Objective·In view of the low funding rate of the Young Scientists Fund of National Natural Science Foundation of China in the medical field,this research conducted an in-depth investigation of the applicants in a medical school and quantitatively analyzed the influencing factors of project establishment,so as to provide reference for further improving the quality of project application and strengthening the training of young medical talents.Methods·A cross-sectional survey was used to select applicants from secondary schools of Shanghai Jiao Tong University School of Medicine and its 13 affiliated hospitals who had experience in applying for the fund from 2020 to 2022.Logistic stepwise regression model was applied to modeling and analysis by using the project application result as the dependent variable and the applicants'basic information and application status as independent variables.Results·The analysis results of 921 applicants showed that educational background(OR=1.86,95%CI 1.14?3.04),graduate university(OR=2.45,95%CI 1.47?4.08),sufficient preliminary work foundation(OR=4.22,95%CI 2.44?7.29),average impact factor of representative works(OR=1.10,95%CI 1.04?1.17),and total self-evaluation score of application documents(OR=1.06,95%CI 1.04?1.08)were the main influencing factors for project approval.The average impact factor and the highest impact factor of the approved representative works showed an increasing trend year by year.In addition,the influencing factors for the approval of young doctors and full-time researchers were different.The longer the graduation time of young doctors,the lower the approval rate.Conclusion·The funding rate of Young Scientists Fund is low,and the requirements for scientific research achievements are increasing year by year.Attention should be paid to early accumulation and improving the quality of application writing.Further measures should be taken to strengthen the early training of young medical talents,improve cultivation measures and consolidate research foundations.

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H₂SO₄ terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Objective    To investigate the feasibility of using magnetic beads to locate small pulmonary nodules. Methods    Twelve rabbits were randomly divided into two groups, 6 in each group. One group underwent thoracotomy after anesthesia and the other group underwent percutaneous puncture under the guidance of X-ray. One and two cylindrical tracer magnets (magnetic beads) with a diameter of 1 mm and a height of 3 mm were injected adjacent to the imaginary pulmonary nodules in left lung in each group. The magnetic beads beside the imaginary nodules were attracted by a pursuit magnet with a diameter of 9 mm and a height of 19 mm. The effectiveness of localization by magnetic beads were determined by attraction between tracer and pursuit magnets. Results    All processes were uneven in 12 rabbits. There was micro hemorrhage and no hematoma in the lung tissue at the injection site of the magnetic beads. When tracked with the pursuit magnets, there was one bead divorce in cases that one bead was injected, but no migration or divorce of the magnetic beads in cases that two magnetic beads were simultaneously injected to localize the small pulmonary nodules. Conclusion    The feasibility of using magnetic beads to locate small pulmonary nodules has been  preliminarily verified.

【Objective】 To compare and analyze clinical efficacy and safety of subxiphoid vs. intercostal video-assisted thoracoscopic surgery (VATS) thymic tumor resection. 【Methods】 We selected 124 patients from January 2015 to March 2019, who received VATS thymic tumor resection in the Thoracic Department of The First Affiliated Hospital of Xi'an Jiaotong University. We divided them into the subxiphoid VATS group with 47 cases and intercostal VATS group with 77 cases to analyze clinical characteristics, postoperation outcomes, complications, pain score, and short-term quality of life. 【Results】 There were no significant differences in operation time, blood loss, the rate of postoperative pneumonia, arrhythmia, phrenic nerve paralysis or myasthenia crisis between the two groups (P>0.05). Average hospital stay: It was shorter in subxiphoid VATS group than intercostal VATS group (P<0.05). Pain score: It was lower the first day and the third day after operation in subxiphoid VATS group than in intercostal VATS group (P<0.05). SF-36 health scale score: 3-month and 12-month postoperation score was higher in subxiphoid VATS group than in intercostal VATS group (P<0.05). 【Conclusion】 Subxiphoid VATS thymic tumor resection is safe and feasible; compared with intercostal approach, it can significantly reduce wound pain and improve short-term quality of life.

Objective    To compare and analyze the short-term efficacy of different surgical methods for Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma. Methods    We selected 82 patients who accepted radical resection of esophagogastric junction carcinoma from March 2015 to March 2018 in our department, including 53 males and 29 females, aged 48-72 (61±6) years. The patients were divided into four groups according to the surgical method: a left thoracotomy group (n=14), a laparoscopic left small thoracotomy group (n=33), a thoracoscopic Ivor-Lewis group (n=17), and a thoracoscopic McKeown group (n=18). Their clinical characteristics, operative situations, postoperative complications and survival rate were analyzed. Results    Among the four groups, the left thoracotomy group cost the shortest operation time, followed by laparoscopic left small thoracotomy group, thoracoscopic McKeown group and thoracoscopic Ivor-Lewis group. The thoracoscopic McKeown group/laparoscopic left small thoracotomy group had the least bleeding. The fewest lymph nodes were dissected in the left thoracotomy group and the most in the thoracoscopic McKeown group. The laparoscopic left small thoracotomy group had the lowest total complication rate and the incidence of pneumonia and arrhythmia among the four groups (P<0.05). There was no significant difference in survival rate among the four groups (P>0.05). Conclusion    For Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma, thoracoscopy combined with laparoscopic radical resection is safe and reliable. Laparoscopic left small thoracotomy has the advantages of minimal invasiveness and complete lymph node dissection, especially for the patients with poor cardiopulmonary function, which will significantly shorten operation time and reduce postoperative complications, so it is worth to be popularized.

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both and , which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially the AKT/FOXO3a/BIM pathway.

Objective To evaluate the effects of autophagy on contrast-induced acute kidney injury (CI-AKI) in rat models.Methods Eighteen male rats were divided into control group (Con),CI-AKI group (CI-AKI) and rapamycin-pretreated group (Rapa).In the CI-AKI group,CI-AKI was induced by intraperitoneal injection of iohexol (12.25 g/kg I).In the Rapa group,rapamycin was given by intraperitoneal injection with a dose of 5 mg/(kg ·d) for consecutive 7 days,and then injected with iohexol (12.25 g/kg I).Rats in the Con group were injected by the same dose of saline.The renal function,renal histopathology,and the levels of LC3 Ⅱ / Ⅰ and Beclin-1 as well as catalase (CAT) in the kidneys of rats were evaluated one day after the injection.Results Compared with the Con group,serum creatinine in the CI-AKI group was significantly increased ((239.93±27.00)μmol/L) vs (51.70±10.59) μmol/L,P＜0.05),and the content of CAT was significantly decreased ((14.86 ± 0.32) U/mg vs (18.72±1.46) U/mg,P＜0.05).In the CI-AKI group,renal tubules were severely injured,and the expression of autophagy-related proteins LC3 Ⅲ / Ⅰ and Beclin-1 in renal tissue was increased.Compared with the CI-AKI group,the pretreatment of rapamycin (Rapa group) increased the expression of LC3 Ⅱ / Ⅰ and Beclin-1 as well as the content of CAT in renal tissue ((17.62±1.86) U/mg vs (14.86±0.32) U/mg,P＜0.05),and inhibited the increase of contrast-induced serum creatinine ((187.62± 47.76) μmol/L vs (239.93±27.00) μmol/L,P＜0.05) and renal tubule injury.Conclusions The results showed that contrast administration can induce autophagy activation in kidneys,while enhancing autophagy can attenuate contrast-induced oxidative stress injury and related renal injury.

Aim To investigate the effects of diterpene ginkgolides meglumine injection (DGMI ) on amino acids and monoamine neurotransmitters in rats with cerebral ischemia/reperfusion injury.Methods In-traluminal suture was applied to establish middle cere-bral artery occlusion (MCAO/R)model with ischemia for 1.5 h and reperfusion for 24 h.After the adminis-tration of DGMI (i.v.),the levels of amino acid and monoamine neurotransmitters in brain tissue were de-tected through HPLC-ECD.Results DGMI down-reg-ulated the concentrations of aspartic acid, glutamic acid,glycine and γ-aminobutyric acid which were in-creased in MCAO/R group.DGMI also reduced the levels of norepinephrine epinephrine,glyoxylic acid, serotonin and 5-HIAA in cortex and hippocampus,and increased adrenaline content compared to the model group.Conclusion DGMI exhibits a protective role in rats with cerebral ischemia /reperfusion injury through regulating amino acids and monoamine neuro-transmitters.

Objective To investigate the efficiency of transduction of recombinant adenovirus-mediated human endothelial nitric oxide synthase (eNOS) into lung tissue by repeated intratracheal transfection in rats.Methods Sixty 3-4 month old male Wistar rats weighing 220-280 g were randomly divided into 2 groups:control group (group C,n =10) and eNOS gene transduction group (group T,n =50).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 35 mg/kg,tracheally intubated and mechanically ventilated (VT 2.5 ml,RR 60 bpm,FiO2 1.0).Recombinant adenovirus carrying human eNOS gene was given as gift by Professor Gerard from Texas University,Southwest Medical Center.In group T 50 μl of the recombinant adenovirus in concentration of 5 × 109 PFU/ml was instilled into trachea every 5 minutes for 12 times,while in group C equal volume of vector conservation solution was instilled instead.Pulmonary arterial blood samples were obtained at 2,5,7,14 and 21 d after intratracheal transfection (n =10 at each time point) for determination of serum NO concentration.The animals were immediately sacrificed after blood sample collection for determination of expression of eNOS protein in the lung tissue and RNA.The eNOS expression in the trachea,bronchus,lung,liver,spleen and kidney was detected by immuno-histochemistry.Results The serum NO concentrations were significantly higher at all time points in group T than in group C.The eNOS expression was detected in the epithelial cells of trachea and bronchi,and endothelial cells of alveoli and pulmonary blood vessels in group T but not in group C.eNOS expression was not detected in liver,spleen and kidney at 7 d after intratracheal transfection in group T.Conclusion Human eNOS gene mediated by recombinant adenovirus was transducted into rat lung tissue with normal enzyme activity by repeated intratracheal administration without being detected in distant organs.

BACKGROUNDUp to now, locally advanced non-small cell lung cancer simutaneously involving carina, heart and great vessels is still regarded as contraindication for surgical treatment. However, the prognosis is very poor in these patients treated with chemotherapy and/or chemoradiotherapy. The aim of this study is to summarize the clinical experiences of carinoplasty combined with heart and great vessel plasty in the treatment of 84 patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels or both in our hospital.

METHODSFrom March, 1988 to December, 2004, carinal resection and reconstruction combined with heart, great vessel plasty was performed in 84 patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels simutaneously. The operative procedures in this series included as follows: (1) Right upper sleeve lobectomy combined with carinal resection and reconstruction, and right pulmonary artery sleeve angioplasty in 9 patients; (2) Right sleeve pneumonectomy combined with partial resection and reconstruction of left atrium, and superior vena cava resection and Gortex grafts in 3 cases; (3) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery sleeve angioplasty and partial resection and reconstruction of left atrium in 3 cases; (4) Right upper sleeve lobectomy combined with carinoplasty, right pulmonary artery sleeve angioplasty and partial resection and reconstruction of left atrium in 10 cases; (5) Left upper sleeve lobectomy combined with carinoplasty and left pulmonary artery angioplasty in 9 cases; (6) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery sleeve angioplasty and resection of the aorta arch sheath in 6 cases; (7) Right upper-middle sleeve lobectomy combined with carinoplasty and right pulmonary artery sleeve angioplasty in 3 cases; (8) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery angioplasty, resection of the aorta arch sheath and partial resection and reconstruction of left artium in 8 cases; (9) Right upper sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and partial resection and reconstruction of left atrium in 4 cases; (10) Left sleeve pneumonectomy combined with partial resection and reconstruction of left atrium in 3 cases; (11) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and superior vena cava resection and reconstruction with Gortex grafts in 23 casese; (12) Right sleeve pneumonectomy combined with partial resection and reconstruction of left atrium in 1 case; (13) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and partial resection and reconstruction of left atrium in 1 case; (14) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and right inferior pulmonary vein sleeve resection and reconstruction in 1 case.

RESULTSThere were two operative death in this series. The operative mordality was 2.38%. A total of 32 patients had operative complications. The incidence of operative complications was 38.10%. The 1-, 3-, 5-and 10-year survival rate was 81.34%, 59.47%, 31.73% and 24.06% respectively.

CONCLUSIONS(1) It is feasible in technique that carinal resection and reconstruction combined with heart, great vessel plasty in the treatment of locally advanced non-small cell lung cancer involving carina, heart and great vessels simutaneously; (2) Multiple modality therapy based on carinal resection and reconstruction combined with heart and great vessel plasty can remarkably increase the survival rate, and improve the prognosis and quality of life in patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels.