1.Quantitative analysis of foot kinematics in patients with early Parkinson′s disease under dual task
Haohao WANG ; Xiaofan XUE ; Dongtao LIU ; Zhou LONG ; Cheng WANG ; Lichun ZHOU
Chinese Journal of Neurology 2024;57(3):255-265
Objective:To investigate the gait characteristics of patients with early Parkinson′s disease (PD) under cognitive dual task, and to provide sensitive kinematic indicators for the early diagnosis, timely treatment and reasonable rehabilitation of PD.Methods:A total of 62 outpatients and inpatients with early non-tremor Parkinson′s disease in Shijingshan Branch of Beijing Chaoyang Hospital Affiliated to Capital Medical University from September 2021 to August 2023 were selected as experimental group (PD group), and 62 healthy controls with comparable age composition ratio were selected as control group. The baseline data, Montreal Cognitive Assessment Scale scores, and the gait assessment scores of the motor part of the Unified Parkinson′s Disease Rating Scale were compared between the 2 groups. The wearable gait analysis device was used to collect the gait parameters of the 2 groups of subjects under single task and dual task, and the foot kinematic characteristics of the patients with early PD were quantified. Independent sample t test and Mann-Whitney U test were used to analyze the gait parameters of the 2 groups. The statistically significant variables were included in Logistic regression analysis to explore the association between gait parameters and PD. Finally, the diagnostic value of the variables was estimated by receiver operating characteristic (ROC) curve analysis. Results:Gait spatio-temporal parameters (per gait cycle): (1) The gait speed of the PD group was slower than that of the control group [(1.01±0.12) m/s vs (1.22±0.18) m/s, t=-7.526] during single task walking. The bipedal support time in the PD group was significantly longer than that in the control group [(0.29±0.05) s vs (0.22±0.06) s, t=6.659]. The differences were both statistically significant (both P<0.001). (2) During dual-task walking, PD patients showed slower gait speed [(0.88±0.11) m/s vs (1.19±0.16) m/s, t=-12.158, P<0.001]. The bipedal support time in the PD group was longer than that in the control group [(0.36±0.05) s vs (0.22±0.05) s, t=12.828, P<0.001]. PD patients had shorter stride length [(109.20±6.21) cm vs (112.77±5.87) cm, t=-3.203, P=0.010]. Stride frequency in the PD group was higher than that in the control group [(114.45±7.10) steps/min vs (110.87±7.16) steps/min, t=2.724, P=0.020]. The single leg support time was longer than that of the control group [(0.49±0.12) s vs (0.45±0.06) s, t=2.643, P=0.020] , and the differences were statistically significant. Gait kinematics parameters: (1) During single task walking, the maximum angle of foot movement in the sagittal plane in the PD group was smaller than that in the control group (17.19°±2.37° vs 19.71°±2.92°, t=-4.691, P<0.001). The minimum angle of movement in the sagittal plane was smaller than that in the control group (-67.08°±4.63° vs -70.10°±3.94°, t=0.395, P=0.001). The minimum horizontal angle of the foot during exercise in the PD group was lower than that in the control group (9.08°±4.02° vs 11.80°±3.60°, t=-3.461, P<0.001). The minimum angle of the foot coronal plane in the PD group was smaller than that in the control group (-10.55°±2.87° vs -12.04°±2.31°, t=2.831, P=0.030; the negative sign only represents the movement direction). The touch angle of the foot in the PD group was significantly lower than that in the control group (11.14°±2.78° vs 12.78°±3.57°, t=-2.779, P=0.030). (2) During dual-task walking, the maximum sagittal angle (15.44°±2.54° vs 18.99°±2.71°, t=-6.673, P<0.05), the minimum angle of sagittal plane (-65.68°±4.73° vs -70.02°±4.04°, t=-4.747, P<0.001; the negative sign only represents the direction of movement), the minimum coronal movement angle (-11.15°± 2.99° vs -13.18°±2.50°, t=3.642, P=0.020), the touch angle (11.01°±3.10° vs 12.83°±4.01°, t=-2.438, P=0.010), the minimum horizontal angle (8.83°±4.04° vs 11.83°±3.63°, t=-3.776, P<0.001), and the change of the angle from the ground (-65.00°±3.54° vs -67.06°±3.61°, t=3.133, P<0.001) in the PD group were all smaller than that in the control group. The differences were all statistically significant. Logistic regression analysis showed that step frequency was positively correlated with PD ( OR=1.124,95% CI 1.040-1.201, P=0.001), minimum angle of coronal plane was positively correlated with PD ( OR=1.501, 95% CI 1.040-2.151, P=0.030). Stride length was negatively correlated with PD ( OR=0.902, 95% CI 0.830-0.978, P=0.010). ROC curve was used to evaluate the diagnostic value of step frequency, stride length and minimum angle of coronal plane. For step frequency, when the maximum Youden index was 0.880, the best cut-off value to distinguish the PD group from the control group was 115.000, the sensitivity was 0.577, the specificity was 0.710, and the area under the curve was 0.656. For the minimum coronal angle, when the maximum Youden index was 0.251, the best cut-off value was -12.575, the sensitivity was 0.728, the specificity was 0.531, and the area under the curve was 0.670. For stride length, when the maximum Youden index was 0, the best cut-off value was 100.91, the sensitivity was 0.950, the specificity was 0.050, and the area under the curve was 0.300. Conclusions:Some gait parameters such as step frequency and minimum angle of coronal plane can be used as kinematic markers to reflect the gait characteristics of early PD, which may be helpful in tracking and evaluating the gait disorder characteristics of early PD patients and predicting the risk of PD. Some gait parameters of PD patients are significantly different from those of healthy people during cognitive-motor dual-task walking.
2.Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway
Jiaxin GAO ; Jianbo WANG ; Yanan XUE ; Jie SUN ; Dan WANG ; Kun HAN ; Yunyu ZHANG ; Yiran YIN ; Xiaofan FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):10-17
ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan(QWBZS) on diabetic encephalopathy(DE) rat model, and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β) signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group(8 rats) and high-fat diet group(40 rats). After 12 weeks of feeding, rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin(STZ) for 2 consecutive days to construct a DE model, and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling, according to blood glucose and body weight, model rats were randomly divided into model group, low, medium and high dose groups of QWBZS(3.15, 6.3, 12.6 g·kg-1), combined western medicine group(metformin+rosiglitazone, 0.21 g·kg-1), with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage, and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage, 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin (FINS) level was detected by enzyme-linked immunosorbent assay(ELISA) and insulin resistance index(HOMA-IR) was calculated. Hematoxylin-eosin(HE) staining was used to observe the morphological changes of hippocampus in rats, ELISA was used to detect the indexes of oxidative stress in hippocampal tissues, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect mRNA expression levels of PI3K, Akt, nuclear transcription factor-κB(NF-κB), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in hippocampus, and Western blot was used to detect the protein expression of PI3K, Akt, phosphorylated(p)-Akt, GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group, FINS and HOMA-IR values of the model group were significantly increased(P<0.01), the path of finding the original position of the platform was significantly increased, and the escape latency was significantly prolonged(P<0.01), the morphology of neuronal cells in hippocampal tissues was disrupted, the levels of reactive oxygen species(ROS) and malondialdehyde(MDA) in hippocampus of rats were increased, and the activity of superoxide dismutase(SOD) was decreased(P<0.05, P<0.01), mRNA expression levels of PI3K and Akt were decreased(P<0.01), mRNA expression levels of NF-κB, TNF-α and IL-1β were increased(P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly decreased, and the protein expression of GSK-3β was significantly increased(P<0.01). Compared with the model group, the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased(P<0.01), the path of finding the original position of the platform and the escape latency were significantly shortened(P<0.01), the hippocampal tissue structure of rats was gradually recovered, and the morphological damage of nerve cells was significantly improved, the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased(P<0.01), the mRNA expression levels of PI3K and Akt were increased(P<0.01), and the mRNA expression levels of NF-κB, TNF-α and IL-1β were decreased (P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly increased(P<0.01), and the expression of GSK-3β was significantly decreased(P<0.01). ConclusionQWBZS can alleviate insulin resistance in DE rats, it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.
3.Screening and diagnostic validity of the comprehensive cognitive domain assessment scale for mild cognitive impair-ment in the Chinese population with Parkinson disease
Xiaofan XUE ; Zhiyue WU ; Anqi HUANG
Journal of Apoplexy and Nervous Diseases 2024;41(5):402-407
Objective To develop an appropriate comprehensive scale for mild cognitive impairment in Parkinson dis-ease(PD-MCI)due to various diagnostic methods for PD-MCI and a lack of consensus on the applicable neuropsychological scales for PD-MCI.Methods A total of 92 non-dementia PD patients with a confirmed diagnosis were enrolled in this study,and all patients were assessed using the comprehensive scale of five cognitive domains recommended by the Chinese version of PD-MCI guidelines and Movement Disorder Society(MDS).Based on the norms of healthy controls assessed by the same scale,the patients were divided into non-cognitive impairment PD group and PD-MCI group.The t-test was used to observe the consistency between groups;the receiver operating characteristic(ROC)curve was used to investigate the cut-off value of each scale with the highest sensitivity and specificity in identifying the impairment in each cognitive domain of PD-MCI;a binary lo-gistic regression analysis was used to determine the specific contents of the comprehensive cognitive domain assessment scale for PD-MCI.Results This study showed that the ten-point comprehensive cognitive domain assessment scale based on long-time memory in Brief Visuospatial Memory Test,Clock Drawing Test,digit span backward test,Trail Making Test A,Verbal Flu-ency Test,Trail Making Test B,Similarities,Boston Naming Test,long-time recall memory in Auditory Verbal Learning Test,and short-time recall memory in Wechsler Memory Scale-IV Logical Memory Test had a significant diagnostic validity in predict-ing PD-MCI,with an area under the ROC curve of 0.971(95%CI 0.941?1.000).Conclusion The recommended cut-off value can be used to perform a subtype analysis of PD-MCI and observe the outcome and clinical specificity of different subtypes of PD-MCI,and therefore,it has a certain clinical significance.
4.Cut-off values of cognitive domain assessment scales for Parkinson disease in Beijing,China
Zhiyue WU ; Xiaofan XUE ; Anqi HUANG
Journal of Apoplexy and Nervous Diseases 2024;41(5):408-412
Objective To establish the delimitation norm of cognitive domain assessment scales for Parkinson dis-ease(PD)in Beijing,China,and to investigate the optimal cut-off values for determining abnormal neuropsychological as-sessments.Methods A total of 33 normal middle-aged and elderly individuals in communities and 89 patients with non-dementia PD were included in this study,and all subjects underwent global cognitive function screening and cognitive do-main assessments.According to whether Montreal Cognitive Assessment(MoCA)score was greater than 25 points,the pa-tients with PD were divided into mild cognitive impairment group(PD-MCI group)and normal cognition group(PD-NC group).In order to compare the consistency between PD-related cognitive domain assessment scales and global cognitive function screening in the diagnosis of PD-MCI,different cut-off values below the appropriate norms(i.e.,1.00 standard deviation,1.28 standard deviations,1.64 standard deviations,1.96 standard deviations below the mean)were examined for sensitivity,specificity,positive predictive value,and negative predictive value to obtain the optimal cut-off value.Results The delimitation norm of PD-related cognitive domain assessment scales was established for Beijing,and the re-sults showed that 1.96 standard deviations had the highest consistency in the diagnosis of PD-MCI and PD-NC,with the best sensitivity and specificity.Conclusion This study establishes the delimitation norm of PD-related cognitive domain assess-ment scales and fills the blank of the unbounded value of most domestic PD cognitive impairment assessment scales,and it also proposes the optimal cut-off value of abnormal neuropsychological assessment,which provides a reference standard for the cognitive domain assessment of PD patients in China and helps clinicians to identify cognitive decline in PD patients and adopt intervention measures in the early stage.
5.Changes in motor symptoms and cognitive function in α-synuclein A53T transgenic mice at different months of age
Xiaofan XUE ; Xinhui LI ; Heng ZHOU
Journal of Apoplexy and Nervous Diseases 2024;41(7):611-618
Objective To investigate the changes in motor symptoms and cognitive levels in α-synuclein A53T transgenic mice at different months of age and possible mechanisms.Methods The α-synuclein A53T transgenic mice and wild C57/BL6J mice,aged 6 months,were selected.The open field test and the rotarod test were used to observe the motor function and emotional response of mice;fear conditioning and the novel object recognition test were used to observe the cognitive function of mice;Western blotting was used to measure the expression level of M1 cholinergic receptor in the hippocampus of the mice in the two groups,and the transcriptome method was used to observe the difference in gene ex-pression in the hippocampus between the two groups.Results Behavioral experiments showed that compared with the wild-type mice,the A53T transgenic mice showed cognitive dysfunction at 12 months of age[novel object recognition test:(36.74±13.33)vs(46.90±6.58),t=-2.368,P=0.027],and this phenomenon occurred before motor symptoms.West-ern blotting showed that there was no significant difference in the level of M1 cholinergic receptor in the hippocampus be-tween the A53T transgenic mice and the wild-type mice(P=0.537).The transcriptome analysis identified 290 differen-tially expressed genes between the two groups,among which there were 20 genes with significant difference,and the sig-nificantly downregulated gene sets in the hippocampus of A53T mice were mainly involved in anti-cellular inflammatory re-sponse and antioxidant level.Conclusion Cognitive dysfunction in A53T transgenic mice occurs earlier than motor symp-toms,with a relatively late time node.Transcriptome tests suggest that cellular inflammatory response and oxidative stress injury might be involved in the early pathological process of cognitive impairment in A53T mice.
6.Acute myeloid leukemia with translocation t (8;16) (p11;p13) and prominent coagulation abnormalities at onset: case report and review of literature
Jiawen DAI ; Feng XUE ; Wei LIU ; Lei ZHANG ; Renchi YANG ; Xiaofan LIU
Chinese Journal of Hematology 2024;45(S1):73-76
Acute Myeloid Leukemia with t (8;16) (p11;p13) is a rare subtype of AML. This article presents a retrospective analysis of a 19-year-old female patient with t (8;16) (p11;p13) AML, focusing on her clinical features and treatment course, alongside a review of relevant literature. The patient was admitted due to skin ecchymosis and gastrointestinal bleeding, rapidly progressing to disseminated intravascular coagulation. Bone marrow examination revealed an abnormal blast morphology resembling early promyeloblasts, and the initial diagnosis was acute promyelocytic leukemia. However, chromosomal analysis identified the t (8;16) (p11.2;p13.3) translocation. The patient was finally diagnosed with acute monocytic leukemia. Following intensive induction chemotherapy, she achieved complete remission, but relapse occurred during consolidation therapy. The overall prognosis was poor. AML with t (8;16) (p11;p13) is relatively rare and characterized by distinct clinical and laboratory features, with a generally unfavorable prognosis. Early recognition by clinicians is crucial for appropriate management.
7.Acute myeloid leukemia with translocation t (8;16) (p11;p13) and prominent coagulation abnormalities at onset: case report and review of literature
Jiawen DAI ; Feng XUE ; Wei LIU ; Lei ZHANG ; Renchi YANG ; Xiaofan LIU
Chinese Journal of Hematology 2024;45(S1):73-76
Acute Myeloid Leukemia with t (8;16) (p11;p13) is a rare subtype of AML. This article presents a retrospective analysis of a 19-year-old female patient with t (8;16) (p11;p13) AML, focusing on her clinical features and treatment course, alongside a review of relevant literature. The patient was admitted due to skin ecchymosis and gastrointestinal bleeding, rapidly progressing to disseminated intravascular coagulation. Bone marrow examination revealed an abnormal blast morphology resembling early promyeloblasts, and the initial diagnosis was acute promyelocytic leukemia. However, chromosomal analysis identified the t (8;16) (p11.2;p13.3) translocation. The patient was finally diagnosed with acute monocytic leukemia. Following intensive induction chemotherapy, she achieved complete remission, but relapse occurred during consolidation therapy. The overall prognosis was poor. AML with t (8;16) (p11;p13) is relatively rare and characterized by distinct clinical and laboratory features, with a generally unfavorable prognosis. Early recognition by clinicians is crucial for appropriate management.
8.Roadmap for modern development of Chinese medicine: Traditional, evidence-based, and digital-intelligent paths
Xiaoyu ZHANG ; Xiaowei ZHANG ; Xiao LI ; Shuangqiu WANG ; Chen ZHAO ; Zhao CHEN ; Liangzhen YOU ; Yin JIANG ; Hongyuan LIN ; Xuxu WEI ; Jun XIONG ; Xiaofan CHEN ; Yinghui JIN ; Xue XU ; Hongcai SHANG
Science of Traditional Chinese Medicine 2024;2(1):14-19
Accelerating the modernization of Chinese medicine (CM) is the focus of CM development in the new era. Looking back over the past 50 years, CMhas progressed along traditional, evidence-based, and digital-intelligent paths. These paths have intertwined andmutually propelled the advancement of CM modernization. This article analyzes the patterns of 3 paths, summarizes the current status of CM development along these paths, and presents a vision for future development.
9.Screening and identification of a polyurethane-degrading bacterium G-11 and its plastic degradation characteristics.
Zhitong JIANG ; Xue CHEN ; Jinhui LEI ; Huizhen XUE ; Bo ZHANG ; Xiaofan XU ; Huijing GENG ; Zhoukun LI ; Xin YAN ; Weiliang DONG ; Hui CAO ; Zhongli CUI
Chinese Journal of Biotechnology 2023;39(5):1963-1975
Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism*
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Polyurethanes/chemistry*
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RNA, Ribosomal, 16S
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Bacteria/genetics*
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Biodegradation, Environmental
10.Clinical characteristics of cognitive impairment in patients with Parkinson disease with or without neurogenic orthostatic hypotension
Journal of Apoplexy and Nervous Diseases 2023;40(6):530-535
Objective Orthostatic hypotension(OH),a result of autonomic dysfunction,is an important risk factor for cognitive impairment in patients with Parkinson disease(PD). However,the direct relationship between cognitive levels and neurogenic OH in patients with PD remains unclear. We aimed to investigate the relationship between cognitive dysfunction and neurogenic OH in patients with PD,and compare the scores of various cognitive domains between patients with PD with asymptomatic OH and those with symptomatic OH. Methods We retrospectively included 79 patients with PD in the Department of Neurology,Xuanwu Hospital,Capital Medical University,including 19 with symptomatic OH,20 with asymptomatic OH,and 40 without OH. All the patients were examined for the presence or absence of OH by beat-to-beat blood pressure monitoring and the active stand test. The OH questionnaire was used to distinguish between symptomatic and asymptomatic OH. Cognitive function was assessed using a global neuropsychological scale. We used one-way analysis of variance and the Kruskal-Wallis test to determine the association between OH and cognitive dysfunction as well as the characteristics of different cognitive domains in different types of patients. Results There was a positive correlation between the years of education and the levels of cognitive function in all PD groups. Patients with symptomatic OH were more likely to develop poor delayed verbal recall at an earlier stage. Patients without OH had impairment in visual space/executive function more frequently. Conclusion Our findings provide new insights into PD with cognitive impairment that patients with symptomatic OH may be more prone to memory impairment due to the underlying pathophysiological mechanism of OH.


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