Objective To investigate the effects of cinnamic aldehyde(CA)on Bcl-2-associated X protein(Bax)and Bcl-2 homologous antagonist/killer(Bak)in vascular endothelial cells of diabetic ulcer wound tissues,as well as on cell apoptosis.Methods ① Forty-eight healthy SPF-grade male SD rats(5 weeks old,weighing 180～220 g)were randomly assigned to a control group(12 rats)and a diabetes group(36 rats).The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding.The diabetes group was further randomly divided into Model group,CA group,and the rb-bFGF group,with 12 animals in each group.Wounds in the Con and Model groups were disinfected and topically treated with normal saline,CA group received topical application of 4 μmol/L CA in PEG 400 gel,and those of the rb-bFGF group were treated with bevacizumab gel.The wound healing rate of each group was calculated at 3,7 and 14 d after intervention.At 14 d after intervention,pathological changes in the wounds were observed with HE staining,and the expression levels of Bax and Bak were detected by Western blotting.② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury.The experimental cells were divided into control group,model group and CA treatment group.Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells.The expression levels of Bax and Bak was detected with immunofluorescence assay,and cell apoptosis was detected by TUNEL staining.Results ①The diabetic rats in the Model group exhibited significantly higher blood glucose level(P<0.05),declined wound healing rate at 7 and 14 d after intervention(P<0.05),and enhanced expression levels of Bax and Bak(P<0.05)when compared with the control group.Pathological observation revealed that,at 14 d after intervention,accompanied with inflammatory reactions,dense infiltration of inflammatory cells,fewer new blood vessels,and continuous fluid exudation in the wound were observed in the Model group,but the control group presented complete epithelialization in full-thickness skin.Compared with the conditions in the Model group,both CA and rb-bFGF treatment improved the epithelialization process,with mature granulation tissues,showing good healing condition,promoted wound healing rate(P<0.05),and decreased the expression levels of Bax and Bak(P<0.05).② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability(P<0.05),reduced protein levels of Bax and Bak(P<0.05),and lower apoptotic rate(P<0.05)when compared with the cells in the model group.Conclusion CA can inhibit the expression of apoptosis-related proteins Bax and Bak,promote the migration and tube formation of vascular endothelial cells,and inhibit the cell apoptosis under high glucose condition,which may be an important reason for its promoting wound healing in diabetic ulcer rats.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective:To systematically evaluate whether the early use of bracing after posterior lumbar fusion has advantages in terms of the improvement of clinical outcomes such as pain, functional disability, fusion rate, and complication rate in patients with lumbar degenerative diseases.Methods:All randomized controlled trials of bracing performed after posterior lumbar fusion in patients with lumbar degenerative diseases were searched in Pubmed, Web of Science, Embase, China national knowledge infrastructure (CNKI) and Wanfang database from January 1990 to May 2022. The data extracted were authors, year of publication, nationality, subject characteristics, sample size, surgical protocol, type and time of bracing, follow-up duration, preoperative and postoperative Oswestry disability index (ODI) and visual analogue scale (VAS), postoperative fusion rate and complication rate. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The use of fix- or random-effect models was depended on the magnitude of heterogeneity. Data analysis was performed using Stata 17.0 statistical software for meta analysis.Results:A total of five randomized controlled trials were included, all in English, with a total of 362 patients (male 144, female 218). The results of meta-analysis showed that there was no statistically significant difference in the improvement of ODI scores [ MD=1.25, 95% CI(-2.39, 4.88), P=0.501]and VAS scores[ MD=0.21, 95% CI(-0.22, 0.63), P=0.340]between the brace group and the control group after operation. In terms of fusion rate, there was no significant difference between the brace group and the control group[ OR=0.59, 95% CI(0.25, 1.38), P=0.224]. In addition, there was also no significant difference in the incidence of postoperative complications between two groups[ OR=1.12, 95% CI(0.58, 2.15), P=0.735]. Conclusion:The early use of bracing after lumbar fusion has no significant advantages in improving symptoms and functional recovery, fusion rate and surgical complications. The necessity of postoperative bracing after posterior lumbar fusion requires further high-quality research to prove.