It is proposed that although allergic rhinitis manifests primarily in the nasal orifices， its root lies in deficiency of the lung and spleen and insecurity of the lung defensive qi， while deficiency of healthy qi with latent pathogen， triggering by external stimuli， and constraint of defensive yang constitute the key pathogenesis. The onset of disease is not caused solely by newly contracted external pathogens. Rather， on the basis of insecurity of the lung-defense qi， external stimuli such as wind-cold and abnormal qi， dust mites， pollen， and sudden climatic changes， activate the latent pathogen， resulting in constraint of defensive yang， disharmony between nutritive and defensive qi， impaired diffusion of lung qi， failure to contain body fluids， and dysfunction of the nasal orifices. The disease progression can be summarized as following steps， deficiency of healthy qi with latent pathogen， activation by external stimuli， constraint of defensive yang， dysfunction of the nasal orifices， incomplete elimination of the pathogen and incomplete recovery of healthy qi. The general therapeutic principle is to consolidate the defensive qi and vent the latent pathogen while regulating the lung and nasal orifices simultaneously. The empirical prescription Xingui Fangzhi Decoction （辛桂防芷汤） is used as the basic formula and modified dynamically according to the attack and remission stages. During the attack stage， treatment focuses on dispelling wind and cold， regulating defensive qi， and venting the latent pathogen； during the remission stage， it emphasizes supplementing qi， consolidating the defensive exterior， and reinforcing the spleen to resolve the latent pathogen.

Post-stroke cognitive impairment （PSCI） is a highly prevalent severe complication after stroke. In traditional Chinese medicines （TCM）， its core pathogenesis is characterized by deficiency in origin and excess in superficiality： wind， phlegm and blood stasis accumulate， cloud the clear orifices and lead to loss of mental activity， and Xingnao kaiqiao is the targeted principal treatment. This review summarizes the research progress on the pharmacological mechanisms of representative Xingnao kaiqiao-type TCM including Acorus tatarinowii ， Curcumae Radix ， Polygala tenuifolia ， borneol and musk， as well as clinical applications of their related compound formulas and Chinese patent medicines in the treatment of PSCI. The results show that these TCM can improve cognitive function through multiple pathways： targeted regulation of blood-brain barrier permeability， inhibition of neuroinflammation mediated by Toll like receptor 4/nuclear factor-κB， high mobility group protein B1 in ischemic brain tissue and other pathways， and activation of brain-derived neurotrophic factor/tyrosine kinase receptor B， cyclic adenosine monophosphate （cAMP）/protein kinase A/cAMP response element-binding protein and other pathways to promote synaptic plasticity. In terms of clinical application， the evidence chains of formulas based on Acorus tatarinowii and Polygala tenuifolia are relatively complete， which are the core medications to improve cognitive function and activities of daily living； Curcumae Radix has protective potential in the prodromal stage with vascular risk factors； borneol enhances the curative effect of compound prescriptions by improving blood-brain barrier function； musk is mainly used in the acute severe stage. At present， most of the mechanism evidence comes from animal experiments， high-quality large-sample clinical studies directly targeting PSCI populations are still scarce. Subsequent large-sample multicenter studies are needed in the future， combined with multi-omics and multimodal imaging techniques to further clarify its deep-seated mechanism of action.

Objective To investigate the research hotspots， development trends， and potential challenges in the field of stroke and exosomes based on bibliometric and visual analyses， and to provide scientific evidence for basic research and clinical translation. Methods The Web of Science database was used to obtain related articles published up to 2024， and CiteSpace and other tools were used to perform visual analyses from various aspects such as publication trends， collaboration networks， co-occurrence and clustering of keywords， and literature burst analysis. Results A total of 1 153 articles were included. The analysis showed an overall increasing trend in the number of publications per year. The institution with the highest number of publications was Henry Ford Health System， the author with the highest number of publications was Professor Chopp， and the journal with the highest number of articles Int J Mol Sci. High-frequency keywords included "extracellular vesicles" "ischemic stroke" and "stroke"， forming 12 research clusters， with neural repair and barrier protection as the key research directions. Conclusion The research on stroke and exosomes has been increasing year by year， with rapid development in recent years and the formation of an interdisciplinary pattern. Future studies should focus on the molecular mechanisms mediated by exosomes and their clinical application in stroke treatment， so as to promote the development of precision medicine and provide new therapeutic approaches.
Stroke ; Exosomes ; Bibliometrics

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

Objective To explore the mechanism of Tongdu Xingshen acupuncture,the clinical efficacy,systemic inflammatory response,blood-brain barrier and intestinal flora in patients with cognitive impairment after ischemic stroke(IS)were studied.Methods Thirty patients(3 cases shedding)with cognitive impairment after IS were included as the disease group,including patients before treatment as the disease group,patients after Tongdu Xingshen acupuncture treatment as the electroacupuncture group,and 30 healthy controls(3 cases shedding)were included as the healthy group.In the electroacupuncture group,on the basis of the basic treatment,Tongdu Xingshen acupuncture was applied,which was 30 min each time,once a day for 14 days.The MMSE,MoCA and MBI scores of the three groups were observed.The fecal and serum samples from all study subjects were collected,and 16S rDNA sequencing technology and ELISA were used to detect the changes of proinflammatory factors IL-6,IL-1β,TNF-α and S100β in serum in intestinal flora and feces.Results Compared with the healthy group,the MMSE,MoCA,and MBI score of patients in the disease group decreased significantly(P<0.05),serum proinflammatory factors and S100β protein content increased significantly(P<0.05),and the Shannon index(P<0.01)and Simpson index(P<0.001)increased significantly.Compared with the disease group,the MMSE,MoCA,and MBI score of the EA group increased significantly(P<0.05),the serum levels of proinflammatory factors and S100β decreased significantly(P<0.05),Shannon index and Simpson index decreased(P>0.05).The dominant bacterial flora in the healthy group mainly included Bacteroides,Bifidobacterium,Bacteroides,Faecalibacterium,Bifidobacteriaceae,Ruminococcaceae,and Bacteroides and other beneficial bacteria(P<0.05).The dominant flora in the disease group included Proteobacteria,Enterobacteriaceae,Escherichia,Klebsiella and other opportunistic bacteria(P<0.05),while the dominant flora in the EA group was consistent with the healthy group,the relative abundance of beneficial bacteria increased significantly(P<0.05),and the relative abundance of opportunistic bacteria decreased significantly(P<0.05).Spearman correlation analysis found that beneficial bacteria were positively correlated with clinical efficacy related indicators,but with serum proinflammatory factors and the content of S100β was negatively correlated.Conclusion Tongdu Xingshen acupuncture can regulate the diversity of intestinal flora to increase the abundance of Bacteroides,Bifidobacterium,Faecalibacterium,and other beneficial bacteria,regulate the intestinal microecological balance,Thereby regulating systemic inflammation and blood-brain barrier function,which plays a role in improving cognitive function.

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

Objective To explore the mechanism of Tongdu Xingshen acupuncture,the clinical efficacy,systemic inflammatory response,blood-brain barrier and intestinal flora in patients with cognitive impairment after ischemic stroke(IS)were studied.Methods Thirty patients(3 cases shedding)with cognitive impairment after IS were included as the disease group,including patients before treatment as the disease group,patients after Tongdu Xingshen acupuncture treatment as the electroacupuncture group,and 30 healthy controls(3 cases shedding)were included as the healthy group.In the electroacupuncture group,on the basis of the basic treatment,Tongdu Xingshen acupuncture was applied,which was 30 min each time,once a day for 14 days.The MMSE,MoCA and MBI scores of the three groups were observed.The fecal and serum samples from all study subjects were collected,and 16S rDNA sequencing technology and ELISA were used to detect the changes of proinflammatory factors IL-6,IL-1β,TNF-α and S100β in serum in intestinal flora and feces.Results Compared with the healthy group,the MMSE,MoCA,and MBI score of patients in the disease group decreased significantly(P<0.05),serum proinflammatory factors and S100β protein content increased significantly(P<0.05),and the Shannon index(P<0.01)and Simpson index(P<0.001)increased significantly.Compared with the disease group,the MMSE,MoCA,and MBI score of the EA group increased significantly(P<0.05),the serum levels of proinflammatory factors and S100β decreased significantly(P<0.05),Shannon index and Simpson index decreased(P>0.05).The dominant bacterial flora in the healthy group mainly included Bacteroides,Bifidobacterium,Bacteroides,Faecalibacterium,Bifidobacteriaceae,Ruminococcaceae,and Bacteroides and other beneficial bacteria(P<0.05).The dominant flora in the disease group included Proteobacteria,Enterobacteriaceae,Escherichia,Klebsiella and other opportunistic bacteria(P<0.05),while the dominant flora in the EA group was consistent with the healthy group,the relative abundance of beneficial bacteria increased significantly(P<0.05),and the relative abundance of opportunistic bacteria decreased significantly(P<0.05).Spearman correlation analysis found that beneficial bacteria were positively correlated with clinical efficacy related indicators,but with serum proinflammatory factors and the content of S100β was negatively correlated.Conclusion Tongdu Xingshen acupuncture can regulate the diversity of intestinal flora to increase the abundance of Bacteroides,Bifidobacterium,Faecalibacterium,and other beneficial bacteria,regulate the intestinal microecological balance,Thereby regulating systemic inflammation and blood-brain barrier function,which plays a role in improving cognitive function.

Objective: To investigate the daily learning time status of elementary school students and understand the implementation of Health Requirements of Daily Learning Time for Secondary and Elementary School Students (GB/T 17223-2012) in schools, so as to provide a reference for strengthening and improving school health and health education in the new era. Methods: A stratified cluster random sampling method was used to select 7 776 primary school students in Shandong Province, and a survey questionnaire was designed based on the Health Requirements for Dayily Learning Time for Secondary and Elementary School Students(GB/T 17223-2012) standard to investigate their daily learning arrangements, sleep and physical activities, and breaks between classes. Comparison of intergroup differences were used by Chi square test and Kruskal-Wallis H test. Results: About 55.88 % of primary school students for daily learning time met the standard. There was a statistically significant difference in the daily learning time achievement rate among primary school students in three grades for first and second grade, third and fourth grade and fifth and sixth grade ( Z=1 629.47, P <0.01), and the fifth and sixth grade had the highest proportion of achieving the standard (85.92%). Specifically, the proportions of students whose class hours, class numbers and morning reading time meeting the standards were 30.07%, 10.20% and 42.19%, respectively. The sleep deficiency rate of primary school studnets was 58.69%, and the physical activity deficiency rate was 65.78%; and there was a statistically significant difference in the rate of insufficient sleep time and physical activity time among primary school students of different grades ( χ 2=56.39, 95.95, P <0.01), with sixth grade students showing the highest rates for both sleep and physical activity deficiencies (64.35%, 73.37%). Additionally, 49.78% of students had recess time below the standard requirements. Conclusion The health status of daily learning time among primary school students in Shandong Province is poor, with insufficient implementation of school standards, and the implementation of standards needs to be further strengthened.

Objective: To understand the implementation of daily study time standard among secondary school students in Shandong Province, so as to provide scientific basis for the formulation and implementation of relevant policies. Methods: From January to May 2023, a multi stage random sampling method was used to select 8 725 middle school students in Shandong Province. A survey questionnaire was designed based on the Requirements for Daily Study Time of Primary and Secondary School Students(GB/T 17223-2012), to investigate indicators such as students daily learning schedule, sleep and physical activity time, break time and scheduling requirements. Results: The compliance rates for daily study time in junior and senior high school students in Shandong Province were 29.2% and 23.6%, respectively, with a statistically significant difference ( χ 2=33.63, P <0.01). Compliance rates for sleep duration, physical activity and recess time, morning and afternoon class hours, and class duration were 19.3%, 26.2%, 30.5%, 73.2% and 16.2%. Class duration compliance was relatively high, with rates of 96.7% in junior high and 94.4% in senior high school students. There was a statistically significant difference in compliance rates for extended class breaks between different educational stages ( χ 2= 81.78, P <0.01), with rates of 84.6% in junior high and 83.4% in senior high school students. As students progressed through their educational stages, compliance rates for physical activities, class breaks, consecutive classes, and total weekly class hours showed a decreasing trend, with rates of 31.8% and 18.3%, 35.7% and 23.1%, 60.5% and 29.6%, 55.2% and 35.1% in junior and senior high school students, respectively. Conclusions The revised standard of Requirements for Daily Study Time of Primary and Secondary School Students(GB/T 17223-2012) optimizes the daily study and life schedule of middle school students to a certain extent. However, daily study time for middle school students in Shandong Province exceeds standard. Relevant departments need to enhance their ability to implement standards and strengthen the supervision of policy standards implementation.

Objective To investigate the inhibitory effects and mechanisms of α-hederin,an active ingredient in Fruc-tus Akebiae,on hepatocellular carcinoma(HCC)cells.Methods HCC cells were divided into four groups and treated with α-hederin(0,10,20,and 30 μmol·L-1)for 24 h and 48 h,respectively.MTT assays were used to detect the cell proliferation rate,flow cytometry(FCM)was used to detect the apoptotic rate,transcriptomics was used to screen signaling pathways in α-hederin-treated HCC cells,RNA interference was exploited to verify the underlying signaling pathway,and real-time quantitative PCR(qRT-PCR)and Western blotting(WB)were used to detect expression changes of the mRNA and protein of TP53(p53),PMAIP1(Noxa),and apoptosis-associated proteins,Caspase9 and Caspase3.Results α-Hederin induced apoptosis by activa-ting apoptosis-associated proteins,PARP,Caspase9 and Caspase3.Transcriptomics,qRT-PCR,and WB results also showed that α-hederin increased the mRNA and protein expression of p53 and Noxa.Furthermore,α-hederin inhibited the protein degradation of p53 and Noxa,reversing the apoptosis decrease in p53/Noxa siRNA-knocked-down HCC cells.In vivo results showed that α-hederin inhibited the growth of HCC tumors.Conclusion α-hederin may induce the apoptosis of HCC cells by activating and stabilizing the p53/Noxa signaling pathway.