ObjectiveTo investigate the effects of Astragali Radix polysaccharides （APS） on the polarization of BV2 microglial cells in an oxygen-glucose deprivation/reoxygenation （OGD/R） model through regulation of the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe OGD/R injury model of BV2 microglia was established and divided into blank group， OGD/R group and APS group （0.4 g·L^-1 APS）. Neuroinflammatory injury was induced by lipopolysaccharide （LPS） and treated with APS. The cells were divided into blank group， LPS group （1 mg·L^-1 LPS） and APS group （0.4 g·L^-1 APS+1 mg·L^-1 LPS）. Cell viability was detected using the cell counting kit-8 （CCK-8） assay. Cell morphology was observed under an inverted microscope. Nitric oxide （NO） content in the cell supernatant was determined by the Griess assay. The secretion levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， IL-10， and IL-4 were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the double-positive rates of ionized calcium-binding adapter molecule-1/inducible nitric oxide synthase （Iba-1⁺/iNOS⁺） and ionized calcium-binding adapter molecule-1/arginase 1 （Iba-1⁺/Arg1⁺）， as well as the nuclear translocation rate of nuclear factor-κB p65 （NF-κB p65）. Protein expression levels of Iba-1， iNOS， Arg1， TLR4， and NF-κB p65 were detected by Western blot. ResultsIn the OGD/R injury model， compared with the blank control group， BV2 microglial cells in the OGD/R group were activated and exhibited amoeboid morphological changes. The secretion levels of NO， TNF-α， and IL-6 were significantly increased （P<0.01）. The double-positive expression rate of Iba-1⁺/iNOS⁺ and the protein expression of Iba-1 and iNOS were significantly increased （P<0.01）. The nuclear translocation rate of NF-κB p65 and the protein expression levels of TLR4 and NF-κB p65 were significantly increased （P<0.01）. The levels of IL-10 and IL-4 were significantly decreased （P<0.01）， and the double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the OGD/R group， the APS group （0.4 g·L^-1） showed reduced cell activation， significantly decreased secretion levels of NO， TNF-α， and IL-6 （P<0.01）， significantly decreased double-positive expression rate of Iba-1⁺/iNOS⁺ and relative protein expression of Iba-1 and iNOS （P<0.01）， significantly decreased nuclear translocation rate of NF-κB p65 and protein expression levels of TLR4 and NF-κB p65 （P<0.01）， significantly increased levels of IL-10 and IL-4 （P<0.01）， and significantly increased double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression （P<0.01）. In the LPS-induced neuroinflammation model， compared with the blank control group， the LPS group showed increased cell activation， significantly increased levels of NO， TNF-α， and IL-6， significantly increased Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the LPS group， the APS group showed reduced cell activation， significantly decreased levels of NO， TNF-α， and IL-6， Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly increased （P<0.01）. ConclusionAPS may reduce microglial activation and promote their polarization toward the M2 phenotype by inhibiting activation of the TLR4/NF-κB signaling pathway， thereby alleviating the neuroinflammatory response induced by OGD/R.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Objective To develop a reminiscence therapy program with Montessori educational philosophy in treatment of elderly people with mild cognitive impairment(MCI)in nursing homes and evaluate its effect.Methods On the basis of Montessori education principles,a reminiscence therapy program was drafted through literature review and had it finalised with expert consultations and a pilot study.Between February and May 2022,70 elderly with MCI were recruited from a nursing home in Liaoning Province using convenience sampling.The recruited elderly were randomly divided into a control group(n=35)and an intervention group(n=35)using a random number table.The elderly in control group received conventional cognitive training only while the elderly in the intervention group received reminiscence therapy in addition to the conventional cognitive training.Cognitive function and ability of daily living(ADL)were compared between the two groups after a 6-week intervention.Results The elderly in intervention group demonstrated statistically significant improvements in both cognitive function and dimensions(visuospatial/executive function,naming ability,delayed recall and orientation,as well as in ADL after a 6-week intervention(all P<0.05).Conclusion The Montessori philosophy based on reminiscence therapy improves cognitive function and activities of daily living in the elderly with MCI,particularly from the perspectives of visuospatial/executive function,naming ability,delayed recall and orientation.

Objective:To explore the effects of circular non coding RNA(Circ)_BICD2 on the proliferation,apoptosis and epithe-lial mesenchymal transformation(EMT)of oral squamous cell carcinoma(OSCC)cells by regulating microRNA(miR)-218-5p/Ras homologous gene family member A(RHOA)axis.Methods:The mRNA expression level of Circ_BICD2,miR-218-5p and RHOA in OSCC cells of Cal-27,SCC-25,SCC-9 and HSC-3,and oral keratinocytes HOK was detected by qRT-PCR.SCC-25 cells were di-vided into control group,sh BICD2 group,sh NC group,sh BICD2+miR-218-5p inhibitor group and sh BICD2+inhibitor NC group.Apoptosis,proliferation,EMT-related protein and RHOA expression were respectively examined.The targeting relationship between miR-218-5p and Circ_BICD2 and RHOA respectively was verified.Results:miR-218-5p has targeted binding sites with Circ_BICD2 and RHOA,respectively.The expression levels of Circ_BICD2,RHOA mRNA and miR-218-5p were the most significant in SCC-25 cells(P＜0.05).Interference of BICD2 decreased Circ_BICD2 and RHOA expression,upregulated miR-218-5p,inhibited cell proliferation and EMT,and promoted apoptosis,miR-218-5p inhibitor reversed the malignant behavior inhibition effect by the in-terference of BICD2 on SCC-25 cells.Conclusion:Interference of Circ_BICD2 can inhibit the proliferation and EMT transformation of SCC-25 cells and induce their apoptosis,which may be related to the regulation of miR-218-5p/RHOA axis.

Objective:To explore the effects of circular non coding RNA(Circ)_BICD2 on the proliferation,apoptosis and epithe-lial mesenchymal transformation(EMT)of oral squamous cell carcinoma(OSCC)cells by regulating microRNA(miR)-218-5p/Ras homologous gene family member A(RHOA)axis.Methods:The mRNA expression level of Circ_BICD2,miR-218-5p and RHOA in OSCC cells of Cal-27,SCC-25,SCC-9 and HSC-3,and oral keratinocytes HOK was detected by qRT-PCR.SCC-25 cells were di-vided into control group,sh BICD2 group,sh NC group,sh BICD2+miR-218-5p inhibitor group and sh BICD2+inhibitor NC group.Apoptosis,proliferation,EMT-related protein and RHOA expression were respectively examined.The targeting relationship between miR-218-5p and Circ_BICD2 and RHOA respectively was verified.Results:miR-218-5p has targeted binding sites with Circ_BICD2 and RHOA,respectively.The expression levels of Circ_BICD2,RHOA mRNA and miR-218-5p were the most significant in SCC-25 cells(P＜0.05).Interference of BICD2 decreased Circ_BICD2 and RHOA expression,upregulated miR-218-5p,inhibited cell proliferation and EMT,and promoted apoptosis,miR-218-5p inhibitor reversed the malignant behavior inhibition effect by the in-terference of BICD2 on SCC-25 cells.Conclusion:Interference of Circ_BICD2 can inhibit the proliferation and EMT transformation of SCC-25 cells and induce their apoptosis,which may be related to the regulation of miR-218-5p/RHOA axis.

Purpose To investigate the feasibility of a deep learning framework to automatically analyze echocardiographic color Doppler videos in detecting valvular regurgitation.Materials and Methods This study retrospectively collected echocardiographic images of 1 109 patients with valvular regurgitation in the Fourth Medical Center of PLA General Hospital,from June 2015 to September 2019 as the training and validation sets.A prospective continuous collection of 1 562 echocardiography images was used as the test set in the Fourth Medical Center of PLA General Hospital from May 13 to June 13,2023,including 378 cases of mitral regurgitation and 223 cases of aortic regurgitation.This study developed deep learning networks to establish view classification model and valvular regurgitation recognition model,including the efficiency of section classification of deep learning models.Results The deep learning view classification model in this study could automatically identify two views for diagnosing mitral regurgitation and aortic regurgitation.The recognition accuracy for the parasternal long axis color Doppler view and the apical four chamber mitral color Doppler view was 1.00 and 0.93,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model for diagnosing mitral regurgitation were 0.847,0.852,0.849 and 0.930,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model in diagnosing aortic regurgitation were 0.857,0.861,0.859 and 0.940,respectively.Conclusion Deep learning algorithms can automatically identify valvular regurgitation and have the potential to become a screening tool for valvular heart disease.

Objective To develop a reminiscence therapy program with Montessori educational philosophy in treatment of elderly people with mild cognitive impairment(MCI)in nursing homes and evaluate its effect.Methods On the basis of Montessori education principles,a reminiscence therapy program was drafted through literature review and had it finalised with expert consultations and a pilot study.Between February and May 2022,70 elderly with MCI were recruited from a nursing home in Liaoning Province using convenience sampling.The recruited elderly were randomly divided into a control group(n=35)and an intervention group(n=35)using a random number table.The elderly in control group received conventional cognitive training only while the elderly in the intervention group received reminiscence therapy in addition to the conventional cognitive training.Cognitive function and ability of daily living(ADL)were compared between the two groups after a 6-week intervention.Results The elderly in intervention group demonstrated statistically significant improvements in both cognitive function and dimensions(visuospatial/executive function,naming ability,delayed recall and orientation,as well as in ADL after a 6-week intervention(all P<0.05).Conclusion The Montessori philosophy based on reminiscence therapy improves cognitive function and activities of daily living in the elderly with MCI,particularly from the perspectives of visuospatial/executive function,naming ability,delayed recall and orientation.

Objective:To explore the role of retinoic acid-related orphan receptor α (RORα) in cognitive impairment induced by chronic alcohol consumption in mice.Methods:(1)The SPF grade RORαflox/flox transgenic mice aged 8 weeks were generated, and 22 transgenic mice were evenly divided into two groups by the method of matching body mass, which were the control group (Con group) and the alcohol group (EtOH group), with 11 mice in each group.(2)Emx1-Cre transgenic mice were used to selectively knock out the RORα gene in the forebrain of RORαflox/flox transgenic mice, producing conditional knockout mice (cKO mice) with the genotype RORαflox/flox-Emx1-Cre+ /+. Fourteen cKO mice were further split into two groups by the method of matching body mass, which were the conditional knockout group (cKO group) and the conditional knockout + alcohol group (cKO + EtOH group), with 7 mice in each group. A chronic alcohol use cognitive impairment model was developed in the EtOH group and cKO + EtOH group through the two-bottle free-choice method, while the Con group and cKO group were given two bottles of water for the same period. Cognitive abilities of mice in all groups were evaluated using behavioral novel object recognition test and Y-maze test.RORα mRNA and protein expression levels in the hippocampus of the Con group and EtOH group were assessed by RT-qPCR and Western blot, respectively.The GraphPad Prism 9.0 software was used for data analysis.One-way ANOVA was used for the comparison of multiple groups and Tukey test was used for further pairwise comparisons.Results:(1) Comparison between Con group and EtOH group: the relative levels of ROR α protein (0.63±0.04) and mRNA (0.78±0.03) in the hippocampus of mice in the EtOH group were significantly lower than those in the Con group((1.00±0.06), (1.00±0.05), both P<0.05). The duration of the EtOH group in the Y maze was significantly lower than that of the Con group ((212.30±32.05) s, (129.30±21.50) s, P<0.05), and the new object recognition index of the EtOH group was lower than that of the Con group ((14.73±25.49)% vs (-15.55±27.88)%, P=0.08). (2)Comparison between Con group and cKO group: the frequency and duration of entering the Y maze of mice in the cKO group ((7.43±2.30) times, (124.10±13.95) s) were lower than those in the Con group ((14.90±3.65) times, (212.30±32.05) s, both P<0.05). There was no statistically significant difference in the new object recognition index between the cKO group and the Con group ( P>0.05). (3) Comparison between the cKO+ EtOH group and the cKO group: the frequency ((2.71±1.11)times) and duration ((161.70±17.95) s) of entering the new heteroarm of Y maze in the KO+ EtOH group were lower than those in the cKO group ((7.43±2.30) times, (124.10±13.95) s, both P<0.05), and there was no statistically significant difference in the new object recognition index ( P>0.05). (4) Comparison between the cKO+ EtOH group and the EtOH group: the frequency of entering new heteroarm of the Y maze in the cKO+ EtOH group ((2.71±1.11)times) was significantly lower than that in the EtOH group (12.18±4.49) ( P<0.05), while there was no statistically significant difference in other behavioral results between the two groups ( P>0.05). Conclusion:Chronic alcohol consumption leads to cognitive impairment through the downregulation of RORα in the hippocampus of mice. Specific knockout of RORα in the forebrain exacerbates cognitive impairment induced by chronic alcohol use. RORα may represent a potential therapeutic target for cognitive impairment resulting from chronic alcohol consumption.

Objective:To explore the role of retinoic acid-related orphan receptor α (RORα) in cognitive impairment induced by chronic alcohol consumption in mice.Methods:(1)The SPF grade RORαflox/flox transgenic mice aged 8 weeks were generated, and 22 transgenic mice were evenly divided into two groups by the method of matching body mass, which were the control group (Con group) and the alcohol group (EtOH group), with 11 mice in each group.(2)Emx1-Cre transgenic mice were used to selectively knock out the RORα gene in the forebrain of RORαflox/flox transgenic mice, producing conditional knockout mice (cKO mice) with the genotype RORαflox/flox-Emx1-Cre+ /+. Fourteen cKO mice were further split into two groups by the method of matching body mass, which were the conditional knockout group (cKO group) and the conditional knockout + alcohol group (cKO + EtOH group), with 7 mice in each group. A chronic alcohol use cognitive impairment model was developed in the EtOH group and cKO + EtOH group through the two-bottle free-choice method, while the Con group and cKO group were given two bottles of water for the same period. Cognitive abilities of mice in all groups were evaluated using behavioral novel object recognition test and Y-maze test.RORα mRNA and protein expression levels in the hippocampus of the Con group and EtOH group were assessed by RT-qPCR and Western blot, respectively.The GraphPad Prism 9.0 software was used for data analysis.One-way ANOVA was used for the comparison of multiple groups and Tukey test was used for further pairwise comparisons.Results:(1) Comparison between Con group and EtOH group: the relative levels of ROR α protein (0.63±0.04) and mRNA (0.78±0.03) in the hippocampus of mice in the EtOH group were significantly lower than those in the Con group((1.00±0.06), (1.00±0.05), both P<0.05). The duration of the EtOH group in the Y maze was significantly lower than that of the Con group ((212.30±32.05) s, (129.30±21.50) s, P<0.05), and the new object recognition index of the EtOH group was lower than that of the Con group ((14.73±25.49)% vs (-15.55±27.88)%, P=0.08). (2)Comparison between Con group and cKO group: the frequency and duration of entering the Y maze of mice in the cKO group ((7.43±2.30) times, (124.10±13.95) s) were lower than those in the Con group ((14.90±3.65) times, (212.30±32.05) s, both P<0.05). There was no statistically significant difference in the new object recognition index between the cKO group and the Con group ( P>0.05). (3) Comparison between the cKO+ EtOH group and the cKO group: the frequency ((2.71±1.11)times) and duration ((161.70±17.95) s) of entering the new heteroarm of Y maze in the KO+ EtOH group were lower than those in the cKO group ((7.43±2.30) times, (124.10±13.95) s, both P<0.05), and there was no statistically significant difference in the new object recognition index ( P>0.05). (4) Comparison between the cKO+ EtOH group and the EtOH group: the frequency of entering new heteroarm of the Y maze in the cKO+ EtOH group ((2.71±1.11)times) was significantly lower than that in the EtOH group (12.18±4.49) ( P<0.05), while there was no statistically significant difference in other behavioral results between the two groups ( P>0.05). Conclusion:Chronic alcohol consumption leads to cognitive impairment through the downregulation of RORα in the hippocampus of mice. Specific knockout of RORα in the forebrain exacerbates cognitive impairment induced by chronic alcohol use. RORα may represent a potential therapeutic target for cognitive impairment resulting from chronic alcohol consumption.

At present,with the development of new diagnostic technologies,the detection rate of aortic dissection has been increasing year by year,but its mortality rate still remains high.Cardiovascular disease is a chronic inflammato-ry disease,and vascular inflammation plays a major role in the progression of aortic dissection.Therefore,this article sys-tematically describes the specific roles and mechanisms of inflammatory cells,inflammatory factors,and inflammasomes in the development of aortic dissection.