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 investigate the relationship between pre-liver transplantation plasma soluble programmed cell death protein 1 (sPD-1) levels and prognosis in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICI). Methods A total of 38 HCC liver transplant recipients who received ICI treatment at Beijing Tsinghua Changgung Hospital from January 2021 to February 2024 were included in the study. The use of ICI drugs was reviewed, and the clinical and pathological characteristics of patients with and without postoperative HCC recurrence were compared. Kaplan-Meier analysis was used to evaluate postoperative survival. Pre-transplant plasma samples were collected from patients treated with ICI, and the sPD-1 levels were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to explore the relationship between sPD-1 expression and clinical pathological features and to analyze the prognosis. The effects of different preoperative ICI discontinuation times on sPD-1 expression were also compared. Results Among the patients, 28 (74%) received anti-programmed cell death protein 1 (PD-1) monoclonal antibodies, 9 (24%) received anti-programmed cell death protein ligand 1 (PD-L1) monoclonal antibodies, and 1 (3%) received bispecific antibodies. Patients were grouped based on whether they had HCC recurrence within 1 year after surgery. Significant differences were found between the two groups in preoperative alpha-fetoprotein levels, tumor number, maximum tumor diameter, capsular invasion, differentiation grade, Ki67 index, conform to Milan criteria, conform to University of California at San Francisco (UCSF) criteria and tumor, node, metastasis (TNM) staging (all P<0.05). The median pre-transplant plasma sPD-1 level was 902 (318, 4 406) pg/mL, and the sPD-1 level was higher in the recurrence group than in the non-recurrence group (P<0.05). Using 2 073 pg/mL as the cut-off value, patients were divided into high and low sPD-1 level groups. Significant differences were found between the two groups in tumor number, postoperative hospital stay and total hospital stay (all P<0.05). Kaplan-Meier analysis showed that the disease-free survival rate was lower in the high sPD-1 level group than in the low sPD-1 level group (P=0.004), while the overall survival rate did not differ significantly between the two groups (P=0.381). In addition, patients who discontinued ICI treatment ≤ 5 half-lives before surgery had higher sPD-1 levels than those who discontinued ICI treatment for >5 half-lives before surgery. Conclusions Pre-transplant plasma sPD-1 levels are closely related to prognosis and may reflect the dynamic changes in the immune microenvironment. For patients with high pre-transplant plasma sPD-1 levels, the indications for liver transplantation should be carefully evaluated, and postoperative management and follow-up should be strengthened. Early intervention should be provided to improve patients' quality of life and prolong their survival.

Objective:To analyze the problems existing in the cases of hospitals infringing upon patients′ informed consent right after the promulgation of the Civil Code of the People′ s Republic of China, and to provide reference for improving the legal system of informed consent. Methods:Search for judgment documents published from January 1, 2021 to June 30, 2023 on the China Judgment Document Network using the keyword " liability dispute for infringing on patients′ informed consent rights", and conduct descriptive and textual analysis on the cases in the judgment documents.Results:68 judgment documents were included in total.There were 11 judgment documents on infringement of patients′ right to informed consent, and all related cases have undergone appraisal. The content of infringement mainly included infringement of patients′ right to know their condition (12/20), infringement of patients′ right to access their medical records (6/20), infringement of patients′ right to bodily integrity without consent (2/20). There were 15 judgment documents which judge that the right of informed consent of patients wasn′t infringed, and only one case in the document has been appraised. The main focus of controversy was the issue of the priority of the exercise of the right to informed consent (2/15), the fulfillment of the obligation to inform the right to informed consent (5/15), the issue of surgery without notification (1/15), and the issue of determining the authenticity of medical records and providing medical materials (7/15).Conclusions:The legal protection of patients′ right to informed consent still faces judicial difficulties such as unclear order of the exercise of rights subject, insufficient specificity of the scope of the exercise of the right, conflicts between the right to informed consent and medical intervention, and lack of unified identification methods for infringement liability. It is suggested to standardize the order of the exercise subject of the right to informed consent, clarify the content of the obligation of the medical party to inform, construct a system for medical intervention, and unify the identification methods for disputes related to the right to informed consent.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

OBJECTIVE To evaluate the safety and suitability of traditional Chinese medicine prescriptions generated by generative artificial intelligence （AIGC）， and to provide research ideas for empowering the traditional Chinese medicine industry with AIGC. METHODS Using the 2020 edition of Chinese Pharmacopoeia and the 5th edition of Traditional Chinese Medicine as corpus， GPT-4 and the real-time networking model developed based on GPT-4 （referred to as the “networking model”） were used for deep learning. The clinical cases included in the consensus of traditional Chinese medicine experts in recent years were extracted manually to regenerate prescriptions based on diagnosis using the GPT-4 model and networking model； traditional Chinese medicine experts conducted blind evaluation and scoring of GPT-4 generated prescriptions， networking model generated prescriptions， and expert consensus prescriptions. At the same time， Turing testing was used to evaluate whether the GPT-4 model and networking model had the same ability as human intelligence. RESULTS The average score of traditional Chinese medicine prescriptions generated by the GPT-4 model showed no statistically significant difference compared to manual prescriptions （P＞0.05）， while the average score of prescriptions generated by the networking model showed no statistically significant difference compared to traditional Chinese medicine prescriptions generated by the GPT-4 model （P＞0.05）. The proportion of model-generated prescriptions mistakenly judged as manual prescriptions in the Turing test was 51.11%. CONCLUSIONS The traditional Chinese medicine prescriptions generated by the GPT-4 model have reached a certain level of safety and suitability， and the GPT-4 model has passed the Turing test. The introduction of AIGC in the diagnosis and treatment process may provide technical support for the rational use of clinical traditional Chinese medicine.

Objective:To investigate the effectiveness and safety of early combined with tirofiban in the treatment of elderly patients with acute ischemic stroke after intravenous thrombolysis with alteplase.Methods:Elderly (60-75 years old) patients with acute ischemic stroke received intravenous alteplase thrombolysis in the Department of Neurology, Traditional Chinese Medicine Hospital of Huangdao District, Qingdao from January 2018 to May 2020 were enrolled prospectively. According to whether tirofiban is combined or not, they were divided into tirofiban group and non-tirofiban group. Tirofiban was pumped intravenously 2 h after intravenous thrombolysis, first 0.4 μg/(kg·min) for 30 min, then 0.1 μg/(kg·min) for 24 h. The efficacy endpoints included National Institutes of Health Stroke Scale (NIHSS) score at 7 d after treatment and modified Rankin Scale (mRS) score at 90 d after onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. The safety endpoints included the incidence of hemorrhagic transformation, symptomatic intracranial hemorrhage (sICH) and mortality within 90 days after onset.Results:A total of 124 patients with acute ischemic stroke were enrolled. The median age was 68 years (range, 60-75 years). There were 73 males (58.9%) and 51 females (41.1%). There were 62 patients (50%) in the tirofiban group and 62 (50%) in the non-tirofiban group. The median baseline NIHSS score was 14. Hemorrhagic transformation occurred in 7 patients (5.6%), of which 2 were sICH (1.6%). The follow-up at 90 d after onset showed that 68 patients (54.8%) had a good outcome, 56 (45.2%) had a poor outcome, of which 4 (3.2%) died. The NIHSS score at 7 d after treatment (5.52±4.79 vs. 7.35±3.80; t=2.357, P=0.020) and the rate of good outcome at 90 d after onset (64.5% vs. 45.2%; χ2=4.689, P=0.030) in the tirofiban group were significantly better than those of the non-tirofiban group, and there were no significant differences among the incidence of hemorrhagic transformation (4.8% vs. 6.5%; P=1.000), sICH (1.6% vs. 1.6%; P=1.000), and 90 d mortality (3.2% vs. 3.2%; P=1.000). Conclusion:After intravenous thrombolysis with alteplase, the early combined treatment with tirofiban in elderly patients with acute ischemic stroke can significantly improve the efficacy and outcome, and will not increase the risk of hemorrhagic transformation, sICH and death.

Objective:To explore the association of expression of NADH dehydrogenase 1 ( ND1), NADH dehydrogenase 3 ( ND3) and taste 2 receptor member 43 ( TAS2R43) genes with severe pneumonia in children. Methods:Thirty severe pneumonia children in the intensive care unit of Zhumadian Central Hospital from May 2016 to May 2018 were enrolled as the severe pneumonia group and 25 healthy children undergoing health examinations in Zhumadian Central Hospital over the same period were selected as the control group.The severe pneumonia group contained 17 boys and 13 girls, with an age of 5.30±1.69.The control group included 13 boys and 12 girls, with an age of 4.96±1.31.Expression of ND1, ND3 and TAS2R43 genes was detected by real-time PCR, and the relative expression of ND1, ND3 and TAS2R43 genes was calculated by 2 -ΔΔCt method. Results:The circulating threshold (Ct) values of ND1, ND3 and TAS2R43 mRNA in the severe pneumonia group were 20.49±0.45, 21.32±0.61 and 32.20±0.46, respectively, and those in the healthy control group were 26.69±0.62, 27.50±0.35 and 26.69±0.49, respectively.The difference between the 2 groups was statistically significant ( t=-14.02, -15.25, -14.19, all P<0.05). The relative expre-ssion of ND1, ND3 and TAS2R43 genes calculated by the 2 -ΔΔCt method in the severe pneumonia group was 51.27 folds, 50.56 folds and 0.02 folds as many as that in the control group. Conclusions:The expression of ND1, ND3 and TAS2R43 genes in severe pneumonia children is abnormal.These 3 genes may be closely related to severe pneumonia in children.

Objective:To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma.Methods:Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ 2) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results:A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy ( P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion:TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.

Objective To study the change patterns of bone microstructural parameters around the magnesium based- implants after implantation in rabbit femur at different implantation time points. Methods The threaded and non-threaded high-purity magnesium (HP Mg, 99.99 wt.%) screws, with a 2 mm diameter and a 7 mm length, were implanted into the femoral condyle of the rabbits. The control group was the drilled and healthy group. Micro-CT scanning and analysis were performed at 8th, 12th and 16th week after operation. The obtained microstructural parameters included bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp). Results At 8th week, BMD and BV/TV in non-threaded magnesium screw group were significantly higher than those in healthy group, Tb.N was significantly higher than that in drilled and healthy group, and Tb.Sp was significantly lower than that in healthy group. At 12th week, BMD, BV/TV and Tb.N in threaded magnesium screw group were significantly higher than those in drilled and healthy group, Tb.Th was significantly higher than that in healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. At 16th week, BMD, BV/TV and Tb.N in non-threaded magnesium screw group were significantly higher than those in drilled and healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. Conclusions The magnesium based-implant promoted higher BMD, BV/TV, Tb.Th, Tb.N and lower Tb.Sp of surrounding implant, indicating that osseointegration and bone growth were in good condition. Magnesium based-implant could effectively promote the regeneration of bone. The results provide a theoretical basis for the orthopedic application of magnesium based-implants in clinic.

Objective: To investigate the acceptance status of internet+health management among hypertensive patients in Xuzhou city and the related influencing factors. Methods: An interviewing questionnaire survey on the acceptance of internet+health management was conducted among 1,200 hypertensive patients from Xuzhou community health service centers selected by randomized cluster sampling and stratified sampling methods from February tp August 2018, 1 116 valid questionnaires were finally obtained with a response rate of 93.0%. The respondents were divided into two groups according to whether they would accept the internet+health management, and the general conditions and health management status of the two groups were compared. Results: The acceptance rate of internet+health management was 71.9% (802/1 116). The univariate analysis showed that age, education level, occupation, and monthly income of hypertensive patients were associated with the acceptance of internet+health management (P<0.05); patients with family history of hypertension, cardiovascular and cerebrovascular complications and high health literacy had higher acceptance rate of internet+health management (P<0.05). Multivariate analysis showed that educational levels of junior high school and above (OR=0.426, 0.318, 0.089), good sleep (OR=0.453) were protective factors for acceptance of internet+health management; while not knowing the diagnostic criteria for hypertension (OR=1.494), not knowing the blood pressure monitoring (OR=2.668), not knowing ECG monitoring (OR=2.247), quitting smoking (OR=2.444), no complications (OR=2.247), and not participating in community health management (OR=1.758) were the risk factors of acceptance of internet+health management for patients with hypertension. Conclusion The acceptance rate of internet+health management among hypertensive patients in Xuzhou city is relatively high. A variety of factors have impact on the acceptance of internet + health management.