ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

This study investigated the therapeutic effects and mechanisms of medical ozone on sepsis- associated kidney injury (S-AKI) induced by lipopolysaccharide in mice. Using enzyme-linked immunosorbent assay, renal histopathological evaluation, detection of renal function biochemical indicators, immunofluorescence staining, and Western blot analysis, the effects of intraperitoneal injection of ozone on inflammation, coagulation, and renal tissue in mice were systematically detected.The results demonstrated that ozone treatment significantly reduced circulating levels of the specific markers (citrullinated histone H3 and myeloperoxidase-DNA complexes) from neutrophil extracellular traps (NETs) in S-AKI mice, with a suppression on inflammatory and tissue factor expression in renal tissue. Furthermore, ozone effectively improved microcirculation dysfunction, reduced tubular damage and interstitial inflammatory infiltration, thereby alleviating pathological changes of kidneys of S-AKI mice. Mechanistic studies revealed that ozone enhances phagocytic clearance of tissue factor-rich microparticles (TF-MPs) by activating the 5'-monophosphate-activated protein kinase (AMPK) / scavenger receptor (SR)-A1 signaling pathway in macrophages. In Sr-a1-/- mice, renoprotective effect of ozone was completely abolished, confirming the critical role of SR-A1 in this mechanism. In summary, this study demonstrates that medical ozone promotes macrophage clearance of TF-NETs complexes through the AMPK/SR-A1 signaling axis, exerting dual protective effects on mice through anti-inflammatory action and microcirculation improvement, which provides novel intervention targets and therapeutic strategies for S-AKI treatment.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.

Purpose In this study,tract-based spatial statistical analysis was used to analyze the diffusion tensor imaging(DTI)data of breast cancer patients after chemotherapy,to observe the changes of white matter microstructure after chemotherapy and their correlation with neuropsychological cognitive test results,and to provide imaging markers for the evaluation of brain injury after chemotherapy for breast cancer.Materials and Methods A total of 29 patients with breast cancer before chemotherapy treatment and 30 patients with breast cancer after chemotherapy treatment were enrolled in the study from November 2022 to June 2023 in the Affiliated Taizhou People's Hospital of Nanjing Medical University.Neuropsychological cognitive test[Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE)]and whole brain DTI examination were respectively performed in the two groups.Fractional anisotropy(FA)and mean diffusivity(MD)were used to compare the differences between the two groups at the structural level.The correlation between the results of DTI and neuropsychological cognitive test was analyzed.Results Compared with the patients with breast cancer before chemotherapy treatment group,patients with breast cancer after chemotherapy treatment group had decreased FA values in bilateral anterior corona radiata,superior corona radiata,corpus callosum body and genu,left posterior thalamic radiation,left external capsule,bilateral superior longitudinal fasciculus,and increased MD values in bilateral anterior corona radiata,superior corona radiata,right posterior corona radiata,corpus callosum body and genu,right posterior thalamic radiation,bilateral superior longitudinal fasciculus.The FA values of left superior corona radiata(r=0.302)and left external capsule(r=0.370)were positively correlated with MMSE results,and the FA values of left outer capsule(r=0.328)were positively correlated with MoCA results(all P<0.05).The MD values of corpus callosum body(r=-0.343)and genu(r=-0.378),left superior corona radiata(r=-0.311),right posterior corona radiata(r=-0.376),right posterior thalamic radiation(r=-0.341)and right superior longitudinal fasciculus(r=-0.392)were negatively correlated with MMSE results(all P<0.05).Conclusion In the chemotherapy group,FA and MD values in multiple brain regions are abnormal,and there is a certain correlation between FA and MD values in some brain regions and neurocognitive test results.The changes of FA and MD values in different brain areas may be potential imaging markers of the abnormal white matter microstructure in breast cancer patients treated with chemotherapy.

Objective:To develop the Discharge Readiness Scale for Patients with Chronic Skin Wounds and evaluate its reliability and validity.Methods:The Discharge Readiness Scale for Patients with Chronic Skin Wounds was developed through literature review, semi-structured interviews, Delphi expert consultation, and a pre-survey. Convenience sampling was employed to select 320 patients with chronic skin wounds hospitalized at Chongming Hospital, Shanghai University of Medicine and Health Sciences and Qingdao Municipal Hospital from June 2023 to December 2024 for formal investigation, conducting scale reliability and validity analysis. The critical ratio method and correlation coefficient method were used for project analysis. Content validity of the scale was assessed using item-level content validity index and average scale-level content validity index, and construct validity was evaluated through exploratory factor analysis and confirmatory factor analysis. Reliability analysis employed Cronbach's α coefficient.Results:A total of 320 questionnaires were distributed, and 304 valid questionnaires were collected, with a valid response rate of 95.0%. The average scale-level content validity index was 0.91, and the item-level content validity index ranged from 0.80 to 1.00. Exploratory factor analysis revealed that the cumulative variance contribution rate of the five common factors was 67.483%. The overall Cronbach's α coefficient for the scale was 0.831. The final constructed scale comprised five dimensions of trajectory stage cognition, wound self-care skills, symptom management, psychosocial adaptation, and health information acquisition and resource utilization, with a total of 26 items.Conclusions:The Discharge Readiness Scale for Patients with Chronic Skin Wounds demonstrates good reliability and validity, providing clinical healthcare professionals with a standardized assessment tool.

Objective:To explore the impact of disease perception control on preoperative self-preparation in patients with carotid artery stenosis, and analyze the mediating role of resourcefulness.Methods:Using convenience sampling, 157 patients with carotid artery stenosis were selected from three tertiary hospitals in Shandong Province between January 2022 and November 2024. Data were collected using a General Information Questionnaire, Brief Illness Perception Questionnaire, Resourcefulness Scale, and Preoperative Self-readiness Scale in Patients Undergoing Elective Surgery. Pearson correlation analysis was conducted to examine the relationships among preoperative self-preparation, resourcefulness, and disease perception control. A mediation model was constructed using the PROCESS macro to investigate the mediating effect of resourcefulness between disease perception control and preoperative self-preparation, with Bootstrap method used for testing mediation effects.Results:A total of 157 questionnaires were distributed, with 147 valid responses received (93.63% response rate). The preoperative self-preparation score for carotid artery stenosis patients was (65.02±23.35). Disease perception control directly influenced preoperative self-preparation and indirectly affected preoperative self-preparation through resourcefulness. The mediation effect accounted for 48.88% of the total effect (-0.807/-1.651) .Conclusions:The results of this study show that both disease perception control and resourcefulness significantly influence preoperative self-preparation in patients with carotid artery stenosis. Future research should further investigate these factors to improve preoperative self-preparation through the enhancement of disease perception control and resourcefulness.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Purpose In this study,tract-based spatial statistical analysis was used to analyze the diffusion tensor imaging(DTI)data of breast cancer patients after chemotherapy,to observe the changes of white matter microstructure after chemotherapy and their correlation with neuropsychological cognitive test results,and to provide imaging markers for the evaluation of brain injury after chemotherapy for breast cancer.Materials and Methods A total of 29 patients with breast cancer before chemotherapy treatment and 30 patients with breast cancer after chemotherapy treatment were enrolled in the study from November 2022 to June 2023 in the Affiliated Taizhou People's Hospital of Nanjing Medical University.Neuropsychological cognitive test[Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE)]and whole brain DTI examination were respectively performed in the two groups.Fractional anisotropy(FA)and mean diffusivity(MD)were used to compare the differences between the two groups at the structural level.The correlation between the results of DTI and neuropsychological cognitive test was analyzed.Results Compared with the patients with breast cancer before chemotherapy treatment group,patients with breast cancer after chemotherapy treatment group had decreased FA values in bilateral anterior corona radiata,superior corona radiata,corpus callosum body and genu,left posterior thalamic radiation,left external capsule,bilateral superior longitudinal fasciculus,and increased MD values in bilateral anterior corona radiata,superior corona radiata,right posterior corona radiata,corpus callosum body and genu,right posterior thalamic radiation,bilateral superior longitudinal fasciculus.The FA values of left superior corona radiata(r=0.302)and left external capsule(r=0.370)were positively correlated with MMSE results,and the FA values of left outer capsule(r=0.328)were positively correlated with MoCA results(all P<0.05).The MD values of corpus callosum body(r=-0.343)and genu(r=-0.378),left superior corona radiata(r=-0.311),right posterior corona radiata(r=-0.376),right posterior thalamic radiation(r=-0.341)and right superior longitudinal fasciculus(r=-0.392)were negatively correlated with MMSE results(all P<0.05).Conclusion In the chemotherapy group,FA and MD values in multiple brain regions are abnormal,and there is a certain correlation between FA and MD values in some brain regions and neurocognitive test results.The changes of FA and MD values in different brain areas may be potential imaging markers of the abnormal white matter microstructure in breast cancer patients treated with chemotherapy.

Objective:To develop the Discharge Readiness Scale for Patients with Chronic Skin Wounds and evaluate its reliability and validity.Methods:The Discharge Readiness Scale for Patients with Chronic Skin Wounds was developed through literature review, semi-structured interviews, Delphi expert consultation, and a pre-survey. Convenience sampling was employed to select 320 patients with chronic skin wounds hospitalized at Chongming Hospital, Shanghai University of Medicine and Health Sciences and Qingdao Municipal Hospital from June 2023 to December 2024 for formal investigation, conducting scale reliability and validity analysis. The critical ratio method and correlation coefficient method were used for project analysis. Content validity of the scale was assessed using item-level content validity index and average scale-level content validity index, and construct validity was evaluated through exploratory factor analysis and confirmatory factor analysis. Reliability analysis employed Cronbach's α coefficient.Results:A total of 320 questionnaires were distributed, and 304 valid questionnaires were collected, with a valid response rate of 95.0%. The average scale-level content validity index was 0.91, and the item-level content validity index ranged from 0.80 to 1.00. Exploratory factor analysis revealed that the cumulative variance contribution rate of the five common factors was 67.483%. The overall Cronbach's α coefficient for the scale was 0.831. The final constructed scale comprised five dimensions of trajectory stage cognition, wound self-care skills, symptom management, psychosocial adaptation, and health information acquisition and resource utilization, with a total of 26 items.Conclusions:The Discharge Readiness Scale for Patients with Chronic Skin Wounds demonstrates good reliability and validity, providing clinical healthcare professionals with a standardized assessment tool.