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Objective To observe the therapeutic effect of inosine on diabetic cognitive impairment (DCI) in rats and to explore its mechanism. Methods SD male rats were randomly divided into the control group, model group, and experimental group, respectively. Rats in the model group and experimental group were treated with high-fat diet combined with the intraperitoneal injection of streptozotocin and were screened out by Morris water maze experiment to obtain the DCI models, except rats in the control group. After successful modeling, rats in the experimental group were intraperitoneally injected with 100 mg/kg inosine, and rats in the control group and the model group were intraperitoneally injected with the same volume of normal saline, once a day, for 4 weeks. Morris water maze test was used to detect the cognitive ability of rats. HE staining was used to observe the morphology of hippocampal neurons. ELISA was used to detect the levels of tumor necrosis factor- α (TNF- α), interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in hippocampus. RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of phosphatidylinositol-3-kinase (PI3K/protein kinaseB (AKT/mammalian target of rapamycin (mTOR) signaling pathway. Results Compared with the control group, the escape latency increased, and the number of crossing the platform decreased in the model group (both P<0. 05). Compared with the model group, the escape latency decreased, and the number of crossing the platform increased in the experimental group (both P<0. 05). In the model group, the hippocampal neurons were loosely arranged and irregularly shaped, and the number was significantly reduced. The hippocampal neurons of the experimental group were relatively neatly arranged and the morphology was regular, and the number increased. Compared with the control group, the levels of TNF-α, IL-1β, IL-6, and MDA in the hippocampus of the model group increased, and the levels of SOD and GSH-Px decreased (all P<0. 05). Compared with the model group, the levels of TNF-α, IL-1β, IL-6, and MDA in the hippocampus of the experimental group decreased, and the levels of SOD and GSH-Px increased (all P<0. 05). The mRNA expression levels of PI3K, AKT, and mTOR and the protein expression levels of PI3K, p-AKT, and p-mTOR were lower in the model group than in the control group (all P< 0. 05). The mRNA expression levels of PI3K, AKT, and mTOR and the protein expression levels of PI3K, p-AKT, and pmTOR in the experimental group were higher than those in the model group (all P<0. 05). Conclusions Inosine can improve the cognition and learning memory in DCI rats, thus alleviating cognitive impairment. The mechanism may be related to activating PI3K/AKT/mTOR signaling pathway and reducing inflammatory response and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective To compare the clinical efficacy, adverse events, and immunological function status after medication of icotinib and gefitinib in the treatment of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations. Methods A total of 176 patients with EGFR mutation⁃positive lung adenocarcinoma confirmed by pathological biopsy at Guangxi Medical University Cancer Hospital from January 2012 to December 2019 were selected as the objects of study, and divided into the icotinib group and gefitinib group according to the targeted treatment regimen. The treatment efficacy were evaluated according to the RECIST 1.1 standard. The incidence of adverse reactions, differences of cellular immunity and humoral immunity indexes were compared between the two groups. Results There was no significant difference between icotinib and gefitinib in terms of objective response rate (60.0% vs 63.2%), disease control rate (94.0% vs 92.1%), median progression⁃free survival (9.5 months vs 8.9 months), median overall survival (21.7 months vs 18.5 months ) as well as overall incidence of adverse reactions (31.0% vs 34.2%) (all P>0.05) . There was no significant difference of cellular immune indicators (CD3+T cells, CD4+T cells, CD8+T cells, CD4+/CD8+, natural killer cells) and humoral immune indicator IgM between two groups (all P>0.05). However, the levels of humoral immune indicators IgG and IgA in gefitinib group were higher than those of icotinib group (all P<0.05). Conclusions The clinical efficacy and adverse events of icotinib and gefitinib are similar in the treatment of advanced lung adenocarcinoma patients with EGFR mutation⁃positive. The cellular immune functions of the two groups are also similar, but the levels of humoral IgG and IgA in gefitinib group are slightly higher than those in icotinib group. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression, distribution, and activity of thyroid-stimulating hormone receptor (TSHR) in human microglia (HMC3). Methods In this study, we used human microglial cells (HMC3) as the experimental group and human thyroid cells and hepatocytes as the controls. Reverse transcription polymerase chain reaction was used to detect the expression of TSHR mRNA to identify the transcript of TSHR mRNA. Western blotting and immunofluorescence staining analysis was used to detect TSHR protein level and the distribution in HMC3 cells. HMC3 cells were divided into the 0, 20, 50, 100, 200 ng/mL thyroid-stimulating hormone receptor-stimulating antibody (TSAb) groups and negative control group. Each group was preincubated with 100 µmol/L phosphodiesterase inhibitor (IBMX) for 60 minutes. The corresponding concentrations of TSAb were added to cells of the TSAb groups and then they were incubated for 24 h. We measured cyclic adenosine monophosphate (cAMP) levels by immu noassay kits to verify the functional activity of TSHR in HMC3 cells. Results TSHR mRNA was detected in HMC3 cells with the same sequence as mRNAs derived from human thyroid cells and hepatocytes. TSHR protein was expressed in the cell membrane of HMC3 cells. Compared with the 0 ng/mL TSAb group, there was no significant statistical difference in cAMP levels in the 20 ng/mL TSAb group. However, cAMP levels increased in the 50, 100, and 200 ng/mL TSAb groups, and the high-concentration group had higher cAMP levels than the low-concentration group (P<0.05 or P<0.01). Conclusion TSHR is expressed in the cell membrane of human microglia and has a signaling function. [ABSTRACT FROM AUTHOR]