Objective:To observe the protective effects and possible mechanisms of dexmedetomidine(DEX)on hippocampal tissues of chronic sleep deprived(CSD)rats.Methods:Healthy male rats were divided into Control group,CSD group,CSD+DEX group,DEX group,and CSD+DEX+ANA-12 group.The CSD model was established by the modified multi-platform method(MMPM),and the rats were deprived of sleep for 18 hours per day for 21 days.DEX was combined with tyrosine kinase receptor B antagonist(ANA-12)for intervention.Starting at 7 days post sleep deprivation for 14 days.At the end of modeling,brain-derived neurotrophic factor(BDNF)protein in hippocampal neu-rons was determined by immunohistochemical staining;pro-inflammatory cytokines in hippocampal tissue homogenates were assessed by enzyme-linked immunosorbent assay;tyrosine kinase receptor B(TrkB)signaling proteins and cyste-ine protein hydrolase 3(caspase-3)were detected by Western blot.Results:Compared with the Control group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD group were significantly increased(P<0.05),while the expression level of BDNF in the hippocampal CA1 region was markedly reduced(P<0.05);Compared with the CSD group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD+DEX group were significantly reduced(P<0.05),while the expression level of BDNF in the CA1 region of the hippocampus was markedly increased(P<0.05);Compared with the CSD+DEX group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD+DEX+ANA-12 group were signifi-cantly increased(P<0.05),while the expression level of BDNF in the CA1 region of the hippocampus was markedly decreased(P<0.05).Conclusion:DEX inhibited CSD-induced hippocampal tissue damage.The possible mechanism is related to the regulation of BDNF/TrkB signaling by DEX.

Objective:To observe the protective effects and possible mechanisms of dexmedetomidine(DEX)on hippocampal tissues of chronic sleep deprived(CSD)rats.Methods:Healthy male rats were divided into Control group,CSD group,CSD+DEX group,DEX group,and CSD+DEX+ANA-12 group.The CSD model was established by the modified multi-platform method(MMPM),and the rats were deprived of sleep for 18 hours per day for 21 days.DEX was combined with tyrosine kinase receptor B antagonist(ANA-12)for intervention.Starting at 7 days post sleep deprivation for 14 days.At the end of modeling,brain-derived neurotrophic factor(BDNF)protein in hippocampal neu-rons was determined by immunohistochemical staining;pro-inflammatory cytokines in hippocampal tissue homogenates were assessed by enzyme-linked immunosorbent assay;tyrosine kinase receptor B(TrkB)signaling proteins and cyste-ine protein hydrolase 3(caspase-3)were detected by Western blot.Results:Compared with the Control group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD group were significantly increased(P<0.05),while the expression level of BDNF in the hippocampal CA1 region was markedly reduced(P<0.05);Compared with the CSD group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD+DEX group were significantly reduced(P<0.05),while the expression level of BDNF in the CA1 region of the hippocampus was markedly increased(P<0.05);Compared with the CSD+DEX group,the expression levels of IL-1β,IL-6,TNF-α and caspase-3 in the hippocampus of rats in the CSD+DEX+ANA-12 group were signifi-cantly increased(P<0.05),while the expression level of BDNF in the CA1 region of the hippocampus was markedly decreased(P<0.05).Conclusion:DEX inhibited CSD-induced hippocampal tissue damage.The possible mechanism is related to the regulation of BDNF/TrkB signaling by DEX.

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective To investigate the value of CT value in differential diagnosis of benign and malignant thyroid calcification.Methods The CT plain scan data of 48 cases of thyroid benign calcification and 26 cases of thyroid malignant calcification confirmed by pathology were analyzed retrospectively,and the CT values of 74 cases of thyroid calcification were measured.The best threshold and the maximum area under the receiver operator characteristic(ROC)curve for differentiating benign and malignant thyroid calcification were determined by plotting ROC curve,and the corresponding specificity,sensitivity,positive predictive value,negative predictive value,false positive rate,false negative rate,accuracy and Jordan index were calculated.Then the optimal threshold value was used as a parameter for differential diagnosis of benign and malignant thyroid calcification,and we adoptted χ2 analyze the statistical difference between benign and malignant thyroid calcification in CT gray value.Results The area under the ROC curve was 0.814,and the 95%confidence interval(CI)was 0.712-0.915.When the CT value was 869.5HU(for the convenience of 870HU),the specificity was 69.2%,the sensitivity was 81.3%,the positive predictive value was 64.3%,the negative predictive value was 82.6%,the false positive rate was 20.8%,and the false negative rate was 30.8%,the accuracy was 75.7%and the maximum of the Youden index was 0.505.When 870HU was taken as the differential diagnosis parameter of thyroid benign and malignant calcification(χ2=16.795,P<0.001).Conclusion When the CT value is 870HU,it has important value in differential diagnosis of benign and malignant thyroid calcification.

Objective:To observe the protective effect and possible mechanism of stellate ganglion block(SGB)on spatial learning memory function impairment in rapid eye movement sleep deprived(RSD)rats.Methods:Thirty-two rats were randomly assigned to Control group,RSD group,SGB group,and rapid eye movement sleep deprivation with stellate ganglion block intervention(RSD+SGB)group.The rats in RSD group and RSD+SGB group were modeled by modified multi-platform method(MMPM),and the rats in SGB group and RSD+SGB group were intervened by the SGB method.Morris water maze(MWM)was selected to evaluate the spatial learning and memory functions of rats in each group,and the expression levels of glutamate(Glu)and aspartate(Asp)in hippocampal tissues of rats in each group were detected by colorimetric assay,and the expression levels of N-methyl-D-aspartate receptor 1(NR1)and caspase-3 in hippocampal tissues of rats in each group were detected by Western Blot.Results:Compared with the RSD group,rats in RSD+SGB group had a significantly shorter escape latency after SGB intervention(P＜0.05),while the number of passes through the original platform position and the percentage of target quadrant time were significantly in-creased(P＜0.05);at the same time,the hippocampal tissues'expression levels of Glu,Asp,NR1,and caspase-3 were all significantly reduced(P＜0.05).Conclusion:SGB protects against RSD-induced impairment of spatial learn-ing memory capacity by reducing hippocampal tissue excitotoxicity and apoptosis induced by excitatory amino acid hyper-activation in RSD rats.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Objective:To establish a quick and convenient method for detecting human adenoviruses (Human adenoviruses, HAdV) based on immunochromatographic assay (ICA).Methods:Two antibody clones, 3C11 and 7E6 were found to bind to all tested HAdVs and then subsequently processed into ICA. The specificity and sensitivity were evaluated using representative strains of the respiratory HAdV types, including HAdV-1, 2, 3, 4, 5, 6, 7, 10 and a gastroenteric type HAdV-41 together with the original throat swabs of 10 HAdV patients confirmed by nuclear acid testing (NAT).Results:The ICA exhibited high specificity to HAdVs and its detection limitation ranged from 0.16 to 10 3 half tissue culture infectious dose (TCID 50)/ml for different types of HAdVs. All clinic samples with successful virus isolation tested by this ICA showed positive result . Conclusions:The ICA developed in the present study will be suitable for HAdVs screening in clinic setting, especially for those of respiratory types.