Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.

A novel animal model of primary blast lung injury and its pathological changes in mice.

BACKGROUND: Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. METHODS: The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. RESULTS: In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1ß, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. CONCLUSION: The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue.

Possible role of glial cell line-derived neurotrophic factor for predicting cognitive impairment in Parkinson's disease: a case-control study.

Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the protection of dopaminergic neurons, but there are few reports of the relationship between GDNF and its precursors (α-pro-GDNF and ß-pro-GDNF) and cognitive impairment in Parkinson's disease. This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson's disease, and to assess their potential as a diagnostic marker. Fifty-three primary outpatients and hospitalized patients with Parkinson's disease (23 men and 30 women) with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study. The patients were divided into the Parkinson's disease with cognitive impairment group (n = 27) and the Parkinson's disease with normal cognitive function group (n = 26) based on their Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. In addition, 26 age- and sex-matched healthy subjects were included as the healthy control group. Results demonstrated that serum GDNF levels were significantly higher in the Parkinson's disease with normal cognitive function group than in the other two groups. There were no significant differences in GDNF precursor levels among the three groups. Correlation analysis revealed that serum GDNF levels, GDNF/α-pro-GDNF ratios, and GDNF/ß-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. To explore the risk factors for cognitive impairment in patients with Parkinson's disease, logistic regression analysis and stepwise linear regression analysis were performed. Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson's disease, and were the common influencing factors for cognitive scale scores. Neither α-pro-GDNF nor ß-pro-GDNF was risk factors for cognitive impairment in Parkinson's disease. A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson's disease (area under the curve = 0.859). This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson's disease have cognitive impairment is 0.859. Together, these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson's disease. However, α-pro-GDNF and ß-pro-GDNF are not useful for predicting cognitive impairment in this disease. This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, China (approval No. XYFY2017-KL047-01) on November 30, 2017.

Aqueous-phase detection of antibiotics and nitroaromatic explosives by an alkali-resistant Zn-MOF directed by an ionic liquid.

An alkali-resistant Zn-MOF directed by [BMI]Br ionic liquid, (BMI)2[Zn3(ptptc)2] (1), based on a π-electron-rich terphenyl-tetracarboxylic acid, has been synthesized under the combination of hydro/solvothermal and ionothermal condition (BMI = 1-butyl-3-methylimidazolium, H4ptptc = p-terphenyl-3,3'',5,5''-tetracarboxylic acid). In 1, the trinuclear Zn(ii) clusters are linked by the organic moieties of the ptptc ligands, resulting in a 3D anionic framework structure with highly disordered [BMI]+ cations filled in the pores. 1 exhibits good chemical stability in water and NaOH solutions (pH range of 7-12), which allow it to detect antibiotics and nitroaromatic explosives in an aquatic system. 1 represents high fluorescence quenching efficiency toward NFs (furazolidone, FZD; nitrofurazone, NZF; nitrofurantoin, NFT), NMs (ronidazole, RDZ; metronidazole, MDZ; dimetridazole, DTZ; ornidazole, ODZ) and nitrophenol (2-nitrophenol, 2-NP; 3-nitrophenol, 3-NP; 4-nitrophenol, 4-NP; 2,4,6-trinitrophenol, TNP) in water solution, respectively.

SUMOylation and deacetylation affect NF-κB p65 activity induced by high glucose in human lens epithelial cells.

AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells (HLECs). METHODS: HLECs (SRA01/04) were cultured with 5.5, 25, and 50 mmol/L glucose media for 24h, and with 50 mmol/L glucose media for 0, 12, and 24h respectively. SUMO1 and SIRT1 expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB). IκBα and NF-κB p65 expressions were detected by WB. With NAC, DTT, MG132 or Resveratrol (RSV) treatment, SUMO1 and SIRT1 expressions were detected by WB. Protein expression localizations were examined by immunofluorescence and co-immunofluorescence. The effects of SUMO1 or SIRT1 overexpression, as well as MG132 and RSV, on the nuclear expression and activity of IκBα and NF-κB p65 were analyzed by immunoblot and dual luciferase reporter gene assay. RESULTS: SUMO1 and SIRT1 expressions were influenced by high glucose in mRNA and protein levels, which could be blocked by NAC or DTT. SUMO1 was down-regulated by using MG132, and SIRT1 was up-regulated under RSV treatment. IκBα nuclear expression was attenuated and NF-κB p65 was opposite under high glucose, while IκBα and NF-κB p65 location was transferred to the nucleus. SUMO1 or SIRT1 overexpression and MG132 or RSV treatment affected the nuclear expression and activity of IκBα and NF-κB p65 under high glucose condition. CONCLUSION: IκBα SUMOylation and NF-κB p65 deacetylation affect NF-κB p65 activity in cultured HLECs under high glucose, and presumably play a significant role in controlling diabetic cataract.

Comparison of 25 MHz and 50 MHz ultrasound biomicroscopy for imaging of the lens and its related diseases.

AIM: To compare the results of 25 MHz and 50 MHz ultrasound biomicroscopy (UBM) regarding the image characteristics of the lens and its related diseases and to discuss the application value of 25 MHz UBM in ophthalmology. METHODS: A total of 302 patients (455 eyes) were included in this study from November 2014 to May 2015. Patient ages ranged from 5 to 89y (mean±SD: 61.0±17.7y). Different cross-sectional images of the lens were collected to compare and analyze the image characteristics and anterior segment parameters using 25 MHz and 50 MHz UBM in axial and longitudinal scanning modes, respectively. SPSS 19.0 for Windows, paired t-tests and B&A plot analysis were used for data analysis, and a value of P<0.05 was considered statistically significant. RESULTS: The 25 MHz UBM images displayed the lens shape more clearly than 50 MHz UBM images. Particularly for cataracts, the whole opacity of the lens was shown by 25 MHz UBM, but 50 MHz UBM only showed part of the lens. The means of the anterior segment parameters obtained using 25 MHz and 50 MHz UBM were as follows: central corneal thickness: 0.55±0.03 and 0.51±0.04 mm, respectively; central anterior chamber depth: 2.48±0.54 and 2.56±0.56 mm, respectively; and central lens thickness: 4.26±0.62 and 4.15±0.56 mm, respectively. A statistically significant difference was found between the results obtained with 25 MHz UBM and those obtained with 50 MHz UBM. The two devices had a good agreement in measuring the anterior segment parameters. CONCLUSION: The 25 MHz UBM had an obvious advantage in showing the lens shape. It can provide reliable imaging of the lens and its related diseases and has a high application value for ophthalmology.

Atorvastatin Treatment for Atrial Fibrillation Reduces Serum High-Sensitivity C-Reactive Protein Levels.

We investigated whether serum hs-CRP levels predict the efficacy of atrial fibrillation (AF) treated with atorvastatin. Bibliographic databases were exhaustively searched for studies relevant to the research topic. Newcastle-Ottawa Scale (NOS) criteria, combined with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), were applied for study quality assessment. Our meta-analysis identified seven cohort studies (2006~2013), providing information on the change in serum hs-CRP levels in AF patients receiving atorvastatin therapy. After atorvastatin treatment, hs-CRP level in AF patients decreased significantly (SMD = 1.02, 95% CI: 0.58-1.47, P < 0.001). Subgroup analysis by country and hs-CRP detection methods suggested a negative relationship between atorvastatin treatment and hs-CRP levels among Chinese AF patients (SMD = 1.34, 95% CI: 1.00-1.69, P < 0.001) and by using ELISA method (SMD = 1.11, 95% CI: 0.51-1.71, P < 0.001), but not among Turkish population and using INA method (all P > 0.05). Egger's test showed no publication bias (P = 0.450). hs-CRP was clearly lowered in AF patients treated with atorvastatin, which may be helpful in the choice of statin agents for AF treatment. However, longer follow-ups are necessary to assess the clinical value of lowering hs-CRP in the clinical setting of AF treatment outcomes.

Effect of Atorvastatin on Serum Levels of Total Cholesterol and High-Sensitivity C-reactive Protein in High-Risk Patients with Atrial Fibrillation in Asia.

PURPOSE: The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. METHODS: By searching English and Chinese language-based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). FINDINGS: Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629-1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653-2.146, P < 0.001). IMPLICATIONS: The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events.

[Optimization of synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid].

OBJECTIVE: To optimize the synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid. METHOD: Using the DNA assembler method, one copy of Glycyrrhiza glabra beta-amyrin synthase (GgbAS), Medicago truncatula oleanolic acid synthase (MtOAS) and Arabidopsis thaliana cytochrome P450 reductase 1 (AtCPR1) genes were introduced into Saccharomyces cerevisiae strain BY-OA, resulting in strain BY-20A. YPD medium with different glucose concentration were then used to cultivate strain BY-2OA. RESULT: Increasing gene copies of GgbAS, MtOAS and AtCPR1 resulted in increased beta-amyrin and oleanolic acid production. The strain BY-2OA produced 136.5 mg x L(-1) beta-amyrin and 92.5 mg x L(-1) oleanolic acid, which were 54% and 30% higher than the parent strain BY-OA. Finally, the titer of oleanolic acid increased to 165.7 mg x L(-1) when cultivated in YPD medium with 40 mg x L(-1) glucose. CONCLUSION: Production of oleanoic acid increased significantly in the yeast strain BY-2OA, which can provide the basis for creating an alternative way for production of oleanoic acid in place of extraction from plant sources.

[Construction of Saccharomyces cerevisiae cell factories for lycopene production].

For microbial production of lycopene, the lycopene synthetic genes from Pantoea agglomerans were integrated into Saccharomyces cerevisiae strain BY4742, to obtain strain ZD-L-000 for production of 0.17 mg · L(-1) lycopene. Improving supplies of isoprenoid precursors was then investigated for increasing lycopene production. Four key genes were chosen to be overexpressed, inclu- ding truncated 3-hydroxy-3-methylglutaryl-CoA reductase gene (tHMG1), which is the major rate-limiting enzyme in the mevalonate (MVA) pathway, a mutated global regulatory factor gene (upc2.1), a fusion gene of FPP synthase (ERG20) and endogenous GGPP synthase (BTS1), which is a key enzyme in the diterpenoid synthetic pathway, and GGPP synthase gene (SaGGPS) from Sulfolobus acidocaldarius. Over-expression of upc2.1 could not improve lycopene production, while over-expression of tHMGI , BTS1-ERG20 and SaGGPS genes led to 2-, 16. 9- and20. 5-fold increase of lycopene production, respectively. In addition, three effective genes, tHMG1, BTS1-ERG20 and SaGGPS, were integrated into rDNA sites of ZD-L-000, resulting in strain ZD-L-201 for production of 13.23 mg · L(-1) lycopene, which was 77-fold higher than that of the parent strain. Finally, two-phase extractive fermentation was performed. The titer of lycopene increased 10-fold to 135.21 mg · L(-1). The engineered yeast strains obtained in this work provided the basis for fermentative production of lycopene.

[The analysis of axial length changes in the phakic eyes after posterior chamber implantation of lens to correct high myopia].

OBJECTIVE: To definitive axial length measuring mode of the phakic eyes after posterior chamber implantation of lens. METHODS: All patients came from the Ophthalmology Hospital of China Medical University. Seventy patients with 135 eyes, aged 21 - 48 years old. Among this group 28 were male, 53 eyes; 42 were female, 82 eyes. A-ultrasound and IOL-Master was used to measure axial length one week before preoperative and three months after ICL implantation. There are two measuring mode in A-ultrasound and IOL-Master: normal and special. All the results were analysed by the SPSS11.5 statistical methods. RESULTS: (1) preoperative AXL of A-ultrasound and IOL-Master average are: (27.81 ± 0.22) mm, (28.02 ± 0.22) mm; (2) postoperative AXL of phakic and Pseudophakic PMMA mode of IOL-Master average are: (28.01 ± 0.22) mm, (28.12 ± 0.22) mm; (3) postoperative AXL of normal and special mode of A-ultrasound average are: (27.82 ± 0.22) mm, (26.40 ± 0.21) mm. CONCLUSION: According to the different measuring mode, there are some difference of AXL between the preoperative and postoperative ICL. The more accurately measuring mode is IOL-Master phakic mode before and after operation. A-ultrasound normal mode can be used if the lens become so turbid that the AXL can't be obtained by IOL-Master.

[Coronary artery and myocardium lesion comparison post atrioventricular ring radiofrequency catheter ablation with different catheters].

OBJECTIVE: To analyze the extent of myocardium and coronary artery lesion post atrioventricular ring radiofrequency catheter ablation with different tip catheters. METHODS: Twenty-one healthy dogs were randomly divided into 64 degrees C/50 W/100 s, 64 degrees C/100 W/100 s, 45 degrees C/45 W/100 s groups and ablated by 4 mm tip catheter, 8 mm tip catheter and irrigated tip catheter respectively. Left atrioventricular ring and right atrioventricular ring ablation were performed in all dogs. After ablation, myocardium lesion volume was calculated as 1/6pi x length x width x depth. Histological examinations were performed at the myocardium tissue at ablation sites. RESULTS: The lesion depths post 8 mm tip catheter ablation (7.18 +/- 1.72) mm and irrigated tip catheter ablation (7.99 +/- 1.77) mm were similar and significantly deeper than that post 4 mm tip catheter ablation (4.54 +/- 1.38) mm, P < 0.01. Similar results were found in terms of lesion volume [(356.76 +/- 94.44) mm(3) post 8 mm tip catheter ablation, (391.69 +/- 109.54) mm(3) post irrigated tip catheter ablation and (191.34 +/- 74.52) mm(3) post 4 mm tip catheter ablation]. Five (5/42, 11.9%) transmural myocardium necrosis and 8 (8/42, 19%) coronary artery lesions were observed post ablations. CONCLUSION: The extents of post ablation myocardium and coronary artery lesion were significantly higher induced by 8 mm tip catheter and irrigate tip catheter compared those by 4 mm tip catheter.