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Acute pancreatitis (AP) is a very common acute disease, and the mortality rate of severe AP (SAP) is between 15% and 35%. The main causes of death are multiple organ dysfunction syndrome and infections. The mortality rate of patients with SAP related to liver failure is as high as 83%, and approximately 5% of the SAP patients have fulminant liver failure. Liver function is closely related to the progression and prognosis of AP. In this review, we aim to elaborate on the clinical manifestations and mechanism of liver injury in patients with AP.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin β3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.

Aims It has been reported that allopregnanolone (APα) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6‐hydroxydopamine (6‐OHDA)‐treated mice by binding to γ‐aminobutyric acid A receptor (GABAAR) and then opening voltage‐gated L‐type Ca2+ channel, but the underlying mechanisms remain elusive. The aim of this study was to explore the possible involvement of GABAAR and calcium/calmodulin‐dependent protein kinase II delta 3 (CaMKIIδ3) in this process. Methods 6‐OHDA‐treated mice and primary cultured midbrain cells were administrated with APα and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)‐positive neurons and their fibers, the expression levels of CaMKIIδ3 and brain‐derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real‐time RT‐PCR, Western blot, and behavioral test. Results Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. This may account for the findings that the exogenous APα enhanced the proliferation and differentiation of NPCs, and ameliorated the nigrostriatal system and behavioral performance in 6‐OHDA‐treated mice. Conclusions Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIδ3, and finally contribute to the restoration of dopaminergic neurons in 6‐OHDA‐treated mice., APα significantly promotes the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increases the expression levels of cell cycle protein and BDNF. This may account for the findings that APα enhances the proliferation and differentiation of NPCs, and ameliorates the deficiency of dopaminergic neurons in 6‐OHDA‐treated mice and primary cultured midbrain cells.

Background Accumulating evidence indicates that intestinal microbiota not only influence development and behavior but also play important roles in the pathogenesis of neurodegenerative diseases. However, the relationships between gut bacteria and diseases of the nervous system remain to be fully explored. Microglial activation has been identified as an important factor affecting the progression of many degenerative diseases. Therefore, we aimed to investigate the effects of Prevotella histicola on neuroinflammation and associated mechanisms in an animal model of dopaminergic neuron death caused by microglia activation. Methods We used the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) to establish an animal model of dopaminergic neuron death induced by microglia activation. LPS was injected into the mouse substantia nigra, followed by gavage with P. histicola. Results P. histicola inhibited LPS-induced microglia activation by increasing the proportion of peripheral regulatory T cells (Treg), thereby increasing the secretion of interleukin (IL)-10, reducing dopaminergic neuron damage, stimulating activation of anti-inflammatory M2 type microglia, and improving exercise capacity. Interestingly, P. histicola treatment suppressed the expression of SUMO-specific protease 3 (SENP3), which plays an important role in LPS-stimulated inflammatory TLR4 signaling. P. histicola treatment also downregulated inflammatory factors including IL-1, IL-6, IL-12, and tumor necrosis factor-alpha (TNFα). Conclusion These results suggest that P. histicola inhibits the TLR4 inflammatory signaling pathway and release of inflammatory factors by regulating the release of IL-10 from FoxP3 + Treg cells in the spleen. Our findings may provide insight into a new therapeutic avenue for attenuating the progression of degenerative diseases involving microglial activation.

Background Differences of genotypes between male and female have been studied in Parkinson’s disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant. Objective The aim of this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD. Methods 613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex. Results Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135–0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167–0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400–0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361–0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228–0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428–0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078–2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102–0.849) compared with male. Conclusion In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.

BackgroundCerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are crucial for early diagnosis and treatment.Objectives and MethodsFour CTX families with mutations in the CYP27A1 gene were enrolled in our study. We investigated the clinical characteristics and molecular genetic features of the probands with CTX. Genetic analysis was performed for detecting gene variants. Sanger sequencing and segregation analysis were conducted for haplotype analysis.ResultsAll the four probands were compound heterozygote for two CYP27A1 variants, including one mutation in c.1263+1G>A (intron 7) splice site, two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) and three pathogenic mutations including c.379C>T, c.1263+1G>A and c.1537C>T previously reported. All of the subjects presented with spastic paraparesis. The other common clinical features included ataxia, childhood-onset diarrhea, cataracts, intellectual disability, tendinous xanthomas and dentate nuclei signal alterations at MRI.ConclusionTwo novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) were reported in our study. The 1263+1G>A mutation was commonly seen in Chinese reported case series (7/25, 28%) and could be a latent hotspot for Chinese CTX mutations. Our study expanded the mutation spectrum of CYP27A1 gene and provide an insightful view of the phenotypic spectrum and genetic characteristics to help early diagnosis and treatment with to improve neurologic dysfunction.

Background Proinflammatory microglia rely predominantly on glycolysis to maintain cytokine production during an inflammatory response. However, during ischemia, where glucose supply is low, inducible nitric oxide synthase (iNOS) production remains high accompanied by an increase in monocarboxylate transporter 1 (MCT1) expression. In this study, we explored whether there is a link between iNOS and MCT1 expressions, and whether pyruvate can act as an energy source to sustain the M1 phenotype. Methods Using a mouse model with laser-induced brain ischemia and cell culture with low-glucose treatment, we examined responses from microglia. Results The expressions of iNOS and MCT1, as well as arginase-1 (ARG1), were increased in the brain of the ischemic mouse model. In the BV2 microglial cell line and primary microglia treated under low glucose condition, iNOS and MCT1 also increased, while ARG1 decreased. The addition of pyruvate under low-glucose or lipopolysaccharide (LPS) treatment enhanced iNOS and MCT1 expressions compared with groups without pyruvate. MCT1 knockdown resulted in decreased iNOS while MCT1 overexpression increased iNOS. Furthermore, inhibitor of nuclear factor-kappaB (NF-κB) reduced both iNOS and MCT1. Conclusion Our data suggested that after proinflammatory microglial polarization, MCT1 is upregulated through the NF-κB signaling pathway, which leads to iNOS production. We speculate that microglia may continuously pick up monocarboxylates such as pyruvate through MCT1 to sustain the M1 phenotype.

Introduction Multiple system atrophy (MSA) is a progressive neurodegenerative disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the cerebellum and blood samples of MSA patients. But few studies focused on the associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed to quantify plasma COQ10 and characterize its association with clinical features. Methods We recruited 40 patients with MSA, 30 patients with Parkinson's disease (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The basic demographic data, motor symptoms, and non-motor symptoms were also assessed. Results Plasma COQ10 levels were significantly different in MSA, PD, and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA patients were lower than that in controls after adjusting for age, gender, and total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity of 97.5% was calculated with the receiver operating characteristic curve. However, COQ 10 levels did not discriminate between the MSA and PD groups (P = 0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms only in MSA-C patients (b = −0.025, P = 0.009). Conclusion The association between decreased COQ10 levels and the severity of motor symptoms in MSA-C patients promotes further research. Plasma COQ10 levels alone may not be a reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in the differential diagnosis of MSA vs PD.

Objective Lymphocyte activation gene-3 (LAG-3) could mediate pathological α-synuclein transmission in neurodegeneration and may be involved in the pathogenesis of Parkinson's disease (PD). The aim of the present study was to explore soluble LAG-3 (sLAG-3) as a potential diagnostic biomarker for PD. Methods Serum sLAG-3 concentrations were measured by a quantitative ELISA for patients with PD, essential tremor (ET) and age- and sex-matched controls. The relationships between sLAG-3 and clinical phenotype were assessed via correlation analysis and logistic regression. Results Serum sLAG-3 levels in patients with PD were significantly higher than those in ET patients and age- and sex-matched controls. The area under the curve of serum sLAG-3 in differentiating PD from age- and sex-matched controls was 0.82. Serum sLAG-3 was associated with non-motor symptoms and excessive daytime sleep. Conclusion sLAG-3 is a candidate novel biomarker for PD. © 2018 International Parkinson and Movement Disorder Society.

Pd-based nanocatalysts (NCs) are the potential substitutes for the Pt-based NCs used in the direct methanol fuel cells (DMFCs) because of their lower cost and comparable catalytic performance. The catalytic performance of Pd-based NCs is highly connected with the morphology, composition and surface structure of the catalysts. Here, solid bimetallic PdAu and hollow PdAu NCs were synthesized by a successive reduction and co-reduction method, respectively, using P123 both as reducing reagent and protectant. Compared with the solid PdAu NCs and commercial Pd black catalyst, the hollow PdAu NCs exhibited enlarged electrochemical surface areas (ECSA), and showed an enhanced electrocatalytic activity and stability for methanol oxidation reaction (MOR) in alkaline solution. The excellent electrocatalytic performance is contributed to the unique hollow structure and alloy effects of the PdAu NCs.

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.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson’s disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson’s disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach’s Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860–0.935, p<0.001). ICC of inter-rater reliability was 0.899 (95% CI 0.848–0.933, p<0.001). PD-CRS had fair concurrent validity with MDRS (ICC = 0.731, 95% CI 0.602–0.816). All the frontal-subcortical items showed significant decrease in PD-MCI compared with the PD-NC group (p≤0.001), but the instrument cortical items did not (confrontation naming p=0.717, copying a clock p=0.620). All the frontal-subcortical and instrumental-cortical functions showed significant decline in PDD compared with the PD-NC group (p≤0.001). The cutoff value for diagnosis of PD-MCI is 80.5 with the sensitivity of 75.7% and the specificity of 75.0%, and for diagnosis of PDD is 73.5 with the sensitivity of 89.2% and the specificity of 98.9%. Revised Chinese version of PD-CRS is a reliable, acceptable, valid, and useful neuropsychological battery for assessing cognition in PD patients.

Background and objective To explore the alterations of microbial 16s ribosomal (rRNA) gene in the feces and blood of Chinese patients with multiple system atrophy (MSA) and its relationships with clinical features. Methods 40 MSA patients (MSA-P/MSA-C: 23/17) and their healthy spouses were recruited. Fecal and blood microbiota were investigated by high-throughput IllUmina Miseq sequencing targeted on the V3-V4 functional region of 16s rRNA gene. The relationships between microbiota and clinical characteristics were analyzed. Results The abundances of Lactobacillus, Gordonibacter, Phascolarctobacterium, and Haemophilus in feces and abundances of Leucobacter, and Bacteroides in blood were different between MSA patients and healthy controls (HC). Combining the taxa from feces and blood, six genera were identified to be predictive of MSA, achieving an area under the curve (AUC) of 0.853. The abundances of Phascolarctobacterium and Ruminococcus in feces were lower in MSA-P than those in MSA-C. The abundances of Blastococcus, Bacillus, and Acinetobacter in blood were different between MSA subtypes. These five genera differentiated MSA subtypes with an AUC of 0.898. Functional predictions indicated that gene functions involving biosynthetic metabolism and bacterial secretion systems were significantly different between the MSA and HC. The differential genera were associated with disease duration, anxiety, and autonomic dysfunctions. Conclusions We confirmed the alterations of microbial 16s rRNA gene in the feces and blood occurs in Chinese patients with MSA. Microbiota dysbiosis was related to MSA clinical manifestations. Elucidating these differences in microbiomes will be helpful to improve our knowledge of the microbiota in the pathogenesis of MSA.

Background The aim of the study was to investigate the genetic risk factors of essential tremor (ET) in Chinese Population. Methods A total of 225 ET patients (25 ET patients also had restless legs syndrome (RLS) and were excluded from final analysis) and 229 controls were recruited. The diagnosis of ET was based on the Consensus Statement of the Movement Disorders Society on tremor. Polymerase chain reaction (PCR) and sequencing were used to detect 12 single nucleotide polymorphisms (SNPs) in seven candidate genes for RLS (HMOX1, HMOX2, VDR, IL17A, IL1B, NOS1 and ADH1B). Results We found that one SNP was associated with the risk of ET in Chinese population after adjusting for age and gender: rs1143633 of IL1B (odds ratio [OR] =2.57, p = 0.003, recessive model), and the statistical result remained significant after Bonferroni correction. Then, we performed a query in Genotype-tissue Expression (GTEx), Brain eQTL Almanac (Braineac) databases and Blood expression quantitative trait loci (eQTL) browser. The significant association was only found between genotype at rs1143633 and IL1B expression level of putamen and white matter in Braineac database, which was more prominent with homozygous (GG) carriers. Conclusions Our study firstly reported the association of IL1B polymorphism with the risk of ET in Chinese population. However, the association might only suggest a marker of IL1B SNP associated with ET instead of the casual variant. Further studies are needed to confirm our finding. Electronic supplementary material The online version of this article (10.1186/s12883-019-1331-5) contains supplementary material, which is available to authorized users.

Morphology and dimensionality are key factors to affect the catalytic activity and durability of Pt-based nanocatalysts. In this work, dendritic porous three-dimensional PtPdRu (PtPdRu-3D) nanocatalysts were fabricated by a facile one-pot hydrothermal strategy with triblock pluronic copolymer P123 as the reducer, stabilizer and structure director. Compared with zero-dimensional PtPdRu (PtPdRu-0D) and two-dimensional PtPdRu (PtPdRu-2D) and commercial Pt/C, PtPdRu-3D showed ultrahigh electrochemical surface areas (ECSA), and demonstrated an outstanding electrocatalytic activity towards methanol oxidation reaction (MOR), specifically 2.9 times higher than that of PtPdRu-0D, 1.3 times higher than PtPdRu-2D, and 1.7 times higher than commercial Pt/C. Besides, durability tests demonstrated that PtPdRu-3D displayed the lowest ECSA decay (from 100% to 80.81%) due to its 3D open-framework surface which can restrain the individual particles from aggregating.

The catalytic performance of Pt-based nanocatalysts is closely related to the morphology and structure of the catalysts. We report herein the preparation of novel PtPd nanocatalysts with a hollow structure through a special galvanic replacement reaction and the high reaction selectivity of one kind of triblock pluronic copolymers. P123 (PEO 19 -PPO 69 -PEO 19 ) has unique selectivity for the reduction of K 2 PdCl 4 and K 2 PtCl 6 . Relative to the commercial Pt/C and PtPd alloy catalysts, the PtPd nanocatalysts exhibited enhanced electrocatalytic activity toward methanol oxidation. The excellent electrocatalytic activity is due to the unique structure of PtPd nanocataysts.

One kind carbon nanosphere supported Pt nanocatalyst (Pt/CN-1) has been successfully synthesized by a facile one-pot hydrothermal synthesis using sucrose as carbon source and triblock pluronic copolymer P123 as reducer and stabilizer. The obtained Pt nanoparticles with an average diameter at 3.0 nm were uniformly distributed on the surface of the carbon nanospheres. The other kind Pt/CN-2 was prepared through the same route just in absence of P123, the carbon sphere was used as both carrier and reducer due to its reducing nature. Characterization demonstrated that the Pt/CN-2 was aggregated seriously without the protection of P123. The electrocatalytic tests indicated that the Pt/CN-1 nanocatalyst exhibited an enhanced electrocatalytic activity toward methanol oxidation in acidic media than that of Pt/CN-2 catalyst and commercial Pt/C catalyst. The promising synthetic method provides a new avenue to prepare carbon spheres supported Pt-based nanocatalysts used for direct alcohols fuel cells (DAFCs).

Study Objectives: The aim of the study was to investigate the relationship between 22 single nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) in the Chinese population. Methods: A total of 250 PD patients and 240 healthy controls were recruited. The SNaPshot technique and the polymer chain reaction were used to detect 22 SNPs. Results: rs8005172 of GALC, rs9468199 of ZNF184 and rs34043159 of IL1R2, were associated with PD (rs8005172: p = 0.009, OR = 0.69, allele model, p = 0.010, additive model, p = 0.015, OR = 2.17, dominant model; p = 0.020, OR = 2.11, dominant model after adjustment; p = 0.036, OR = 1.47, recessive model after adjustment; rs9468199: p = 0.008, OR = 1.52, allele model, p = 0.008, additive model, p = 0.007, OR = 0.22, recessive model, p = 0.005, OR = 0.20, recessive model after adjustment; rs34043159: p = 0.034, OR = 1.31, allele model, p = 0.036, additive model). Conclusion: Our study revealed that GALC, ZNF184, and IL1R2 were associated with PD in the southern Chinese population. GALC was also associated with LOPD. ELOVL7 and ZNF184 were associated with EOPD. In addition, trends of association to PD, between SATB1, NMD3, and FGF20, were also found. Statement of Significance: Genetic play an important role in the pathogenesis factors of Parkinson's disease (PD). We found that GALC, ZNF184, and IL1R2 were associated with PD. GALC was also associated with late onset of PD, while ELOVL7 and ZNF184 were associated with early onset PD. This study is the first to find an association between GALC, ZNF184, and rs2280104 with PD.

Objective Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. Background AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. New/Updated Hypothesis We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. Major Challenges for the Hypothesis The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. Linkage to Other Major Theories Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram-negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood-brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

Background It is debatable whether transcranial sonography (TCS) could be a biomarker for monitoring disease progression. Various phenotypes of Parkinson's disease (PD) may be a major reason contributing to the inconsistency. Objective We classified PD patients into different subtypes and evaluated the correlation between SN echogenicity and disease progression. Methods A total of 411 PD patients were included in this study. TCS evaluations of the substantia nigra (SN) were performed, and motor and non-motor symptoms were assessed by a series of rating scales in all PD patients. Results Three hundred and thirteen patients had appropriate temporal acoustic bone windows, and they were divided into three subgroups according to disease onset age. SN hyperechogenicity (SN+) was found to be associated with age, gender, disease duration, H-Y stage and UPDRS-II scores in 220 middle-age onset patients. Regression analysis identified both disease duration and gender as independent predictors for SN+. When this distinct group was separated into male and female subgroups, the correlation between larger SN echogenicity (SNL) and disease duration was positive in males rather than females. When these middle-age onset male patients were classified as tremor dominant (TD) and non-TD subtypes, it turned out that correlation between disease duration and SNL only existed in male non-TD PD patients. Conclusions Our study demonstrated correlation between the size of SN echogenicity and disease duration in Chinese patients with PD who were male non-TD subtypes with middle-age onset, suggesting the formation of SN echogenicity might be a dynamic process following disease progression in this distinct subtype.

In this paper, we report the controlled-synthesis of PtNi nanoparticles through galvanic displacement reaction and chemical reduction. The size, composition and morphology of the products are characterized by transmission electron microscopy (TEM), powder X-ray diffraction (XRD), energy dispersed X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) analyses. The structure and composition of the PtNi nanoparticles can be controlled by adjusting the synthetic conditions. The possible formation mechanism is obtained from the academic analysis and experimental studies. The results of the magnetic measurement illustrate that the PtNi nanoparticles show a superparamagnetic behavior with a blocking temperature (TB) about 8.0 K.

CoPd nanocatalysts were synthesized by a successive reduction using poly(vinylpyrrolidone) as stabilizer. The structure, morphology, and composition of CoPd nanocatalysts were characterized by transmission electron microscopy (TEM), high-resolution TEM, X-ray powder diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), and inductively coupled plasma mass spectrometry (ICP-MS). The CoPd nanocatalysts showed electrocatalytic performance for methanol oxidation in alkaline medium. The electrocatalytic performance was weakened after dealloying process in acidic solution. The balance of the dealloying effect and the alloying effect should be accentuated in this field in the future.

Androstene derivatives incorporating amino acid methyl esters were prepared, and their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Several compounds exhibited dose-dependent inhibition. The most active compound, methyl ((3S,10R,13S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carbonyl)-L-phenylalaninate (10) significantly suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Mechanistic studies revealed that compound 10 markedly inhibits phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and subsequent transcription factor (NF-κB) and activator protein-1 (AP-1) activation. Furthermore, compound 10 decreased LPS-activated microglial neurotoxicity in a condition medium/HT-22 neuroblastoma co-culture model. Taken together, these results suggest 10 is a potential lead compound for the development of a novel therapeutic agent for neurodegenerative diseases.

At present, in social transition period of China, reform of higher education is in full swing, with workload, job difficulty of university teachers greatly increased than before. Plus unique values and personality characteristics of the Millennial Generation, mental health of university teachers of the Millennial Generation has aroused more and more attention. However, research is still not enough. In this paper, questionnaire survey method was used to analyze the relationship between occupational stress, positive coping style, negative coping style, job burnout and mental health of university teachers of the Millennial Generation, and explore which path has the greatest effect on mental health with university survey data of Shaanxi Province, China from January 2016 to June 2016.It is found that occupational stress can produce significant positive predictive effect on negative coping style and job burnout, and have a significant negative predictive effect on positive coping style; Negative coping style has significant positive predictive effect on job burnout and mental health of university teachers of the Millennial Generation; Positive coping style has significant negative predictive effect on job burnout and mental health of university teachers of the Millennial Generation; Job burnout of university teachers of the Millennial Generation has significant positive predictive effect on mental health; Among all the paths that affect mental health, occupational stress has the greatest effect on mental health through job burnout. This study reveals the mechanism of influence of occupational stress on mental health of university teachers of the Millennial Generation, which can provide decision-making reference for colleges and universities to formulate strategies to intervene university teachers of the Millennial Generation’s mental health problems from individual psychological level and strengthen mental health management of university teachers of the Millennial Generation.

Fatigue is common in patients with Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) G2385R variant predisposes individuals to develop PD in China. The aim of this study was to evaluate whether the LRRK2 G2385R variant is associated with fatigue in patients with PD.Fatigue was evaluated by the Parkinson Fatigue Scale (PFS) in 329 PD patients and 180 controls, a cut-off score of ≥3.3 was used to define the presence of fatigue. All the enrolled PD patients were assessed by a comprehensive battery of motor and non-motor questionnaires. PD patients were genotyped for the G2385R variant. Associations of fatigue with the clinical assessments and with the G2385R variant in PD patients were analyzed by logistic regression.Fatigue frequency was 55.62%. A logistic regression model found that the female sex (OR = 10.477; 95%CI: 2.806-39.120; p 0.001), motor function (OR = 1.060; 95%CI: 1.012-1.110; p = 0.013), sleep disturbance (OR = 0.943; 95%CI: 0.910-0.976; p = 0.001) and depression severity (OR = 0.843; 95%CI: 0.736-0.965; p = 0.013) collectively predict the presence of fatigue in PD patients. After adjustment for demographics and associated clinical factors, the G2385R variant was associated with an increased risk for the presence of fatigue (OR = 10.699; 95% CI = 2.387-47.958; p = 0.002) in the PD population in this study.We confirm that fatigue in PD patients is common, and we have strengthened the associations between fatigue and female sex, motor severity and non-motor symptoms, particularly depression and sleep disturbances. Overall, we found that carriers of the G2385R variant were more prone to fatigue than non-carriers in PD patients.

Pt nanoparticles are synthesized by a facile one-pot hydrothermal synthesis using one kind triblock Pluronic copolymers as reducer and stabilizer for the first time. The size of the Pt nanoparticles can be controlled through simply varying the reaction conditions. The morphology and structure of the Pt nanoparticles were well characterized by different techniques. The electrocatalytic test indicated that the obtained Pt nanoparticles exhibit a better electrocatalytic performance for methanol oxidation in acidic media compared to the commercial Pt/C catalyst. The results of this paper provide a promising approach to prepare Pt-based nanocatalysts for direct alcohols fuel cells (DAFCs).

Proton exchange membrane fuel cells (PEMFCs) have found a wide variety of commercial applications to resolve the energy crisis and environmental pollution. Then the design of novel Pt-based catalysts with enhancing catalytic activity, stability and low amount of Pt used are crucial. Pt-alloy catalysts, core-shell structured Pt-based catalysts, Pt-monolayer catalysts, Pt-based catalysts with high index, nanoporous Pt-based catalysts, hollow Pt-based nanocatalysts, and non-noble catalysts are the common way to resolve the question partly. Among these catalysts, hollow Pt-based catalysts used in PEMFCs have received much attention due to the increased surface area, low density, improved utilization of the unit Pt. In this review, we present a summarization of the progress made for synthesizing hollow Pt-based nanocatalysts using different techniques. Hollow pure Pt catalysts, Pt-based alloy catalysts and other correlative hollow precious nanomaterials are covered. Galvanic replacement method is still the most used and prospective method in this field. Finding facile and appropriate sacrificial template and controllable shape will be the key in the development of this method. We also summarize other different methods and discuss the foreground of these methods in the future. The emergent challenges and future developments of hollow Pt-based nanocatalysts are also discussed in this paper.

Background.HTRA2has already been nominated as PARK13 which may cause Parkinson’s disease, though there are still discrepancies among these results. Recently, Gulsuner et al.’s study found thatHTRA2p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson’s disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson’s disease. We performed this study to validate the condition ofHTRA2gene in Chinese familial essential tremor and familial Parkinson’s disease patients, especially essential tremor.Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson’s disease patients, and 100 healthy controls.Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups.Conclusions.HTRA2exonic variant might be rare among Chinese Parkinson’s disease and essential tremor patients with family history, andHTRA2may not be the cause of familial Parkinson’s disease and essential tremor in China.

Objective Fatigue is a common nonmotor symptom in Parkinson's disease (PD); however, the Parkinson's disease fatigue scale (PFS), which is designed to measure fatigue in PD, has not been validated in China. The aim of this study was to determine the validity and reliability of the Chinese version of the PFS in PD patients. Methods A total of 115 PD patients were evaluated at baseline and after 7 days. Assessments included the PFS, the Fatigue Severity Scale (FSS), and scales assessing motor, cognition, depression, and anxiety. Acceptability was assessed in terms of the rate of missing data and floor and ceiling effects. Cronbach's alpha was calculated to determine internal consistency. Test–retest reliability was assessed using the intraclass correlation coefficient (ICC). Spearman's rank correlation coefficients were used to calculate convergent and divergent validity between PFS scores and scales assessing clinical characteristics. Results No data were missing for the PFS. Compared with the original scoring method, the binary scoring method had relatively large floor effects (5.21% vs. 17.39%) and ceiling effects (0.90% vs. 4.31%). The internal consistency and test–retest reliability of the PFS were satisfactory (original scoring method: Cronbach's alpha = 0.97, ICC = 0.94; binary scoring method: Cronbach's alpha = 0.94, ICC = 0.94). The PFS score exhibited strong convergent validity with FSS score (correlation coefficient = 0.87). PFS score was weakly to moderately correlated with disease duration and with measures of disease stage, motor function, depression, and anxiety (range of correlation coefficients: 0.25–0.48). There was no significant correlation between PFS score and either onset age or MoCA score (range of correlation coefficients: −0.05 to 0.12). Conclusion The Chinese version of the PFS is a valid measure for assessing fatigue in PD.

Background Our study was aimed to validate a modified RBD (REM sleep behavior disorder) single question (RBD1Q-C), study the prevalence of probable RBD (pRBD) in a rural community based on RBD1Q-C and investigate the association between pRBD and Parkinson’s disease (PD). Methods The validation study of RBD1Q-C included 32 Chinese participants (14 idiopathic RBD patients and 18 controls). All participants underwent a polysomnogram (PSG). We then conducted a door-to-door survey to estimate the prevalence of pRBD assessed by RBD1Q-C, and its association with PD among 19614 residents who lived in Malu community of Shanghai, China. Results RBD1Q-C demonstrated a high sensitivity of 100 %, a moderate specificity of 55.6 %. The agreement between RBD1Q-C and PSG-based RBD diagnosis was good (k = 0.552). PPV of the RBD1Q-C was 63.6 % and NPV was 100 %. The prevalence of pRBD in Malu community was 4.9 %. In people over 50 years old, presence of pRBD was significantly associated with increased risk of having PD (odds ratio = 2.61, 95 % CI: 1.56–4.39). Conclusion RBD1Q-C was shown to be a useful screening tool. Based on the RBD1Q-C, we found that pRBD was not rare in Chinese rural population and associated with odds of PD, calling for more attention from patients, caregivers and physicians. Electronic supplementary material The online version of this article (doi:10.1186/s12883-016-0640-1) contains supplementary material, which is available to authorized users.

Syringic acid (SA), a naturally occur-ring O‑methy-lated trihydroxybenzoic acid monomer extracted from Dendrobium nobile Lindl., has been demonstrated to attenuate renal ischemia‑reperfusion (I/R) injury. However, the role of SA in myocardial I/R injury is unclear. The present study aimed to clarify the cardioprotective effect of SA in myocardial I/R injury in vitro and explore the potential molecular mechanisms. In the present study, it was revealed that pretreatment with SA increased the viability and inhibited oxidant stress in H9c2 cardiomyocytes that had suffered hypoxia/reoxygenation (H/R). SA also markedly downregulated B‑cell lymphoma 2 (Bcl‑2) expression and inhibited the expression of Bcl‑2‑like protein 4 (Bax) and cleaved caspase‑3 in H9c2 cardiomyocytes induced by H/R. In addition, SA significantly alleviated H/R-induced the phosphorylation of p38 mitogen‑activated protein kinase (p38MAPK) and c‑Jun N‑terminal kinase (JNK) in H9c2 cardiomyocytes. In conclusion, the present study demonstrated that SA inhibits the apoptosis of H9c2 cardiomyocytes following H/R injury via reduced activation of the p38MAPK and JNK signaling pathways. The results support the therapeutic usage of SA in the treatment of myocardial infarction.

High hardness and abrasiveness, low ROP and seriously deviation are the features of Shanle block Xishanyao formation in Turpan-Hami Oilfield, whose lithology was conglomerate, glutenite, interbedded sandstone, large angle of bedding and many fractures. To enhance ROP at this high hardness and abrasive region, designing of PDC bit is introduced based on crown shape, blade, teeth, bit hydraulics and so on. The designed bit had a good performance in the test of Well He-3 at Shanle block.

Objectives Multiple system atrophy (MSA) is a progressive neurodegenerative disorder that causes early sustained disability and poor health‐related quality of life (HrQoL). The clinical features and their effects on the HrQoL of patients in China have received little attention in the research literature. We evaluated the clinical characteristics and HrQoL of Chinese patients with MSA. Materials and Methods A total of 143 patients with MSA from the Department of Neurology, Shanghai Ruijin Hospital, were enrolled in the study from March 2014 to May 2017. Basic demographic data, motor symptoms, non‐motor symptoms, and HrQoL were assessed and compared with data from 198 patients with idiopathic Parkinson's disease (PD) who were matched by age, gender, and disease duration. Factors influencing the HrQoL of MSA patients were also analyzed. Results The ratio of patients with predominant parkinsonism (MSA‐P) and prominent cerebellar ataxia (MSA‐C) was 95:48 among the 143 MSA patients. MSA‐P patients had a longer disease duration (p = 0.002), higher levodopa equivalent daily dose (p