Ischemic stroke(IS)is the most common type of stroke,and the treatment of acute ischemic stroke(AIS)is highly time-dependent.There is considerable individual heterogeneity in the tolerance of brain tissues to ischemia,and some patients may still be benefitted from treatment beyond conventional time window.The application of multimodal imaging in evaluating the core infarct area and ischemic penumbra enabled individualized treatment decisions guided by"tissue window",hence significantly expanded treatment opportunities for patients beyond conventional time window.The application value of multimodal imaging in screening ones able to be benefitted from treatment beyond conventional time window,treatment decision-making and predicting prognosis of AIS patients beyond conventional time window,as well as the challenges and future directions of multimodal imaging in this field were reviewed in this article.

BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

Objective:To investigate the possibility of 1,8-cineole in the prevention of Streptococcus mutans(S.mutans)induced dental caries in rats.Methods:40 specific pathogen-free rats were randomly divided into 5 groups(n=8):distilled water group(negative control group),chlorhexidine group(positive control group),and eucalyptin low(MIC),medium(2MIC)and high(4MIC)dose groups.The plates were streaked with saliva samples,and calculated the number of S.mutans colonies and the ratio of the total number of colonies.Keyes' method was used to evaluate the caries damage of the jaws specimens.Results:At the end of the experiment,the proportion(％)of S.mutans in the oral cavity of the drug groups decreased(P＜0.000 1),but there was no significant difference between the drug group and the positive control group(P＜0.05).At the end of the experiment,compared with the negative control group,the scores of each grade in the drug group decreased(P＜0.05),but there was no significant differ-ence between positive control group and each 1,8-cineole group(P＞0.05),and among the 3 1,8-cineole dose groups(P＞0.05).Conclusion:1,8-cineole at the MIC can inhibit the growth of S.mutans in the oral cavity of rats with dental caries and reduce the frequency and severity of dental caries.

Ischemic stroke(IS)is the most common type of stroke,and the treatment of acute ischemic stroke(AIS)is highly time-dependent.There is considerable individual heterogeneity in the tolerance of brain tissues to ischemia,and some patients may still be benefitted from treatment beyond conventional time window.The application of multimodal imaging in evaluating the core infarct area and ischemic penumbra enabled individualized treatment decisions guided by"tissue window",hence significantly expanded treatment opportunities for patients beyond conventional time window.The application value of multimodal imaging in screening ones able to be benefitted from treatment beyond conventional time window,treatment decision-making and predicting prognosis of AIS patients beyond conventional time window,as well as the challenges and future directions of multimodal imaging in this field were reviewed in this article.

Objective:To investigate the possibility of 1,8-cineole in the prevention of Streptococcus mutans(S.mutans)induced dental caries in rats.Methods:40 specific pathogen-free rats were randomly divided into 5 groups(n=8):distilled water group(negative control group),chlorhexidine group(positive control group),and eucalyptin low(MIC),medium(2MIC)and high(4MIC)dose groups.The plates were streaked with saliva samples,and calculated the number of S.mutans colonies and the ratio of the total number of colonies.Keyes' method was used to evaluate the caries damage of the jaws specimens.Results:At the end of the experiment,the proportion(％)of S.mutans in the oral cavity of the drug groups decreased(P＜0.000 1),but there was no significant difference between the drug group and the positive control group(P＜0.05).At the end of the experiment,compared with the negative control group,the scores of each grade in the drug group decreased(P＜0.05),but there was no significant differ-ence between positive control group and each 1,8-cineole group(P＞0.05),and among the 3 1,8-cineole dose groups(P＞0.05).Conclusion:1,8-cineole at the MIC can inhibit the growth of S.mutans in the oral cavity of rats with dental caries and reduce the frequency and severity of dental caries.

BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

[Objective]To summarize and analyze the research progress of flavonoids in the prevention and treatment of diabetes mellitus and its complications.[Methods]The role of flavonoids in diabetes mellitus and diabetic complications was summarized by searching the databases of Web of Science,PubMed,China National Knowledge Infrastructure,VIP,Wanfang and others for the reports of flavonoids and diabetes mellitus and diabetic complications from January 2013 to December 2022,and the role of flavonoids in diabetes mellitus and diabetic complications was summarized.[Results]Studies have confirmed that flavonoids(herbal flavonoid extracts,naringenin,galangal,kaempferol,etc.)are effective in preventing and treating diabetes and diabetes-induced retinopathy,nephropathy,cardiomyopathy,osteoporosis and diabetic foot.Overall regulation and comprehensive treatment are the characteristics of flavonoid components,which can inhibit inflammation,reduce oxidative stress,repair mitochondrial function,lower blood glucose,relieve insulin resistance and are able to influence the expression of related factors from multiple signaling pathways,thus treating diabetes and its complications.[Conclusion]The elaboration of the pharmacodynamic material basis,mechanism of action and constitutive relationship of Chinese medicine flavonoids against diabetes mellitus and its complications in multiple ways and at multiple levels are key issues to be solved in the development of flavonoids and an important direction for future research.

Objective:To explore the clinical and imaging characteristics of patients with unruptured intracranial aneurysms accompanied by sentinel headache.Methods:Forty patients with unruptured intracranial aneurysms confirmed by DSA/CTA and accompanied by sentinel headache admitted to Department of Neurology, First Affiliated Hospital of Xiangnan University from January 2018 to August 2023 were selected as the study subjects; the clinical and imaging characteristics of these patients were summarized. Forty-four patients with unruptured intracranial aneurysms without sentinel headache and 40 patients with subarachnoid hemorrhage caused by ruptured intracranial aneurysms admitted to the hospital at the same period were selected as controls. The differences in aneurysm length (maximum diameter), morphology, tumor length (maximum diameter)/neck width (AR), and risk score for rupture of intracranial aneurysms (scores of population, hypertension, age, size of aneurysm, earlier aneurysm rupture, site of aneurysm [PHASES]) among the 3 groups were analyzed.Results:Among the 40 patients with unruptured intracranial aneurysms accompanied by sentinel headache, 20 (50%) presented with pain localized at the lateral frontal and orbital regions, 3 (7.5%) with pain at the posterior neck region, and 17 (42.5%) with irregular headache sites; 34 (85%) had new onset headache, and 6 (15%) had changes in headache nature besides chronic headache; 24 patients (60%) had posterior communicating artery aneurysm, 12 (30%) had internal carotid artery aneurysm, 1 (2.5%) had middle cerebral artery aneurysm, and 3 (7.5%) had vertebral artery dissection aneurysm; 36 (90%) had irregular aneurysm morphology. Compared with patients with unruptured intracranial aneurysms without sentinel headache, patients with unruptured intracranial aneurysms accompanied by sentinel headache and those with subarachnoid hemorrhage caused by ruptured intracranial aneurysms had larger aneurysm length (maximum diameter), higher proportion of irregular morphology, higher AR value, and higher PHASES scores, with significant differences ( P<0.05). Compared with patients with subarachnoid hemorrhage caused by ruptured intracranial aneurysms, patients with unruptured intracranial aneurysms accompanied by sentinel headache had larger aneurysm length (maximum diameter) and higher PHASES scores, with significant differences ( P<0.05). Conclusion:Sentinel headache is common in patients with unruptured posterior communicating artery aneurysms, and the relatively specific headache pattern is sudden periorbital pain or posterior neck pain; patients with unruptured intracranial aneurysms accompanied by sentinel headache have a higher rupture risk due to the larger size, more irregular shape, higher AR value of the aneurysm, therefore, same attention should be payed to these patients as those with ruptured aneurysms in clinical practice.