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 serum autotaxin(ATX),energy balance re-lated protein(Adropin)and inflammatory factors and poor prognosis in patients with dilated cardiomyopathy(DCM).Methods A total of 105 DCM patients admitted to Qingdao Huangdao District Traditional Chinese Medicine Hospital from June 2017 to February 2020 were selected as the DCM group,and 100 healthy volun-teers who came to the hospital for physical examination during the same period were selected as the control group.The levels of serum ATX,Adropin and inflammatory factors[hypersensitive C-reactive protein(hs-CRP)and interleukin-6(IL-6)]in the two groups were detected,and the correlation between serum ATX,Adropin and inflammatory factors was analyzed by Pearson correlation analysis.Patients in DCM group were divided into good prognosis group and poor prognosis group according to the occurrence of endpoint events during follow-up.Logistic regression was used to analyze the risk factors of poor prognosis in DCM patients,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum ATX and Adropinfor poor prognosis in DCM patients.Results The serum levels of ATX,hs-CRP and IL-6 in DCM group were higher than those in control group,and the level of Adropin was lower than that in control group,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum ATX level was posi-tively correlated with hs-CRP and IL-6,and serum Adropin level was negatively correlated with hs-CRP and IL-6(P＜0.05).New York Heart Association(NYHA)functional classification m to Ⅳ and serum ATX lev-el in the poor prognosis group were higher than those in the good prognosis group,the heart failure duration and left ventricular end-diastolic diameter were higher than those in the good prognosis group,the left ventric-ular ejection fraction(LVEF)and serum Adropin levels were lower than those in the good prognosis group,the difference was statistically significant(P＜0.05).Logistic regression model analysis showed that NYHA functional classification Ⅲ to Ⅳ and high ATX were risk factors for poor prognosis in DCM patients,and high Adropin and high LVEF were protective factors for poor prognosis in DCM patients(P＜0.05).ROC curve a-nalysis showed that the area under the curve(AUC)of serum ATX and Adropin in predicting poor prognosis of DCM patients was 0.841 and 0.793,respectively,and the AUC of combined prediction of poor prognosis of DCM patients was greater than that of single prediction.Conclusion Serum ATX is abnormally elevated and serum Adropin is abnormally decreased in DCM patients,both of which are closely related to inflammatory factors.Detection of serum ATX and Adropin levels can provide reference for prognosis assessment of DCM patients.

Objective To investigate the effects of fentanyl citrate on pain in aged rats with hip fracture and its underlying mechanisms. Methods Thirty aged rats with hip fracture were divided into model group (n=10), fentanyl citrate group (n=10), and fentanyl citrate + Sar-SP group (n=10). Additionally, healthy rats from the same period were included as normal group (n=10).Rats in the fentanyl citrate group received intravenous tail injection of 10 μg/kg fentanyl citrate, while those in the fentanyl citrate + Sar-SP group underwent intrathecal injection of 10 μL Sar-SP for fentanyl citrate intervention. Rats in the normal and model groups received intravenous tail injection of an equal volume of saline. Pain threshold, weight-bearing capacity, temperature, and dorsoventral thickness of the hind paws were measured before treatment (0 h) and at 1, 6, 24, and 168 h post-treatment. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and glutamic acid (Glu) in the spinal cord tissue of rats. Immunohistochemical staining was employed to observe the positive expression rates of ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), and substance P (SP) in the spinal cord tissue. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was conducted to detect the relative expression levels of SP and tachykinin receptor 1 (TACR1) mRNA in the hippocampus tissue of rats. Western blot analysis was performed to assess the relative expression levels of vimentin (VIM), nuclear receptor corepressor 1 (NOCR), ciliary neurotrophic factor receptor (CNTFR), and epidermal growth factor receptor (EGFR) proteins in the spinal cord tissue. Results Compared with the normal group, rats in the model group exhibited decreased pain threshold and weight-bearing capacity, increased hind paw temperature and dorsoventral thickness, as well as elevated levels of TNF-α, IL-6, IL-1β, and Glu, increased positive expression rates of Iba-1 and GFAP, heightened positive expression rate and relative mRNA expression levels of SP and TACR1, and augmented relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 0 h before treatment and at 1, 6, 24, and 168 h post-treatment (P < 0.05). Compared with the model group, rats in the fentanyl citrate group showed increased pain threshold and weight-bearing capacity, decreased hind paw temperature and dorsoventral thickness, as well as reduced levels of TNF-α, IL-6, IL-1β, and Glu, decreased positive expression rates of Iba-1 and GFAP, lowered positive expression rate and relative mRNA expression levels of SP and TACR1, and decreased relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 1, 6, 24, and 168 h post-treatment(P < 0.05). Compared with the fentanyl citrate group, rats in the fentanyl citrate+Sar-SP group demonstrated decreased pain threshold and weight-bearing capacity, increased hind paw temperature and dorsoventral thickness, elevated levels of TNF-α, IL-6, IL-1β, and Glu, increased positive expression rates of Iba-1 and GFAP, heightened positive expression rate and relative mRNA expression levels of SP and TACR1, and elevated relative protein expression levels of VIM, NOCR, CNTFR, and EGFR in the spinal cord tissue at 1, 6, 24, and 168 h post-treatment(P < 0.05). Conclusion The improvement in pain in aged rats with hip fracture by fentanyl citrate may be associated with the reduction of SP expression in the spinal cord that inhibits glial cell activation and exhibits anti-inflammatory effects.

Objective:To investigate the cerebral blood flow autoregulation and cerebrovascular reactivity in patients with cerebral small vessel disease (SVD) and depression.Methods:Eighty patients who were treated in Dalian Municipal Central Hospital Affiliated with Dalian University of Technology from May 2020 to may 2021 were selected and divided into observation group and control group according to the existence of depression. Transcranial Doppler sonography combined with standing and lying position test, breath holding test and breath exchange test were used to observe the "w" wave slope, the "w" wave slope, the "w" wave velocity and the "w" wave velocity cerebral blood flow velocity difference, breath holding index, pulsation index (PI) change rate before and after breath holding, resistance index (RI) change rate before and after breath holding, mean velocity (Vm), PI, RI change rate before and after breath exchange. The correlation between depression score and blood flow index was analyzed.Results:There were 38 and 29 patients occurred "w" wave in the control group and observation group respectively, and the rate were 95.0% (38/40) and 72.5% (29/40) respectively ( χ2 = 7.44, P = 0.006). The slope of "w" descending branch of Vm and the slope of "w" ascending branch of Vm in the observation group were smaller than those of the control group respectively: (1.26 ± 0.23) cm/s vs. (2.45 ± 1.00) cm/s, (1.38 ± 0.71) cm/s vs. (2.56 ± 0.77) cm/s, the difference of which had statistical meanings ( P<0.05). The difference of cerebral blood flow velocity of Vm after different positions in the observation group was higher than that in the control group significantly: (7.20 ± 3.07) cm/s vs. (2.93 ± 1.46) cm/s ( P<0.05). The breath holding index PI change rate, RI change rate before and after breath holding test in the observation group were lower than those in the control group statistically: (0.88 ± 0.33)% vs. (1.49 ± 0.27)%, (14.42 ± 9.31)% vs. (21.51 ± 8.79)%, (11.07 ± 1.70)% vs. (15.31 ± 6.73)% ( P<0.05). The change rates of Vm, PI and RI in the observation group before and after ventilation were lower than those in the control group ( P<0.05). There was a negative correlation between depression score and "w" wave slope (Vm), breath holding index, Vm change rate before and after ventilation, and a positive correlation between depression score and cerebral blood flow velocity difference (Vm) in supine and upright position with statistical meanings ( P<0.05). Conclusions:Depression could lead to the decline of cerebral blood flow autoregulation and cerebrovascular reactivity in patients with SVD. And with the aggravation of depression, the decline of cerebral blood flow autoregulation and cerebrovascular reactivity in patients with SVD is more serious.

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 investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Objective:To explore the feasibility of low-dose 4DCT scanning in simulation and target delineation for solitary pulmonary tumors (SPTs).Methods:23 patients with SPTs received 4DCT scanning simulation with the conventional scanning (CON), low voltage (LV), low current (LA) and low voltage combined with low current (LVA) in sequence. Based on the 4DCT images derived from the four sets of scanning parameters, the internal gross tumor volume (IGTV CON, IGTV V, IGTV A, IGTV VA) of SPTs were delineated and matched. Taking IGTV CON as reference, the tumor displacement and the centroid position of IGTV V, IGTV A and IGTV VA were compared with IGTV CON. The radiation doses under different scanning parameters were compared. Results:The volumes of IGTV CON, IGTV V and IGTV A were (12.26±12.30) cm 3, (12.21±12.16) cm 3 and (11.87±11.70) cm 3, respectively ( P=0.337). IGTV VA was (11.34±11.07) cm 3, significantly smaller than IGTV CON ( P=0.005). There was no significant difference in the centroid positions of IGTV CON, IGTV V, IGTV A and IGTV VA in three directions ( P=0.491, 0.360, 0.136). The Dice′s similarity coefficient (DSC VA) was significantly lower than DSC V and DSC A ( P=0.004, 0.030). The tumor displacement measured by the four sets of 4DCT images was similar in the LR direction ( P=0.470), and also in the AP direction ( P=0.108). For the displacement in the SI direction, LVA scanning was smaller than CON ( P=0.015). The radiation doses under four different scanning conditions were (397.0±140.3) mGy·cm, (175.0±61.8) mGy·cm, (264.8±95.3) mGy·cm and (116.8±41.2) mGy·cm, respectively ( P<0.001). Conclusions:LV or LA scanning exert no significant effect on the volume, centroid position of IGTV and the tumor displacement in 4DCT simulation for SPTs. The radiation dose that patients receive under LV and LV scanning is lower than that of CON. Consequently, LV or LA scanning is feasible in 4DCT simulation and target delineation for SPTs.

Objective:To investigate the relationship between the volume ratio of ischemic leukoaraiosis (LA) and cognitive level and arterial perfusion.Methods:Fifty-four patients, who was hospitalized in Dalian Central Hospital and diagnosed as LA clinically during the time of March to December in 2012, were selected to collect the information of the volume ratio of white matter disease, MoCa score and the average flow rate of carotid artery. The correlation between the volume ratio of white matter disease and MoCa score, cognitive impairment and the average flow rate of carotid artery were analyzed.Results:The volume ratio of LA lesions was negatively correlated with MOCA score ( r = -0.59, P<0.01); the volume ratio of LA lesions was negatively correlated with the mean flow rate of internal carotid artery ( r = -0.37, P<0.01). Quantity order of the area under receiver operating characteristic (ROC) curve of MoCA cognitive subgroup was as following: delayed memory (1.000)> visual space/executive function (0.970) = abstract force (0.970)> language ability (0.960)> attention (0.888). Conclusions:The larger the volume ratio of leukopathy in LA patients, the more serious the cognitive impairment, especially the cognitive impairment of impairment of memory delay, visual space/executive function, abstract ability and language ability.

Objective To study the effects of mechanical load on in vivo degradation performance of high-purity magnesium (HP Mg, 99.99 wt.%) quantitatively. Methods Cylindrical Mg specimens, with a 2 mm diameter and a 14 mm length, were mounted in polyetheretherketone (PEEK) rings to bear compressive stresses ［（6.2±0.6） MPa］, tensile stresses ［（4.6±0.1） MPa］ or no stress (as control). The specimens under different stress states were implanted subcutaneously in dorsal abdominal regions of SD rats for 4 weeks. The mass loss, residual volume and surface morphology of the specimens and staining of surrounding soft tissues were used to analyze the degradation rate of HP Mg. Results Specimens and rings were completely encapsulated by membranous tissues after implantation for 4 weeks. No significant differences in the degradation rates were noted between specimens bearing stress and the control. The corrosion layers of specimens under each stress state were uniform. Conclusions The compressive and tensile stresses (4-6 MPa) could not affect significantly HP Mg degradation performance in vivo. The research findings provide theoretical references for the design and clinical application of Mg-based degradable implants.