Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective: To understand the potential categories of health risk behaviors among adolescents in the Wuling Mountain Area and their association with school connectedness, so as to provide reference for formulating classified and effective intervention measures. Methods: From March to June 2023, 3 386 middle and high school students from eight schools in the Wuling Mountain Area were selected using the multistage stratified cluster random sampling method. A basic information questionnaire, health risk behaviors questionnaire, and school connectedness scale were utilized for the survey. The latent classes of adolescent health risk behaviors in the Wuling Mountain Area were investigated by using latent class analysis, while an multinomial Logistic regression model was employed to analyze the association between latent classes and school connectedness. Results: Adolescent health risk behaviors in the Wuling Mountains Area were classified into three latent classes: high risk class of episodic behaviors ( 5.64 %), high risk class of implicit behaviors (26.90%), and low risk class of implicit behaviors (67.45%). Gender, ethnicity, and family type revealed significant differences in the distribution of the three latent classes ( χ 2=117.91, 22.55, 21.51, P <0.05). The results of the regression model analysis showed that, with the low risk class as the reference category, high school connectedness scores were associated with the high risk class of episodic behaviors ( OR=0.89, 95%CI = 0.88- 0.91) and the high risk class of implicit behaviors ( OR=0.90, 95%CI =0.89-0.91)( P <0.05). Conclusions The characteristics of adolescent health risk behavior classes in the Wuling Mountain Area are obvious. The high risk class of episodic behaviors and the high risk class of implicit behaviors are negatively correlated with school connectedness. Corresponding measures should be taken to enhance adolescents sense of belonging in school and reduce the aggregation and co occurrence of health risk behaviors.

Objective To explore the mechanism of Baihu Decoction in the treatment of acute lung injury based on network pharmacology and molecular docking technology;To carry out experimental verification.Methods The active components and targets of Baihu Decoction were searched through TCMSP and BATMAN-TCM databases,and human gene searches were conducted in GeneCards,NCBI,and OMIM databases.PPI network construction and GO and KEGG pathway enrichment analysis were conducted to determine the important signaling pathways of Baihu Decoction and acute lung injury.Molecular docking of main active components and core target proteins was performed.The effects of Baihu Decoction on survival rate and inflammatory cytokine content in acute lung injury lethal model mice were observed through animal experiments.Results Totally 211 common targets for Baihu Decoction and acute lung injury were screened,and identified effective components such as quercetin,kaempferol,and stigmasterol,etc.Analysis of KEGG pathway enrichment indicated that Baihu Decoction exerted its pharmacological effects in acute lung injury through a variety of signal pathways,including Toll-like receptor signaling pathway,NOD-like receptor signaling pathway,T cell receptor signaling pathway,and MAPK signaling pathway.Molecular docking results showed that Baihu Decoction had good binding strength with MAPK14,STAT3,JUN,MAPK1,MAPK3,FOS and RELA.The results of animal experiments showed that compared with the model group,the survival rate of mice in the Baihu Decoction group was significantly increased,the degree of pathological injury in the lung tissue was reduced,and serum IL-6,TNF-α contents decreased significantly(P<0.05).Conclusion Baihu Decoction can treat acute lung injury by reducing pathological injury to lung tissue and releasing of inflammatory factors.

Objective: To monitor the prevelance of Neisseria meningitidis among healthy children and adolescents aged 3-18 in Anhui Province, so as to provide support for epidemic cerebrospinal meningitis prevention and control. Methods: From September to October in 2021 and 2022, 4 033 healthy children and adolescents aged 3-18 were selected by stratified random sampling from Anhui Province, including areas north of the Yangtze River (Bozhou, Fuyang, Bengbu, Huainan, Chuzhou, Hefei) and areas south of the Yangtze River (Wuhu, Maanshan, Tongling, Anqing, Chizhou, Xuancheng) and the secretions of children and adolescents were collected from the posterior pharyngeal wall above the uvula, and the strains were identified by bacterial culture and nucleic acid detection. McNemar test and Kappa consistency test were used for statistical analysis. Chisquare test and Chisquare trend test were used to compare the rates. Results: The carrier rates of Neisseria meningitidis were 0.47% and 1.07%, respectively. The sensitivity of nucleic acid detection was higher. Among the detected bacteria, group B accounted for the largest proportion of 76.74%. It was followed by group C (4.65%), group Y (4.65%), group W 135 (2.33%) and group X (2.33%). The bacteria bearing rate of male students was higher than that of female students (χ2=11.44); with the increase of age, the bacteria bearing rate of children and adolescents showed an increasing trend (χ2trend=42.69); the bacterial bearing rate of children and adolescents in the north of the Yangtze River was higher than that in the south of the Yangtze River (χ2=23.19); the bacteria bearing rate of children and adolescents without immune history was higher than that with immune history (χ2=11.02)(P<0.01). Conclusions Neisseria meningitidis group B has become an epidemic strain in Anhui Province, and senior children and adolescents have become the key population of epidemic prevention and control. It is necessary to continue to do a good job in the surveillance of epidemic cerebrospinal meningitis disease and focuse on group B disease cases, so as to prevent the occurrence of cluster outbreaks in schools.

Objective: To explore the causal relationship between adolescent school connectedness and the co-occurrence with health risk behaviors among junior high school students, so as to provide the reference for reducing the occurrence of adolescents health risk behaviors among junior high school students. Methods: A total of 924 students from two junior high schools in Jishou City were selected by the convenience sampling and cluster sampling methods, and two follow up surveys were conducted at 6 month intervals in April (T1) and October (T2) of 2023 using the Adolescent Health Risk Behavior Questionnaire and the School Connection Scale. The scores of the co-occurrence of school connectedness and health risk behaviors among junior high school students were compared by different survey periods and genders using the t-test, and cross lagged analyses were performed using Mplus 8.3 software. Results: School connectedness scores among junior high school students in T1 and T2 surveys were (38.86±7.46) (37.87± 7.71 ) and co-occurrence of health risk behaviors scores were (1.64±0.68) (1.83±0.53), respectively, and the differences between the scores of the 2 surveys were statistically significant ( t=4.24, -4.14, P <0.05). The correlation between school connectedness and co-occurrence of health risk behaviors were statistically significant in both surveys ( r =-0.46 to -0.33, P <0.05). Cross lagged analyses showed that school connectedness in T1 negatively predicted the co-occurrence of health risk behaviors in T2 ( β =-0.08), and the co-occurrence of health risk behaviors in T1 negatively predicted the school connectedness in T2 ( β =-0.15) ( P <0.05). Conclusions There is a longitudinal causal relationship between school connectedness and co-occurrence of health risk behaviors among junior high school students. School connectedness should be improved through various ways to reduce the co-occurrence of health risk behaviors.

Objective: To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents. Methods: A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence. Results: The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05). Conclusion The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.

ObjectiveTo investigate the effect and mechanism of modified Shuyuwan （SYW） on hippocampal myelin sheath injury in vascular dementia （VD） model rats. MethodSixty male SD rats of SPF grade were randomly divided into sham operation group， model group， and high-， medium- and low-dose modified SYW groups， with 12 rats in each group. The VD model was induced by bilateral carotid artery ligation in rats of the groups except for those of the sham operation group. After modeling， rats were screened by the water maze test， followed by drug treatment by gavage. Specifically， rats in the modified SYW groups were treated with modified SYW at 10， 5， 2.5 g·kg^-1·d^-1， accordingly， and those in other groups were administered with the same amount of normal saline. After intragastric administration for 28 days， the spatial learning and memory abilities of rats were detected by the water maze test. The hippocampal neuron structure was observed by hematoxylin-eosin （HE） staining. The content of hippocampal tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， and glutamate （Glu） was observed by biochemical detection. The hippocampal expression of myelin basic protein （MBP）， astrocyte activation marker glial fibrillary acidic protein （GFAP）， and connexin 43 （Cx43） was detected by immunofluorescence detection. The myelin sheath structure in the hippocampus was observed by the electron microscope. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor （AMPAR） and Cx43 protein expression was detected by Western blot. ResultCompared with the sham operation group， the model group showed prolonged escape latency （P<0.01）， decreased times of crossing the original platform and percentage of target quadrant detention time （P<0.01）， disordered neuron structure in the hippocampal CA1 region， loose myelin sheath lamella with blurry edge， up-regulated expression levels of TNF-α， IL-6， and Glu in the hippocampal CA1 region， especially Glu （P<0.01）， reduced expression of AMPAR （P<0.01）， increased protein expression of p-AMPAR and Cx43 （P<0.01）， significantly dwindled protein expression of MBP in the myelin sheath， and enhanced fluorescence co-labeled by GFAP and Cx43. Compared with the model group， the modified SYW groups showed shortened escape latency （P<0.05）， increased times of crossing the original platform and percentage of target quadrant detention time （P<0.05）， closely arranged hippocampal neuron structure， denser myelin sheath lamella with clear edge， down-regulated expression levels of TNF-α， IL-6， and Glu in the hippocampal CA1 region， especially Glu （P<0.01）， up-regulated AMPAR （P<0.01）， reduced protein expression of p-AMPAR and Cx43， especially in the high-dose group （P<0.01）， significantly elevated protein expression of MBP in the myelin sheath， and weakened fluorescence co-labeled by GFAP and Cx43， especially in the high-dose group. ConclusionModified SYW can improve the learning and memory abilities of VD rats， and the mechanism may be related to the inhibition of Cx43 expression， reduction of the release of Glu， inhibition of AMPAR-mediated inflammatory response to reduce the production of astrocyte marker GFAP， and promotion of the expression of MBP protein to alleviate myelin injury.

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.

BACKGROUND: Vascular intimal hyperplasia (IH) is one of the key challenges in the clinical application of smalldiameter vascular grafts. Current tissue engineering strategies focus on vascularization and antithrombotics, yet few approaches have been developed to treat IH. Here, we designed a tissue-engineered vascular scaffold with portulaca flavonoid (PTF) composition and biomimetic architecture.METHOD: By electrospinning, PTF is integrated with biodegradable poly(e-caprolactone) (PCL) into a bionic vascular scaffold. The structure and functions of the scaffolds were evaluated based on material characterization and cellular biocompatibility. Human vascular smooth muscle cells (HVSMCs) were cultured on scaffolds for up to 14 days. RESULTS: The incorporation of PTF and preparation parameters during fabrication influences the morphology of the scaffold, including fibre diameter, structure, and orientation. Compared to the PCL scaffold, the scaffolds integrated with bioactive PTF show better hydrophilicity and degradability. HVSMCs seeded on the scaffold alongside the fibres exhibit fusiform-like shapes, indicating that the scaffold can provide contact guidance for cell morphology alterations. This study demonstrates that the PCL/PTF (9.1%) scaffold inhibits the excessive proliferation of HVSMCs without causing cytotoxicity. CONCLUSION The study provides insights into the problem of restenosis caused by IH. This engineered vascular scaffold with complex function and preparation is expected to be applied as a substitute for small-diameter vascular grafts.