Vascular cognitive impairment (VCI) is a progressive cognitive impairment caused by cerebrovascular disease or vascular risk factors. It is the second common type of cognitive impairment after Alzheimer's disease. VCI can be caused by a variety of signal and metabolic pathways. Its core mechanism is that cerebrovascular disease destroys the neurovascular unit composed of neurons, glial cells, and cerebrovascular endothelial cells. This article summarizes and discusses the known mechanisms of VCI, in order to deepen the understanding of the molecular pathological process of VCI and provide ideas for its prevention and treatment.

Objective To investigate the effects of desmopressin acetate and pituitrin on the proliferation,contraction,and secretion of hepatic stellate cells (HSCs).Methods The human HSC cell line LX-2 was selected as the research model.And three groups were designed:blank control group,desmopressin acetate group (three subgroups:1 × 10-10 mol/L,1 × 10-9 mol/L,and 1 × 10-8 mol/L desmopressin acetate),and pituitrin group (three subgroups:0.1 U/L,1.0 U/L,and 10.0 U/L pituitrin).Water-soluble tetrazolium salt (WST)-1 assay was used to evaluate cell proliferation;collagen gel contraction assay was used to assess cell contraction;enzyme-linked immunosorbent assay (ELISA) was used to identify cell secretion.The data was subjected to one-way analysis of variance.Results (1) The results of WST-1 assay showed that the values of A450 in three desmopressin acetate subgroups (1× 10-10 mol/L,1 × l0-9 mol/L,and 1 × 10-8 mol/L) were 0.459±0.017,0.467±0.024,and 0.436±0.015,respectively.And the values of A450 in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 0.495±0.011,0.507±0.015,and 0.501±0.009,respectively.Compared with the control group,the desmopressin acetate at high concentration significantly inhibited the cell proliferation (P ＜ 0.05),but the pituitrin at three different concentrations significantly promoted the cell proliferation (P ＜ 0.05).(2) The collagen gel area ratios in three desmopressin acetate subgroups (1 × 1010 mol/L,1 × 10-9 mol/L,and 1 × 10-8 mol/L) were 77.07±4.42,75.85±3.70,and 72.74±3.92,respectively.And the collagen gel area ratios in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 57.83±3.96,50.28±6.69,and 43.56±7.68,respectively.Compared with the control group,the pituitrin at three different concentrations significantly reduced the collagen gel area (P ＜ 0.01).(3) The matrix metalloproteinase (MMP)-2 concentrations in three desmopressin acetate subgroups (1× 10-10 mol/L,1 × 10-9 mol/L,and 1×108 mol/L) were 13.321±0.098,12.230±0.153,and 12.061±0.126,respectively.And the MMP-2 concentrations in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 12.899±-0.150,13.662±0.152,and 13.698±0.119,respectively.Compared with the control group,the desmopressin acetate at low concentration significantly increased the secretion of MMP-2 (P ＜ 0.01);the desmopressin acetate at high concentration significantly decreased the MMP-2 concentration (P ＜ 0.05);the pituitrin at three different concentrations significantly increased the MMP-2 concentration (P ＜ 0.01).The transforming growth factor-beta 1 (TGF-β1) concentrations in three desmopressin acetate subgroups (1×10-10 mol/L,1×10-9 mol/L,and l×10-8 mol/L) were 5.233±0.102,17.749±0.188,and 36.060±0.227,respectively.And the TGF-β1 concentrations in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 15.615±0.099,38.460±0.209,and 49.053±0.115,respectively.Compared with the control group,desmopressin acetate and pituitrin significantly promoted the secretion of TGF-[β1 in a concentration-dependent manner (P ＜ 0.01) and pituitrin had a stronger effect than desmopressin acetate (P ＜ 0.01).Desmopressin acetate and pituitrin had no effect on the secretion of the collagenase type Ⅰ and Ⅲ (P ＞ 0.05).Conclusion Desmopressin acetate and pituitrin can induce the changes in the function and morphology of HSCs and may increase vascular resistance in the hepatic sinus.However,desmopressin acetate has less influence on HSCs than pituitrin.

ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang （GQT） on intestinal mucosal barrier function in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups （n=8 per group）： blank group， model group， mesalazine sustained-release granule group （0.52 g·kg^-1）， high-dose GQT group （2.23 g·kg^-1）， and low-dose GQT group （1.12 g·kg^-1）. Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index （DAI） of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin （HE） staining and Alizarin blue-periodic acid-Schiff （AB-PAS） staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 （ZO-1） and mucin 2 （MUC2）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pro-inflammatory cytokines interferon-γ （IFN-γ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-17A， and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets （Th1， Th17）， regulatory T cells （Treg）， and regulatory B cells （Breg） in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet， forkhead box protein P3（FoxP3）， nuclear transcription factor（NF）-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， signal transducer and activator of transcription 3（STAT3）， and phosphorylated STAT3 （p-STAT3）. ResultsCompared with the model group， both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores （P<0.05）， alleviated colonic inflammation， and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group， both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion， indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue （P<0.05）， suppressed IFN-γ， IL-6， and TNF-α secretion （P<0.05）， elevated IL-10 secretion （P<0.05）， but had no significant effect on IL-17A. At the same time， high- and low-dose GQT intervention increased the activation of CD4⁺ FoxP3⁺ Treg cells （P<0.05） and suppressed activation of CD4⁺ IFN-γ⁺ Th1 cells （P<0.05）. Western blot showed that GQT downregulated T-bet， NF-κB p65， and STAT3 protein expression （P<0.05）， upregulated FoxP3 （P<0.05）， and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 （P<0.05）. ConclusionGQT can upregulate the activation of CD4⁺ FoxP3⁺ Treg cells， reduce the activation of CD4⁺ IFN-γ⁺ Th1 cells， inhibit the secretion of IFN-γ， IL-6， and TNF-α， and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue， thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways， ultimately regulating the activation of transcription factors T-bet and FoxP3.