OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

To investigate the association between sleep-related phenotypes and the risk of malignancy in pulmonary nodules, and to provide complementary evidence from a general population cohort and genetic analyses.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Objective: To explore the association of latent profiles of mobile phone dependence and self control with physical exercise among junior high school students, so as to provide references for the prevention of mobile phone dependence and the improvement of self control among junior high school students. Methods: From April to May 2024, a stratified random cluster sampling method was used to select a total of 2 311 students from grade 7 to grade 9 in three public junior high schools in Xiangxi Autonomous Prefecture, Hunan Province. Latent profile analysis was conducted to identify the latent profiles of mobile phone dependence and self control among junior high school students. Pearson correlation analysis was used to examine the correlation between mobile phone dependence and self control, and Chi square test was used to analyze the distribution differences of latent profiles of adolescents across different demographic characteristics. Multiple Logistic regression analysis was applied to explore the association between mobile phone dependence, self control, and physical exercise. Results: Four latent profiles of mobile phone dependence and self control were identified: low dependence-moderate self control group ( n =885, 38.3%), moderate dependence-low self control group ( n =910, 39.4%), high dependence-no self control group ( n =232, 10.0%), and no dependence-high self control group ( n =284, 12.3%). Significant differences were observed in the distribution of latent profiles across gender, grade and only child status ( χ 2=10.85, 35.72, 13.85， P <0.05). Logistic regression analysis showed that, after controlling for demographic variables, compared with the low dependence-moderate self control group, physical exercise was negatively associated with the moderate dependence-low self control group ( OR =0.79) and the high dependence-no self control group ( OR =0.81), while positively associated with the no dependence-high self control group ( OR =1.58) ( P <0.01). Conclusions The influence of physical exercise on junior high school students different potential profile types of mobile phone dependence and self control is different. Schools and families should adopt targeted physical exercise interventions based on the characteristics of different profiles to promote the physical and mental health of junior high school students.

Objective: To analyze the heterogeneity of mobile phone dependence development trajectory in middle school students and its association with loneliness and selfcontrol ability, so as to provide reference for the prevention of mobile phone dependence in middle school students. Methods: A total of 941 grade 1 students from 4 public middle schools in Xiangxi Autonomous Prefecture, Hunan Province were selected for the followup survey by random cluster sampling from October 2023 to April 2024 and October 2024. Mobile Phone Addiction Index (MPAI), University of California, Los Angeles Loneliness Scale-20 (UCLA-20) and Selfcontrol Scales (SCS) were used for questionnaire survey. The heterogeneity of the developmental trajectory of middle school students mobile phone dependence was analyzed by the latent growth curve model (LGMM), and the influencing factors of the developmental trajectory of middle school students mobile phone dependence were explored by multiple Logistic regression analysis. Results: The development trajectory of middle school students mobile phone dependence could be divided into four categories: C1 "low risk slow decline group (n=438,44.6%)", C2 "medium risk slow rise group (n=272,29.7%)", C3 "high risk rapid decline group (n=73,8.6%)" and C4 "high risk rapid rise group (n=158,17.1%)". There were significant differences in the distribution of mobile phone dependence development track heterogeneity subgroups among sex, only child, lodging, and leftbehind students (χ2=117.79, 44.88, 37.09, 130.50, P <0.01). The results of the multinomial Logistic regression model analysis showed that, with C1 group as the reference, C2, C3, and C4 were positively correlated with students loneliness [OR(95%CI)=1.04 (1.02-1.06), 1.11(1.08-1.14), 1.12(1.09-1.14)]; C2 and C4 groups were negatively correlated with students selfcontrol [OR(95%CI)=0.97(0.96-0.99), 0.95(0.93-0.97)] (P<0.01). Conclusions The development trajectory of mobile phone dependence among middle school students is heterogeneous. Reducing the loneliness of individuals and cultivating good selfcontrol ability are helpful to alleviate mobile phone dependence behavior among middle school students.

BACKGROUND:Buqi Huoxue Compounds have significant clinical efficacy in treating ischemic stroke with Qi deficiency and phlegm stasis;however,the exact mechanism of action is not clear. OBJECTIVE:To observe the effect of Buqi Huoxue Compounds on the expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy related protein Beclin1 and p62 in a rat model of cerebral ischemia/reperfusion. METHODS:Forty male Sprague-Dawley rats were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group and autophagy inhibitor group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia/reperfusion injury was established.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the autophagy inhibitor group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given 3-methyladenine 2 hours before gavage and at days 1-3 of gavage.The sham operation group and model group were given equal amounts of saline by gavage for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology and expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy-related proteins Beclin1 and p62 in the ischemic cortical region of rats were detected at 24 hours after the final administration. RESULTS AND CONCLUSION:Zea-Longa scoring results showed that the neurological function of rats was severely damaged after modeling and neurological deficit of rats in the Buqi Huoxue Compounds group was less than that in the model group and the autophagy inhibitor group(P＜0.05).TTC staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and autophagy inhibitor group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was lower than that in the model group and the autophagy inhibitor group(P＜0.05).The results of hematoxylin-eosin staining in ischemic brain tissues showed that there were large gaps between nerve cells in the model group and cell arrangement was not neat,and cytoplasmic agglutination and pyknosis were observed.Immunohistochemical staining results showed that vascular endothelial growth factor was mostly expressed in neuronal cells,glial cells and capillary endothelium;basic fibroblast growth factor and brain-derived neurotrophic factor were mostly expressed in neuronal cells and glial cells;and there was no significant difference in the expression of vascular endothelial growth factor,basic fibroblast growth factor,and brain-derived neurotrophic factor among the four groups(P＞0.05).The results of western blot assay showed that compared with the sham operation group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the model group;compared with the model group,Beclin1 protein expression was increased(P＜0.05)and p62 protein expression was reduced(P＜0.05)in the Buqi Huoxue Compounds group;compared with the Buqi Huoxue Compounds group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the autophagy inhibitor group.To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury in rats by promoting autophagy.

ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

Objective To explore the efficacy and safety of flexible ureteroscopic lithotripsy(FURL)combined with flexible negative-pressure sheath in treating patients with 3-4 cm renal calculi with CT value＜1100 Hu,and to identify a safe and effective treatment option for patients with such calculi.Methods A retrospective analysis was conducted on the clinical data of 95 patients undergoing surgical treatment at the Department of Urology,the Second People's Hospital of Anhui Province during Jun.2022 and May 2024.The patients were divided into two groups,including 42 in the FURL with flexible negative-pressure sheath group(FURL group),and 53 in the percutaneous nephrolithotomy(PCNL)group.General data,perioperative indicators,and complication rates were compared between the two groups.Results There were no statistically significant differences between the FURL group and PCNL group in stone-free rate(SFR)3 days postoperatively(83.3％vs.88.7％),1 month postoperatively(95.2％vs.92.5％),and 3 months postoperatively(97.6％vs.94.3％),as well as operation time[(77.65±9.05)min vs.(79.10±8.14)min](P＞0.05).The FURL group had shorter hospital stay[(5.98±1.12)days vs.(9.38±1.57)days],lower decrease in hemoglobin level[(3.17±0.85)g/L vs.(4.98±1.72)g/L],lower visual analog scale(V AS)score on postoperative day 1[(2.60±0.63)vs.(3.77±1.09)]and day 3[(2.29±0.99)vs.(2.70±0.89)],lower postoperative white blood cell count[(7.05±1.66)× 109 cells/L vs.(11.24±2.90)× 109 cells/L],lower C-reactive protein level[(25.73±7.57)ng/L vs.(31.14±5.53)ng/L],lower blood urea nitrogen level[(6.12±1.43)mmol/L vs.(9.85±3.07)mmol/L],and lower serum creatinine level[(84.48±11.57)μmol/L vs.(114.43±21.48)μmol/L](all P＜0.001).The total incidence of complications was also lower in the FURL group(4.8％vs.18.9％,P＜0.05).Conclusion FURL combined with flexible negative-pressure sheath can achieve comparable SFR as PCNL without extending operation time,and it can shorten hospital stay,reduce intraoperative blood loss,have little impact on renal function,reduce inflammatory response and decrease the incidence of complications.

Objective To investigate the mechanism underlying the inhibitory effect of Buyang Huanwu Decoction(BYHWD)on vascular aging.Methods Eighteen male SD rats were randomized into young group,intraperitoneal D-galactose injection-induced aging group,and BYHWD gavage group.The changes in pulse wave velocity(PWV),vascular SA-β-gal activity,and expressions of p16,p21 and SA-β-gal of the rats were examined.Serum exosomes were isolated from the rats,and after characterization using NTA and TEM and for surface markers and vascular cell markers,were examined for miR-590-5p expression using qRT-PCR.The M1/M2 macrophage ratio and cytokine levels were evaluated using immunofluorescence staining and qRT-PCR.Bioinformatics analysis and dual-luciferase reporter assays were carried out to predict the potential target genes of miR-590-5p and validate its targeting relationship with SLC8A3,whose expressions were detected in the vascular tissues of the rats by Western blotting.Results Compared with the young rats,the aging rats exhibited significantly increased PWV in the abdominal aorta with elevated vascular expressions of p16,p21 and SA-β-gal,which were all reversed by BYHWD treatment.The isolated serum exosomes were positive for CD63,CD81,CD31 and SM-22,and the exosomes from aging rats showed significantly downregulated expression of miR-590-5p,which was upregulated after BYHWD treatment.The aging rat vessels showed an increased M1/M2 macrophage ratio with elevated M1-specific cytokines and reduced M2-specific cytokines,and BYHWD treatment effectively inhibited M1 polarization of the macrophages.Pearson analysis revealed a negative correlation between exosomal miR-590-5p upregulation and the M1/M2 ratio.Bioinformatics analysis and dual-luciferase assays confirmed that miR-590-5p targets SLC8A3.Western blotting demonstrated increased SLC8A3 expression in aging rat vessels,which was downregulated after BYHWD treatment.Conclusion BYHWD attenuates vascular aging in rats by modulating macrophage M1 polarization and suppressing vascular inflammation via exosomal miR-590-5p-mediated downregulation of SLC8A3.

Objective:To develop a convolutional neural network model of whole slide imaging of cerebrospinal fluid cells for rapid and accurate identification and classification of tumor cells in cerebrospinal fluid.Methods:A total of 8 692 cerebrospinal fluid cytology smears from Huashan Hospital Affiliated to Fudan University from January 2nd, 2019, to December 27th, 2024. As randomly assigned, the training set included 4 941 benign and 1 745 malignant samples, while the validation set comprised of 1 368 benign and 638 malignant samples. Whole-slide digital images were acquired using a cytopathology scanner, cells (clusters) were annotated for classification, and a deep learning model was constructed via tiled image patches for cell detection and classification. Model performance was evaluated using accuracy, sensitivity, specificity, and other indicators. The classification efficiency of manual microscopy was compared.Results:The model achieved a mean precision of 96.75% for cerebrospinal fluid cell classification. For malignant tumor cells, the classification accuracy was 96.61% (mAP=98.36%, AUC=0.97). Subtype classification accuracies for epithelial/epithelioid tumors and small round cell tumors were 97.13% (AUC=0.98) and 95.58% (AUC=0.93), respectively. Compared with manual microscopy, which took (9.70±0.82) minutes for classifying 200 cells, (18.27±1.21) minutes for 500 cells, and often exceeded 60 minutes or infeasible for full slides, the AI model took (3.46±0.49) seconds for 200 cells, (6.76±0.82) seconds for 500 cells, and a median of 48.57 seconds for full slides ( P<0.001), representing an efficiency improvement of approximately 161-170 times, significantly enhancing diagnostic efficiency. Conclusion:This fully automated hierarchical deep learning model enables efficient and accurate tumor cell identification and classification in CSF, providing an effective auxiliary tool for the rapid diagnosis of meningeal carcinomatosis.