Objective:To investigate the changes in the expression of miR-146a-5p and steroidogenic acute regulatory protein (StAR) in the blood vessels of rats with hypertension complicated with sepsis, and to preliminarily evaluate the underlying mechanisms of vascular lesions in hypertension complicated with sepsis.Methods:Twenty-four clean-grade healthy male Wistar rats, aged 12 weeks, weighing 250-270 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group, sepsis group, hypertension group, and hypertension complicated with sepsis group. In sham operation group, laparotomy was performed, and sterile normal saline was subcutaneously infused using a micro-osmotic pump for 4 weeks. The sepsis model was established by cecal ligation and perforation after anesthesia in sepsis group. The hypertension model was established by subcutaneously infusing angiotensin Ⅱ at a rate of 500 ng·kg -1·min -1 for 4 weeks using a micro-osmotic pump in hypertension group. In hypertension complicated with sepsis group, angiotensin Ⅱ was subcutaneously infused, and 4 weeks later the sepsis model was established by cecal ligation and perforation. Blood pressure was measured at the end of establishing the model in each group, and blood samples of the abdominal aorta and specimens of aorta were obtained under deep anesthesia, and the serum tumor necrosis factor-alpha (TNF-α) concentration was determined by enzyme-linked immunosorbent assay. The systolic and diastolic functions of the aorta were detected using the aortic vascular ring assay. The collagen volume fraction (CVF) was calculated after Masson staining. The expression of α-smooth muscle actin (α-SMA) and StAR was detected using the immunohistochemical staining assay, and the thickness of the aortic wall was measured. The expression of StAR mRNA and miR-146a-5p was detected using quantitative real-time polymerase chain reaction. Results:Compared with sham operation group, the aortic contraction rate was significantly decreased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in the other three groups, and the systolic blood pressure and CVF were significantly increased, the thickness of the aortic wall was increased, the expression of α-SMA was up-regulated, and the thickness of the aortic wall was increased in hypertension and hypertension complicated with sepsis groups ( P<0.05). Compared with sepsis group, the systolic pressure was significantly increased, the aortic contraction rate was decreased, CVF was increased, the expression of α-SMA was up-regulated, the thickness of the aortic wall was increased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in hypertension complicated with sepsis group ( P<0.05). Compared with hypertension group, the aortic contraction rate was significantly decreased, the diastolic rate was increased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in hypertension complicated with sepsis group ( P<0.05). Conclusions:Down-regulation of miR-146a-5p and up-regulation of StAR in the blood vessels of rats with hypertension complicated with sepsis may be associated with the vascular lesions caused by hypertension complicated with sepsis.

Objective:To evaluate the pulmonary protective effect of individualized positive end-expiratory pressure (PEEP) ventilation guided by driving pressure in patients undergoing rib fracture surgery.Methods:In this prospective randomized controlled trial, 80 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients of either sex, aged 18-64 yr, with a body mass index of 19-28 kg/m 2, who underwent elective open reduction and internal fixation of unilateral rib fractures at the Third Hospital of Hebei Medical University from March to October 2024, were selected and divided into 2 groups ( n=40 each) by the random number table method: fixed PEEP ventilation group (group C) and driving pressure-guided individualized PEEP ventilation group (group DP). Group C adopted the ventilation strategy of fixed PEEP with 5 cmH 2O. Group DP adopted the ventilation strategy guided by the driving pressure: PEEP was titrated from 10 cmH 2O, being gradually decreased to 3 cmH 2O at intervals of 1 cmH 2O. Each PEEP level was maintained for 10 respiratory cycles, and the driving pressure of the last cycle was calculated, and the PEEP that could achieve the lowest driving pressure was selected and applied. Lung ultrasound examinations were performed immediately after entering the operating room (T 0) and at 30 min after entering the anesthesia recovery room (T 3), and the lung ultrasound score was recorded. The occurrence of severe postoperative pulmonary complications within 7 days was recorded. Arterial blood gas analysis was performed at T 0, 1 h after PEEP setting (T 1), at the end of suture at the surgical site (T 2) and at T 3, and the oxygenation index was calculated. The peak airway pressure, PEEP and driving pressure were recorded at T 1 and T 2. The duration of the indwelling thoracic drainage tube use and length of postoperative hospital stay were recorded. Results:The incidence of severe postoperative pulmonary complications within 7 days after surgery was 28%(11/40) in group C and 10% in group DP, and the incidence was significantly lower in DP group than in C group ( P<0.05). Compared with group C, the lung ultrasund score was significantly decreased at T 3, the oxygenation index was increased at T 1-3, the PEEP was increased and the driving pressure was decreased at T 1-2, and the length of postoperative hospital stay was shortened in group DP ( P<0.05). Conclusions:Driving pressure-guided individualized PEEP ventilation can decrease the risk of severe postoperative pulmonary complications, alleviate postoperative lung injury and provide a certain degree of lung protection in patients undergoing rib fracture surgery.

Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease（Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%（ n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%（ n=60) considered its effectiveness comparable, and 20.59%（ n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%（ n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom（ P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.

Objective To explore the diagnosis,treatment and prognostic factors of urachal carcinoma(UrC),aiming to provide reference for the standardized diagnosis and treatment of this disease.Methods A retrospective analysis was conducted on the clinical data of 75 UrC patients confirmed with postoperative pathology treated in our hospital during Mar.2010 and Mar.2023.All patients underwent surgical treatment,and 35 received postoperative chemotherapy.Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors.Kaplan-Meier curves were adopted to calculate the cumulative survival rates and overall survival(OS).Results Among the 75 patients,the male to female ratio was 2.8∶1 and the mean age was(58.4±2.2)years.Median follow-up was 60 months and median OS was 48 months.The 3-year survival rate was 67.3％and the 5-year survival rate was 38.8％.There were 19 cases(25.3％)of CK7 positive,60 cases(80.0％)of Sheldon stage Ⅲ and above,and 26 cases(34.7％)of postoperative recurrence.CK7 positive(P=0.001),Sheldon staging Ⅲ+Ⅳ(P=0.005)and postoperative recurrence(P=0.003)were independent prognostic factors.Conclusion Urachal carcinoma is a rare malignant tumor in males with occult onset.CK7 positive,Sheldon staging and postoperative recurrence were independent prognostic factors of this disease.

Objective To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics(RG)technology,in combination with chemotherapy drug,gemcitabine(GEM),against pancreatic cancer cells.Methods The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study.The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay.CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses[multiplicities of infection(MOI):0,0.1,1.0,3.0]on the survival rate of pancreatic cancer cell lines(Panc02,PANC-1,SW1990,BxPC-3)and normal pancreatic ductal epithelial cells(HPDE6-C7)after treatment for 24,48 or 72 h.Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice(6 weeks old)were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group.PBS(100 μL/animal)or OvFlu-GM-CSF virus(1× 107PFU/100 μL)was given to the mice of the corresponding groups through intratumoral injection,while GEM(100 mg/kg)was injected intraperitoneally,once per 3 days,for totally 9 times.Changes in tumor volume and survival rate were monitored.Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues.HE staining was performed to observe the pathological changes in major organs(heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured to evaluate the safety of the recombinant oncolytic virus.Results The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells.At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0(P＜0.01).The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time(P＜0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells(HPDE6-C7).In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment(P＜0.01),and enhanced the infiltration of T cells in the tumor tissues.No obvious pathological changes were observed in the above-mentioned major organs.Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.Conclusion RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host's anti-tumor immune response.

Objective To investigate the therapeutic effect of combination treatment of transcatheter arterial chemoembolization(TACE),micro wave ablation(MW A)and targeted immunotherapy for hepatocellular carcinoma(HCC).Methods The clinical data of HCC patients,who were admitted to the Affiliated Central Hospital of Jiangnan University of China to receive TACE from August 2016 to August 2023,were retrospectively analyzed.Based on the inclusion criteria,a total of 252 patients were included in this study.According to the therapeutic scheme,the patients were divided into combination group(receiving TACE,MWA,targeted therapy and immunotherapy,n=41),and control group(receiving TACE alone,n=211).The overall survival(OS)and progression-free survival(PFS)of the two groups were statistically analyzed.After propensity score matching at 1∶1 ratio,the clinical effects of the two groups were analyzed.According to different data,t-test,test,Kaplan-Meier curve,logarithmic rank test,Cox regression analysis,or Cox proportional risk model analysis was used to make statistical analysis.Results Multivariate regression analysis showed that tumor number,maximum diameter,invasion of large vessels,tumor capsule,AFP level,glutamic oxalacetic transaminase,BCLC stage and Child-Pugh stage were the independent risk factors for patient survival.Imaging response and combination treatment were the protective factors for survival.After propensity score matching,a total of 37 pairs of patients were obtained,and the baseline data were comparable between the groups.The differences in OS and PFS between the two groups were statistically significant.Combination treatment of TACE,MWA,targeted therapy and immunotherapy could significantly prolong OS and PFS in HCC patients.Conclusion Compared with TACE alone,combination use of TACE,MWA,targeted therapy and immunotherapy is a more effective therapeutic scheme for HCC,it can remarkably and effectively improve OS and PFS in HCC patients.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.

Objective To explore the diagnosis,treatment and prognostic factors of urachal carcinoma(UrC),aiming to provide reference for the standardized diagnosis and treatment of this disease.Methods A retrospective analysis was conducted on the clinical data of 75 UrC patients confirmed with postoperative pathology treated in our hospital during Mar.2010 and Mar.2023.All patients underwent surgical treatment,and 35 received postoperative chemotherapy.Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors.Kaplan-Meier curves were adopted to calculate the cumulative survival rates and overall survival(OS).Results Among the 75 patients,the male to female ratio was 2.8∶1 and the mean age was(58.4±2.2)years.Median follow-up was 60 months and median OS was 48 months.The 3-year survival rate was 67.3％and the 5-year survival rate was 38.8％.There were 19 cases(25.3％)of CK7 positive,60 cases(80.0％)of Sheldon stage Ⅲ and above,and 26 cases(34.7％)of postoperative recurrence.CK7 positive(P=0.001),Sheldon staging Ⅲ+Ⅳ(P=0.005)and postoperative recurrence(P=0.003)were independent prognostic factors.Conclusion Urachal carcinoma is a rare malignant tumor in males with occult onset.CK7 positive,Sheldon staging and postoperative recurrence were independent prognostic factors of this disease.

Objective:To investigate the changes in the expression of miR-146a-5p and steroidogenic acute regulatory protein (StAR) in the blood vessels of rats with hypertension complicated with sepsis, and to preliminarily evaluate the underlying mechanisms of vascular lesions in hypertension complicated with sepsis.Methods:Twenty-four clean-grade healthy male Wistar rats, aged 12 weeks, weighing 250-270 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group, sepsis group, hypertension group, and hypertension complicated with sepsis group. In sham operation group, laparotomy was performed, and sterile normal saline was subcutaneously infused using a micro-osmotic pump for 4 weeks. The sepsis model was established by cecal ligation and perforation after anesthesia in sepsis group. The hypertension model was established by subcutaneously infusing angiotensin Ⅱ at a rate of 500 ng·kg -1·min -1 for 4 weeks using a micro-osmotic pump in hypertension group. In hypertension complicated with sepsis group, angiotensin Ⅱ was subcutaneously infused, and 4 weeks later the sepsis model was established by cecal ligation and perforation. Blood pressure was measured at the end of establishing the model in each group, and blood samples of the abdominal aorta and specimens of aorta were obtained under deep anesthesia, and the serum tumor necrosis factor-alpha (TNF-α) concentration was determined by enzyme-linked immunosorbent assay. The systolic and diastolic functions of the aorta were detected using the aortic vascular ring assay. The collagen volume fraction (CVF) was calculated after Masson staining. The expression of α-smooth muscle actin (α-SMA) and StAR was detected using the immunohistochemical staining assay, and the thickness of the aortic wall was measured. The expression of StAR mRNA and miR-146a-5p was detected using quantitative real-time polymerase chain reaction. Results:Compared with sham operation group, the aortic contraction rate was significantly decreased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in the other three groups, and the systolic blood pressure and CVF were significantly increased, the thickness of the aortic wall was increased, the expression of α-SMA was up-regulated, and the thickness of the aortic wall was increased in hypertension and hypertension complicated with sepsis groups ( P<0.05). Compared with sepsis group, the systolic pressure was significantly increased, the aortic contraction rate was decreased, CVF was increased, the expression of α-SMA was up-regulated, the thickness of the aortic wall was increased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in hypertension complicated with sepsis group ( P<0.05). Compared with hypertension group, the aortic contraction rate was significantly decreased, the diastolic rate was increased, the expression of StAR protein and mRNA was up-regulated, the expression of miR-146a-5p was down-regulated, and the serum TNF-α concentration was increased in hypertension complicated with sepsis group ( P<0.05). Conclusions:Down-regulation of miR-146a-5p and up-regulation of StAR in the blood vessels of rats with hypertension complicated with sepsis may be associated with the vascular lesions caused by hypertension complicated with sepsis.