[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

Abstract Recently, the Ministry of Education issued Guiding Opinions on Comprehensively Promoting the Construction of Healthy Schools hereinafter referred to as the Guiding Opinions, which systematically established the goal system, key tasks, critical measures, and safeguard mechanisms for the construction of healthy schools in the new era. Against the backdrop, comprehensively promoting the construction of healthy schools has become a core project for implementing the concept of "Health First", carrying out joint prevention and control of multiple diseases, and responding to national action plans. Based on a systematic analysis of the internal logic between healthy school construction and the "education powerhouse strategy", the study deeply expounds on its core mission as a "foundational project for talent cultivation" and a "hub for the integration of five educations". Combining the eight key tasks and three critical measures clarified in the Guiding Opinions, it constructs a multi dimensional, systematic, and operable implementation path from the aspects of concept leadership and practice internalization, data monitoring and closed loop management, team support and environmental optimization, literacy promotion and evaluation innovation, innovation drive and characteristic development,digital empowerment and smart governance. The study provides a forward looking and strategic comprehensive solution for improving the collective health literacy of students and building a comprehensive prevention and control system for common campus diseases in the new era.

To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.

Objective To explore the characteristics and influencing factors of drug-induced liver injury(DILI)associated with the postoperative use of propacetamol,and to provide guidance for rational clinical medication.Methods A retrospective analysis was conducted on hospitalized patients who underwent surgical treatment and were administered propacetamol from January 2022 to June 2024.Cases were screened based on established inclusion and exclusion criteria.Statistical analyses were performed on patients'demographic data,medication information,liver function indicators before and after medication,comorbid conditions,and concomitant medications to assess the incidence and influencing factors of propacetamol-related DILI.A multivariate Logistic regression analysis was conducted to identify related risk factors.Results A total of 7,579 patients were sampled,of which 2,114 met the inclusion criteria.Among them,531 patients(25.1%)experienced DILI,primarily presenting with abnormal liver function indicators.This included elevated alanine aminotransferase in 379 cases(71.4%),elevated aspartate aminotransferase in 197 cases(37.1%),elevated alkaline phosphatase in 209 cases(39.4%),and elevated total bilirubin in 92 cases(17.3%).Univariate analysis revealed that there were significant differences in gender,height,age,weight,body mass index(BMI),duration of propacetamol use,total medication dosage,concomitant use of hepatic-metabolized antibiotics,and history of liver disease between the DILI group and non-DILI group(P<0.05).Multivariate Logistic regression analysis showed that patient gender,BMI,total propacetamol dosage,liver-related diseases,and concomitant use of hepatic-metabolized antibiotics as independent risk factors for DILI(P<0.05).Conclusion The use of propacetamol for postoperative analgesia presents a risk for liver injury,and the risk is particularly pronounced in males,obesity,high-dose dosing,patients with underlying hepatic disease,and comorbid hepatic metabolism of antimicrobial drug use.It is recommended to strengthen the monitoring of liver function in clinical application,strictly control the dosage and duration of treatment,and avoid co-administration with hepatotoxic drugs to ensure the safety of drug use.

Objective:To compare the consistency and efficacy of ultrasound and CT in the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer, and to explore the clinical value of the combined application of multimodal imaging.Methods:The 119 thyroid cancer patients underwent surgical treatment from January to September 2023 in Zhongshan Hospital Affiliated to Dalian University were retrospectively analyzed. All patients underwent ultrasound and CT examinations before operation. The results of postoperative histopathology examination were taken as the gold standard, the efficacy of ultrasound and CT in preoperative diagnosis of cervical lymph node metastasis was compared.Results:A total of 1 721 cervical lymph nodes were detected in 119 patients with thyroid cancer, among which 1 378 lymph nodes were benign, and 343 lymph nodes were malignant, the rate of malignant lymph nodes was 19.93% (343/1 721). Among them, the proportion of malignant lymph nodes in area Ⅵ was the highest, 22.58% (245/1 085), followed by area Ⅲ, 21.26% (37/174). The sensitivity of CT in diagnosing cervical lymph node metastasis in patients with thyroid cancer was significantly higher than that of ultrasound diagnosis: 58.46% (38/65) vs. 38.46% (25/65), the specificity was significantly lower than that of ultrasound diagnosis: 85.19% (46/54) vs. 96.30% (52/54), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in accuracy between CT and ultrasound ( P>0.05). Conclusions:In the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer by ultrasound and CT, ultrasound examination has no radiation risk, while CT examination has a higher diagnostic efficiency.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective Comparing the clinical efficacy of moxifloxacin and azithromycin in the treatment of Mycoplasmal pneumoniae pneumonia(MPP).Methods MPP patients admitted to our hospital from January 2023 to May 2024 were selected and randomly divided into the observation group and the control group.Both groups were given conventional treatment such as salbutamol and budesonide aerosol inhalation.Additionally,the control group was given azithromycin 0.5 g,ivd,qd,and the observation group was given moxifloxacin 0.4 g,ivd,qd.After one week of treatment,the efficacy,symptom disappearance time and adverse drug reactions occurrence of the two groups were compared.The serum inflammatory markers[white blood cell count(WBC),interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT)],immunoglobulin indicators(IgA,IgG,IgM),T lymphocyte subset indicators(CD3+,CD4+,and CD4+/CD8+)before and after treatment were compared between the two groups.Results A total of 80 patients were included and each group was 40 patients.After treatment,the total effective rate of observation group(95.00％)was higher than that of control group(75.00％)(P＜0.05).The disappearance time of symptoms(cough,fever,and lung rales)in the observation group was significantly lower than that in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in both groups significantly increased,while the levels of serum IL-6,CRP,PCT,WBC,IgA,IgM,and IgG significantly decreased(P＜0.05),with the observation group showing better results(P＜0.05).There was no significantiy difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Moxifloxacin is more effective than azithromycin in the treatment of MPP,which can relieve symptoms,improve immune function,reduce inflammatory response,and has a relatively good safety profile.

BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

Objective To investigate the impact of pharmaceutical services provided by clinical pharmacists on rational drug use and cost control in hepatobiliary surgery under the Diagnosis Related Groups(DRGs)payment model,aming to provide evidence for improving the rationality of drug therapy and saving medical costs.Methods Patients classified under DRGs disease codes HB15,HB13,and HB11 from November 2022 to April 2024 were selected as study subjects.A total of 195 patients were included,with 106 in the intervention group and 89 in the control group.The intervention group received multidimensional clinical pharmaceutical services in addition to the standard care provided to the control group.The rational drug use rate,medication costs,total hospitalization expenses,and length of hospital stay were observed between the two groups.A cost-benefit analysis was employed to evaluate the economic impact of providing pharmaceutical services to hepatobiliary surgical patients.The cost indicator was the clinical pharmacy services cost,and the benefit indicators were the reductions in total hospitalization expenses and medication costs.The benefit-cost ratio(B/C)was calculated,and sensitivity analysis was performed.Results The intervention group showed significantly higher rational use rates of prophylactic antimicrobial agents(drug selection:83.96％vs.46.07％,P＜0.01;treatment duration:84.91％vs.56.18％,P＜0.01)and parenteral nutrition drugs(97.17％vs.73.03％,P＜0.01)compared to the control group.Additionally,the intervention group had significantly reduced the length of hospital stay,total hospitalization expenses,medication costs,and insurance over-expenditure compared to the control group(P＜0.05).Furthermore,clinical pharmacist intervention led to a reduction in medication costs by 4 320.05(2 555.00,5 088.25)yuan(CNY)and total hospitalization expenses by 8 891.12(5 135.05,10 074.03)yuan(CNY).The B/C ratios were 14.24(8.42,16.77)and 29.30(16.92,33.20),respectively,indicating economic efficiency.Sensitivity analysis supported these results.Conclusion Under the DRGs payment model,clinical pharmaceutical services guided by drug therapy pathways contribute to improving rational drug use in hepatobiliary surgery and provide clear economic benefits,playing a positive role in reducing medical costs.