OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

In recent years, clinicians have paid more attention to the biological and esthetic effects of the 2 mm keratinized mucosa width (KMW) around dental implant. How to increase the keratinized mucosa is the focus of clinicians. While the free gingival graft (FGG) is still the gold standard of keratinized mucosa augmentation, alveolar ridge preservation (ARP), connective tissue graft (CTG) and apically positioned flap (APF) can also be used to obtain more than 2 mm keratinized mucosa width when they are used before implantation, with implantation, within the implant-healing phase, with second stage of implantation or after rehabilitation according to different indications. This article comprehensively summarizes the influencing factors of timing and surgical procedures for keratinized mucosa augmentation, providing guidance for clinicians to treat peri-implant keratinized mucosa deficiencies.

Objective To screen the core genes of diabetic kidney disease(DKD)based on bioinformatics,ex-plore the therapeutic targets of DKD,and discuss its possible regulatory mechanism.Methods The expression da-ta matrix of glomerular transcriptome in patients with DKD in GEO database(GSE30528,GSE47183)was extrac-ted,and the differentially expressed genes(DEGs)were screened by bioinformatics methods to identify the core differential genes,and then gene expression and enrichment analysis(GSEA)were conducted to predict effective targets.Results By screening and identifying the mRNA expression matrix of DKD,five core genes were screened out.Among them,C1orf21 and NPHS1 were significantly down regulated,and CD48,COL1A2,and TGFBI were up regulated.NPHS1 and CD48 were significantly related to immune differences,intercellular communication,and cell surface interaction.Through receiver operating characteristic curve(ROC)analysis and GSEA analysis and drug target prediction,it might be of great significance for the treatment of DKD.Conclusion The core genes screened in this study have significant correlation with DKD,which may be used as effective markers for the treat-ment of diabetes.And then,this study provides a theoretical basis for the treatment and identification of DKD.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective To develop engineered bacterial membrane biomimetic nanoparticles,Angiopep-2 E.coli membrane(ANG-2 EM)@PDA-PEI-CpG(ANG-2 EM@PPC),for efficient targeted drug delivery in the treatment of glioma,and to provide theoretical and technical support for targeted glioma therapy.Methods The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory,and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation.ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes.Western blotting,agarose gel electrophoresis,and transmission electron microscopy(TEM)were used to verify the preparation.Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC.Regarding cell experiments,CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils.A flow chamber model was designed and constructed,and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment.Neutrophil death patterns were characterized by fluorescence microscopy,and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced.Regarding animal experiments,a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified.The tumor model mice were divided into three groups,including DiR group,EM@PPC group,and ANG-2 EM@PPC group(all n=3),which were injected with DiR,ANG-2 EM@PDA-PEI-CpG,and EM@PDA-PEI-CpG via the tail vein,respectively(all at 10 mg/kg).Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain.The tumor model mice were further divided into PBS group,PDA group,PC group,PPC group,EM@PPC group,and ANG-2 EM@PPC group(all n=4),which were injected with PBS,PDA,PC,PPC,EM@PPC,and ANG-2 EM@PPC injected via the tail vein,respectively(all at 10 mg/kg).Imaging was performed in vivo to observe tumor regression,and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics.TUNEL staining(brain tissue)and HE staining(brain,heart,liver,spleen,lung and kidney tissues)were performed to evaluate the therapeutic effect.Results The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles,with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm.Due to the coating of ANG-2 EM,the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm,with a clear bacterial membrane layer on the surface.Stability was maintained for at least one week.ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay.Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition.Compared with the EM@PPC group,the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced(uptake efficiency 24.9%vs.31.1%).Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis(NETosis)to apoptosis.Western blot confirmed the production of neutrophil apoptotic bodies,and flow cytometry showed that the production rate was as high as 77.7%.Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs(heart,liver,spleen,lungs,and kidney)in the DiR group,the EM@PPC gropu,and the ANG-2 EM@PPC group(P＞0.05),but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group(P＜0.05).Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier(BBB),and exhibited high affinity to and internalization by neutrophils located in brain tumors.Compared with PBS,PDA,PC,and PPC groups,the survival rate and body mass of mice in the EM@PPC group were improved,tumor fluorescence intensity was weakened,and apoptotic cells were increased.These trends were even more prominent in the ANG-2 EM@PPC group.No abnormality was found in the HE staining of any group.Conclusion An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared,capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy.This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Objective:To explore the effect of postoperative delirium risk management in elderly patients with hip fragility fracture based on failure mode and effect analysis (FMEA) theory, and to provide a basis for reducing the incidence of postoperative delirium.Methods:A total of 50 patients admitted to the First Affiliated Hospital of Sun Yat-sen University due to hip fragility fractures from January to December 2019 were selected as the control group, and 50 patients admitted to the First Affiliated Hospital of Sun Yat-sen University for hip fragility fractures from January to December 2020 were selected as the observation group. The control group received routine care, and the observation group implemented risk control intervention measures based on FMEA theory on the basis of the control group. The risk priority number (RPN) value, incidence of delirium, duration of delirium, pain score, satisfaction, and average length of hospital stay were compared between the two groups of patients in each link of failure risk.Results:The RPN values of each link failure risk of the observation group were 100.80 ± 13.39, 103.96 ± 9.96, 103.76 ± 8.04, delirium duration was (36.33 ± 9.07) min, pain scores were 1.86 ± 0.76, 4.16 ± 1.17, average length of stay was (8.98 ± 4.64) days, and incidence of delirium was 6.0% (3/50), the RPN values of each link failure risk of the control group were 274.10 ± 8.48, 291.00 ± 10.10, 287.78 ± 11.64, delirium duration (78.70 ± 20.10) min, pain scores 2.26 ± 1.02, 4.74 ± 1.19, average length of stay was (11.50 ± 7.66) days, and incidence of delirium was 22.0% (11/50). The differences between two groups showed significant differences ( t values were 1.99-93.24, χ2=4.07, P<0.05). The patient satisfaction score of the observation group was 99.36 ± 1.01, which was higher than that of the control group 89.63 ± 2.62, and the difference was statistically significant ( t=24.50, P<0.05). Conclusions:The perioperative implementation of postoperative delirium risk management model based on FMEA theory in elderly patients with hip fractures can reduce the incidence of postoperative delirium, relieve pain, shorten hospital stay, and improve satisfaction degree. It is worthy of clinical promotion.

Objective:To evaluate the clinical effect of Limb dysfunction after the comprehensive treatment of ischemic stroke by Traditional Chinese Medicine (TCM).Methods:A total of 160 patients with limb dysfunction after ischemic stroke. Who in line with the inclusion criteria, were randomly divided into 2 groups by random number table, 80 cases each. These patients were treated in Multicenter Union Hospital from June 2017 to Janunry 2019. The patients in the control group were given basic Western medicine treatment and rehabilitation training, while the patients in the observation group were given a comprehensive treatment combined with traditional Chinese medicine based on the control group (Chinese herbs, herbal fumigation and ear point press). Both groups were treated for 4 weeks and follow-up for 2 months. The Fugl-Meyerscale were used to evaluate the degree of limb dysfunction and balance dysfunction, the National Institutes of Health Stroke Scale were used for assessing the damage extent of nerve function, the Barthel index for evaluating the mobility of daily life. The clinical efficacy was evaluated according to the method of Brunnstrom assessment.Results:After treatment, the Limb strong spasm (1.57 ± 0.36 vs. 1.98 ± 0.53, t=5.724), Hemianesthesia (1.37 ± 0.31 vs. 1.80 ± 0.36, t=8.096), Inhibited bending and stretching (1.31 ± 0.25 vs. 1.84 ± 0.46, t=9.055) in the observation group were significantly lower than those in the control group ( P<0.01). The Fugl-Meyer activity and balance rating in the observation group were significantly higher than those in the control group ( t values were 2.739, 4.705, respectively, P<0.05 or P<0.01). The total effective rate of observation group was 93.3% (78/80), the control group was 73.3% (71/80), and there exist statistical significance ( χ2=4.783, P=0.028) in the two group’s comparative difference. Conclusion:The comprehensive TCM treatment can improve the hemiplegia syndrome of ischemic stroke patients and their limb activity and balance function, promote their neural functional recovery, enhance the activity of their daily life and clinical efficacy.

Objective:To summarize the surgical treatment of malignant carotid body tumor (MCBT).Methods:A retrospective analysis of 14 MCBT patients admitted at our hospital from Mar 2005 to Nov 2019 was made, and the imaging data, surgical records, perioperative complications and follow-up data were collected.Results:There were 8 males and 6 females, with an average age of (40.8±11.3) years. 10 patients underwent surgical resection of CBT, with one case undergoing tumor enucleation only, nine cases underwent internal carotid artery reconstruction, and all patients underwent intraoperative lymph node biopsy.Tumors were completely removed in all 10 patients. No perioperative death or cerebral infarction occurred. The intraoperative blood loss was (955±658.5) ml. Four patients had permanent nerve injury after surgery. The follow-up time ranged 1-132 months. There were no cases of cerebral infarction or death, and the reconstructed graft remained patent. Apart from the 2 patients who developed tumor metastasis after surgery, other patients recovered uneventfully with no disease progression.Conclusions:Surgery is still the main treatment for MCBT, but MCBT is large and Shamblin class is more advanced. Therefore, complete tumor removal and reconstruction of the carotid arteries are difficult. Surgery should seek to completely remove the tumor and neck lymph node biopsy should be performed to determine the lymph node metastasis.

Endoplasmic reticulum (ER) stress is an important mediator causing inflammatory response, which additionally exerts secondary injury after intracerebral hemorrhage (ICH) to influence brain function recovery through a variety of cell signaling and response, to regulate neural cells survival or death. Therefore, further understanding about the relation between ER stress and inflammatory response as well as the signal transduction pathway can provide new therapeutic strategies and evidence for treatment of ICH. The present review summarizes the process of ER stress activation and the relation between inflammatory response and ER stress activation after ICH.