With the aging of the world's population,the incidence of Alzheimer's disease (AD) is continuously increasing.Currently,AD has become one of the most severe challenges faced by modern medicine.Genistein is a flavonoid phytoactive substance,whose structure is similar to that of estrogen,allowing it to mimic the effects of estrogen and possess various biological activities.Due to its multi-pathway targeting and low toxicity characteristics,it is considered to be an effective potential therapeutic source for AD.In this paper,the pharmacokinetics of genistein are introduced,and its neuroprotective effects and mechanisms in AD are reviewed from the aspects of its estrogen-like action,antioxidant,anti-inflammatory,anti-β-amyloid,regulation of cholinergic neurotransmission and inhibition of Tau protein phosphorylation.

Objective:A rare case of δ-globin gene (HBD) mutation in Guangdong Province was analyzed to provide reference for avoiding misdiagnosis of δ-thalassemia in clinic.Methods:The patient was admitted to Guangdong Maternal and Child Health Hospital, and the peripheral blood sample was collected for hematological phenotypes [mean erythrocyte volume (MCV), mean erythrocyte hemoglobin content (MCH), hemoglobin (Hb)] and Hb typing analysis. The routine deletion and mutation of α-thalassemia and β-thalassemia genes were analyzed by PCR-flow fluorescence hybridization. At the same time, DNA sequencing was used to analyze the type of HBD mutation.Results:The results of hematological phenotypes analysis showed that MCV was 87.9 fl, MCH was 29.3 pg, and Hb content was 140 g/L. The results of Hb typing showed that the contents of Hb F, Hb A 2, Hb A 2 variant, and Hb A were 0.4%, 1.3%, 0.6%, and 97.7%, respectively. No abnormality was found in α-thalassemia and β-thalassemia genes by routine deletion and mutation detection. According to DNA sequencing analysis, the patient had HBD: c.349 C>G variant. Conclusion:The low Hb A 2 content (reference value is 2.5% - 3.5%) in this case is due to the mutation of HBD, HBD: c.349 C>G variant is rare in Chinese population.

Objective:To investigate the regulatory effects and mechanism of mannose-binding lectin(MBL) on autophagy during the differentiation of 3T3-L1 adipocytes, and provide the feasibility for targeting autophagy to prevent obesity and related pathological conditions in natural immunity.Methods:3T3-L1 preadipocytes were cultured in vitro and induced to differentiation. Cell differentiation and lipid accumulation were analyzed by oil red O staining and CCK-8 was used to detect the effect of different concentrations of MBL (0, 1, 5, 10 μg/ml) on cell proliferation ability at different differentiation stages. Western blot was used to analyze the expression of MBL(10 μg/ml) on the key autophagy factors LC3B, Beclin1 and p62 protein at different stages of differentiation, and the changes of lipid droplet accumulation under the intervention of MBL were observed by oil red O staining. The protein and mRNA expression of autophagy key factors under the intervention of different concentrations of MBL were detected by Western blot and qRT-PCR. And autophagy flow analysis based on autophagic degradation was used to further illustrate the autophagic activity. The expression and phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling molecules were analyzed by Western blot. Results:The results of oil red O staining showed that 3T3-L1 preadipocytes could achieve complete differentiation after 10 days of induction. CCK-8 showed that the concentration of MBL (1-10 μg/ml) in the experimental group had no effect on cell proliferation at different differentiation stages. During the differentiation of 3T3-L1 preadipocytes, Western blot and qRT-PCR showed that the expression of autophagy-related proteins and mRNA levels was enhanced in the MBL treated group, and presented a concentration-dependent relationship. Oil red O staining showed that the lipid droplets in adipocytes at different stages of differentiation are reduced to varying degrees under the intervention of MBL. Fluorescence microscopy results further confirmed that MBL enhanced the autophagy activity of adipocytes by increasing the synthesis of autophagosomes. Moreover, under the intervention of MBL, the phosphorylation level of AMPK was significantly up-regulated, while the phosphorylation level of mTOR was significantly down-regulated, also showing a concentration-dependent relationship.Conclusions:MBL accelerates the autophagy process during the differentiation of 3T3-L1 adipocytes through AMPK/mTOR signaling pathway, reduces lipid accumulation, providing a possible functional pathway for the treatment of obesity and related metabolic diseases.

In order to study the signal pathway secreting type Ⅰ interferon in porcine alveolar macrophages (PAMs) infected with porcine circovirus type 2 (PCV2), the protein and the mRNA expression levels of cGAS/STING pathways were analyzed by ELISA, Western blotting and quantitative reverse transcriptase PCR in PAMs infected with PCV2. In addition, the roles of cGAS, STING, TBK1 and NF-κB/P65 in the generation of type I interferon (IFN-I) from PAMs were analyzed by using the cGAS and STING specific siRNA, inhibitors BX795 and BAY 11-7082. The results showed that the expression levels of IFN-I increased significantly at 48 h after infection with PCV2 (P<0.05), the mRNA expression levels of cGAS increased significantly at 48 h and 72 h after infection (P<0.01), the mRNA expression levels of STING increased significantly at 72 h after infection (P<0.01), and the mRNA expression levels of TBK1 and IRF3 increased at 48 h after infection (P<0.01). The protein expression levels of STING, TBK1 and IRF3 in PAMs infected with PCV2 were increased, the content of NF-κB/p65 was decreased, and the nuclear entry of NF-κB/p65 and IRF3 was promoted. After knocking down cGAS or STING expression by siRNA, the expression level of IFN-I was significantly decreased after PCV2 infection for 48 h (P<0.01). BX795 and BAY 11-7082 inhibitors were used to inhibit the expression of IRF3 and NF-κB, the concentration of IFN-I in BX795-treated group was significantly reduced than that of the PCV2 group (P<0.01), while no significant difference was observed between the BAY 11-7028 group and the PCV2 group. The results showed that PAMs infected with PCV2 induced IFN-I secretion through the cGAS/STING/TBK1/IRF3 signaling pathway.
Animals ; Cells, Cultured ; Circovirus ; Interferon Type I/genetics* ; Macrophages, Alveolar/virology* ; Membrane Proteins/metabolism* ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

Objective:To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation.Methods:We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes.Results:The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group ( P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size ( P=0.030), UCGD ( P=0.003) and lymphovascular invasion (LVI) ( P=0.032) were associated with disease recurrence. UCGD ( P=0.036) and LVI ( P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD ( P=0.001), LVI ( P=0.038) were the independent factors of disease recurrence. UCGD ( P=0.007) and LVI ( P=0.037) were also found to be the independent factors of disease progression. Conclusions:Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Objective:To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation.Methods:We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes.Results:The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group ( P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size ( P=0.030), UCGD ( P=0.003) and lymphovascular invasion (LVI) ( P=0.032) were associated with disease recurrence. UCGD ( P=0.036) and LVI ( P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD ( P=0.001), LVI ( P=0.038) were the independent factors of disease recurrence. UCGD ( P=0.007) and LVI ( P=0.037) were also found to be the independent factors of disease progression. Conclusions:Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Objective:To investigate the regulatory effects and mechanism of mannan-binding lectin (MBL) on adipogenic differentiation of 3T3-L1 preadipocytes.Methods:3T3-L1 preadipocytes were induced to differentiate into adipocytes in vitro, and stimulated with different concentrations of MBL (0, 1, 10, 20 μg/ml). Firstly, changes in cell proliferation ability were detected by CCK-8. Then lipid accumulation was analyzed by Oil red O staining and intracellular triglyceride content determination. Further, the expression of adipogenic differentiation-related factors PPARγ and C/EBPα at protein and mRNA levels were detected by Western blot and qRT-PCR, respectively. Finally, Western blot was used to analyze the expression and phosphorylation of Akt, a signal molecule related to adipogenic differentiation. Results:MBL at the concentrations of 0, 1, 10 and 20 μg/ml had no effect on the proliferation of 3T3-L1 preadipocytes. The level of triglyceride in MBL treatment groups decreased in a dose-dependent manner on 3 d after 3T3-L1 preadipocyte differentiation. Results of Oil red O staining showed that the number of lipid droplets in MBL treatment groups reduced significantly, and the absorbance values also decreased significantly in a concentration-dependent manner. Western blot and qRT-PCR results showed that the expression of PPARγ and C/EBPα at both protein and mRNA levels in MBL treatment groups decreased significantly in a dose-dependent manner, and the phosphorylation level of Akt was significantly down-regulated as well.Conclusions:MBL regulates the adipogenic differentiation of 3T3-L1 preadipocytes via Akt signaling pathway.

Provirus integration site Moloney murine leukemia virus (Pim-1) is a proto-oncogene reported to be associated with cell proliferation, differentiation and survival. This study was to explore the neuroprotective role of Pim-1 in a rat model subjected to optic nerve crush (ONC), and discuss its related molecules in improving the intrinsic regeneration ability of retinal ganglion cells (RGCs). Immunofluorescence staining showed that AAV2- Pim-1 infected 71% RGCs and some amacrine cells in the retina. Real-time PCR and Western blotting showed that retina infection with AAV2- Pim-1 up-regulated the Pim-1 mRNA and protein expressions compared with AAV2-GFP group. Hematoxylin-Eosin (HE) staining, γ-synuclein immunohistochemistry, Cholera toxin B (CTB) tracing and TUNEL showed that RGCs transduction with AAV2-Pim-1 prior to ONC promoted the survival of damaged RGCs and decreased cell apoptosis. RITC anterograde labeling showed that Pim-1 overexpression increased axon regeneration and promoted the recovery of visual function by pupillary light reflex and flash visual evoked potential. Western blotting showed that Pim- 1 overexpression up-regulated the expression of Stat3, p-Stat3, Akt1, p-Akt1, Akt2 and p-Akt2, as well as βIII-tubulin, GAP-43 and 4E-BP1, and downregulated the expression of SOCS1 and SOCS3, Cleaved caspase 3, Bad and Bax. These results demonstrate that Pim-1 exerted a neuroprotective effect by promoting nerve regeneration and functional recovery of RGCs. In addition, it enhanced the intrinsic regeneration capacity of RGCs after ONC by activating Stat3, Akt1 and Akt2 pathways, and inhibiting the mitochondrial apoptosis pathways. These findings suggest that Pim-1 may prove to be a potential therapeutic target for the clinical treatment of optic nerve injury.

The quality inspection of magnetic resonance imaging (MRI) performance parameters is an important means to ensure the image quality and the reliability of diagnosis results. There are some problems in the manual calculation and eye recognition of the quality inspection parameters, such as strong subjectivity and low efficiency. In view of these facts, an automatic analysis system for MRI quality detection based on QT is proposed and implemented in C++ language. The image processing algorithm is introduced to automatically measure and calculate the quality inspection parameters. The software with comprehensive functions is designed to systematically manage the quality inspection information of MRI. The experimental results show that the automatically calculated parameters are consistent with the manually calculated ones. Accordingly, the accuracy and reliability of the algorithm is verified. The whole system is efficient, convenient and easy to operate, and it can meet the actual needs of MRI quality inspection.
Algorithms ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; standards ; Reproducibility of Results

Through summarizing and analyzing a large number of documents and reports of large academic conferences in China, the current situation and the prospect of individualized drug delivery model were analyzed based on folate metabolic gene in pharmaceutical care. Folate metabolic genemethylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G were related with development of multiple diseases. Its polymorphism guidesindividualized drug administrationto increase the efficacy of drugs or decrease adverse effects.