the proliferation of SH-SY5Y cells(P<0.001),promoted the level of ROS(P<0.001),MDA(P<0.001),NADPH oxidase(P<0.01),cytochrome c in cytoplasm(P<0.01)and induced apoptosis(P<0.001)and the relative expression of pro-apoptosis protein Bax and cleaved caspase-3(P<0.01),reduced cytochrome c protein in mitochondria(P<0.01)and the relative expression of anti-apoptosis protein(P<0.01).PPF pretreatment alleviated the proliferation inhibition,oxidative stress and apoptosis promotion of SH-SY5Y cells induced by MPP+(P<0.001),and the effects of 40 μM and 80 μM on cells were more significant.Conclusion PPF pretreatment can alleviate the oxidative stress of SH-SY5Y cells induced by MMP+ and reduce apoptosis rate.

Research progress in the treatment of Parkinson's disease with depression / 临床神经病学杂志

Parkinson's disease(PD)depression is one of the most common non-motor symptoms of PD,but depression is often ignored in the early stages of PD and is not treated in time.With the progression of the disease,the symptoms of depression become more prominent,and patients tend to commit suicide in severe cases,which seriously reduces the quality of life of patients.At present,although there are many clinical treatment methods for PD with depression,but the clinical effect is not clear,and there is still a lack of effective therapeutic intervention means and methods.In this paper,the more common treatment methods are summarized,to develop an individualized treatment plan for PD patients with depression.

Prevalence and related risk factors of minor hallucinations in newly diagnosed Parkinson's disease patients / 临床神经病学杂志

Objective To screen the prevalence and related risk factors of minor hallucinations(MH)in newly diagnosed Parkinson's disease(PD).Methods From November 2018 to December 2022,274 newly diagnosed patients with untreated PD were enrolled in the PD Clinic of Brain Hospital Affiliated to Nanjing Medical University.According to the score of item 2 of the unified PD rating scale Ⅰ(UPDRSⅠ),the PD patients with MH were selected(MH group,score≥2).The patients matched in age,sex,education and course of disease level were screened in non-MH PD patients(NMH group,score = 0).Cognitive function,depressive symptoms,anxiety symptoms,sleep quality,non-motor symptoms,rapid eye movement sleep disorder(RBD)symptoms,activities of daily life,motor function and disease severity were evaluated with appropriate scales.The differences between two groups were compared,and the risk factors of MH in PD patients were analyzed by univariate and multivariate progressive Logistic regression.Results Among the 274 newly diagnosed PD patients,11 cases(4.01%)had MH.Compared with those in NMH group(22 cases),MH group had higher Hamilton depression scale(HAMD)scores,higher Hamilton anxiety scale(HAMA)scores,higher PD non motor symptoms(PDNMS)scores and higher RBD scores(all P＜0.05).Univariate Logistic regression analysis showed that high HAMD scores,high HAMA scores,high PDNMS scores and high RBD scores were risk factors for MH in PD patients(all P＜0.05).Multivariate Logistic regression analysis showed that high HAMD score(OR =1.182,95%CI:1.004-1.392,P =0.045)and high RBD score(OR =4.448,95%CI:1.066-18.557,P =0.041)were independent risk factors for MH in PD patients.Conclusions MH may occur in newly diagnosed PD patients with probability.Depression and RBD are independent risk factors for MH in PD patients.Attention should be paid to screening patients like this and early intervention measures should be taken.

Research progress on the relationship between Parkinson's disease and diabetes / 临床神经病学杂志

Parkinson's disease and diabetes are common neurodegenerative diseases and metabolic diseases respectively,and the number of patients is increasing continuously in recent years.Both diseases are chronic diseases,and their occurrence and progression are regulated by genetic and environmental factors.Currently,there is a large amount of literature suggesting potential connections between the two diseases in different aspects.This article reviews the research progress in the epidemiology,pathogenesis,clinical symptoms and the impact of diabetes drugs on Parkinson's disease,so as to provide guidance for the prevention and treatment of the two diseases.

Research progress of bright light therapy in the treatment of sleep disorders related to Parkinson's disease / 临床神经病学杂志

Sleep disturbance is a common non-motor symptom of Parkinson's disease(PD),which seriously affects the quality of patients'life.Bright light therapy is a treatment that uses daylight or artificial light to regulate circadian rhythms.Recent studies have shown that bright light therapy may have effect on PD-related sleep disorders,but the mechanism is still unclear.Due to the influence of many factors,there is no unified standard to guide the application of bright light therapy.Based on this,this article reviews the mechanism and application of bright light therapy in the treatment of PD-related sleep disorders.

Research progress of neuromodulation in the treatment of Parkinson's disease / 上海交通大学学报（医学版）

Parkinson's disease(PD)is a common degenerative neurological disorder,characterized by static tremor,bradykinesia,myotonia and postural abnormalities.Dopaminergic drugs are the main drugs in the treatment of PD,but long-term use will lead to drug efficacy loss,and even cause some adverse reactions such as dyskinesia and"on-off"phenomenon.Neuromodulation is a kind of biomedical engineering technology that can stimulate or inhibit the activity of brain neurons and regulate the changes of neuroplasticity by means of electric energy,magnetic field,ultrasound and other methods,so as to achieve treatment and improvement of diseases.In the non-drug treatment of PD,neuromodulation,as a new therapeutic means,has shown good efficacy,and has the advantages of small adverse reactions and easy tolerance.Based on this,this article reviews the research progress of several common neuromodulation in PD,including deep brain stimulation,transcranial magnetic stimulation,transcranial direct current stimulation and transcranial focused ultrasound.

6-hydroxydopamine induces mechanical hyperalgesia reaction in rats through p38 MAPK signaling pathway / 神经解剖学杂志

Objective:To study the regulatory mechanism of p38 MAPK signaling pathway participate in hyperalge-sia reaction in Parkinson's disease(PD)rats model induced by 6-hydroxy dopamine(6-OHDA).Methods:Forty male Sprague Dawley(SD)rats were randomly divided into four groups:Sham group(Sham),model group(6-OHDA),p38 MAPK inhibitor SB203580 treatment group(6-OHDA+SB203580)and p38 MAPK activator anisomycin(ANS)treatment group(6-OHDA+ANS).PD model was established by intra-striatal injection of 6-OHDA stereotactically.6-OHDA+SB203580 and 6-OHDA+ANS groups was injected with 6-OHDA to establish PD model,and treated with inhibitor SB203580 or activator ANS respectively.The von Frey hairs were applied to measure the mechanical paw with-draw threshold(PWT)of rats.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of IL-6,IL-1β,and TNF-α in rat dorsal root ganglion(DRG).The mRNA levels of genes IL-6,IL-1β,TNF-α,and p38 MAPK in rat DRG was detected by real time RT-PCR.Results:In the DRG of 6-OHDA included PD rats,the expres-sion levels of IL-6,IL-1β,TNF-α,and p38 MAPK were significantly increased(P＜0.05),and the PWT of rats were significantly decreased(P＜0.05).The application of activator ANS further increased the expression levels of IL-6,IL-1β,TNF-α,and p38 MAPK,and the PWT of rats were decreased.After application of inhibitor SB203580,the ex-pression levels of IL-6,IL-1β,TNF-α and p38 MAPK were significantly decreased in the DRG of rats(P＜0.05),and the PWT were significantly increased in rats(P＜0.05).Conclusion:6-OHDA induces mechanical hyperalgesia reaction in rats,and the molecular mechanism is related to activation of the p38 MAPK signalling pathway.

Exploration of Role of Yin and Yang Syndrome Differentiation in Parkinson's Disease / 中国实验方剂学杂志

The syndrome differentiation of Yin and Yang has the function of controlling the other six principles in the eight principles syndrome differentiation，which is a higher level or general induction of the disease. In the clinical process of traditional Chinese medicine，syndrome differentiation of Yin and Yang runs through the whole process of disease diagnosis and treatment. For Parkinson's disease，syndrome differentiation of Yin and Yang is particularly important. Different symptoms，the transformation of pathogenesis during the development of the disease and the treatment of traditional Chinese and western medicine all reflect the characteristics of Yin and Yang opposition restriction，mutual root and mutual use，and the transformation of ebb and flow. This article discusses the background，application and value of Yin-Yang syndrome differentiation from three aspects：the origin and application of yin-yang syndrome differentiation，the basis of Parkinson's disease syndrome differentiation，and the status and role of Yin-Yang syndrome differentiation in Parkinson's disease. It is of great significance to guide the diagnosis and treatment of Parkinson's disease with "Yin-Yang as the key point".

Tianma Goutengyin and Its Single Herb in Treatment of Parkinson's Disease： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a kind of chronic progressive neurodegenerative disease that has a high prevalence rate in recent years， especially in the elderly. PD belongs to the category of "tremor disease" and "tremor" in traditional Chinese medicine， and Tianma Goutengyin is a classic prescription contained in the Synopsis of The New Significance of Patterns and Treatment in Miscellaneous Diseases（《中医内科杂病证治新义》）. This article explored the theory of Tianma Goutengyin in the treatment of PD， and based on network pharmacological research， the article summarized relevant research on Tianma Goutengyin and its single herb in the treatment of PD. Moreover， it discussed the clinical applications and mechanisms of Tianma Goutengyin and its single herb in the treatment of PD. It is found that the mechanisms of Tianma Goutengyin in treating PD may be related to resisting oxidative stress， inhibiting inflammatory response， regulating neurotransmitters， and protecting dopamine （DA） neurons. Besides， the main components of the single herb in Tianma Goutengyin for treating PD are gastrodin， rhynchophylline， geniposide， gardenial alcohol， eucommitol glycoside， motherwort alkaloid， baicalin， pachyman， and achyranthes bidentata sterol. They can improve the related symptoms of PD patients by inhibiting inflammatory response， resisting oxidative stress， affecting calcium ion concentration， restoring mitochondrial function， and and protecting DA neurons. This article summarized the research progress of Tianma Goutengyin and its single herb in treating PD， so as to provide a reference for the prescription and medication of Tianma Goutengyin in the treatment of PD and subsequent research on the mechanisms of Tianma Goutengyin and its single herb in the treatment of PD and give play to the advantages of traditional Chinese medicine in the treatment of PD.

Airborne PM2.5 and Parkinson's disease: An updated meta-analysis / 环境与职业医学

Background An association between atmospheric fine particulate matter (PM2.5) exposure and Parkinson's disease (PD) has been suggested by previous studies, but the results of current epidemiological studies are still inconclusive. Objective To systematically evaluate the relationship between exposure to ambient PM2.5 and the risk of PD, as well as to explore potential influencing factors, aiming to provide scientific evidence for formulating early prevention strategies for PD. Methods Cochrane Library, PubMed, Web of Science, Medline, Embase, China National Know-ledge Infrastructure (CNKI), Wanfang Database, and VIP Chinese Science and Technology Journal Database were queried. The search terms included Parkinson's disease, particulate matter 2.5, and PM2.5 in both Chinese and English. Cohort studies examining the association between atmospheric PM2.5 exposure and the risk of PD were collected and searched from the inception of each database to June 26, 2023. The identified literature was screened, and the basic information of the included studies and their research subjects, outcome indicators, quantitative results of each study, as well as the information required by bias risk assessment were extracted. The Newcastle-Ottawa Scale was employed to assess the risk of literature bias. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis were conducted in Stata 15.0 software. Results Twelve cohort studies were identified. A total of 17443136 participants with follow-up periods ranging from 3.5 to 22 years were included in the analysis. The meta-analysis, utilizing a random-effects model, revealed that PD risk was elevated by 6% after exposure to PM2.5 [HR=1.06 (95%CI: 1.02, 1.11), P=0.006]. The subgroup analysis demonstrated that exposure to PM2.5 increased PD risk by 6% in North America [HR=1.06 (95%CI: 1.00, 1.12), P=0.033] and by 17% in East Asia [HR=1.17 (95%CI: 1.02, 1.33), P=0.020]. However, the effect was not statistically significant in Europe. PD risk exhibited a 7% rise [HR=1.07 (95%CI: 1.02, 1.14), P=0.011] in individuals aged 60 years and older, which was different from that in individuals younger than 60 years. Exposure to various concentrations of PM2.5 was observed to associate with an elevated risk of PD. The inclusion of adjustments for PD-related comorbidities did not alter the conclusion that ambient PM2.5 exposure might elevate the risk of PD. The studies with a follow-up duration exceeding 5 years and reporting more than 1000 PD cases suggested a significant increase in the risk of PD due to ambient PM2.5 exposure [HR=1.06 (95%CI: 1.01, 1.12), P=0.012; HR=1.06 (95%CI: 1.01, 1.11), P=0.027, respectively]. Conversely, no significant association was identified between ambient PM2.5 exposure and the risk of PD within the cohorts with a follow-up duration of less than 5 years and reporting fewer than 1000 PD cases [HR=1.09 (95%CI: 0.95, 1.26), P=0.214; HR=1.12 (95%CI: 0.98, 1.02), P=0.092, respectively]. The sensitivity analysis showed that the results were stable. The publication bias analysis and the combined trim-and-fill method showed that the results were robust. Conclusion The risk of PD could be increased by ambient PM2.5 exposure and influenced by age and area. The research results might be affected by the duration of follow-up and the quantity of PD cases reported.

Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway / 中国药房

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Effect of transcranial direct current stimulation on cognitive function and quality of life in patients with Parkinson's disease: a meta-analysis / 中国康复理论与实践

ObjectiveTo evaluate the effect of transcranial direct current stimulation (tDCS) on the cognitive function and quality of life in patients with Parkinson's disease. MethodsRandomized controlled trials (RCTs) on tDCS for Parkinson's disease were searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang Data from the inception to September, 2023. Control group was administered standard Parkinson's medications or placebo, physical therapy, and cognitive rehabilitation, while treatment group received tDCS additionally. The quality of the researches was evaluated using the Cochrane Risk of Bias Tool. Data synthesis and analysis were performed using RevMan 5.4 and Stata 17.0, with heterogeneity and sensitivity analyses. ResultsEight articles were included. tDCS significantly improved the scores of Montreal Cognitive Assessment (MD = 2.00, 95%CI 1.13 to 2.87, P < 0.001). However, there was no significant difference in the scores of Parkinson's Disease Questionnaire (MD = 0.73, 95%CI -5.78 to 7.23, P = 0.830), Beck Depression Inventory-Ⅱ(MD = -0.77, 95%CI -7.14 to 5.60, P = 0.810), and Unified Parkinson Disease Rating Scale-Ⅲ (MD = 1.60, 95%CI -0.77 to 3.97, P = 0.190). ConclusiontDCS may improve cognitive function of patients with Parkinson's disease.