BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

Objective:To explore the adjunctive diagnostic value of transcranial sonography (TCS) combined with olfactory test in early Parkinson′s disease (PD) and the clinical value of both in the cognitive function of PD patients.Methods:TCS and olfactory test were performed in 157 early PD patients(PD group) and 157 healthy controls(control group) in the Second Affiliated Hospital of Soochow University from January 2018 to January 2022. The differences in clinical characteristics, TCS, and olfactory test results between the two groups were analyzed. The values of TCS, olfactory test, and their combination in diagnosing early PD were evaluated using clinical diagnosis as the gold standard. The correlations of the midbrain area, the midbrain substantia nigra hyperechoic area, and the third ventricle width in TCS examination with the cognitive score were analyzed in the PD group. According to the olfactory test scores, 157 patients with early PD were divided into two groups: 110 cases of PD with olfactory dysfunction (PD-OD) and 47 cases of PD without olfactory dysfunction (PD-NOD). The differences in clinical scores and TCS results between the two groups were compared.Results:The midbrain substantia nigra hyperechoic area, substantia nigra hyperechoic positivity rate, third ventricle width, and olfactory dysfunction rate were higher in the PD group compared to the control group, while the midbrain area and olfactory test scores were lower than those in the control group (all P<0.001). The sensitivity and the coincidence rate of TCS combined with the olfactory test for early PD diagnosis (90.0%, 77.1%) were higher than those of TCS alone (60.0%, 71.3%) and olfactory test alone (70.1%, 72.3%), but the specificity (63.7%) was lower than that of both alone (82.8% for TCS and 75.2% for olfactory test), (all P<0.001). MoCA score, visual space and executive ability, memory, attention, and language were positively correlated with the area of the midbrain ( rs=0.38, 0.32, 0.27, 0.25, 0.23; all P<0.05) and negatively correlated with the width of the third ventricle ( rs=-0.39, -0.22, -0.39, -0.22, -0.32; all P<0.05), and orientation was negatively correlated only with the width of the third ventricle ( rs=-0.24, P<0.05). The MoCA score of PD-OD group[22(18, 25)] was lower than that of PD-NOD group[24(20, 26)]( P=0.040). Conclusions:The combination of TCS and olfactory test can enhance the sensitivity and diagnostic agreement rate for early PD diagnosis, providing some auxiliary value. The cognitive function of PD patients is positively correlated with the midbrain area and negatively correlated with the width of the third ventricle. The cognitive function of PD patients with olfactory dysfunction is lower than that of PD patients without olfactory dysfunction. TCS and olfactory test may help assess cognitive function in PD patients.

ObjectiveTo explore the effects and possible mechanism of Wenshen Tongdu Formula （温肾通督方， WTF） on spinal cord injury. MethodsThirty-six C57BL/6 female mice were randomly divided into sham operation group， model group and WTF group， with 12 mice in each group. The spinal cord injury model was established in the model group and the WTF group using the modified Allen's method， while in the sham operation group the spinal cord was only exposed. Since the 1st day after surgery， 50 g/（kg·d） of WTF solution was given to the WTF group by gavage， while 20 ml/（kg·d） of normal saline was given to the sham operation and model group by gavage， all for 14 days. Before surgery and on the 1st， 7th， and 14th days after surgery， the motor function of the mice was evaluated using the inclined plane test and hind limb motor function score （by BMS）. On the 3rd day after surgery， the nerve electrophy-siology was detected through electromyography and motor evoked potential； the spleen length was measured， and B cells in the spleen were sorted by magnetic beads； the differential expression of proteins were detected through proteomics technology； and the protein expression of mitochondrial outer membrane transport porin 20 （Tom20） and downstream cleaved caspase-3 in spleen B cells were measured using Western blotting. On the 14th day after surgery， MRI was used to observe the recovery of the spinal cord. ResultsCompared to those in the sham operation group at the same time， the BMS scores and subscores and the inclined plane test angle in the model group were reduced on the 1st， 7th and 14th days after surgery； the peak value of electromyogram and motor evoked potential were reduced， and the spleen length was shortened， while the expression of Tom20 and cleaved caspase-3 increased in splenic B cells increased （P＜0.05）. Compared to those in the model group at the same time， the BMS subscores on the 14th day and the angle of the inclined plane test on the 7th and 14th days after surgery increased in the WTF group； the peak value of electromyography and motor evoked potential， as well as the length of spleen increased， and the expression of Tom20 and cleaved caspase-3 decreased （P＜0.05）. The proteomics results showed that there were 100 differential proteins in the WTF group versus the model group， of which 37 were up-regulated and 63 were down-regulated. GO enrichment analysis showed that differential proteins mainly played their roles in oxygen binding， exogenous apoptosis negative feedback， zinc ion response， and oxygen transport. KEGG enrichment analysis showed that differential proteins were mainly concentrated in metabolic pathways， Huntington's disease， oxidative phosphorylation and other pathways. Subcellular localization showed that differential proteins were associated with mitochondria. Magnetic resonance imaging on the 14th day after surgery showed that the spinal cord structure of the mice in the sham operation group was intact， and the segments were clear， with normal spinal cord signal； the low signal area in the spinal cord injury area increased in the model group， and the spinal cord became significantly thinner； the injured segment had obvious depression in the WTF group， but the structure was more complete than that in the model group. ConclusionWTF may promote spinal cord injury repair by regulating immune function， and its mechanism may be related to inhibiting pyroptosis of spleen B cells.

Objective:To explore the pathological mechanism of SN hyperechogenicity by investigating the characteristics of substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in the postural instability gait difficulty and tremor dominant subtypes of Parkinson′s disease (PD), and the correlation between them.Methods:A total of 155 PD patients recruited in Parkinson′s Disease Specialty in the Second Affiliated Hospital of Soochow University from January 2019 to December 2021 were divided into postural instability gait difficulty group( n=95) and tremor dominant group( n=60). Meanwhile, 49 healthy gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group. All subjects underwent TCS and blood test, and the echo of SN between the postural instability gait difficulty group and tremor dominant group, serum iron metabolism parameters among the three groups were compared. The postural instability gait difficulty group and tremor dominant group were subdivided into with SN hyperechogenicity (SN+ )subgroup and without SN hyperechogenicity (SN-) subgroup respectively according to TCS results, and the differences in serum iron metabolism parameters between the subgroups were further compared. The association between SN hyperechogenicity and serum iron metabolism parameters of the postural instability gait difficulty group and tremor dominant group were further analyzed. Results:The total area of bilateral SN+ , the area of SN+ on the larger side, and the ratio of the total area of SN+ to the midbrain area (S/M) in postural instability gait difficulty group were larger than those in tremor dominant group (all P<0.001). The value of serum ceruloplasmin and transferrin in both postural instability gait difficulty group and tremor dominant group were lower than those in control group (all P<0.001), and compared with tremor dominant group and control group, the postural instability gait difficulty group had lower serum ferritin(all P<0.01). In both postural instability gait difficulty group and tremor dominant group, serum ceruloplasmin in SN+ subgroup was lower than that in SN-subgroup ( P=0.001, 0.032). Moreover, there was a negative correlation between serum transferrin and the area of SN hyperechogenicity in two subgroups(postural instability gait difficulty group: rs=-0.454, P<0.001; tremor dominant group: rs=-0.494, P<0.001). Conclusions:Compared with the tremor dominant patients, the postural instability gait difficulty patients have larger area of SN hyperechogenicity and lower serum ferritin level. The area of SN hyperechogenicity is significantly negatively correlated with serum transferrin level, indicating that the production of this imaging characteristics is related to iron metabolism.

Objective:To explore the value of machine learning models based on multiple structural MRI features for diagnosis of Parkinson disease (PD).Methods:The clinical and imaging data of 60 PD patients (PD group) diagnosed in the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2017 to August 2019 and 56 normal elderly people (NC group) recruited from the community were retrospectively analyzed. All subjects underwent brain MR imaging. Multiple structural MRI features were extracted from cerebellum, deep nuclei and of brain cortex based on different partition templates. The Mann-Whitney U test, as well as least absolute shrinkage and selection operator regression were used to select the most discriminating features. Finally, logistic regression (LR) and linear discriminant analysis (LDA) classifier combined with the 5-fold cross-validation scheme were used to construct the models based on structural features of cerebellum, deep nuclei and cortex, and a combined model based on all features. The receiver operating characteristic curves were drawn, and the diagnostic performance and clinical net benefit of each model were evaluated by the area under curve (AUC) and the decision curve analysis (DCA). Results:In total, four cerebellum (asymmetry index of Lobule Ⅵ volume, asymmetry index of Lobule ⅦB cortical thickness, asymmetry index of total gray matter volume and absolute value of right Lobule Ⅵ gray matter volume), 3 deep nuclei (absolute value of right nucleus accumbens volume, absolute and relative value of total nucleus accumbens volume) and 3 cortex features (local gyration index of left PFm, local fractal dimension of right superior frontal gyrus and sulcal depth of left superior occipital gyrus) were selected as the most discriminating features, and the related models were constructed. In validation set, the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LR classifier were 0.692, 0.641, 0.747 and 0.816; the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LDA classifier were 0.726, 0.610, 0.752 and 0.818. The diagnostic efficiency of the combined models based on LR and LDA classifiers were significantly better than those of other models ( P<0.05). The DCA curve demonstrated that the combined models based on LR and LDA classifiers showed the highest clinical net benefit. Conclusion:The combined models with all structural features of cerebellum, deep nuclei and cortex included based on LR and LDA classifiers showed favorable performance and clinical net benefit for diagnosis of PD, which have the potential application value in clinical diagnosis.

Objective:To perform cross-cultural adaption of the KING′s Parkinson′s Disease Pain Scale (KPPS), explore its reliability and validity in Chinese Parkinson′s disease (PD) patients, and to create the new version of the pain scale which adapts to the Chinese PD patients.Methods:This study enrolled 225 patients, including 121 men and 104 women who were selected from the Outpatient Center of Movement Disorders Clinic of the Second Affiliated Hospital of Soochow University from July 2018 to July 2020. All patients completed the evaluation of the Chinese Version of KPPS (KPPS-CV). According to the preliminary evaluation results, the expert group modified KPPS-CV after discussion, and developed a Modified KPPS-CV (MKPPS-CV). These patients then completed the MKPPS-CV evaluation during the 3-month follow-up. Cross-cultural adaptation was performed according to published international guidelines that include translation, back-translation, expert review, and pretesting. The following psychometric properties were evaluated: basic item analysis; floor and ceiling effects; construct validity; content validity; criterion validity (Spearman′s rho between the KPPS-CV and Numeric Rating Scale); internal consistency reliability (Cronbach′s alpha); test-retest reliability (intra-class correlation coefficient, ICC).Results:In item analysis, 50% of the items had poor discrimination (critical ratio<3.0), and floor effect was found in all domains (proportion of 0 point>15%). The items were reclassified after exploratory factor analysis. The content validity of item 3, item 10 and item 11 was low (item-level content validity index<0.78). Criterion validity showed the highest correlations (Spearman′s rho>0.88) between the KPPS-CV and Numeric Rating Scale. While overall scale reliability was minimally acceptable at 0.46, which showed a poor reliability of this scale. Test-retest reliability was excellent for each item (Spearman's rho>0.85). The Cronbach′s alpha of MKPPS-CV (0.76) was higher than that of KPPS-CV (0.46). It showed a great improvement after the modifying.Conclusions:When using scales that are not developed for local populations, differences in culture and clinical practices should be taken into account. MKPPS-CV is an acceptable, valid measure to evaluate pain in Chinese PD patients, which is more suitable for Chinese people.

Gastrointestinal symptoms are common nonmotor symptoms of Parkinson′s disease, which are related closely to occurrence and progress of Parkinson′s disease, as well as throughout its whole process. For example, constipation can be an important symptom in prodromal stage of Parkinson′s disease, and gastroparesis would weaken the effect of drug by interfering pharmacokinetics. However, insufficient attention has been paid to the gastrointestinal symptoms of Parkinson′s disease presently, and there are few effective treatments, which compromise the quality of patients′ life greatly. The intervention focus on gut-brain axis, microbiota and gastrointestinal barrier may play a positive role in improving gastrointestinal symptoms and delaying the process of Parkinson′s disease.

The non-motor symptoms of Parkinson′s disease have received more and more attention, and they have become a hot spot in the study of Parkinson′s disease. The non-motor symptoms related to Parkinson′s disease, including sensory disturbances, neuropsychiatric symptoms, sleep disturbances, and autonomic dysfunctions were reviewed in this article, and their clinical manifestations, evaluation methods, and managements were emphasized.