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 explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective:To explore the application value of CT-guided percutaneous coaxial needle biopsy (CT-PTCB) in the diagnosis of malignant tumors.Methods:A retrospective case series study was conducted. The clinical data of 802 suspected malignant tumor patients who underwent CT-PTCB upon admission to Beijing Chaoyang District Huanxing Cancer Hospital from January 2019 to December 2023 were analyzed. All patients underwent imaging follow-up combined with CT-PTCB or surgical pathology to determine the final diagnosis. The CT-PTCB puncture effect, diagnosis effect and incidence of complications were recorded.Results:Among the 802 patients, 488 (60.8%) were male and 314 (39.2%) were female, with the age of (51±11) years. The puncture sites included 610 cases (76.1%) in the chest, 169 cases (21.1%) in the abdomen, 17 cases (2.1%) in the bones, and 6 cases (0.7%) in the pelvic cavity. The success rate of CT-PTCB puncture upon admission was 99.5% (798/802), the diagnostic accuracy was 96.5% (774/802), and the false negative rate was 3.5% (28/802). The incidence of pneumothorax and bleeding in patients undergoing pulmonary CT-PTCB was 13.0% (75/575) and 17.9% (103/575), respectively; the incidence of puncture bleeding in patients undergoing liver CT-PTCB was 0.8% (1/125), and the incidence of pain was 1.6% (2/125); the incidence of pneumothorax in patients undergoing mediastinal CT-PTCB was 8.7% (2/23); no obvious complications were observed in other puncture sites. All complications were cured through active treatment.Conclusions:The application of CT-PTCB for the diagnosis of malignant tumors has high success rate and diagnosis rate, and is safe and minimally invasive.

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective:To explore the application value of CT-guided percutaneous coaxial needle biopsy (CT-PTCB) in the diagnosis of malignant tumors.Methods:A retrospective case series study was conducted. The clinical data of 802 suspected malignant tumor patients who underwent CT-PTCB upon admission to Beijing Chaoyang District Huanxing Cancer Hospital from January 2019 to December 2023 were analyzed. All patients underwent imaging follow-up combined with CT-PTCB or surgical pathology to determine the final diagnosis. The CT-PTCB puncture effect, diagnosis effect and incidence of complications were recorded.Results:Among the 802 patients, 488 (60.8%) were male and 314 (39.2%) were female, with the age of (51±11) years. The puncture sites included 610 cases (76.1%) in the chest, 169 cases (21.1%) in the abdomen, 17 cases (2.1%) in the bones, and 6 cases (0.7%) in the pelvic cavity. The success rate of CT-PTCB puncture upon admission was 99.5% (798/802), the diagnostic accuracy was 96.5% (774/802), and the false negative rate was 3.5% (28/802). The incidence of pneumothorax and bleeding in patients undergoing pulmonary CT-PTCB was 13.0% (75/575) and 17.9% (103/575), respectively; the incidence of puncture bleeding in patients undergoing liver CT-PTCB was 0.8% (1/125), and the incidence of pain was 1.6% (2/125); the incidence of pneumothorax in patients undergoing mediastinal CT-PTCB was 8.7% (2/23); no obvious complications were observed in other puncture sites. All complications were cured through active treatment.Conclusions:The application of CT-PTCB for the diagnosis of malignant tumors has high success rate and diagnosis rate, and is safe and minimally invasive.

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.