Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

To examine the risk factors for developing diabetes on its 3-year outcome in an elderly population with impaired fasting glucose (IFG). We selected the 328 elderly with impaired fasting glucose in Binhai new area of Tianjin as the research object. All subjects participated in objective examinations such as physical activity ability tests, blood tests and anthropometric examinations, and completed the questionnaire survey. Between baseline and 3-year outcome, 56 of the subjects with IFG at baseline have developed diabetes. After multivariate adjustments, we found that higher incidence of diabetes was associated with higher fasting plasma glucose (OR=9.30, 95%CI 2.84-30.48, P<0.01) and reduced grip strength/weight (OR=0.88, 95%CI 0.82-0.94, P<0.01). Moreover, the combination of higher fasting plasma glucose and lower grip strength/weight would lead to higher incidence of diabetes compared with higher fasting plasma glucose or lower grip strength/weight alone (P<0.05). In this study, high fasting plasma glucose and low muscle strength were associated with blood glucose worsening in three years in IFG patients. In addition to blood glucose levels, physical activity is also a risk factor for diabetes in older adults.

OBJECTIVETo observe the effects of micro-invasive embedding combined with montelukast sodium and simple montelukast sodium for children cough variant asthma (CVA).

METHODSA total of 240 patients were randomly assigned into an observation group and a control group, 120 cases in each one. Considering of cases dropping, 101 patients in the observation group and 105 cases in the control group were included. Montelukast sodium chewable tablets were applied before sleep for 3 months in the control group, 5 mg a time, once a day. Based on the treatment as the control group, micro-invasive embedding was used for 3 months in the observation group, twice in the first month and once in the other two months. The acupoints were Feishu (BL 13), Danzhong (CV 17), Dingchuan (EX-B 1), and Zusanli (ST 36). Follow-up was conducted 9 months after treatment in the two groups. The cough score, serum immunoglobulin (IgE, IgG, IgA), platelet activating factor (PAF) were observed before and after treatment. The indices were compared before and after treatment and at follow-up, including pulmonary function indices[peak expiratory flow rate (PEF), forced expiratory volume at the 1st second (FEV1)], and small airway function indices[forced expiratory flow rate with remaining 25% vital capacity (MEF25%), forced expiratory flow rate with remaining 50% vital capacity (MEF50%), forced expiratory flow rate with remaining 75% vital capacity (MEF75%) and mid expiratory flow rate (MEF25%-75%)]. Also, the total effects were evaluated.

RESULTS①The total effective rate in the observation group was 93.1% (94/101), which was better than 87.6% (92/105) in the control group (<0.05). The cough disappearance time of the cured children in the observation group was (10.38±2.64) d, and it was shorter than (10.72 ±2.60) d of those in the control group (<0.05). After treatment, the cough score apparently decreased compared with those before treatment in the two groups (both<0.05), with better result in the observation group (<0.05). At follow-up, the recurrence frequency of the observation group was (1.43±1.20), and it was less than (1.91±1.71) in the control group (<0.05). ②The levels of serum IgA and IgG after treatment in the two groups increased, and those of serum IgE and PAF decreased, compared with those before treatment. There was statistically significance except IgG in the control group before and after treatment (all<0.05), with better Results in the observation group after treatment (all<0.05). ③ Compared with those before treatment, all the pulmonary function indices were improved obviously after treatment and at follow-up in the two groups (all<0.05), without statistically significance between the two groups (both>0.05). ④ There was no statistically significance before and after treatment on small airway function indices in the two groups (all>0.05). The indices at follow-up increased compared with those before treatment in the two groups (all<0.05), with better Results in the observation group (all<0.05).

CONCLUSIONSMicro-invasive embedding combined with montelukast sodium achieved de-finite effect for children CVA, which can improve the body's immune and microcirculation. The effect is better than that of simple montelukast sodium on improving small airway function, etc.