Salicylaldehyde-Cobalt(II)-Catalyzed C-H Alkoxylation of Indoles with Secondary Alcohols.

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.

Midbrain/pons area ratio and clinical features predict the prognosis of progressive Supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.

Current approaches for the management of Parkinson's disease in Chinese hospitals: a cross-sectional survey.

BACKGROUND: Chinese guidelines for management of Parkinson's disease (PD) have been issued and updated regularly since 2006. We undertook a cross-sectional survey to evaluate the impact of the latest edition (2014) on current approaches to the management of PD based on previous pilot works. METHODS: Seven hundred and seventeen participants, divided into 3 groups (GPs, Neurologists, and Specialists), recruited from 138 randomly chosen hospitals from 30 cities across China, participated by completing the questionnaire describing their current approaches before and after the guidelines were issued. RESULTS: Considerable discrepancies in management were apparent across the three categories, with different selection of first-choice medication for PD patients. There were also variations in management of concurrent psychiatric symptoms and dementia. Notably, over 50% of participants reported improvements in PD recognition and management by following the guidelines. CONCLUSIONS: The increasing use of Chinese clinical practice guidelines for PD management is having a positive impact on the optimization of care, which in turn offers important economic benefits.

Motor-symptom laterality affects acquisition in Parkinson's disease: A cognitive and functional magnetic resonance imaging study.

BACKGROUND AND OBJECTIVES: Asymmetric onset of motor symptoms in PD can affect cognitive function. We examined whether motor-symptom laterality could affect feedback-based associative learning and explored its underlying neural mechanism by functional magnetic resonance imaging in PD patients. METHODS: We recruited 63 early-stage medication-naïve PD patients (29 left-onset medication-naïve patients, 34 right-onset medication-naïve patients) and 38 matched normal controls. Subjects completed an acquired equivalence task (including acquisition, retention, and generalization) and resting-state functional magnetic resonance imaging scans. Learning accuracy and response time in each phase of the task were recorded for behavioral measures. Regional homogeneity was used to analyze resting-state functional magnetic resonance imaging data, with regional homogeneity lateralization to evaluate hemispheric functional asymmetry in the striatum. RESULTS: Left-onset patients made significantly more errors in acquisition (feedback-based associative learning) than right-onset patients and normal controls, whereas right-onset patients performed as well as normal controls. There was no significant difference among these three groups in the accuracy of either retention or generalization phase. The three groups did not show significant differences in response time. In the left-onset group, there was an inverse relationship between acquisition errors and regional homogeneity in the right dorsal rostral putamen. There were no significant regional homogeneity changes in either the left or the right dorsal rostral putamen in right-onset patients when compared to controls. CONCLUSIONS: Motor-symptom laterality could affect feedback-based associative learning in PD, with left-onset medication-naïve patients being selectively impaired. Dysfunction in the right dorsal rostral putamen may underlie the observed deficit in associative learning in patients with left-sided onset.© 2016 International Parkinson and Movement Disorder Society.

Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression.

As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor α (LXRα) agonist), or peroxisome proliferator-activated receptor gamma (PPARγ) siRNA. Western blotting for PPARγ, LXRα, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRα-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.

Mortality from Parkinson's disease in China: Findings from a five-year follow up study in Shanghai.

INTRODUCTION: The mortality of Parkinson's disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. METHODS: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. RESULTS: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson's disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. CONCLUSIONS: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits.

22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ-LXRα-ABCA1 pathway in cholesterosis of the gallbladder.

Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets associated with cholesterosis in GBECs. In conclusion, the present findings indicate that the anti-lipid deposition action of 22(R)-hydroxycholesterol combined with pioglitazone involves the activation of the PPARγ-LXRα-ABCA1 pathway, increased ABCA1 expression and the efflux of cholesterol from GBECs. Thus, 22(R)-hydroxycholesterol synergistically combined with pioglitazone to produce a remarkable effect on lipid deposition in cholesterosis GBECs.

Life and disease status of patients with Parkinson's disease during and after zero-COVID in China: an online survey.

BACKGROUND: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. METHODS: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. RESULTS: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). CONCLUSIONS: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.

Analysis of genome-wide association study-linked loci in Parkinson's disease of Mainland China.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous single-nucleotide polymorphisms (SNPs) that can modulate the risk of developing Parkinson's disease (PD). METHODS: We investigated the association of previously identified loci in a Mainland Chinese population to identify a possible ethnic-specific effect with GWAS analysis. Seventeen SNPs were genotyped from those loci using case-control methodology to analyze a total of 1,737 individuals. RESULTS: Strong evidence of an association for reference SNP 894278 (rs894278) and rs11931074 on 4q22 throughout the α synuclein (SNCA) region was observed in our study. The SNP rs894278 confers risk via a dominant model and an additive model, whereas the minor allele G of rs11931074 reduces the risk of PD progression. The minor allele frequency of rs11724635 produced weaker signals for PD, but this was not replicated in the genotype after adjusting for age and sex. CONCLUSIONS: This study yields new clues about GWAS-linked data in patients with PD from Mainland China.

A new strategy of minimally invasive surgery for cholecystolithiasis: calculi removal and gallbladder preservation.

BACKGROUND: Cholecystolithiasis is a common disease. Cholecystectomy is the main treatment method but is associated with various complications in some patients. This study explores a novel, minimally invasive surgery for the removal of calculi and the preservation of the gallbladder using a laparoscope combined with the soft choledochoscope. METHOD: A retrospective analysis was conducted between January 2010 and December 2012 in 65 patients with cholecystolithiasis who underwent the minimally invasive surgery for calculi removal and gallbladder preservation. RESULTS: In 61 cases of gallstone removal, the gallbladder was preserved perfectly with no complications. The other 4 cases were switched to laparoscopic cholecystectomy because of tiny stones blocking the cystic duct or submucosal stones. The success rate was 93.8%. Follow-up included both clinical assessment and ultrasound examination every 6 months after the operation. The patients with preoperative symptoms were symptom-free, and gallbladder function was well preserved. The overall stone recurrence rate was 4.92% at a mean follow-up of 26 months (range 6-40). CONCLUSIONS: Using the laparoscope combined with the soft choledochoscope for gallbladder-preserving cholecystolithotomy can remove stones, preserve gallbladder function, and effectively avoid the various complications of cholecystectomy. In our follow-up, gallbladder function was not affected and the stone recurrence rate was quite low.

Links between COVID-19 and Parkinson's disease/Alzheimer's disease: reciprocal impacts, medical care strategies and underlying mechanisms.

The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson's disease (PD) and Alzheimer's disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed.

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis.

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease: Past, Present, and Future.

Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson's disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients' motor and non-motor symptoms, reduce "OFF" time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy.

Mechanisms of motor symptom improvement by long-term Tai Chi training in Parkinson's disease patients.

BACKGROUND: Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms. METHODS: Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction. RESULTS: Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1ß. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training. CONCLUSIONS: Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020).

Prevalence of freezing of gait in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Freezing of gait (FOG) is considered one of the most disturbing and least understood symptoms in Parkinson's disease (PD). The reported prevalence rates of FOG in PD vary widely, ranging from 5 to 85.9%. OBJECTIVE: We conducted a systematic review and meta-analysis to provide a reliable estimate of the average point prevalence of FOG in PD, and we further investigated the study characteristics that might have influenced the estimate. METHODS: We searched different databases to identify studies that report the prevalence of FOG in PD or include relevant raw data for further calculation. The last inclusion date was February 20, 2020. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used for the quality assessment, and articles that met the predefined criteria were included in the quantitative analysis. RESULTS: Sixty-six studies were selected from 3392 references. A weighted prevalence of 50.6% in 9072 PD patients experienced FOG based on the special questionnaires (the FOG-Q and NFOG-Q), which was about twice as high as that assessed by the specific items of the clinical rating scales (UPDRS item2.14 and MDS-UPDRS item3.11) (23.2%) or simple clinical questions (25.4%). The weighted prevalence was 37.9% for early stage (≤ 5 years) and 64.6% for advanced stage (≥ 9 years). Moreover, a higher prevalence was calculated from the population-based studies than that in multicenter and single-center studies (47.3% vs. 33.5% and 37.1%, respectively). CONCLUSION: The result from this systematic review confirms that FOG is very common in PD and its prevalence is usually underestimated in hospital settings. Importantly, a more accurate assessment of FOG in future clinical researches would involve the use of special FOG scale rather than a single item on a scale or a general clinical inquiry.

Proteasome inhibitor lactacystin induces cholinergic degeneration.

OBJECTIVE: Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture. METHODS: We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the AnnexinV-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA. RESULTS: We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly. CONCLUSIONS: Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.

Gait Characteristics and Brain Activity in Parkinson's Disease with Concomitant Postural Abnormalities.

To explore the underlying pathogenic mechanism of Parkinson's disease (PD) with concomitant postural abnormalities (PDPA) through the relationship between its gait and brain function characteristics. PD patients from the neurology outpatient clinic at Ruijin Hospital were recruited and grouped according to whether postural abnormalities (including camptocormia and Pisa syndrome) were present. PD-related scale assessments, three-dimensional gait tests and brain resting-state functional magnetic imaging were performed and analyzed. The gait characteristics independently associated with PDPA were decreased pelvic obliquity angle and progressive downward movement of the center of mass during walking. PDPA features included decreased functional connectivity between the left insula and bilateral supplementary motor area, which was significantly correlated with reduced Berg Balance Scale scores. Functional connectivity between the right insula and bilateral middle frontal gyrus was decreased and significantly correlated with a decreased pelvic obliquity angle and poor performance on the Timed Up and Go test. Moreover, through diffusion tensor imaging analysis, the average fractional anisotropy value of the fibers connecting the left insula and left supplementary motor area was shown to be decreased in PDPA. There is decreased functional connectivity among the insula, supplementary motor area and middle frontal gyrus with structural abnormalities between the left insula and the left supplementary motor area; these changes in brain connectivity are probably among the causes of gait dysfunction in PDPA and provide some clues regarding the pathogenic mechanisms of PDPA.

Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum.

Pituitary adenylate cyclase activating polypeptide (PACAP) exhibits a protective effect against neural injury in vitro and in vivo. However, it has not been reported whether peripheral intravenous administration of PACAP could confer benefits in animal models of Parkinson's disease (PD). Furthermore, the underlying molecular mechanisms responsible for these effects are poorly understood. In the present experiments, we determined the effects and mechanism of action of intravenously administered PACAP27 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Our results indicate that intravenous injection of PACAP27 offers neuroprotective effects in the MPTP-induced PD mouse model which may not be directly associated with the expression levels of the monoamine transporters. However, this effect may be correlated with its ability to selectively regulate not only K(ATP) subunits, but D2 receptors in the striatum. Our findings suggest that the benefit of PACAP may accompany with changes not only in dopaminergic neurotransmission, but also in cholinergic neurotransmission that are relatively associated with the K(ATP) subunits and D2 receptors in the striatum.

Sleep disorders in Chinese patients with Parkinson's disease: validation study of a Chinese version of Parkinson's disease sleep scale.

To evaluate the Chinese version of the Parkinson's disease sleep scale (PDSS) as an instrument for measuring sleep disorders in Chinese patients with Parkinson's disease (PD). The objective of the present study was to carry out a metric analysis of a Chinese version of PDSS using a cross-sectional study of 126 patients with PD who participated in the study. Usual measures for PD patients including the Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA) were applied by neurologists. The intra-class correlation coefficient was 0.880, and test-retest reliability for total PDSS score was 0.914. The Mean total PDSS score was 118.38+/-26.07. There was a significant correlation between the PDSS and PSQI, between the PDSS and ESS, between the PDSS and GDS, between the PDSS and HAMA, between the PDSS and the disease durations, and between the PDSS and the LDE, respectively. The Chinese version of PDSS met some basic standards required for sleep disorders measures. It could lead to better understanding the sleep disorders of PD of China in future studies.

Bone morphogenetic protein-12 inducing tenogenic differentiation of mesenchymal stem cells enhances healing of linea alba incision.

The objective of this study was to investigate the curative effects of mesenchymal stem cells' tenogenic differentiation on linea alba incision healing induced by bone morphogenetic protein-12. Mesenchymal stem cells were isolated and induced by 10 ng/ml of bone morphogenetic protein-12 for 48 h. Expression of scleraxis, collagen I and collagen III were examined at 48 h, 5 and 7 days to investigate the tenogenic differentiation. The expression of scleraxis increases continually even in the absence of bone morphogenetic protein-12 for 5 days (P<0.01). The expression of collagen I and III requires persistent inducing. Then fifty Sprague-Dawley rats were randomly divided into five groups: negative control, positive control, sham group, native mesenchymal stem cells and tenogenically differentiated mesenchymal stem cells. Tensiometric testing and modified semiquantitative histological analysis were performed to explore the curative effects. The tension levels in the positive control, sham, native mesenchymal stem cells and tenogenically differentiated mesenchymal stem cells were 44, 41.8, 51.6 and 69.7%, respectively, compared with the negative control. Tenogenically differentiated mesenchymal stem cells exhibited a greater increase in tension compared with positive control, sham and native mesenchymal stem cell groups (P<0.05). From the sections stained with Masson's Trichrome, collagen organization and amount of tenogenically differentiated mesenchymal stem cells was better than the other three groups (P<0.05). In conclusion, mesenchymal stem cells' tenogenic differentiation induced by bone morphogenetic protein-12 can enhance linea alba incision healing.