Objective:To investigate the current status of the teaching methods used in the integrated basic and clinical courses and the approaches for improving such teaching methods, and to improve the teaching quality of the integrated basic and clinical courses for "4+4" Medical Doctor Program in Peking Union Medical College.Methods:Students in the Class 2020 of "4+4" Medical Doctor Program who completed the integrated courses from September 2020 to August 2021 were enrolled as subjects. Questionnaire surveys and interviews were performed for the subjects in terms of class hours, integration effect, and self-learning methods. R4.0.0 software was used to perform a statistical analysis of data.Results:The mean weekly class hours of existing modules were (27.59±2.61) hours per week, which was higher than the expectation of students. There was a negative linear correlation between weekly class hours and mean satisfaction score of each module ( r=-0.71, P=0.022). The integration of basic and clinical medical courses had a mean satisfaction score of 2.652. The median preview time for case-based learning/problem-based learning was 30 minutes. Conclusions:In the reform of the integration of basic and clinical medical courses, it is crucial to select and apply proper teaching methods. In order to further improve teaching effect, it is advised to reduce the class hours of theoretical lectures and carefully design and prepare learning materials, and the teaching contents should be organized according to the internal logic of knowledge and the association between clinical knowledge and the knowledge learned during the stage of basic medicine.

Objective To evaluate the safety and effectiveness of excessive dynamic airway collapse(EDAC)treated by laser.Methods 13 patients with EDAC confirmed by bronchoscopy from January 2018 to August 2022 were selected and divided into a simple EDAC group(6 cases)and an EDAC combined with tracheobronchomalacia(TBM)group(7 cases)based on whether they were combined with TBM.All patients underwent laser tracheobronchoplasty under bronchoscope.Symptoms,airway collapse,oxygenation index,modified version of British Medical Research Council dyspnoea scale(mMRC)and 6 min walking test before and after treatment were compared to evaluate the therapeutic effect.Results 13 patients underwent 17 times of laser tracheobronchoplasty with laser power of 8～15 W,and 4 patients underwent 2 times of laser tracheobronchoplasty.After treatment,the clinical symptoms of cough,sputum,shortness of breath and dyspnea were improved in all patients.1 week post-treatment,the EDAC group showed a significant improvement in airway lumen stenosis,with a significant statistical difference(P<0.05),1 month post-treatment,enhancements were observed in airway stenosis,oxygenation index,FEV1%,6-minute walk test,and mMRC,which remained stable over a 6 month follow-up.In the EDAC + TBM group,significant enhancements in airway stenosis,oxygenation index,and mMRC were noted 1 week post-treatment,with statistical significance(P<0.05).Between 8 d～6 months post-treatment,some patients exhibited a recurrence of airway stenosis,necessitating comprehensive interventions like balloon dilation,cryotherapy,and stent insertion.Local necrosis and granuloma occurred in some patients after laser therapy,and no serious complications associated with laser intervention were found in all patients.Conclusion Laser tracheobronchoplasty is a safe and effective technique for the treatment of EDAC.For patients with EDAC alone,the therapeutic effect is good,but for patients with EDAC combined with TBM,the long-term effect is not good.

Objective To develop the automated preparation of 18F-Alfatide II using newly-designed 18F-minireactor and perform 18F-Alfatide D microPET/CT imaging in tumor.Methods The automated preparation of 18F-Alfatide H was developed by using 18F-microreactor and water phase Al18F-chelating method,and the radiochemical yield and quality analysis were measured.The nude mice bearing breast tumor ZR-75-1 and nasopharyngeal tumor CNE1 were established(n = 3 respectively).MicroPET/CT imaging was performed at 0.5,1.0 and 2.0 h after the injection of 18F-Alfatide II.The region of interest(ROI)was depicted and the tumor/muscle(T/M)ratio was calculated.Results 18F-Alfatide II was automatically prepared with the total synthesis time of 40 min,the radiochemical yield of(28±6)%(no decay corrected,n=11),and the radiochemical purity >97%.All quality analysis indexes accorded with the radiopharmaceutical requirements.18F-Alfatide II microPET/CT images of ZR-75-1 and CNE1 tumors were clear due to the high radioactivity uptake of tumor lesions(T/M ratio was greater than 4.0 at 1.0 h after injection).Conclusion Based on the 18F-minireactor,the,8F-Alfatide II can be prepared successfully with short synthesis time and high radiochemical yield,which can help the application studies in 18F-Alfatide II microPET/CT imaging.

Objective: To investigate the feasibility of early monitoring doxorubicin (DOX)-induced cardiotoxicity by apoptosis molecular imaging of 2-(5-[¹⁸F]fluoro-pentyl)-2-methyl-malonic acid (¹⁸F-ML-10) PET/CT. Methods: Forty-seven BALB/c mice were randomly divided into the chemotherapy group (n=30) and the control group (n=17) according to the random number table. The mice in chemotherapy group were intraperitoneally injected with DOX (4 mg/kg) once a week for 3 weeks and mice in the control group were injected with the same amount of normal saline. All mice were subjected to ¹⁸F-fluorodeoxyglucose (FDG) and ¹⁸F-ML-10 PET/CT imaging at day 0, 2, 9, 16, and left ventricular ejection fraction (LVEF) was continuously monitored using cine cardiac MR (cine-CMR) imaging. The region of interest (ROI) was delineated on PET/CT images, and the maximum percentage activity of injection dose per gram of tissue (%ID/g) was calculated. The mice were sacrificed after imaging, and the heart tissue was taken for HE staining and TdT-mediated dUTP nick end labeling (TUNEL) assay. One-way analysis of variance, independent-samples t test and Pearson correlation analysis were used to analyze the data. Results: In the chemotherapy group, the myocardial ¹⁸F-FDG uptake on day 0, 2, 9, 16 were (63.3±14.5), (93.7±24.0), (153.6±20.6) and (135.8±32.5) %ID/g respectively, and ¹⁸F-ML-10 uptake were (0.09±0.02), (0.18±0.03), (0.22±0.04) and (0.55±0.12) %ID/g respectively. Compared with baseline (day 0), ¹⁸F-FDG and ¹⁸F-ML-10 uptake were significantly increased in the chemotherapy group at each time point after DOX administration(F=6.823, 20.848, both P<0.01). The myocardial ¹⁸F-ML-10 and ¹⁸F-FDG uptake were essentially unchanged at all time points in the control group(F=2.036, 1.155, both P>0.05). TUNEL and HE staining indicated that the cardiomyocytes in the chemotherapy group showed obvious apoptosis and vacuolization, and the apoptotic index (AI) was positively correlated with the ¹⁸F-ML-10 uptake (r=0.950, P<0.01). The cine-CMR imaging results showed that the LVEF in the chemotherapy group continued to decrease after DOX administration (F=4.507, P<0.05), and significant difference was identified at day 16 (t=2.980, P<0.05). There was a significant negative correlation between ¹⁸F-ML-10 uptake and LVEF (r=-0.709, P=0.01). Conclusions Both ¹⁸F-FDG and ¹⁸F-ML-10 PET/CT imaging can early assess DOX-induced cardiotoxicity in vivo. Given the high targeting specificity of ¹⁸F-ML-10, it may have a greater clinical transformation advantage over ¹⁸F-FDG in early assessment of cardiotoxicity.

Objective To investigate the tumor/ non-tumor (T/ NT) ratio during 99 Tcm-hydrazinon-icotinamide(HYNIC)-( poly-( ethylene glycol), PEG) 4-Glu( cyclo ( Arg-Gly-Asp-D-Phe-Lys ( PEG4 ))) 2 ( 99 Tcm-3PRGD2 ) SPECT/ CT imaging and clinical pathological features of breast cancer. Methods Forty-five female patients (age range: 39-76 (53.0±9.5) years) with suspected breast malignant nodules or mas-ses from October 2016 to June 2017 were prospectively enrolled. Patients underwent 99 Tcm-3PRGD2 SPECT/CT imaging before breast puncture and surgery. All subjects had pathological results, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER-2), Ki-67 and mi-crovessel density ( MVD) were obtained by immunohistochemistry and fluorescence in situ hybridization(FISH). Two-sample t test and Kruskal-Wallis H test were used to analyze the data. Results Invasive duc-tal carcinoma was pathologically confirmed in 35 of 45 patients. There were 7 patients in stage Ⅰ, 11 pa-tients in stage ⅡA and 17 patients in stage ⅡB. The Luminal A subtype, Luminal B subtype, ERBB2+subtype, Basal-like subtype were found in 6, 9, 9 and 11 patients, respectively. The T/ NT ratio was signifi-cantly higher in the stageⅡB patients than that in stageⅠ+ⅡA patients (4.54±1.46 vs 3.32±1.72, t= -2.24, P<0.05). Patients with ERBB2+ subtype had higher T/ NT ratio compared to patients with Basal-like sub-type: 5.80(3.90, 6.70) vs 2.80(2.20,3.50), H= 11.06, χ2 = 15.31, both P<0.05. Besides, the T/ NT ra-tios in the HER-2 positive group and lymphatic metastasis group were significantly higher than those in the HER-2 negative group and group without lymph node metastasis (t values: -3.99, -2.51, both P<0.05). MVD of HER-2 positive group was higher than that of HER-2 negative group (t= 7.13, P<0.01). Conclu-sion The T/ NT ratio during 99 Tcm-3PRGD2 SPECT/ CT imaging has relations with TNM staging, lymph node infiltration and HER-2 in breast cancer.

Objective To study curative efficacy of cyclophosphamide combined with VAD regimen in treatment of multiple myeloma and its effects on coagulation function.Methods 78 patients of multiple myeloma who received therapy from July 2013 to July 2016 in our hospital were selected as research objects, and divided into the control group and the observation group , the control group was treated with VAD regimen, while the observation group was treated with cyclophosphamide combined with VAD regimen.Then coagulation factor and anti-coagulation factor activity, adverse reaction, therapeutic effect after treatment between two groups were compared.Results After treatment, decreased blood coagulation factor, Protein C, protein S and antithrombin were increased between two groups , the difference was not statistically significant.Incidence of adverse reactions in observation group was less than the control group[15.38%(6/39)vs 46.15%(18/39)], the difference was statistically significant(P<0.05);The total effective rate of observation group was statistically higher than that in the control group [ 89.74%( 35/39 ) vs 58.97%( 23/39 ) ] , the difference was statistically significant(P<0.05).Conclusion Cyclophosphamide combined with VAD regimen is well for multiple myeloma, which can effectively improve the patient's condition, improve the life quality of patients, and will not cause a greater impact on blood coagulation function.

Objective To investigate the association of cysteine aspartic acid specific protease 8 (CASP 8) gene-652 6N Insertion/Deletion polymorphisms and susceptibility of type 2 diabetes mellitus (T2DM). Methods CASP 8 gene -652 6N I/D polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing in 414 controls and 410 patients with T2DM. Results I/I, I/D and D/D genotype frequency were 56.5%, 38.9%, 4.6%in controls and 58.0%, 32.9%, 9.0%in T2DM group respectively (P<0.05). The risk in D/D genotype people was 1.916 times than I/I genotype (adjusted OR=1.916, 95%CI=1.199~3.054, P<0.05). The fasting blood sugar of D/D genotype people was significantly higher than that of I/D and I/I genotype people (P<0.05). Conclusions CASP 8 gene-652 6N I/D polymorphisms are associated with T2DM outbreak.

Objective: To investigate the effects of andrographolide on extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and tumor necrosis factor-α (TNF-α) expression in lipopolysaccharide (LPS)-activated macrophages. Methods: LPS-activated mouse peritoneal macrophages were cultured in media with different concentrations of andrographolide. Cytotoxicity of andrographolide was detected by cell counting kit-8. The macrophages were lysed, and then expressions of phosphorylated ERK1/2, JNK and p38 and nuclear factor-κB inhibitor (IκBα) protein were detected by Western blotting and TNF-α mRNA expression was detected by reverse transcription-polymerase chain reaction. Supernatants of the macrophages were used to detect content of TNF-α protein by enzyme-linked immunosorbent assay. Results: Andrographolide at 1-100 μg/mL showed no cytotoxicity on LPS-activated mouse peritoneal macrophages. Andrographolide inhibited ERK1/2 phosphorylation in LPS-activated murine peritoneal macrophages, which was concentration-dependent (P<0.01). Andrographolide at 1-25 μg/mL had no effects on phosphorylation levels of JNK and p38 and IκBα degradation in LPS-stimulated mouse peritoneal macrophages. In activated macrophages, TNF-α expression was inhibited by 12 μg/mL andrographolide and 20 μmol/L PD98059 (inhibitor of ERK1/2 signaling pathway) at both mRNA expression and protein secretion levels. Conclusion: In LPS-activated macrophages, andrographolide may inhibit the expression of TNF-α by inhibiting ERK1/2 signaling pathway.

Objective To identify human leucocyte antigen (HLA)-A* 0201-restricted hepatitis C virus (HCV)-cytotoxic T lymphocyte (CTL) epitopes. Methods Based on the prediction results of RANKpep and SYFPEITHI prediction programs, six candidate CTL epitopes were selected and synthesized. The affinity of candidate CTL epitopes to HLA-A* 0201 molecules of T2 cells was explored. Subsequently, enzyme-linked immunosorbent spot (ELISPOT) assay and intracellular cytokine staining (ICS) were utilized to determine whether candidate CTL epitopes could induce the recall positive response in peripheral blood mononuclear cells (PBMC) of HLA-A* 0201 positive HCV-1b-infected patients. Results Among six candidate CTL epitopes, peptides C_181(LLSCLTTPV) and NS2_172 (VLQAGLIRV) had high affinity to HLA-A* 0201 molecules. Moreover, the affinity was proportional to the concentration of peptide. Furthermore, among ten HLA-A* 0201 positive HCV-1b-infected patients, the frequencies of C_181 and NS2_172-specific interferon (IFN)-γ-producing cells were 0-19 spots forming cells (SFC)/1 × 105 PBMC and 0-20 SFC/1 × 105 PBMC, respectively.The percentages of C_ 181 and NS2_172-specific IFN-γ+ CD8+ T lymphocytes in total CD8+ T lymphocytes were 0.006%-0.065% and 0.005%-0.080%, respectively. Conclusion Peptides C_181 (LLSCLTTPV) and NS2_172 (VLQAGLIRV) are identified as novel HLA-A* 0201-restricted HCV-CTL epitopes.

Objective To investigate hypolipemic treatment of hyperlipidemic panereatiti(HLP)with integrated traditional Chinese and western medicine.Methods Cinical data of 20 patients of HLP were analyzed retrospectively.Eight patients in the control group were treated with conventional therapies,while 12 patients in the treatment group were treated as follows:①Enema with 180ml solution(50% magnesium sulfate 30 ml.Glycerin 60ml,water 90ml).②Rhubarb gastrogavage with 9 g tid.③Intravenous drip with 24 g salvia miltiorrhiza qd.Results The treatment group had significant difference comparing with the control group in terms of the serum TG in 48 hours(P<0.01),time of autonomous bowel movement recover(P<0.01),days of abdominal pain disappear(P<0.05),days of hospitalization(P<0.01).Conclusion The treatment of Enema with 180 ml solution.Rhubarb gastrogavage with 9g tid,and Intravenous drip with 24 g salvia miltiorrhiza qd can relieve the symptoms of HLP and decrease blood-fat greatly.