Objective To investigate the effect of long-term high-fat diet on cognitive function and hippocampus neurons ultrastructure in obese rats.Methods Forty SD rats were randomly assigned to a high fat diet (HFD) group and a common diet (CD) group.Meanwhile,HFD-induced obese rat model were established.The spatial learning and memory were measured by the Morris water maze,and the neurons ultrastructural changes in rat hippocampus CA1 region at the corresponding period were observed by transmission electron microscopy.Results The average weight of rats was 25％,28％,and 22％ higher in the HFD group than in the CD group at the 12,16,and 20 weeks,respectively;the Lee's indexes were 6％,4％,and 8％ higher;the average swimming latency were 52％,44％,and 40％ longer;the average swimming distance were 85％,45％,and 51％ longer;the average swimming speed were 57％,34％,and 18％ higher;the duration of staying in the target quadrant were 32％,54％,and 63％ shorter;and the average times of crossing the plate form were 30％,34％,and 34％ shorter,respectively (all P ＜0.001).In comparison of ultrastructure in hippocampus CA1 region of rats at corresponding time points,the amounts of degenerated and necrosis neurons,of the deformed and vacuolar mitochondria,and of the less rough endoplasmic reticulum were significantly more at 12,16,and 20 weeks in the HFD group than in the CD group.Conclusions Long-term HFD-induced obesity damages the structure of neurons in the hippocampus,impairs spatial learning and memory function,and accelerates cognitive aging in rats.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.