OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

OBJECTIVE: To observe the effects of acupoint catgut embedding (ACE) on gut microbiota and fecal short-chain fatty acids (SCFAs) levels in patients with Parkinson's disease (PD) with constipation. METHODS: A total of 80 PD patients with constipation were randomly divided into an observation group and a control group, 40 cases in each group. Additionally, 40 healthy individuals were recruited as a healthy control group. The control group received conventional Western medical treatment for PD combined with polyethylene glycol (PEG), once daily for eight weeks. The observation group received additional ACE treatment at bilateral Tianshu (ST25), Zusanli (ST36), and Shangjuxu (ST37), once every two weeks for eight weeks. The healthy control group received no intervention. The spontaneous bowel movements (SBMs) per week and patient assessment of constipation quality of life (PAC-QOL) scores were assessed at baseline and after treatment in the two groups. Fecal samples were collected at the end of treatment for the observation and the control groups and at baseline for the healthy control group. Gut microbiota composition and diversity were analyzed using 16S rRNA method, and SCFA levels were measured using high-performance liquid chromatography (HPLC). RESULTS: Compared before treatment, the observation group showed a significant increase in SBMs (P<0.01), and PAC-QOL scores including physical discomfort, psychosocial discomfort, worry and concern, and total score were significantly reduced (P<0.01) after treatment; the control group also showed a reduction in PAC-QOL total score after treatment (P<0.01). After treatment, the observation group had significantly more SBMs (P<0.01), and lower PAC-QOL physical discomfort, psychosocial discomfort, worry and concern scores, and total score (P<0.01), and higher PAC-QOL satisfaction score (P<0.01) than the control group. Compared with the healthy control group, the control group showed decreased Chao1 and Ace indices (P<0.01). Compared with the healthy control group, the relative abundance of Prevotella and Roseburia was increased (P<0.05), while that of Enterobacter and Ruminococcus torques (six species in total) was decreased (P<0.05) in the control group. Compared with the control group, the observation group had increased relative abundance of Dialister, Parabacteroides, and Ruminococcus torques (P<0.05), and decreased relative abundance of Prevotella and Eubacterium ruminantium (P<0.05). Compared with the healthy control group, the control group had increased fecal SCFA levels (P<0.05); compared with the control group, the observation group had reduced fecal SCFA levels (P<0.05). Compared with the healthy control group, acetic acid, propionic acid, and butyric acid levels were elevated in the control group (P<0.05); compared with the control group, acetic acid, propionic acid, and butyric acid levels were decreased in the observation group (P<0.05). CONCLUSION ACE could increase spontaneous bowel movements and improve the quality of life in PD patients with constipation, which may be related to the regulation of gut microbiota composition and SCFA levels.
Humans ; Constipation/metabolism* ; Male ; Gastrointestinal Microbiome ; Acupuncture Points ; Female ; Middle Aged ; Parkinson Disease/complications* ; Aged ; Fatty Acids, Volatile/metabolism* ; Catgut ; Feces/microbiology* ; Acupuncture Therapy ; Quality of Life ; Adult

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2 * and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata ( P <0.001) and compacta ( P <0.001), SN ( P <0.001), red nucleus (RN, P <0.001), globus pallidus ( P <0.001), putamen (PUT, P = 0.021), and thalamus ( P = 0.029) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT ( P <0.001), RN ( P = 0.003), SN ( P = 0.017), and caudate nucleus ( P = 0.017) than MSA patients, and lower iron content in RN ( P = 0.001), PUT ( P <0.001), globus pallidus ( P = 0.004), SN ( P = 0.015), and caudate nucleus ( P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.86). CONCLUSIONS: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION PROSPERO (CRD42022344413).
Humans ; Parkinson Disease/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Iron/metabolism*

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

Pain is one of the common non-motor symptoms in patients with Parkinson disease and is characterized by early onset， a high incidence rate， and diverse types of discomfort， which seriously affects the quality of life of patients. Based on the related concepts of pain in Parkinson disease and the current status of research in China， this article reviews the commonly used non-pharmaceutical interventions for alleviating pain in patients and their mechanisms， in order to provide a basis for developing pain management regimens.
Parkinson Disease ; Pain

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

Objective To investigate the state of anxiety and depression in patients with Parkinson disease due to high-altitude exposure in Tibet， China and its impact on quality of life. Methods A total of 93 patients with Parkinson disease who attended Tibet Autonomous Region People’s Hospital from February 2023 to November 2024 were enrolled， and basic information and assessment scales were collected. The Unified Parkinson’s Disease Rating Scale Part Ⅲ （UPDRS-Ⅲ） and Hoehn-Yahr （H-Y） stage were used to evaluate disease severity； Parkinson’s Disease Quality of Life Questionnaire （PDQ-39） was used to evaluate the quality of life of patients； the diagnostic criteria for depression and anxiety in Parkinson disease were used for the diagnosis of depression and anxiety in patients with Parkinson disease； Hamilton Depression Scale （HAMD） and Hamilton Anxiety Scale （HAMA） were used to assess the severity of depression and anxiety. Results Among the 93 patients with Parkinson disease， the prevalence rates of depression and anxiety were 59.1% and 44.1%， respectively. There were significant differences between the depression group and the non-depression group in the somatization， despair， cognitive impairment， block factor， and day-night changes of anxiety， but there were no significant differences in sleep disorders and body weight between the two groups. The depression group had significantly higher PDQ-39 scores than the non-depression group， and the anxiety group had significantly higher PDQ-39 scores than the non-anxiety group. Depressive state was negatively correlated with folate and was positively correlated with blood homocysteine. Anxiety state was positively correlated with H-Y stage and UPDRS Ⅲ score. Conclusion There are relatively high prevalence rates of depression and anxiety in patients with Parkinson disease in Tibetan plateau area， which significantly affects the quality of life of patients.
Parkinson Disease ; Depression ; Anxiety

Objective To investigate the clinical features of dyskinesia and related risk factors in female patients with Parkinson disease （PD）. Methods A cross-sectional study was conducted among the female patients who met the diagnostic criteria for PD at the outpatient service of PD in Aerospace Center Hospital， and demographic data and clinical data were collected and compared between groups， including levodopa equivalent daily dose （LEDD）， Unified Parkinson’s Disease Rating Scale-Ⅲ（UPDRS-Ⅲ）， UPDRS-Ⅳ， scores of non-motor symptoms （cognition and depression）， presence or absence of dyskinesia， and single levodopa dose （LD） during the onset of dyskinesia. A binary logistic regression analysis was used to investigate the influencing factors for dyskinesia in female patients with PD. Results A total of 146 female PD patients were enrolled， among whom 30 patients had dyskinesia， with an incidence rate of 20.5%. Compared with the non-dyskinesia group in terms of clinical features， the dyskinesia group had a significantly younger age of onset [（54.3±12.5） years vs （62.7±10.0） years， P<0.001]， a significantly longer disease duration [（9.9±3.7） years vs （4.5±3.7） years， P<0.001]， a significantly higher severity of disease [H-Y stage： （2.65±0.58） vs （2.35±0.83）， P=0.03]， a significantly longer duration of LD administration [（7.5±3.2） years vs （3.2±2.6） years， P<0.001]， a significantly higher LEDD [（703.2±203.9） mg vs （442.1±226.3） mg， P<0.001]， and significantly lower body weight [（54.1±8.2） kg vs （60.0±8.7） kg， P=0.001] and BMI [（20.9±3.1） kg/m2 vs （23.4±3.1） kg/m2， P<0.001]. The multivariate logistic regression analysis showed that high BMI （OR=0.770， P=0.005） was a protective factor against dyskinesia in female PD patients， while long disease duration （OR=1.304， P=0.001） and high LEDD （OR=1.003， P=0.012） were risk factors for dyskinesia. Conclusion There is a relatively high incidence rate of dyskinesia in female PD patients， which should be taken seriously in clinical practice， and high BMI is a protective factor， while long disease duration and high LEDD are risk factors for dyskinesia in female PD patients.
Parkinson Disease ; Dyskinesias ; Levodopa

Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression

Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a variety of motor and non-motor symptoms. Many studies have shown that the transmembrane protein 175 (TMEM175) gene may be a potential target for the treatment of PD and other neurodegenerative disorders, but the specific pathogenic mechanism remains unclear. TMEM175 is a lysosomal protein-coding gene that encodes a lysosomal proton channel protein. This article reviews the research advances in the characterization of the TMEM175 gene and its encoded proteins, the clinical features of mutant PD, and related pathogenic mechanism. It is shown that the TMEM175 gene has an impact on the pathogenesis of PD, and patients with different mutation sites tend to have different ages of onset and clinical features. Compared with the patients without TMEM175 mutations, the patients with TMEM175 mutations tend to have an earlier age of onset, more severe motor symptoms, and more susceptibility to cognitive impairment and non-motor symptoms. This article systematically reviews the TMEM175 gene, in order to assist in the early diagnosis of PD and the discovery of new disease-modifying therapies and treatment strategies.
Parkinson Disease