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Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases. However, the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains unclear. In this study, rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) for five weeks. The mobility of rats was evaluated by forced swimming test, while their cognitive capabilities were evaluated by Y-maze test. Expression of sortilin, α-synuclein, p-JUN, and c-JUN proteins in the substantia nigra were detected by western blot analysis. In addition, immunofluorescence staining of sortilin and α-synuclein was performed to detect expression in the substantia nigra. The results showed that, compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (5 mg/kg) + CPA co-treated rats, motor and memory abilities were reduced, surface expression of sortin and α-synuclein in dopaminergic neurons was reduced, and total sortilin and total α-synuclein were increased in CPA-treated rats. MN9D cells were incubated with 500 nM CPA alone or in combination with 10 μM SP600125 (JNK inhibitor) for 48 hours. Quantitative real-time polymerase chain reaction analysis of sortilin and α-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone, but the combination of CPA and SP600125 could inhibit this expression. Predictions made using Jasper, PROMO, and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents. A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this prediction. After sortilin expression was inhibited by sh-SORT1, expression of p-JUN and c-JUN was detected by western blot analysis. Long-term adenosine A1 receptor activation levels upregulated α-synuclein expression at the post-transcriptional level by affecting sortilin expression. The online tool Raptor-X-Binding and Discovery Studio 4.5 prediction software predicted that sortilin can bind to α-synuclein. Co-immunoprecipitation revealed an interaction between sortilin and α-synuclein in MN9D cells. Our findings indicate that suppression of prolonged adenosine A1 receptor activation potently inhibited sortilin expression and α-synuclein accumulation, and dramatically improved host cognition and kineticism. This study was approved by the University Committee of Animal Care and Supply at the University of Saskatchewan (approval No. AUP#20070090) in March 2007 and the Animals Ethics Committee of University of South China (approval No. LL0387-USC) in June 2017.

Objective To construct prediction models for moderate/severe bronchopulmonary dysplasia （BPD） in extremely preterm infants at different days after birth. Methods The preterm infants with BPD at a gestational age of < 28 weeks at the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to December 2019 were retrospectively selected. They were divided into the mild-BPD group and moderate/severe-BPD group. The significant variables screened by using single-factor analysis were subject to risk assessment analysis by multivariate Logistic regression analysis. Early prediction models were established， and the predictive performance was validated and evaluated. Results Ninety extremely preterm infants were included in this study， including 58 cases （64.4%） in the mild-BPD group and 32 cases （35.6%） in the moderate/severe-BPD group. Multiple Logistic regression analysis showed birth weight， maternal pre-pregnancy body mass index （BMI） ≥ 25 kg/m2， 1-minute Apgar score≤7 after birth and pneumonia were the influencing factors for moderate/severe BPD at 7 days after birth. Preeclampsia， maternal pre-pregnancy BMI≥25 kg/m2， pneumonia and hsPDA were the risk factors for moderate/severe BPD at 14 days postnatal age. Preeclampsia， maternal pre-pregnancy BMI≥25 kg/m2， days of invasive mechanical ventilation and hsPDA were the risk factors for moderate/severe BPD at 28 days after birth. The area under the receiver operating characteristic （ROC） curve of the prediction models for 7， 14 and 28 days after birth were 0.864 （95% CI 0.776-0.952）， 0.860 （95% CI 0.774-0.946） and 0.863 （95% CI 0.783-0.944）， respectively. A nomogram was constructed based on high risk factors， the calibrated curve was close to the reference line， and the predicted value was close to the actual value， indicating good calibration of the model. Conclusions The risk factors for moderate/severe BPD in preterm infants vary slightly on 7， 14 and 28 days after birth， mainly the birth weight， maternal pre-pregnancy BMI ≥ 25 kg/m2， 1-minute Apgar score≤7， pneumonia， preeclampsia， hsPDA and days of invasive mechanical ventilation. The predictive models based on different factors at different time points have good predictive value， which can provide guidance for clinical practice.

Many methods, including single factor index method, Nemero comprehensive index method, potential ecological risk index method and geoaccumulation index method, have been employed to evaluate soil heavy metal pollution. However, no well-developed or standard method has yet been established. Herein, 77 samples of farmland soil in south Jining were collected and analyzed. The results show that average concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb and Zn in the samples were 16.7, 0.270, 88.4, 33.0, 0.050, 40.4, 29.3 and 89.1 mg/kg, respectively. The values of Hg and Cd were 1.50 and 1.39 times higher than the benchmark value of the Huang-Huai-Hai Plain and values of other elements were 0.26-0.52 times higher than the benchmark value. All of the samples were evaluated by bivariate correlation analysis method, and the results show that soils are polluted by Hg. The enrichment coefficient method and geoaccumulation method were employed to evaluate the pollution level of 8 elements (As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) in the target area soil. Both results show that there was light accumulation of Hg and Cd, while other elements were at normal levels. Combining heavy metal concentration in the selected area, the biotoxicity index of heavy metals, ecological effect and environmental effect, and the potential biological hazard index method were applied to evaluate the biological risk. The results show that the potential hazard sequence is as follows: Hg>Cd>As>Cu>Pb>Ni>Cr>Zn with obvious differences to the accumulation level. Although there was only light accumulation of Hg and Cd, their potential hazards contributed up to 81.26% of the total contribution of potential ecological risk index. The result was schematized by using MapGIS. It showed that about 6.83% of the selected area had the problem of strong or very strong potential ecological risk, and the remainder was at the medium level. Despite the junction of Fuxing River, Yaolou River and Jinghang canal faced the problem of very strong potential biological risk. According to the investigation on the anthropogenic emission sources in the research area, it was found that the risk had positive correlation with coal mining activities. Therefore, taking effective measures to remedy the polluted soil, especially the remediation of the Hg and Cd pollution, will be of great significance to prevent the further deterioration of the soil environment.

Objective: To observe the efficacy of Dahuang Fuzi decoction in patients with severe acute pancreatitis (SAP), and to provide valuable medical evidences for a treatment of SAP with combined traditional Chinese and western medicine., Methods: A prospective, multi-center, randomized, controlled clinical trial was designed. Two hundred and six adult patients with SAP admitted to intensive care unit (ICU) in three tertiary university teaching hospitals in Dalian from January 2007 to February 2010 were randomly divided into two groups: soapsuds enema control group (control group, n=101) and Dahuang Fuzi decoction enema study group (study group, n=105). The levels of serum amylase, albumin (Alb), D-lactic acid, endotoxin and diamine oxidase (DAO), high-sensitive C-reactive protein (hs-CRP), immunoglobulin (IgG, IgA, IgM), complements (C3, C4), tumour necrosis factor-α (TNF-α), interleukins (IL-6, IL-8) were determined before and after treatment for 2, 4, 7 days. The bowel sound, gastrointestinal function score, the acute physiology and chronic health evaluation II (APACHEII) score and the length of mechanical ventilation (MV), the length of stay in ICU, the mortality rate and average hospital expenses within 28 days were compared., Results: Compared with control group, in the study group the levels of serum amylase, DAO, D-lactic acid and endotoxin were lowered, the Alb was increased, the levels of TNF-α, IL-6, IL-8, hs-CRP were decreased, the function of body immunity was enhanced, intestinal peristalsis was enhanced, gastrointestinal function score and APACHEII score were improved, the length of MV was reduced, the length of stay in ICU was diminished, the 28-day mortality and average hospital expenses were lowered [4 days amylase (U/L): 357.35±137.54 vs. 492.95±189.42, 2 days DAO (kU/L) : 5.20±0.59 vs. 5.45±0.72, 4 days D-lactic acid (mmol/L): 3.31±0.48 vs. 4.15±0.55, 2 days endotoxin (kEU/L): 0.29±0.11 vs. 0.34±0.14, 4 days Alb (g/L): 34.75±3.56 vs. 32.53±3.44, 2 days TNF-α (ng/L): 3.08±0.45 vs. 3.36±1.11, 2 days IL-6 (ng/L): 298.54±67.82 vs. 313.56±73.91, 4 days IL-8 (ng/L): 30.48±8.56 vs. 45.16±10.81, 2 days hs-CRP (mg/L): 32.56±11.83 vs. 40.42±15.10, 4 days IgG (g/L): 7.05±2.56 vs. 9.53±2.94, 2 days IgA (mg/L): 1 600±170 vs. 1 400±140, 4 days IgM (mg/L): 1 310±280 vs. 1 650±290, 4 days C3 (g/L): 1.11±0.09 vs. 1.50±0.15, 4 days C4 (g/L) : 0.32±0.11 vs. 0.41±0.10, 2 days bowel sound (times/min): 1.26±0.45 vs. 1.15±0.41, 2 days gastrointestinal function score: 2.24±0.98 vs. 2.42±1.05, 4 days APACHEII score: 16.4±6.8 vs. 20.1±7.1, the length of MV (days): 6.5±3.1 vs. 10.1±4.6, the length of stay in ICU (days): 11.3±6.3 vs. 13.8±7.5, mortality: 8.6% vs. 16.8%, average hospital expenses (yuan): 72 thousands vs. 86 thousands, P<0.05 or P<0.01]., Conclusion: Dahuang Fuzi decoction may enhance the intestinal peristalsis, protect the gastrointestinal barrier function, reduce the bacteria and endotoxin translocation and the releasing of inflammation mediators, protect the function of body immunity, reduce the length of MV, the length of stay in ICU, and lower the 28-day mortality and average hospital expenses, and it can improve the prognosis of patients with SAP.