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Objective:To investigate the effects of 30% ethanol elution fraction of Artemisia absinthium extract with macroporous resin (AAEM-30%) on the dendritic cell (DC) and immunity of mice. Methods:AAEM-30% was obtained from the alcoholic extracts of A. absinthium by AB-8 macroporous resin, and its polysaccharide, flavonoid, and terpenoid contents were determined. The expressions of AAEM-30% on DC surface molecular cluster of differentiation (CD) 40, CD80 and CD86 were detected in vitro by flow cytometry, and the expressions of DC cytokines IL-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The effect of AAEM-30% on the immune function of ICR mice was measured in vivo with different doses (50 and 100 mg/kg) and different administration methods (subcutaneous injection, intraperitoneal injection, and gavage). Results:The contents of polysaccharides, flavonoids, and terpenoids in AAEM-30% were 24.30%, 22.50% and 28.19%, respectively. AAEM-30% significantly enhanced the expression of CD40, and CD86 and the secretion of IL-6 and TNF-α (all P<0.001). Compared with the control group, no statistically significant differences were found in the body mass of mice compared with the three administration methods (all P>0.05). The thymus index in the 50 and 100 mg/kg AAEM-30% intraperitoneal injection groups and the spleen index in the 50 mg/kg AAEM-30% gavage group were increased (all P<0.05). CD19 + cells increased in the 100 mg/kg AAEM-30% intraperitoneal injection group ( P<0.01) and in the 50 mg/kg AAEM-30% gavage group ( P<0.05). The CD11b + and CD11c + counts increased in the 100 mg/kg AAEM-30% gavage group ( P<0.05). The number of CD4 + and CD8 + T lymphocytes was increased by both gavage and intraperitoneal administration (all P<0.05). Conclusions:AAEM-30% can promote the maturation of DC and enhanced the immunity of mice without obvious side effects.
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Objective:To quantitatively evaluate the retinal ischemia in different retinal regions of diabetic retinopathy (DR) patients in ultra-widefield fluorescein fundus angiography (UWFA) images with ischemic index (ISI), and to explore its correlation with diabetic macular edema (DME).Methods:A cross-sectional study was conducted.Seventy-nine eyes of 79 patients with DR were enrolled in Renmin Hospital of Wuhan University from September 2017 to October 2020, including 44 males (44 eyes) and 35 females (35 eyes) aged 31 to 73 years old, with an average age of (55.95±8.80) years.UWFA and spectral-domain optical coherence tomography (SD-OCT) were performed in all patients.Patients were divided into DME group (37 eyes) and non-DME group (42 eyes) according to the presence or absence of DME in OCT images.The retina in middle phase UWFA images were divided into posterior, middle peripheral and far peripheral regions by ImageJ software, and ISI in each region was calculated.Central macular thickness (CMT) was automatically calculated using the built-in software of the OCT equipment.The correlation between ISI and CMT was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037). Written informed consent was obtained from each patient prior to any medical examination.Results:The ISI of the total, posterior, middle peripheral and far peripheral retina was 2.460 (0.603, 5.640)%, 2.670 (1.062, 9.574)%, 1.382 (0.245, 4.378)% and 0.000 (0.000, 1.262)%, respectively, with a statistically significant difference among different regions ( χ2=65.307, P<0.001). There were statistically significant differences in ISI between the total and far peripheral, the posterior and middle peripheral, the posterior and far peripheral, the middle and far peripheral (all at P<0.01). ISI of the total, posterior and middle peripheral retina in DME group were significantly higher than those in non-DME group ( U=424.000, P=0.001; U=403.000, P<0.001, U=493.000, P=0.005), but there was no significant difference in the ISI of the far peripheral region between the two groups ( U=609.000, P=0.061). There was no statistically significant correlation between ISI and CMT in the total, posterior, middle peripheral and far peripheral retina in DME group ( rs=-0.134, -0.018, -0.152, -0.163; all at P>0.05). Conclusions:The retinal non-perfusion area in DR eyes is mainly located in the posterior and middle peripheral retina.The ISI of the posterior and middle peripheral retina in DME eyes is significantly higher than that in eyes without DME.ISI of each retinal region may not be related to the severity of DME.
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{L-End}Objective To analyze the correlation between occupational burnout and sleep quality among steelworkers. {L-End}Methods A total of 11 491 steelworkers from a large steel enterprise in Gansu Province were selected as the research subjects using convenient sampling method. The Burnout Questionnaire and the Pittsburgh Sleep Quality Index Scale were used to investigate their occupational burnout and sleep quality. Hierarchical regression analysis was used to analyze the effects of occupational burnout on the sleep quality. {L-End}Results The detection rate of occupational burnout and sleep disorder were 50.4% and 39.0%, respectively. There was a positive correlation between the level of occupational burnout and the total score of sleep quality (Spearman correlation coefficient=0.454, P<0.05). The results of hierarchical regression analysis, adjusting for confounding factors such as gender, age, marital status, education level, alcohol consumption, exercise, weekly working hours, seniority, work shift, noise exposure, dust exposure, and high-temperature work, showed that the score of occupational burnout was positively related to the score of sleep quality(P<0.01), explaining 16.0% of the variance in the score of sleep quality among these steelworkers. {L-End}Conclusion The detection rate of occupational burnout and sleep disorders are relatively high among the steelworkers in this enterprise. Higher levels of occupational burnout are associated with poorer sleep quality. Alleviating occupational burnout among steelworkers may contribute to improving their sleep quality.
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Background Steel workers are exposed to occupational hazardous factors such as dust, noise, and heat, and often work in shifts, making them prone to sleep disorders. Objective To explore potential influencing factors of sleep disorders among workers in a steel enterprise in Gansu Province, and provide a basis for reducing the risk of sleep disorders among them. Methods From January to March 2022, a self-made questionnaire combined with the Pittsburgh Sleep Quality Index (PSQI) were used to investigate the employees of a steel enterprise in Gansu Province. According to their PSQI scores, they were divided into a normal sleep group and a sleep disorder group. The general demographic variables of the two groups were balanced by 1∶1 propensity score matching (PSM). Multiple logistic regression was used to analyze the contributing factors of sleep disorders. Restricted cubic spline (RCS) model was used to analyze potential dose-response relationship between weekly working hours and sleep disorders. Results The prevalence of sleep disorders in the steel workers was 48.06% (6029/12544). After PSM, 5847 pairs were successfully matched, and the distributions of matched variables were well balanced between the two groups. The results of multiple logistic regression showed that hypertension (OR=1.39, 95%CI: 1.24, 1.56), diabetes mellitus (OR=1.34, 95%CI: 1.07, 1.66), three-shift system (OR=1.26, 95%CI: 1.12, 1.41), dust exposure (OR=1.14, 95%CI: 1.01, 1.29), noise exposure (OR=1.23, 95%CI: 1.09, 1.39), heat exposure (OR=1.16, 95%CI: 1.04, 1.29), and work injury (OR=1.22, 95%CI: 1.02, 1.46) increased the risk of sleep disorders. Compared with workers with < 10 years of service, those with 10-20 years (OR=1.31, 95%CI: 1.19, 1.44), 20-30 years (OR=1.34, 95%CI: 1.19, 1.52), and ≥30 years of service (OR=1.35, 95%CI: 1.19, 1.53) had a higher risk of sleep disorders. Compared with non-exercise workers, the risk of developing sleep disorders was lower in workers with occasional exercise (OR=0.61, 95%CI: 0.56, 0.66) and regular exercise (OR=0.55, 95%CI: 0.49, 0.62). The RCS model showed that the weekly working hours and sleep disorders in the steel workers showed a nonlinear dose-response relationship (P<0.05 for overall trend, P<0.05 for nonlinear test). The relationship between weekly working hours and sleep disorders showed a "U" shaped distribution, with a significant increase in the risk of sleep disorders when the weekly working hours exceeded 49 h. Conclusion The non-occupational influencing factors of sleep disorders of employees in the steel enterprise include hypertension, diabetes, physical exercise, and occupational influencing factors include length of service, weekly working hours, shifts, dust exposure, noise exposure, heat exposure, and work injuries. It is recommended to consider both occupational and non-occupational factors to formulate appropriate sleep disorder prevention and control measures for steel employees to reduce the risk of sleep disorders.
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Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.
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Fluorescein fundus angiography (FFA) is an important examination to observe retinal vascular diseases, but the observation of peripheral retina is limited through traditional FFA.Ultra-widefield fluorescein angiography (UWFA) is a new technique which helps to expand the field of view in retina, and explores peripheral retinopathy clearly.To accurately quantify the retinal non-perfusion area, ischemic index (ISI) was proposed.It is calculated by the ratio of the retinal non-perfusion area to the total retinal area by manual description of non-perfusion area in UWFA images.As a reliable index for evaluating retinal ischemia, it is of great significance to study ISI in the classification, treatment and prognosis of retinal vascular diseases such as diabetic retinopathy (DR) and retinal vein occlusion (RVO). This article reviewed the progress in application and development of ISI in retinal vascular diseases.
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Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.
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Objective:To observe and preliminarily discuss the distribution characteristics of the non-perfusion area (NP) of the retina in different stages of diabetic retinopathy (DR) and its changes with the progression of DR.Methods:A retrospective clinical study. From October 2018 to December 2020, 118 cases of 175 eyes of DR patients diagnosed in Eye Center of Renmin Hospital of Wuhan University were included in the study. Among them, there were 64 males with 93 eyes and 54 females with 82 eyes; the average age was 56.61±8.99 years old. There were 95 eyes of non-proliferative DR (NPDR), of which 25, 47, and 23 eyes were mild, moderate, and severe; 80 eyes were proliferative DR (PDR). Ultra-wide-angle fluorescein fundus angiography was performed with the British Optos 200Tx imaging system, and the fundus image was divided into posterior, middle, and distal parts with Image J software, and the ischemic index (ISI) was calculated. The difference of the retina in different DR staging groups and the difference of ISI were compared in the same area. The Kruskal-Wallis test was used to compare the ISI between the different DR staging groups and the Kruskal-Wallis one-way analysis of variance was used for the pairwise comparison between the groups.Results:The ISI of the posterior pole of the eyes in the moderate NPDR group, severe NPDR group, and PDR group were significantly greater than that in the distal periphery, and the difference was statistically significant ( χ 2=6.551, 3.540, 6.614; P=0.000, 0.002, 0.000). In severe NPDR group and PDR group, the ISI of the middle and peripheral parts of the eyes was significantly greater than that of the distal parts, and the difference was statistically significant ( χ 2=3.027, 3.429; P=0.015, 0.004). In the moderate NPDR group, there was no significant difference in ISI between the peripheral and distal parts of the eye ( χ 2=2.597, P=0.057). The ISI of the posterior pole of the eyes in the moderate NPDR group and the PDR group was significantly greater than that in the middle periphery, and the difference was statistically significant ( χ 2=3.955, 3.184; P=0.000, 0.009). In the severe NPDR group, there was no significant difference in ISI between the posterior pole and the middle periphery of the eye ( χ 2=0.514, P=1.000). Compared with the mild NPDR group and the moderate NPDR group, the ISI of the whole retina, posterior pole, middle and distal parts of the PDR group was larger, and the difference was statistically significant ( χ 2=-7.064, -6.349,-6.999, -5.869, -6.695, -6.723, -3.459, -4.098; P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000, 0.003, 0.000). Conclusion:The NP of the eyes with different DR stages is mainly distributed in the posterior pole and the middle periphery. The higher the severity of DR, the greater the NP in the posterior and middle periphery.
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Diabetic retinopathy (DR) is a common ocular complication in patients with diabetes, and diabetic macular edema (DME) is the main cause of vision loss in patients with DR, so the early diagnosis and treatment of DME is of an important clinical significance.Optical coherence tomography (OCT) can provide high-quality imaging of retina and choroid.It has been widely used in clinical practice and can be used for long-term follow-up of the diagnosis and treatment of DME.Recent studies have found various characteristic changes in retina and choroidal layer of DME on OCT, including vitreomacular interface abnormalities, disorganization of retinal inner layers, inner segment-outer segment (IS-OS) continuity destruction, external limiting membrane continuity destruction, outer retinal tubulations, hyperreflective foci, intraretinal cystic fluid, subfoveal neuroretinal detachment, low optical reflectivity, subfoveal choroidal thickness change, and choroidal vascularity index change, etc.These changes are related to the prognosis of DME, so they can be used as biomarkers of DME.This paper reviews the research progress in this field.
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Objective:To investigate the anti-intestinal effect and mechanism of Wnt/β-catenin signaling pathway in Wuzhishan CallicarpanudifloraHook.etArn in Hainan Province.Methods:The colony formation assay was used to detect the effect of Wuzhishan CallicarpanudifloraHook.etArn on the proliferation of intestinal cancer cells in Hainan Province. The effect of Wuzhishan CallicarpanudifloraHook. etArn on the colony growth of intestinal cancer cells was detected by HE staining. The effect of Wuzhishan CallicarpanudifloraHook.etArn on transmembrane protein of intestinal cancer cell line IFITM1 was detected by laser confocal microscopy. Immunocytochemistry was used to detect the effect of Wuzhishan CallicarpanudifloraHook.etArn on the tumor suppressor protein of intestinal cancer cells. Western Blot was used to detect the expression of Wnt/β-catenin signaling pathway-related proteins.Results:With the increase of Wuzhishan CallicarpanudifloraHook.etArn in Hainan Province concentration, the colony number of SW480 and SW620 cells was down-regulated and the inhibition rate was up-regulated in a dose-dependent manner. Compared with that in control group(con group), the colony size of SW480 and SW620 cells in group Wuzhishan CallicarpanudifloraHook.etArn in Hainan Province group (Lhzz group) decreased, the cell morphology was blurred and the number of colony cells decreased significantly. Compared with that in con group, the green fluorescence intensity of IFITM1 transmembrane protein expression in SW480 and SW620 cells in Lhzz group decreased, the number of colony formation decreased, the volume decreased, and the nucleus showed pyknosis and irregular shape. The expression of tumor suppressor protein DCC in SW480 cells in Lhzz group was significantly higher than that in con group (2.13 ± 0.33 vs. 1.05 ± 0.16, t = 3.542, P < 0.05). The expression level of tumor suppressor protein DCC in SW620 cells in con group was significantly higher than that in con group (1.89 ± 0.26 vs. 0.96 ± 0.12, t = 3.466, P < 0.05). The expression level of oncoprotein DCC in SW620 cells in con group was significantly higher than that in con group (0.64 ± 0.11 vs. 0.38 ± 0.05, t = 3.154, P < 0.05), and the expression level of tumor suppressor protein in SW620 cells in con group was significantly higher than that in con group (0.52 ± 0.09 vs. 0.24 ± 0.03, t = 3.143, P < 0.05), and the expression level of β-catenin in SW480 and SW620 cells in Lhzz group was significantly higher than that in con group ( P < 0.05). Conclusions:Wuzhishan CallicarpanudifloraHook.etArn in Hainan Province can inhibit the proliferation of intestinal cancer cells by activating Wnt/β-catenin signaling pathway.
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As coronavirus disease 2019 (COVID-19) pandemic poses a substantial global public health threat, traditional Chinese medicine (TCM) was used in 91.50% of the COVID-19 cases in China, showing encouraging results in improving symptom management and reducing the deterioration, mortality, and recurrence rates. A total of 166 modified herbal formulae consisting of 179 single herbal medicines were collected for treating COVID-19 in China. Glycyrrhizae Radix et Rhizome, Scutellariae Radix, and Armeniacae Semen Amarum are the most frequently utilized in clinics, most of which are antipyretic (47, 26.26%), expectorant and cough-suppressing (22, 12.29%), and dampness-resolving (21, 11.73%) from traditional descriptions. A total of 1212 chemical components containing -sitosterol, stigmasterol, and quercetin were primarily selected. Additionally, using complex system entropy and unsupervised hierarchical clustering, 8 core herbal combinations and 10 new formulae emerged as potentially useful candidates for COVID-19. Finally, following scaffold analysis, self-organizing mapping (SOM) and cluster analysis, 12 clusters of molecules yielded 8 pharmacophore families of structures that were further screened as pharmacological targets in human metabolic pathways for inhibiting coronavirus. This article aims to make more easily accessible and share historical herbal knowledge used in contemporary treatments in a modern manner to assist researchers contain the global spread of COVID-19.
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Objective To evaluate the effect of atorvastatin preconditioning on cognitive function in isoflurane-anaesthetized mice.Methods Forty-eight healthy male C57BL/6 mice,aged 3 months,weighing 27-41 g,were divided into 3 groups (n =16 each) using a random number table:control group (group C),isoflurane anesthesia group (group Ⅰ) and atorvastatin preconditioning plus isoflurane anesthesia group (group AI).Atorvastatin 10 mg/kg was given through a gastric tube into the stomach at the same time every day for 7 consecutive days in group AI.In Ⅰ and AI groups,1.5% isoflurane was inhaled for 6 h with fresh gas flow of 2 L/min at 1 day after the end of administration.Open field test and Morris water maze test were performed at 1 day after the end of anesthesia.The mice were sacrificed at 1 day after the end of Morris water maze test,and hippocampi were isolated for determination of caspase-3,Bax and Bcl-2 expression (by Western blot) and contents of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α) and soluble Aβ1-42 in hippocampal tissues (by enzyme-linked immunosorbent assay).Results There was no significant difference in the parameters of open field test among the three groups (P>0.05).Compared with group C,the escape latency was significantly prolonged at each time point,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were increased,the expression of caspase-3 and Bax was up-regulated,and Bcl-2 expression was down-regulated in Ⅰ and AI groups (P<0.05).Compared with group Ⅰ,the escape latency was significantly shortened at each time point,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were decreased,the expression of caspase-3 and Bax was downregulated,and Bcl-2 expression was up-regulated in group AI (P<0.05).Conclusion Atorvastatin preconditioning can improve cognitive function in isoflurane-anaesthetized mice,and the mechanism may be association with attenuating hippocampal inflammatory responses,inhibiting over-expression of Aβ1-42 and inhibiting neuronal apoptosis.
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Interest in rare diseases research and orphan drugs development has been increased distinctly in recent years. The number of affected people with rare diseases is considerable around the world and the formulation of national and international incentive policies to accelerate orphan drugs development, aiming at offering facilities and necessary conditions for patient access to treatment, gains favorable results. In particular, more measures should be taken to catalyze further progress due to behindhand level in this field in China. Additionally, therapeutic methods of rare diseases were also discussed.
الموضوعات
Humans , China , Orphan Drug Production , Rare Diseases , Genetics , Therapeuticsالملخص
@# Objective To assess the clinical efficacy and safety of amantadine monotherapy and concomitant amantadine with salvia miltiorrhiza compound or selegiline of the treatment of Parkinson's disease.Methods The clinical trial was performed in the multicenter, open label study. Amantadine group: 35 cases, amantadine plus salvia miltiorrhiza compound group: 34 cases and amantadine plus selegiline group: 29 cases. The clinical efficacy had been assessed with modified Webster scale (WR) and motor dysfunction rating scale for Parkinson's disease (MDRSPD) with interval of two months for one year. The safety data included blood glucose, hepatic and renal function tests, blood and urine routine tests.Results The clinical improved rates were 42.9% (WR) and 37.1% (MDRSPD) in amantadine group, respectively. The clinical score was improved in 34.2% (WR) and 26.5% (MDRSPD) in amantadine plus salvia miltiorrhiza compound group, respectively. The clinical improvement was 51.1% (WR)and 48.3% (MDRSPD) in amantadine plus selegiline group, respectively. There were no significant differences among these three groups (t-test,P>0.05). The clinical marked efficacy rates in assessment of MDRSPD were 2.8% in amantadine group, 11.8% in amantadine plus salvia miltiorrhiza compound group and 27.6% in amantadine plus selegiline group, respectively. There was significant difference between amantadine group and amantadine plus selegiline group, but no significant difference between amantadine group and amantadine plus salvia miltiorrhiza compound group. The adverse event rates were 27.8% in amantadine group, 8.8% in amantadine plus salvia miltiorrhiza compound group and 31.0% in amantadine plus selegiline group, respectively. All these events were mild, of short duration and resolved without treatment. Conclusion There was some efficacy rate in all three groups. Comparing with amantadine group, there was higher marked efficacy rate in amantadine plus selegiline group.