BACKGROUND: Docetaxel is a commonly used anti-tumor drug in clinic, especially as the first-line drug for advanced non-small cell lung cancer (NSCLC). However, the molecular mechanism of docetaxel against NSCLC is still unclear. Increasing studies have shown that metabolic reprogramming of tumor cells plays an important role in tumorigenesis. The aim of this study was to investigate the effects of docetaxel on the metabolic pathway of NSCLC cells based on metabolomics analysis and biological means. METHODS: First, we performed CCK8 assay to analyze the effects of docetaxel on cell viability of NSCLC cells and also to screen the appropriate drug concentration. Then, the differential metabolites of docetaxel-treated and untreated NSCLC cells were analyzed by gas chromatography-mass spectrometry based metabolomics. Finally, the effects of docetaxel on the expression levels of key enzymes that regulate the relevant metabolic pathways were determined by Western blot. RESULTS: Docetaxel inhibited cell viability of A549 and H1299 cells in a concentration- and time-dependent manner. With the prolonged treatment time of docetaxel, the apoptotic sensitive protein poly (ADP-ribose) polymerase (PARP) was gradually activated to form a P89 fragment. Metabolomics analysis showed that eight metabolites were significantly changed in both A549 and H1299 cells following docetaxel treatment, which were mainly in the tricarboxylic acid (TCA) cycle pathway. Moreover, after docetaxel treatment, the protein expression levels of isocitrate dehydrogenases, the key regulators of the TCA cycle, were obviously decreased in both A549 and H1299 cells. CONCLUSIONS Our findings suggest that the effect of docetaxel-induced proliferation inhibition and apoptosis in NSCLC might be associated with down-regulation of isocitrate dehydrogenases and suppression of the TCA cycle pathway.
A549 Cells ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; pathology ; Docetaxel ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Metabolomics

Objective: To evaluate the predictive accuracy of fine needle aspiration (FNA) and BRAF V600E mutation in distinguishing papillary thyroid carcinoma and other thyroid nodules. Methods: This retrospective cohort study included 93 patients with papillary thyroid carcinoma who treated at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine from September 2016 to May 2018. There were 21 males and 72 females with age of (43.2±11.3) years (range: 19 to 67 years). All the patients got the examinations of FNA and BRAF V600E mutation by Amplification Refractory Mutation System, and subsequently underwent thyroid surgeries. The results of cytopathology, frozen section and pathology were collected and analyzed. The predictive accuracy of FNA cytology and BRAF V600E mutation was calculated. Results: In the 93 collected cases, 91 were diagnosed as papillary thyroid carcinoma postoperation, and the accurate predictive rate was 97.8%. Subgroup analysis was performed according to Bethesda System, the predictive rates were: unsatisfactory (Ⅰ) 6/6, benign (Ⅱ) 0/0, atypia of undetermined significance or follicular lesion of undetermined significance (Ⅲ) 16/17, follicular neoplasm or suspicious for follicular neoplasm (Ⅳ) 97.2% (35/36), suspicious for malignancy (Ⅴ) 100% (28/28), and malignant (Ⅵ) 6/6, respectively. Conclusion Thyroid nodules with BRAF V600E mutation can be strongly speculated as papillary thyroid carcinoma.

Objective To investigate the immediate oral feedback after objective structure clinical examination (OSCE) for postgraduate year 1 & 2 surgery residents (PGY1 & 2).Methods 37 PGY1 and 38 PGY2 wereevaluated.The examination was composed of 6 stationsand limited to15 minutes per station.Each station was evaluated by centesimal system score.Immediate oral feedback was given in the last2 minutes.A questionnaire was given to each resident and examiner at the end of OSCE.All data analyses were conducted using SPSS version 22.0,repeated measures ANOVA and LSD test were used,and correlations were tested by the Pearson correlation test.Results The average scores for PGY1 & 2 were (68.97 ± 5.40) and (68.35 ± 5.00),the between-and inter-round differences in average score were not statistically significant.There was no significant correlation about theevaluation of the residents' performance during OSCE between the examiners and the residents.The necessity and effectiveness of immediate oral feedback were confirmed by both the examiners and the residents.Conclusions Immediate oral feedback isfeasible with limited impact on OSCE score,but the plan should be furtherrefined.Follow-up study isnecessary to identify the long-term effect on the clinical competency.

Objective To explore the technique and significance of intraoperative neuromonitoring (IONM) for scarless in the neck endoscopic thyroidectomy (SET) via breast approach.Methods From Apr.2015 to Oct.2015,101 consecutive patients undergoing SET with IONM were included.During the operation,patients received radical resection of the thyroid cancer by Wang's seven-step method.The lymph nodes in the central area were dissected and Wang's multi-functional separation forceps were implemented for recurrent laryngeal nerve (RLN) positioning,monitoring and protection.Also,time required for RLN positioning and exposure,postoperative transient and permanent RLN damage incidence were calculated to assess the feasibility of IONM under SET.Results Among 101 patients,130 RLNs in total were exposed.The average time required for RLN positioning under IONM was (3.26 ± 1.08)min,with round-nerve management time of (13.95 ± 4.58)min.Nerve signal change happened in 16.9％(22/130) patients.Positive predictive value was 13.6％ and negative predictive value was 100％.The overall accuracy rate was 85.4％.Conclusion IONM during SET is feasible,and can be helpful for the localization and functional protection of RLN and was useful to predict vocal cord paralysis.

Objective To investigate the effectiveness and rationality of objective structured clinical examination (OSCE) used as achievement assessment for Postgraduate Year 1 surgery residents.Then the form and content of training and examination can be improved according to test results.Methods 31 Postgraduate Year 1 surgery residents were involved in the examination.The examination was composed of 5 stations,which were case analysis,wound dressing change,plaster fixation,laparoscopic simulator basic skills and irregular wound debridement suture.Each station was evaluated by centesimal system score and limited in 15 minutes.A questionnaire on their opinion and perception of the examination was given to each resident at the end of examination.A total number of 31 questionnaires were issued and recycled.The difficulty,discrimination and reliability of each station were calculated,and the correlation between each station was analyzed.Results The average OSCE score was (74.66 ± 4.39).The difficulty of total stations was 0.747.The distinction was 0.578 and the reliability was 0.402.The second station was lowest difficulty,and the fifth station was most difficult.Every station's discrimination was larger than 0.400.The reliability of the second and the fourth station was low.There was moderate correlation between the first station and the second station,as well as the first station and the fourth station.But there was no significant correlation between other stations.Residents' questionnaire survey showed that the fourth and the fifth stations were considered as the most difficult,and the second station was the simplest.They thought the fourth was most helpful for clinic.They performed best at the second station and worst at the fifth station.Conclusions OSCE can effectively evaluate the efficacy of the resident training.The residents' practical competency skills can be assessed better by examination simulating complex clinical scenario.Besides,after examination,we need to objectively evaluate the assessment efficiency,and dynamically adjust the training content and examination form according to residents' subjective opinions.

Objective To investigate the serum γ-glutamyl transferase(γ-GT)level and its clinical significances in hepatitis B virus(HBV)-liver failure(LF)patients.Methods γ-GT levels were detected in 89 LF patients,30 cases with cirrhosis and 30 healthy controls.Difference of serum γ-GT between survival group and death group in LF patients and dynamics of γ-GT after hospitalization were studied. Survival rate between γ-GT increase group and decrease group were compared.The associations of γ-GT with model for end stage live disease(MELD)and prealbumin were calculated.Results At baseline,the γ-GT levels in LF,cirrhosis and healthy control groups were(149.61 ± 69.86),(123.96 ± 59.52)and (48.28 ± 10.25)U/L,respectively,the difference among groups was significant(F= 178.150,P<0.05).The survival group in LF patients showed significant increase of γ-GT one week after hospitalization compared with death group([75.27 ± 10.34]vs[29.47 ± 5.05],t=5.40,P<0.05). The γ-GT increase group showed higher survival rate than γ-GT decrease group[76.19%(48/63)vs 23.08%[6/26],χ2=21.76,P<0.05].Serum γ-GT level in LF patients was positively correlated with both MELD score and prealbumin(r=0.709 and -0.627,respectively,both P<0.05).Conclusions The rise of γ-GT may indicate a better prognosis in LF patients.Serum γ-GT positively correlates with prealbumin and both could reflect the regeneration of hepatocytes.

Objective: To summarize the preliminary experience with transoral endoscopic thyroidectomy via vestibular approach (TOETVA). Methods: A total of 150 consecutive patients with thyroid disease underwent TOETVA from November 2014 to February 2017 at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine. The patients were comprised of 138 females and 12 males. The mean age of the patients was (31.7±7.6) years (ranging from 15 to 51 years). There were 108 patients of differential thyroid carcinoma (T1 or T2 ≤3 cm, cN0 or cN1a, M0) and 42 patients of benign thyroid disease (solid nodule ≤6 cm). The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, complications and results of follow-up. Results: Two cases were converted into open surgery due to an incredible unexpected tumor size and tracheal invasion, respectively. One hundred and three patients with papillary carcinoma underwent transoral central neck dissection (CND), with the mean operation time of (146±34) minutes for hemithyroidectomy with CND, and (187±36) minutes for total or near total thyroidectomy with CND. The mean number of lymph node yields was 8.2±4.7, and the lymph node metastasis rate was 41.7% (43/103). Regarding postoperative complications, transient hoarseness occurred in 3 patients, and permanent recurrent laryngeal nerve occurred in 2 patients. One patient had local infection or transient mental nerve palsy. Transient hypocalcemia occurred in 31.8% of 22 patients who underwent total, near-total, or subtotalthyroidectomy, and no permanent hypocalcemia was registered. Mean hospital stay after operation was (3.5±0.6) days (ranging from 2 to 5 days). Mean follow-up period was (11.5±7.8) months (ranging from 1 to 28 months), no recurrence or metastasis occurred. Conclusions TOETVA is feasible and safe for strictly selective patients. It brings perfect cosmetic effect. Long-term follow-up and further study is needed to assess its curative effect.

The article summarized the workflow of instructional design by using ADDIE model.The model is a recirculation of assessment,design,development,implementation and evaluation,by which the quality of education can be improved continuously.After the initial assessment it was found that the model can basically reach the general goal for training the junior doctors.For the problem of residents' irregular study and great difference of individual clinical skills,some suggestions for improvement were made.It included adjusting the time and content of training,individualized teaching,reforming examination form and increasing objective measurement to assess the effectiveness of training.All of them can effectively improve the effectiveness of basic surgical training in surgical school.

OBJECTIVETo summarize the experiences of applying three-dimensional (3D) technique in scarless endoscopic thyroidectomy (SET) via anterior chest approach.

METHODSMedical records of patients who undenvent SET using 3D technique from December 2013 to May 2014 were retrospectively reviewed. A total of 32 patients who had a preoperative ultrasound-guided fine-needle aspiration cytology diagnosis of unilateral papillary thyroid carcinoma and underwent lobectomy associated with central lymph node dissection were included in this study. All patients were female with a mean age of (37 ± 10) years at diagnosis. In addition, 45 female patients who underwent traditional endoscopic thyroidectomy at the same period were randomly selected as control.

RESULTSAll surgical procedures were successfully finished. The mean surgical time in 3D group was (91. 7 ± 11. 4) minutes, and mean hospitalization time was (3. 2 ± 0. 5) days. Contemporary hoarseness was observed in one patient, and no bleeding, infection, hypocalcemia and other postsurgical complications were observed. Compared to the traditional endoscopic surgery group, 3 D group had significantly shorter surgical time of lobectomy ((23. 2 ± 5. 1) minutes vs. (28. 0 ± 5. 0) minutes, t = 4. 156, P = 0. 000). Negative results were seen in the time taking of creating surgical space ((14. 6 ± 3. 3) minutes vs. (15. 6 ± 2. 5) minutes), central lymph node dissection ((25. 1 ± 5. 4) minutes vs. (24. 4 ± 6. 3) minutes) and total surgical time ((91.7 ± 11. 4) minutes vs. (96. 1 ± 13. 0) minutes).

CONCLUSIONApplication of 3D technique in endoscopic surgery can offer 3D vision of the surgical field, thus significantly shorten lobectomy time and more easily to achieve fine dissection and functional protection of recurrent laryngeal nerves, parathyroids and other vital anatomic structures.

Adult ; Biopsy, Fine-Needle ; Carcinoma ; diagnosis ; surgery ; Carcinoma, Papillary ; Endoscopy ; methods ; Female ; Humans ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Operative Time ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; surgery ; Thyroidectomy ; methods

Objective To determine the occurrence and baseline predictive factors of early neurological deterioration ( END) among mild ischemic stroke patients.Methods Mild ischemic stroke patients admitted in the hospital were prospectively enrolled.Univariate and multivariate Logistic recession analyses were used to analyze the demographic data, risk factors of ischemic stroke, clinical, brain imaging and laboratory data.Risk factors of END were identified.Results From June 2012 to August 2013, a total of 319 patients with mild ischemic stroke were enrolled, 45 patients (14.1%) of them experienced END.Univariate analysis showed that baseline NIHSS ( U=3522.000,P=0.000), baseline systolic blood pressure (t=2.871,P=0.004), proportion of symptomatic large artery severe stenosis or occlusion (χ2 =52.564,P=0.000) and proportion of large artery atherosclerosis among TOAST subtypes (χ2 =47.287,P=0.000) in END group were significantly higher than those in non-END group. Multivariate logistic regression analysis showed that baseline systolic blood pressure>142 mmHg (1 mmHg=0.133 kPa) (OR=3.954, 95%CI:1.693-9.236, P=0.001), symptomatic large artery severe stenosis or occlusion (OR=3.170, 95%CI:1.170-8.583, P=0.023) and baseline NIHSS (OR=2.038, 95%CI:1.359-3.057, P=0.001) were associated with END.Conclusions About 14.1% of the mild ischemic stroke patients can occur END.Baseline systolic blood pressure>142 mmHg, symptomatic large artery severe stenosis or occlusion and higher baseline NIHSS were the independent risk factors of END.