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Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.
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Objective:To investigate the correlation between serum brain-derived neurotrophic factor (BDNF) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, and to evaluate its predictive value for PSCI.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from April 2018 to September 2020 were prospectively enrolled. Cognitive impairment was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after onset. Multivariate logistic analysis was used to determine the independent correlation between serum BDNF and PSCI, and receiver operating characteristics (ROC) curve was used to evaluate its predictive value for PSCI. Results:A total of 511 patients with acute ischemic stroke were enrolled, including 332 males (65.0%), aged 60.67±10.18 (range 49-80) years. The median score of the National Institutes of Health Stroke Scale (NIHSS) at the baseline was 5.0 (interquartile range 2.7-6.7), and 413 patients (80.8%) had anterior circulation stroke. The median of serum BDNF was 11.54 μg/L (interquartile range 6.13-16.25 μg/L). PSCI occurred in 310 patients (60.7%). Univariate analysis showed that there were significant differences in age, history of previous transient ischemic attack, baseline NIHSS score and serum BDNF between the PSCI group and the non-PSCI group (all P<0.05). Multivariate logistic analysis showed that there was a significant independent correlation between serum BDNF and PSCI (odds ratio 0.514, 95% confidence interval 0.356-0.807; P=0.005). ROC curve analysis showed that the area under the curve of serum BDNF predicting PSCI was 0.863 (95% confidence interval 0.830-0.896; P<0.001). The best cut-off value was 10.78 μg/L, and the sensitivity and specificity were 74.9% and 86.8% respectively. Conclusion:Higher baseline serum BDNF was a protective factor for PSCI and had good predictive value for PSCI.
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Objective:To explore the correlation between serum microRNA(miR)-124 and miR-181c expression and the treatment outcome of Solitaire stent thrombectomy in patients with acute cerebral infarction and its influencing factors.Methods:Eighty-one patients with acute cerebral infarction performed Solitaire stent thrombectomyfrom June 2018 to October 2020 in the Affiliated Hospital of Jining Medical College were selected. The predictive value of miR-124, miR-181c expression in patients with acute cerebral infarction were analyzed.Results:In 81 patients, 21 patients with poor outcome(poor outcome group) and 60 patients with favorable outcome (favorable outcome group). The ratio of age ≥ 60 years in poor outcome group was higher than that in the favorable outcome group: 76.19% (16/21) vs. 46.67% (28/60), there was statistical difference ( χ2 = 5.46, P<0.05). The levels of miR-124, miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were higher than those in poor outcome group: 2.81 ± 0.82 vs. 2.24 ± 0.74, 3.01 ± 1.52 vs. 2.07 ± 1.04, 3.25 ± 1.67 vs. 1.86 ± 0.92; and the levels of miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were lower than those in the poor outcome group: 1.43 ± 0.59 vs. 1.79 ± 0.65, 1.35 ± 0.62 vs. 1.94 ± 0.79, 1.24 ± 0.60 vs. 2.16 ± 1.08, there were statistical differences ( P<0.05). The results of Logistic multivariate analysis showed that the age, the levels of miR-124, miR-181c before operation and postoperative 1-day, 7-day were influencing factors for the treatment outcome of Solitaire stent thrombectomy. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-124, miR-181c on the postoperative 7-day were 0.806, 0.861, and were higher than those before operation and the postoperative 1-day, the diagnostic sensitivity were 71.43%, 76.19%, the specificity were 88.33%, 85.00%. Conclusions:The expression of miR-124 and miR-181c in the serum of acute cerebral infarction is related to the outcome of Solitaire stent thrombectomy, especially the expression level on the postoperative 7-day has better application value. It can be used to predict the outcome of surgery.
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[Objective] To screen and identify the new Y-STR loci from the Y chromosome and examine the polymorphism of these Y-STR loci. [Method] To seek and locate the position of 5 Y-STR loci, including DYS709, DYS720, DYS721, DYS722, and DYS723, and perform sequencing of these 5 Y-STR loci. Then to investigate the polymorphism in unrelated Chinese Han males. [Results] Five Y-STR loci were identified from Y chromosome sequence. By scrutinizing the physical position on Y chromosome of previously reported Y-STRs, we found that three loci were novel and two loci overlapped with two loci published only online. All loci could be male-specifically amplified with a product size ranging from 185 bp to 278 bp. After 108 males of the Chinese Han Population (Guangzhou) were examined, we found 5 DYS709, 11 DYS720 alleles, 4 DYS721 alleles, 6 DYS722 alleles, and 6 DYS723 alleles. A total of 95 haplotypes were identified, 84 of which were unique, and with a haplotype diversity of 0.997 2±0.001 2(HD±SE). [Conclusion] This set of Y-STRs can be used as Y chromosome genetic makers in related fields.
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[Objective] To propose a criterion for making conclusions on paternity tests based on STR genotyping. [Method] To use binomial distribution formula to calculate minimal numbers of STR loci that must be tested for different scenarios in paternity testing. [ Results ] We proposed a set of criteria for making STR paternity testing conclusions. For triplet tests, concluded "paternity positive" for the following four cases when the cumulative paternity index (PI) was greater than 10 000: 1) no inconsistent STR locus was detected in 15 loci (PE > 0.571 4/locus) or 2) only one inconsistent STR locus was detected in 19 loci or 3) only two inconsistent STR loci were detected in 28 loci or 4) only three inconsistent STR loci were detected in 35 loci; otherwise, concluded "paternity negative" when at least four inconsistent STR loci had been detected. For single parent tests, concluded "paternity non-exclusive" for the following cases when the cumulative PI was greater than 10 000: 1) no inconsistent STR locus was detected in 18 loci (PE>0.411/locus) or 2) only one inconsistent STR locus was detected in 29 loci or 3) two inconsistent STR loci were detected in 41 loci; concluded "paternity negative" when three or more inconsistent loci were detected. [Conclusion] Our experience has proven that these criteria are robust in STR paternity testing.