BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Houpo Sanwutang， included in the Catalogue of Ancient Classical Prescriptions （Second Batch）， was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining， statistical analysis， and data processing， combined with modern articles， this study employed bibliometrics to investigate the historical origin， composition， decoction methods， clinical application， and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty， it is recommended that 110.4 g Magnolia Officinalis Cortex， 55.2 g Rhei Radix et Rhizoma， and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first， and 1 000 mL should be taken from the decocted liquid. Following this， Rhei Radix et Rhizoma should be added for further decoction， and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL， and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi， relieving stuffiness and fullness， removing food stagnation， and regulating bowels. It can be used in treating abdominal distending pain， guarding， constipation， and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

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.

Objective To evaluate the application value of simultaneous amplification and testing for Myco-bacterium tuberculosis(SAT-TB)in evaluating the curative effect of initial treatment of smear-positive pul-monary tuberculosis patients.Methods A total of 62 newly treated smear positive pulmonary tuberculosis pa-tients from June 2022 to June 2023 in Guangzhou Panyu District Chronic Disease Control Station were selected as the study objects,and the curative effect was evaluated by liquid-based sandwich cup method,Roche culture method and SAT-TB detection method.All patients received the standard anti-tuberculosis treatment regimen of 2HRZE/4HR standard regimen,and sputum samples were detected by liquid-based sandwich cup method,Roche culture method,and SAT-TB detection method at the 2nd,4th,and 8th week of treatment,respectively.Results Among 62 patients,54 cases were positive and 8 cases were negative using Roche culture method,47 cases were positive and 15 cases were negative using SAT-TB detection method.60 cases were positive and 2 cases were negative by Mycobacterium tuberculosis(MTB)-DNA test.The positive rates of the three methods were 87.10％(54/62),75.81％(47/62)and 96.77％(60/62),respectively.Taking Roche culture method re-sults as the standard,the sensitivity of SAT-TB detection method and MTB-DNA was 97.87％(46/47)and 90.00％(54/60),and the specificity was 46.67％(7/15)and 100.00％(2/2),respectively.There were signifi-cant differences between Roche culture method and SAT-TB detection method and MTB-DNA test(x2=20.070,P＜0.05,x2=13.985,P＜0.05),the difference between the results of SAT-TB detection method and MTB-DNA test was also statistically significant(x2=8.365,P＜0.05).The negative conversion rates of MTB in sputum samples were 69.35％(43/62),29.03％(18/62)and 41.94％(26/62)at the 2nd,4 th,and 8 th weeks,respectively.77.42％(48/62),59.68％(37/62),58.06％(36/62),82.26％(51/62),79.03％(49/62),75.81％(47/62).There were significant differences in the negative conversion rates of MTB in sputum sam-ples between SAT-TB and liquid-based sandwich cup method at the 2nd and 4th weeks(x2=8.365,P＜0.05,x2=4.465,P＜0.05),while there was no significant difference between the results of Roche culture method at the 2nd,4th and 8th weeks(x2=1.726,P＞0.05,x2=0.000,P＞0.05,x2=0.046,P＞0.05).Conclusion The use of SAT-TB detection method in clinical practice to evaluate the efficacy of smear positive pulmonary tuberculo-sis patients could accurately and quickly assess the negative conversion rate and treatment effect of patients,and provide a reliable basis for guiding clinical treatment.It could be considered as an effective auxiliary diag-nosis and evaluation method of curative effect,worthy of promotion and practical application.

Objective:To investigate the current status of malnutrition and its influential factors among patients with stroke and dysphagia, and to develop and validate a malnutrition risk prediction model.Methods:Using a convenience sampling method, 150 patients with stroke and dysphagia admitted to Wenzhou Central Hospital from January 2019 to December 2023 were included in this study. Through a review of the literature and expert consultations, 15 influential factors were identified: age, gender, body mass index (BMI), history of smoking alcohol consumption , number of hospitalizations, education level, Barthel index, history of hypertension, history of diabetes, coronary heart disease, presence of limb disabilities, hemoglobin levels, Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale score. Patients were categorized into malnutrition and normal groups based on the occurrence of malnutrition. The influential factors for malnutrition were analyzed, and a malnutrition risk prediction model was constructed using regression analysis. The model was presented using a nomogram and subsequently validated.Results:Among the 150 patients with stroke and dysphagia, the average age was (59.34 ± 6.46) years, with 83 females and 67 males. Of these patients, 66 (44.00%) were found to be malnourished. The following factors were identified as independent risk factors for malnutrition in patients with stroke and dysphagia: age (χ2 = 4.03, P = 0.045), BMI ( t = 6.33, P < 0.001), alcohol consumption (χ2 = 3.90, P = 0.048), number of hospitalizations (χ2 = 9.45, P = 0.024), Barthel index (χ2 = 7.78, P = 0.020), presence of limb disabilities (χ2 = 4.64, P = 0.031), hemoglobin levels (χ2 = 4.38, P = 0.036), and GCS score (χ2 = 9.83, P = 0.007) (all P < 0.05). Patients who were older, had a BMI < 18.5 kg/m2, consumed alcohol, had more than five hospitalizations, a Barthel index < 40, limb disabilities, abnormal hemoglobin levels, or a GCS score ≤ 11 were more likely to experience malnutrition (all P < 0.05). The C-index for predicting malnutrition was 0.851, with a 95% CI of (0.809, 0.892). The maximum Youden index was 0.562, with a sensitivity of 84.1% and specificity of 72.1%. Conclusion:The risk factors for malnutrition in patients with stroke and dysphagia include advanced age, alcohol consumption, more than five hospitalizations, limb disabilities, and abnormal hemoglobin levels. Protective factors against malnutrition in these patients are a BMI > 23.9 kg/m2, a Barthel index > 60, and a GCS score ≥ 14. The prediction model demonstrates a significant predictive value for the occurrence of malnutrition in patients with stroke and dysphagia.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

Objective:To explore the health behavior of middle-aged and young stroke patients and analyze its influencing factors.Methods:From April to July 2023, convenience sampling was used to select 172 middle-aged and young stroke patients admitted to the First Affiliated Hospital of Naval Medical University as the research subject. A survey was conducted using the General Information Questionnaire, Health Behavior Scale for Stroke Patients, Health Belief Scale, and Multidimensional Scale of Perceived Social Support. Spearman correlation was used to analyze the correlation between health behavior, social support, and health beliefs among middle-aged and young stroke patients. Multiple linear regression was used to analysis the influencing factors of health behavior among middle-aged and young stroke patients. A total of 172 questionnaires were distributed, and 8 questionnaires with missing items and short response times were excluded, and 164 valid questionnaires were collected, with a valid response rate of 95.34%.Results:Among 164 middle-aged and young stroke patients, the total score of the Health Behavior Scale for Stroke Patients was 64.50 (57.00, 80.75), and the average score of the items was 2.58 (2.28, 3.23). Multiple linear regression analysis showed that factors affecting the health behavior of middle-aged and young stroke patients were whether it was the first onset, the time required to reach nearby medical institution, health belief, and social support ( P<0.05) . Conclusions:The health behavior of middle-aged and young stroke patients is above the medium level. In the process of intervening in the health behavior of middle-aged and young stroke patients, medical and nursing staff should pay attention to patients with recurrent stroke and poor access to medical services, while also improving patients' health belief and social support to promote patients' health behavior and reduce stroke recurrence.

Objective:To explore the mediating effect of coping style on disease perception and pre-hospital delayed behavioral intention in patients with acute ischemic stroke.Methods:This study was a cross-sectional study. From February to July 2023, convenience sampling was used to select 205 patients with acute ischemic stroke admitted to the First Affiliated Hospital of Naval Medical University as the study subject. The survey was conducted using the General Information Questionnaire, Stroke Pre-Hospital Delay Behavior Intention, Brief Illness Perception Questionnaire, and Simplified Coping Style Questionnaire.Results:205 questionnaires were filled out, 195 valid questionnaires, and the validity rate of the questionnaire was 95.1%. The Stroke Pre-Hospital Delay Behavior Intention score of patients with acute ischemic stroke was (63.61±16.12). Pre-hospital delayed behavioral intention in patients with acute ischemic stroke was positively correlated with disease perception and negative coping ( r=0.360, 0.266; P<0.01), and negatively correlated with positive coping ( r=-0.279, P<0.01). The mediating effects of positive and negative coping on disease perception and pre-hospital delayed behavioral intention in ischemic stroke patients were 0.111 and 0.097, respectively, accounting for 26.89% and 23.49% of the total effect. Conclusions:There is a partial mediating effect of coping strategies between disease perception and pre-hospital delayed behavioral intention in ischemic stroke patients. In the process of stroke management, medical and nursing staff can reduce pre-hospital delayed behavioral intentions by improving disease cognition and coping style.