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Li Dong,1 Yu-Min Zheng,2 Xiao-Guang Luo,3 Zhi-Yi He2 1Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiao-Guang LuoDepartment of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaEmail guanche537@126.comZhi-Yi HeDepartment of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaEmail yizizhan40559@163.comBackground: Parkinson’s disease is a common neurodegenerative disease in the elderly. The incidence of various cancers in Parkinson’s disease patients is significantly lower than in healthy people. Parkinson’s disease patients are individuals with a high tendency for inflammation, whose peripheral immune system is represented in an activated state. We hypothesized that the hyperinflammatory predisposition of Parkinson’s disease patients is pathogenic.Methods: DBA/1 mice were used to simulate “highly inflammatory individuals”, and the carcinogen DEN was used to induce malignancy. Hematoxylin & eosin (H&E) staining was used to observe the formation of lung tumors. Apoptosis of neurons was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immunohistochemistry and flow cytometry were used to observe CD4, CD28, major histocompatibility complex II (MHCII), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and programmed death 1 (PD-1). The ionized calcium binding adaptor molecule-1 (IBA-1) + inducible nitric oxide synthase (iNOS) was used to label M1 microglia, and IBA-1 + arginase 1 (Arg1) was used to label M2 microglia by immunofluorescence. The expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and anti-inflammatory cytokines IL-10 and IL-4 was detected by ELISA.Results: DBA/1 mice with high inflammatory tendency showed a continuous increase of peripheral inflammation, promoting intracranial inflammation, decreasing the tumor incidence and increasing the neurodegeneration under induction of malignant change. CD28 and CTLA-4/PD-1 reduced the T-cell-dominated inflammatory response, reduced the intracerebral inflammatory response, protected from neurodegeneration, and increased the incidence of tumor. Combination of CTLA-4 and PD-1 blocker can overactivate T cells, worsen peripheral and intracranial inflammation, reduce the incidence of tumor, cause damage to dopamine neurons, and promote the occurrence of neurodegeneration.Conclusion: High inflammatory tendency induced by malignant stimulation through the imbalance of CD28 and CTLA-4/PD-1 leads to dopamine neuron injury.Keywords: high inflammatory tendency, malignant stimulation, CD28, CTLA-4/PD-1, dopamine neuron injury

In this study, we investigated the beneficial effects of high endogenous levels of n-3 polyunsaturated fatty acids (PUFAs) on skeletal muscle repair and regeneration using a mouse cardiotoxin (CTX, 20 μM/200 μL) -induced gastrocnemius muscle injury model. Transgenic fat-1 mice expressing the Caenorhabditis elegans fat-1 gene, encoding n-3 fatty acid desaturase, showed higher n-3 PUFA levels and lower n-6/n-3 PUFA ratios in gastrocnemius muscle tissues. Hematoxylin and eosin and Masson’s trichrome staining of gastrocnemius sections revealed increased muscle fiber size and reduced fibrosis in fat-1 mice on days 7 and 14 after CTX injections. Gastrocnemius muscle tissues from fat-1 mice showed reduced inflammatory responses and increased muscle fiber regeneration reflecting enhanced activation of satellite cells on day 3 after cardiotoxin injections. Gastrocnemius muscle tissues from cardiotoxin-treated fat-1 mice showed reduced levels of pro-apoptotic proteins (Caspase 3 and Bax) and increased levels of anti-apoptotic proteins (Bcl-2 and Survivin). Moreover, eicosapentaenoic acid (EPA) reduced the incidence of apoptosis among cardiotoxin-treated C2C12 mouse myoblasts. These findings demonstrate that higher endogenous n-3 PUFA levels in fat-1 mice enhances skeletal muscle repair and regeneration following cardiotoxin-induced injury.

Background The global incidence and mortality rates of liver cancer, which is the second leading cause of cancer-related deaths worldwide, are increasing. However, information on its epidemiology and clinical prognosis is limited. This study aimed to characterize the epidemiology and prognostic factors of secondary liver cancer to aid in the pretreatment evaluation of the disease. Methods Patients diagnosed with secondary liver cancer between 2010 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included. Kaplan-Meier analysis and Multivariate Cox regression analysis were performed to screen for significant factors associated with secondary liver cancer. Results A total of 85,738 secondary liver cancer patients were identified; in this population, the first primary site was the lung (25.9%), followed by the colorectum, pancreas, stomach, breast, and cecum. Patients with primary tumors of the colorectum, cecum and breast had longer median survival time. Advanced age, male gender, black race, poor differentiation or lack of differentiation, regional lymph node metastases, and presence of distant metastasis were associated with poor prognosis. Conclusions In this study, novel findings on the role of the primary site and synchronous distant metastasis to specific organs in patients with secondary liver cancer were described. These findings have significant implications in clinical diagnosis and treatment, and provide a better understanding of secondary liver cancer in the general population.

BackgroundStroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural–urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015.MethodsWe used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.ResultsWe analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrendtrendtrendtrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural–urban difference from −14.4% to −11.2%; cerebrovascular assessment: from −20.3% to −16.7%; clopidogrel: from −2.1% to −10.3%; anticoagulant for atrial fibrillation: from −10.9% to −8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%).ConclusionsFrom 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Lung and systemic inflammation are associated with impaired lung function and increased mortality in patients with chronic obstructive pulmonary disease (COPD). Theophylline and glucocorticoids have been shown to have an anti-inflammatory effect in some respiratory diseases. However, corticosteroid insensitivity is a major barrier to the anti-inflammatory management of COPD. This study aimed to explore whether a combined treatment of theophylline and dexamethasone (Dex) could decrease cigarette smoke extract (CSE)-induced inflammation via prevention of a reduction in histone deacetylase 2 (HDAC2) expression and through inhibition of the PI3K/Akt pathway, which may be related to corticosteroid sensitivity. The half-maximal inhibitory concentration (IC(50)) of Dex (IC(50)-Dex) was used to as a marker of corticosteroid sensitivity. IC(50)-Dex was determined through observation of Dex inhibition of tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 release. Using reverse transcription quantitative PCR and western blotting, U937 cells treated with CSE were assessed for HDAC2 expression levels and phosphorylation levels of Akt. Theophylline and Dex pre-treatment was shown to significantly reduce the CSE-induced release of IL-8 and TNF-α. The combination of theophylline and Dex pretreatment also reversed corticosteroid insensitivity in CSE-induced U937 cells and inhibited the PI3K/AKT pathway to a greater extent than theophylline treatment alone. CSE-treated U937 cells showed a reduction in HDAC2 mRNA and protein expression compared with the control group. However, this effect was reduced after pre-incubation with the combined therapy or theophylline alone. In conclusion, pretreatment with theophylline and Dex decreased CSE-induced inflammation via inhibition of the PI3K/Akt pathway and increase in HDAC2 protein expression.

Objectives. Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons in the substantia nigra. The present study investigated miR-141-3p/sirtuin1 (SIRT1) activity in a 1-methyl-4-phenylpyridinium- (MPP+-) induced PC12-cell model of PD. Methods. PC12 cells were exposed to MMP+ following induction of differentiation by nerve growth factor (NGF). miR-141-3p and SIRT1 expressions were examined using RT-qPCR and western blot. Cell viability was evaluated using the MTT assay. Apoptosis percentage, reactive oxygen species (ROS) production, and mitochondrial membrane potential (Δψm) were evaluated using flow cytometry. Expression of Nuclear factor-kappa B- (NF-κB-) related proteins was determined by western blot. Bioinformatic analysis, RT-qPCR, and luciferase reporter assay were used to confirm the interaction between miR-141-3p and SIRT1. Results. miR-141-3p was upregulated, and SIRT1 was downregulated in MPP+-treated PC12 cells. MPP+ treatment also upregulated nitric oxide synthase 1 (Nos1) and α-synuclein. miR-141-3p induced apoptosis, oxidative stress, mitochondrial dysfunction, and downregulated the SIRT1 mRNA expression. The luciferase reporter assay showed that SIRT1 was the target of miR-141-3p. SIRT1 transfection attenuated apoptosis, ROS production and maintained Δψm. SIRT1 also downregulated Nos1, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6(IL-6) and upregulated B cell lymphoma 2 (Bcl-2) protein. In addition, SIRT1 activator resveratrol blocked the effects of miR-141-3p mimic on Nos1, α-synuclein, and mitochondrial membrane potential. SIRT1 inhibitor sirtinol reversed the biological effects of miR-141-3p. Conclusion. Increased miR-141-3p induced apoptosis, oxidative stress, and mitochondrial dysfunction in MPP+-treated PC12 cells by directly targeting the SIRT1 expression. Our study provided a potential therapeutic strategy for PD.

AMD3100 is a small-molecule inhibitor of the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis, while its role in aggrecan metabolism is unclear. We hypothesized that the AMD3100 modulates the transforming growth factor-β1 (TGF-β1)-induced expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) in chondrocytes. We evaluated expression of CXCL12/CXCR4 and TIMP-3 in the knee joints of rats with and without osteoarthritis (OA) by immunohistochemistry, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The rats were divided into sham control, destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), and DMM/phosphate-buffered saline (PBS)-treated groups. After 6 weeks, the rats were euthanized and subjected to histological and immunohistochemical analyses. Also, interleukin (IL)-1-pretreated primary chondrocytes were cultured in the presence of empty control (−, −), CXCL12a (+,−), CXCL12a + small interfering RNA (siRNA) CXCR4 (+,+), or CXCL12a + siNC (+NC), and the expression levels of target markers were evaluated by Western blotting and real-time reverse transcription PCR (RT-PCR). The CXCL12/CXCR4 levels were higher, and the expression of TIMP-3 was lower, in the OA rats compared to the healthy control rats. The rats in the DMM/AMD3100-treated group revealed a markedly decreased immunological response and mild pathology. Treatment with CXCL12a increased expression of aggrecan and disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) and suppressed that of TIMP-3 in IL-1-pretreated primary chondrocytes. TGF-β1 increased expression of TIMP-3, and this increase was reversed by CXCL12a via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, these effects were inhibited by the CXCR4 antagonist AMD3100 and the PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY303511","term_id":"1257646067","term_text":"LY303511"}}LY303511. In conclusion, inhibition of the CXCL12a/CXCR4 signaling axis maintained TIMP-3 expression via the PI3K/Akt pathway. Our findings provide insight into the mechanism by which AMD3100 prevents OA.

Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by the selective and progressive death of dopaminergic (DA) neurons in the substantia nigra. Increasing evidence suggests that inflammation is important in the degeneration of DA neurons. The purinergic receptor subtype P2X7 receptor (P2X7R) is key in the activation and proliferation of microglia. The present study aimed to examine whether inhibiting purinergic P2X7 receptors is neuroprotective in a rat model of PD, specifically via inhibiting p38 mitogen‑activated protein kinase (MAPK). In an intranigral lipopolysaccharide (LPS) rat model of PD, immunohistochemical analysis revealed enhanced expression of P2X7R was observed in microglia. The administration of the P2X7R antagonist, brilliant blue G (BBG), reduced activation of the microglia and the loss of nigral DA neurons. In addition, immunohistochemistry and western blot analysis revealed the phosphorylation level of p38 MAPK increased in the microglia of the LPS‑injected rats, which was inhibited by BBG treatment. The p38 MAPK inhibitor, SB203580, reduced microglial activation and the loss of DA neurons. Thus, these findings suggested that inhibition of P2X7R by BBG attenuated microglial activation and the loss of substantia nigra DA neurons via p38 MAPK in the rat LPS model of PD.

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860; 95% CI: 0.779–0.940; S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

Inverse Synthetic Aperture Radar has been proved to be a powerful tool in imaging moving targets in military and civilian applications. The target's movement with respect to the radar sensor provides the angular diversity required for range-Doppler ISAR imagery and image blur due to its motion error. For real targets such as plane, ship and tank have complicated motion components which are unknown to the radar. This paper is a brief review of universally used motion compensation techniques employed in ISAR for a clear and focused image.

The present study aimed to investigate the effects of the phosphoinositide 3‑kinase (PI3K)/Akt signaling pathway on the Wnt/β‑catenin signaling pathway in rats with focal cerebral ischemia‑reperfusion injury. A total of 96 rat focal cerebral ischemia‑reperfusion models, established according to a modified version of Longa's method, were randomly divided into four groups: Sham‑operated (S), cerebral ischemia‑reperfusion injury (I), cerebral ischemia‑reperfusion + basic fibroblast growth factor (bFGF) post‑processing and, finally, cerebral ischemia‑reperfusion + bFGF post‑processing + PI3K inhibitor LY294002 (LY). Each group consisted of 24 rats and each group was divided into four subgroups according to the indicated reperfusion times of 12, 24, 48 and 72 h. The morphological changes of the cortical tissue and the cellular apoptosis were determined using hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling method, respectively. The expression levels of phosphorylated (p‑)Akt, glycogen synthase kinase‑3β (GSK‑3β) mRNA and β‑catenin in the cortical tissue were detected at different time‑points. The number of apoptotic cells and the expression levels of p‑Akt, GSK‑3β mRNA and β‑catenin in the I and LY groups were significantly higher compared with those in the S group (P

Rapid allele-specific PCR primer was designed base on Cytb 155 A/T single nucleotide polymorphism, DNA was extracted by alkaline lysis and the PCR reaction systems including denatured and annealing temperature and cycle numbers were optimized. The results were performed to authenticate Ranae Oviductus and its 4 adulterants. When 100×SYBR Green I was added in the PCR product at 90 ℃ denatured 3 s, 62 ℃ annealing 20 s and 32 cycle. Ranae Oviductus visualized strong green fluorescence under 365 nm UV lamp whereas adulterants appeared negative. The whole process can be completed in 40 minutes．The established method provides the technical support for authentication of the Ranae Oviductus.

Given that cyclooxygenase-2 (COX-2) plays a crucial role during cerebral ischemia and Apobec-1 is a critical regulator of COX-2 mRNA stabilization in gastrointestinal settings, the correlation of COX-2 and Apobec-1 was investigated in neurogenic cells and rat model of cerebral ischemia. After neurogenic SH-SY5Y, NG108-15 and PC12 cells were exposed to oxygen-glucose deprivation, cell viability, LDH leakage and Apobec-1 expression were determined. The effect of Apobec-1 overexpression on injury severity of oxygen-glucose deprivation, COX-2 expression, C-to-U editing of COX-2 mRNA were measured in vitro. Then the correlation of Apobec-1 level and injury severity was analyzed in cells with oxygen-glucose deprivation and in rats with middle cerebral artery occlusion. Apobec-1 expression was elevated along with upregulation of COX-2 and injury severity of oxygen-glucose deprivation in the three cell lines. Apobec-1 overexpression aggravated injury of oxygen-glucose deprivation in vitro and could be correlated to injury severity in vivo. Meanwhile, Apobec-1 increased COX-2 expression and COX-2 mRNA stabilization in neurogenic cells, and failed to catalyze C-to-U editing of COX-2 mRNA. Apobec-1 could upregulate COX-2 expression in neurogenic cells by stabilizing COX-2 mRNA, and might aggravate injury of oxygen-glucose deprivation in neurogenic cells as well as in rats with cerebral ischemia.

Background: Macrolide antibiotics have anti-inflammatory effects which are utilized for the treatment of chronic inflammatory airway diseases. Recently, their anti-inflammatory effects have been proposed to be beneficial in patients with chronic obstructive pulmonary disease (COPD). Objectives: Since the molecular mechanisms of anti-inflammatory effects are associated with inhibition of activator protein 1 (AP-1) and nuclear factor (NF)-ĸB, and both are reported to be involved in the expression of γ-glutamylcysteine synthetase (γ-GCS), we set out to determine if these drugs influence the oxidant-antioxidant balance in human bronchial epithelial (HBE) cells. Methods: 16HBE cells were preincubated with erythromycin (EM) at different concentrations and times and then exposed to hydrogen peroxide (0.01 mM). Levels of interleukin (IL)-8 and glutathione (GSH), and activity of γ-GCS and γ-GCS heavy subunit (γ-GCS-HS) protein production were assayed. AP-1 and NF-ĸB binding to the 5′-flanking region of IL-8 and γ-GCS-HS genes was assessed by electrophoretic mobility-shift assay. Results: The increase in IL-8 levels and activity of AP-1 induced by H2O2 were abrogated by preincubation of the cells with EM (5 µg/ml) for 36 h. We also showed that preincubation with EM for 48 h inhibited H2O2-induced GSH levels, γ-GCS activity and expression of γ-GCS-HS, and decreased AP-1 binding to the γ-GCS-HS 5′-flanking region. Conclusions: The confirmation of antioxidants maintaining enzyme suppression by EM raised concerns on whether this drug could disrupt the oxidant/ antioxidant balance during long-term use. These data provide important insights into the treatment of inflammatory lung diseases with macrolide antibiotics.

The time dependence of Sm2+ fluorescence in orthorhombic BaCl2 was investigated between 77 and 300 K. The thermal quenching mechanism of the 4f–4f emissions of Sm2+ was examined. The position of the lowest level of Sm2+ 4f55d states was calculated from the temperature dependence of 5D1 lifetime by the two-step quenching model and was estimated in good approximation from the emission and excitation peaks by the electron–phonon coupling theory. A growing process of 5D0–7F0 emission and a double-decay process of 5d–4f emission were observed in the time-resolved fluorescence. They show clearly the population transfer among the Sm2+ excited states via thermal transition.

Phorbol myristate acetate (PMA), as a potent tumor promoter, may induce microglial senescence. The present study investigated the effect of PMA infection on microglial senescence. From 58 male Sprague‑Dawley rats, 10 were randomly selected and divided into a PMA injection group, containing five rats (0.5 µg/µl PMA) and a control group, containing five rats (commensurable 0.9% saline). Immunofluorescent staining of Iba‑1 and enzyme‑linked immunosorbent assay analyses of the expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1 β were performed in these two groups. The remaining 48 rats were randomly divided into the following three groups, each containing 16 rats: Repeated injection control group (commensurable normal saline, once a week for 4 weeks), single PMA injection group (0.5 µg/µl PMA, once in the first week) and repeated injection PMA group (0.5 µg/µl PMA, once a week for 4 weeks). The expression levels of p21, detected using double immunofluorescence staining with Iba‑1, and β‑galactosidase, via double immunohistochemical staining of Iba‑1, were examined in these three groups. The results indicated that a single injection of PMA did not change the microglial morphology and had no significant effects on the expression levels of TNF‑α and IL‑1β, compared with the control group (P>0.05). Following four repeated injections of PMA, the microglia in the substantia nigra presented with features of senescence, characterized by increased expression levels of β-galactosidase (P

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Th17 cells and interleukin-17 (also called IL-17A) have been found to be increased in peripheral blood and skin in patients with SSc. IL-21 is a potent inducer of Th17 differentiation that is produced by activated T cells, and whose relationship with Th17 cells in SSc is unclear. Here, using a bleomycin (BLM)-induced mouse model of skin fibrosis, we detected the frequency of CD4+/IL-17+ (Th17) cells, CD4+/IL-21+ T cells and IL-21+ Th17 cells in peripheral blood, skin and lungs, as well as the serum content of IL-17A and IL-21. In addition, we assessed the differentiation of CD4+ T cells cultured from these mice into Th17 cells in response to treatment with IL-21. Compared with the control mice, Th17 cell counts and IL-17A levels were significantly increased and correlated with inflammatory and fibrotic indices in the skin and lungs of the BLM-induced fibrosis mice. Moreover, serum levels of CD4+/IL-21+ T cells, IL-21+ Th17 cells, and IL-21 were significantly increased in these mice, and correlated positively with serum levels of Th17 cells. In vitro experiments showed that IL-21 treated CD4+ T cells derived from BLM-induced mice differentiated into Th17 cells. Our results indicate that Th17 cells and IL-17A contributes to inflammatory and fibrotic processes in the skin and lungs in a BLM-induced mouse model of SSc. Moreover, the expansion of the Th17 cell population may be subsequent to IL-21 promotion of the differentiation of CD4+ T cells in these mice.

Objective To clarify the relationship between the quantitatively assessed cube-copying test (CCT) and clinical profiles of cognitive and motor ability in Chinese patients with Parkinson disease (PD). Methods We gave the Montreal Cognitive Assessment (MoCA), which includes the CCT, to evaluate the cognitive function of 102 outpatients with PD. We also gave the Unified Parkinson's Disease Rating Scale (UPDRS) II and III and the Hoehn-Yahr scale to evaluate the patients' motor function and disease severity, respectively. We used Maeshima's method for quantitative assessment of the CCT, and calculated CCT errors by adding incomplete connections and plane-drawing errors. We divided the patients into 2 groups based on normal (no errors) versus abnormal (≥1 errors) CCT scores. Results We found 34 patients with normal scores and 68 with abnormal scores. The 2 groups had significant differences in age of onset, MoCA score, UPDRS II and III scores, and cognitive deterioration rate. CCT errors correlated inversely with cognitive domains except for orientation. Executive function was most commonly affected in both groups. We found correlations between numbers of CCT errors and left-limb movement, fine hand movement, postural instability and gait disorders, UPDRS II and III scores, and cognitive and motor deterioration rates. Conclusions The quantitatively assessed CCT may be useful in estimating cognitive and motor dysfunction in patients with PD, and in monitoring disease progression.

The relation between the LRRK2 mutation and its effect on Parkinson’s disease (PD) has always caught a lot attention. Recent studies found that the G2385R polymorphism of LRRK2 may increase the risk of PD in Asian populations. Here we tried to clarify the relationship between the LRRK2 G2385R variant and the clinical profiles including motor complication in Chinese PD patients. We identified the LRRK2 variant in the Chinese Han population in northern China and evaluated the relationship between the G2385R variant and clinical profiles through comparison between 36 carriers and 139 non-carriers. We found that G2385R carriers scored significantly higher in motor fluctuation and dyskinesia than non-carriers. Logistic regression analysis showed that the G2385R variant was an independent risk factor for motor fluctuation in females (odds ratio = 12.538, 95 % CI 2.216–70.942, P = 0.004), and a Chi-squared test showed that the frequency of dyskinesia tended to be higher in the carrier group compared to the non-carrier group (16 vs. 4.4 %, P = 0.050, OR = 4.127, 95 % CI 1.074–15.864). These findings indicate that the variant was closely related to the occurrence of motor complication. Additionally, the G2385R variant was significantly related to the early-onset of PD in female carriers (20.0 vs. 1.5 %, odds ratio = 16.25, 95 % CI 1.557–169.618, P = 0.020). Our study found that the G2385R variant was significantly associated with motor complications and that this variant was an independent risk factor for motor fluctuation in females. These findings provide the necessary preliminary data to better understand the unique profile of PD G2385R variant carriers.

To investigate the impact of treatment with low dose roxithromycin on clinical symptoms and CT scores in patients with stable bronchiectasis.Fifty patients with bronchiectasis in stable condition were randomly assigned to a control group and a treatment group. Patients in the control group received ambroxol hydrochloride tablet 90 mg 3 times a day. Patients in the treatment group received roxithromycin disperse tablet 0.15 g every day and ambroxol hydrochloride tablet 90 mg 3 times a day. The course of treatment lasted for 6 months. Quality of life was assessed using St. George's respiratory questionnaire (SGRQ). The British Medical Research Council (MRC) dyspnea scale was used to assess the degree of dyspnea. The score for CT evaluation of the thorax, quality of life and SGRQ were performed for all patients before and after the treatment.After 6 months, the scores for quality of life (48 ± 13) were lower compared to that (58 ± 15) before treatment in the control group; however, the scores for bronchial wall thickening of bronchiectasis (1.8 ± 0.5) were higher than that (1.8 ± 0.4) before study. The scores for the extent of bronchiectasis (2.7 ± 1.6), the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) were reduced after treatment as compared to those before treatment [(4.8 ± 2.3), (1.8 ± 0.5), (9.5 ± 3.3)] in the treatment group, (all P0.01). The degree of dyspnea (1.3 ± 0.4) and quality of life (42 ± 12) were lower than those before treatment [(1.89 ± 0.45), (56 ± 15)] in the treatment group. Furthermore, the scores for extent of bronchiectasis (2.7 ± 1.6), the scores for the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) in the treatment group were significantly improved as compared with those [(4.8 ± 2.0), (1.8 ± 0.5), (9.7 ± 3.6)] in the control group respectively after treatment. At the same time, the degree of dyspnea (1.3 ± 0.4) in the treatment group was significantly improved as compared with that (1.7 ± 0.4) in the control group after treatment.The scores for the bronchial wall thickening of bronchiectasis were increased in patients with stable bronchiectasis. Low dose roxithromycin combined with ambroxol hydrochloride significantly improved degree of dyspnea, reduced scores for extent of bronchiectasis, scores for the bronchial wall thickening of bronchiectasis and the global CT score as compared to treatment with ambroxol hydrochloride alone in patients with bronchiectasis in stable condition.