Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

Objective To investigate the expression of long non-coding RNA(lncRNA)small nucleolar RNA host gene(SNHG)25 and microRNA(miR)-497-5p in glioma tissues and their relationship with clinical features and prognosis.Methods A total of 157 glioma patients admitted to the hospital from January 2019 to January 2020 were selected as the glioma group,and 100 patients who underwent surgical treatment due to craniocerebral injury in the same hospital during the same period were selected as the control group.The ex-pression levels of lncRNA SNHG25 and miR-497-5p were detected in glioma tissues and normal brain tissues resected during operation.The patients were followed up for 3 years.The correlation between the expression levels of lncRNA SNHG25 and miR-497-5p was analyzed,and the relationship between the expression level of lncRNA SNHG25 and miR-497-5p and the clinical characteristics and prognosis of patients were analyzed.Re-sults Compared with the control group,the expression level of lncRNA SNHG25 in the glioma group was in-creased(P＜0.05),and the expression level of miR-497-5p was decreased(P＜0.05).Compared with the maximum diameter of tumors＜4 cm,World Health Organization(WHO)central nervous system tumor grade Ⅰ-Ⅱ,the expression level of lncRNA SNHG25 was increased and the expression level of miR-497-5p was decreased in glioma tissues with the maximum diameter of tumors ≥4 cm and WHO central nervous sys-tem tumor grade Ⅲ-Ⅳ(P＜0.05).The expression level of lncRNA SNHG25 in glioma patients was nega-tively correlated with miR-497-5p(r=-0.370,P＜0.05).The cumulative survival rate of lncRNA SNHG25 high expression group was lower than that of lncRNA SNHG25 low expression group(P＜0.05),and the cu-mulative survival rate of miR-497-5p low expression group was lower than that of miR-497-5p high expression group(P＜0.05).Grade Ⅲ-Ⅳ of WHO central nervous system tumor grade and high expression of lncRNA SNHG25 were risk factors for poor prognosis of glioma patients(P＜0.05),while high expression of miR-497-5p was a protective factor(P＜0.05).Conclusion The expression of lncRNA SNHG25 is increased and the expression of miR-497-5p is decreased in glioma tissues,which is related to the maximum diameter of tumor and high WHO central nervous system tumor grade,and can lead to poor prognosis of glioma patients.

Objective:To investigate the effects of 40 Hz and 70 Hz frequency flash stimulation on the ability of learning memory and autonomous exploratory in young rats.Methods:Twenty-seven SPF grade male SD rats aged 19-21 days were divided into control group (Ctr group), 40 Hz group and 70 Hz group with 9 in each group according to the random number table.The rats in Ctr group were not given flash stimulation, while rats in the 40 Hz and 70 Hz group were received 40 Hz, 70 Hz flash stimulation (1.5 h/d for 39 days), respectively.The Morris water maze experiment was used to assess the learning and memory ability of rats, and the open field experiment was used to evaluate the ability of autonomous exploratory of rats.Nissl staining was used to assess the morphology of Nissl bodies in the hippocampus CA1 region of the rats.The local field potentials (LFPs) collected from the primary visual cortex (V1 area) region by electrophysiological experiments was used to verify the synchronization of flash evoked neural oscillations.SPSS 23.0 software was used for statistical analysis.The repeated measures ANOVA and one-way ANOVA were used to analyze normal distribution measurement data, and LSD and Tamhane tests were used for further pairwise comparison.The Kruskal-Wallis test was used for non-normal distribution measurement data.Results:(1) The flash stimulation of 40 Hz and 70 Hz both can effectively caused synchronization of neural oscillations in the primary visual cortex of healthy young rats.(2) The results of repeated measures ANOVA analysis showed that there was no interaction effect of grouping and time in the escape latency of young rats in the Morris water maze positioning navigation phase( F=1.326, P>0.05 ). The escape latency had time main effect ( F=40.025, P<0.05), but no grouping main effect ( F=2.039, P>0.05). With the increase of learning days, the escape latency of young rats in each group decreased significantly.There was no interaction effect of grouping and time in the total distance of young rats ( F=2.029, P>0.079). It had time main effect ( F=32.052, P<0.05), but not grouping main effect ( F=2.390, P>0.05) on total distance.With the increase of learning days, the total distance of young rats in each group significantly shortened.On the 6th day of the Morris water maze experiment, there was no statistically significant difference among groups in terms of time in the target quadrant and the number of crossing platforms ( F=2.511, 0.802, both P>0.05). The results of the open field experiment showed that the total distance traveled in the center of young rats in each group was statistically significant ( H=8.935, P<0.05), the total distance traveled in the center in the 70 Hz group (3.80 (2.25, 6.93) m)was significantly longer than that in the 40 Hz group (0.80 (0.72, 1.46) m), P<0.05). The percentage of time spent in the center was statistically significant in the three groups ( H=11.050, P<0.05). Young rats in the 70 Hz group spent significantly higher percentage of time in the center(3.20(2.43, 8.30)) than those in the 40 Hz group (0.95 (0.37, 1.06 ), P<0.05 ). (3) Nissl staining results showed that Nissl bodies in the hippocampal CA1 area of young rats in Ctr, 40 Hz and 70 Hz group were all arranged neatly and tightly, no edema was found in the surrounding stroma, and no obvious inflammatory cell infiltration was found. Conclusion:70 Hz frequency flash stimulation may promote the ability of learning memory and autonomous exploratory of young rats.

Objective:To prepare 99Tc m-hydrazinonicotinamide(HYNIC)-αCD8/Fab ( 99Tc m-αCD8/Fab), and explore the predictive value of 99Tc m-αCD8/Fab SPECT/CT imaging for the efficacy of anti-programmed death-1 (PD-1) immunotherapy. Methods:The αCD8/Fab was modified with HYNIC- N-hydroxysuccinimide (NHS) and IRDye800-NHS to form HYNIC-αCD8/Fab and IRDye800-αCD8/Fab (Dye-αCD8/Fab), respectively. 99Tc m-αCD8/Fab was prepared in sodium bicarbonate buffer (pH=8.5), with SnCl 2 being used as the reducing agent. The labeling yield and radiochemical purity of 99Tc m-αCD8/Fab and its stability in PBS and fetal bovine serum (FBS) were tested in vitro. The mouse spleen and human peripheral blood lymphocytes were isolated for cell-specific binding and blocking experiments of 99Tc m-αCD8/Fab in vitro. SPECT/CT imaging was used to analyze the specific binding ability of the 99Tc m-αCD8/Fab probe in CT26 colon cancer mouse models (BALB/c). The near infrared fluorescence imaging and SPECT/CT imaging were performed to detect the intra-tumoral CD8 + T cell infiltration after anti-PD-1 therapy in tumor bearing mice, and the results were further verified by HE and immunofluorescence staining. CD8 + T cell depletion study was performed to determine the role of CD8 + T cells in the tumor responses to anti-PD-1 therapy. Two-way analysis of variance was used to compare the data difference. Results:The labeling yield of 99Tc m-αCD8/Fab was 90% with a high radiochemical purity (95%) and good stability in vitro (radiochemical purity still more than 80% after 720 min in PBS and FBS). 99Tc m-αCD8/Fab could specifically bind to mouse CD8 + T cells ((10.30±0.81) percent added radioactive dose (%AD)/10 6 cells), compared with the binding ability in human peripheral blood lymphocytes group and CD8 antibody blocking group ((1.78±0.61) and (1.59±0.25) %AD/10 6 cells; F=10.07, P<0.001). SPECT/CT imaging showed that 99Tc m-αCD8/Fab had markedly higher tumor uptake in the CT26 colon cancer mouse models. Near-infrared fluorescence imaging showed that the tumor uptake of 99Tc m-αCD8/Fab in the responsive group was significantly higher than in the nonresponsive group after anti-PD-1 treatment ((8.9±1.1)% vs (7.1±0.8)%; F=4.69, P=0.024), and SPECT/CT imaging found the similar result. HE and immunofluorescence staining of tumor and lymph nodes showed that the proportion of lymphocyte infiltration was higher in the responsive group. Furthermore, CD8 + T cell depletion significantly reversed the therapeutic effect of anti-PD-1 immunotherapy in tumor-bearing mice. Conclusions:In this study, 99Tc m-αCD8/Fab was successfully obtained. CD8-specific SPECT imaging could sensitively visualize the tumor-infiltrating CD8 + T cells, suggesting the potential application value to predict and evaluate the efficacy of immunotherapy in the clinical settings.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Objective: To study the effects of different holding gun methods and gun weight on health when standing guard, and propose a way to support the health of long-term standing guard soldiers. Methods: We created different percentile mannequins by Classic JACK, and adjusted the standing guard posture based on its standards for soldiers. The pressure on lumbar L4/L5 and moment on ankles and knees were analysied for different holding gun methods and gun weight. Then the mathematical models of joint load, gun weight and body mass index were studied by multiple regression analysis. Results: Holding gun methods and gun weight influence the force characteristics on ankles, knees and lumbar L4/L5. Holding gun with a brace and hands applying downward force -2 kgf could significantly reduce lumbar L4/L5 pressure. When the hand force is -5, -3, -4, -3, -2, -1, 0, 1, 2 kgf, and the weight of the gun is 0, Lumbar vertebrae L4/L5 joint pressure of people with different body mass index(P₁, P₅, P₅₅, P₉₅, P₉₉) are the smallest, respectively 269, 281, 321, 408, 444 N, and the same change trend occurs when the weight of the gun is 2, 4, and 8 kg.The moment on ankles and knees were less with the same holding gun method and the hands downward force ranged from 0 to -4 kgf, and the higher the body mass index is, the more the hands downward force needed to make the moment on ankles and knees zero. That is, the moment on ankles could be zero when the hands downward force ranged from -1 to -3 kgf, the moment on knees could be zero when the hands downward force ranged from -1.1 to -3.7 kgf. Conclusion To reduce the pressure on lumbar L4/L5 and moment on ankles and knees, so as to cut down occupational risk of long-standing operation, we advise the long-term standing guard soldiers holding gun with a brace and hands applying downward force -2 kgf.

Objective: To investigate the roles of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), retinoic acid-inducible geneⅠ-like receptors (RLRs) and nucleotide binding oligomerization domain-like receptors (NLRs) in the pathogenesis of dengue fever (DF) and the induction of immune responses to dengue virus. Methods: Blood samples were collected from patients with DF at three different time points to isolate peripheral blood mononuclear cells (PBMCs) by density gradient centrifugation. Then PBMCs were used to extract ribonucleic acid (RNA). Expression of genes was detected by polymerase chain reaction (PCR) array. Results: Expression of genes relating to PRRs signaling pathways in DF patients increased significantly in the early stage of the disease as compared with those in healthy controls, but decreased gradually during the recovery period. Expression of genes encoding TLR7 and TLR8 was enhanced at the early stage of DF. No significant changes in the expression of TLR3 and TLR9 genes were observed during the course of the disease. The genes encoding RIG-Ⅰ, MDA5 and LGP2 of RLRs family as well as NOD2 and OAS2 of NLRs family were all up-regulated. Conclusion Signaling pathways mediated by PRRs including TLR7/8, RIG-Ⅰ, MDA5 and so on play an important role in the pathogenesis of DF and the induction of immune responses to dengue virus.

Objective To observe the effects of liraglutide on GRP78,ATF4,CHOP and TRB3 protein and mRNA expression in rats which fed with high fat diet,and to explore the effect of liraglutide on ATF4/CHOP pathway of pancreas in rats fed with high fat diets.Methods Forty-four male Wistar rats were randomly divided into the control group,high fat group,intervention group 1 and intervention group 2,11 cases in each group.The control group was fed with common food,other 3 groups were fed with high fat diet for 8 weeks.Then the intervention group 1 was given with liraglutide (100 μg · kg-1 · d-1) by subcutaneous injection;the intervention group 2 was given liraglutide (200 μg · kg-1 · d-1) by subcutaneous injection.After 2 weeks medication intervention,the rats were killed.Five rats were taken from each group and performed the hyperinsulinemic englycemic clamp experiment under waking state for calculating the glucose infusion rate (GIR).The fasting blood glucose (FBG),fasting insulin (FINS),serum free fatty acid (FFA),total cholesterol (TC),triglyeeride (TG),low density lipoprotein cholesterol (LDL-C) and high density lipoprotein(HDL) were examined,and islet beta cell function index(HOMA-β) were calculated.PCR and Western blot method were used to detect the expression of pancreas GRP78,ATF4,CHOP and TRB3 protein and mRNA.Results Compared with the control group,the levels of FBG,FFA,TC,FINS,TG and LDL-C in the high fat group were significantly increased,the levels of HDL-C,GIR and HOMA-β were significantly decreased(P＜0.05 or P＜0.01);compared with the high fat group,the levels of HDL-C,GIR and HOMA-β in the intervention group 2 were increased(P＜0.05 or P＜0.01),the other indicators were significantly decreased;compared with the intervention group 1,blood FGB,FFA,TC in the intervention group 2 were decreased,while the levels of GIR and HOMA-β were increased(P＜0.05).Compared with the control group,expression of GRP78,ATF4,CHOP and TRB3 protein and mRNA in the high fat group were significantly increased;compared with the high fat group,the expression of GRP78,ATF4,CHOP and TRB3 protein and mRNA in the intervention group 1 and 2 were gradually decreased with the liraglutide concentration increase.Conclusion Liraglutide can improve insulin resistance and protect pancreatic beta cells in a concentration-dependent manner,its mechanisms may involve in the pancreatic endoplasmic reticulum ATF4/CHOP pathway.

Objective To investigate the dynamic changes of dengue viral loads and IgM antibody in patients with dengue fever ( DF) and to analyze their relationships with disease severity. Methods A to-tal of 1 508 serum samples were collected from 1 140 hospitalized patients including 1 050 mild cases and 90 severe cases within 10 days after the onset of DF in Guangzhou in 2014. The viral loads were determined by using fluorescence quantitative RT-PCR. ELISA was performed to measure the dengue virus ( DENV)-spe-cific IgM antibody. Results In general, the DENV viral loads in patients declined gradually from 108 copies/ml on day 1 to 103 copies/ml on day 10 after the onset of DF. The viral loads in severe cases were significantly higher than those in mild cases on days 5 to 7 (P<0. 05). The positive rates of DENV RNA in serum samples also decreased with the disease progression from 100% on day 1 to 40% on day 10. Com-pared with the mild cases, the patients with severe DF showed higher positive rates of DENV RNA on day 6 and day 8 (P<0. 05). The DENV-specific IgM antibody could be detected on day 2 and the secretion of IgM antibody increased gradually with the disease progression. The levels of IgM antibody in mild cases were sig-nificantly higher than those in severe cases (P<0. 001). The positive rates of IgM antibody in patients in-creased form 8% on day 2 to 95% on day 6. Higher positive rates of IgM antibody were detected in mild ca-ses on days 5 and 6 as compared with those in patients with severe DF (P<0. 05). Conclusion High viral load and low level of IgM antibody during the fastigium of DF were closely associated with the disease severity.

Objective To introduce the construction and clinical application of nursing assessment information model to prevent deep vein thrombosis ( DVT) . Methods The electronic nursing assessment sheet was designed and perfected, the correct rate and nursing assessment length of DVT were compared. Results After the application of DVT nursing assessment information model, the correct rate of DVT assessment increased from 80%to 98% (χ2 =49. 64,P<0. 01);the assessment length decreased from (5. 36 ± 3. 02)min to (1. 24 ± 2. 89)min (t=7. 63,P<0. 05). Conclusions The application of DVT nursing assessment information model can improve nursing staff members'work efficacy and protect patients'safety.