Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Mirror therapy has been widely used in practice as an effective rehabilitaiton method. Mirror integrated therapy combined mirror therapy with some other technologies, such as virtual reality, functional electrical stimulation, augmented reality, etc., to enhance the task orientation, and improve the efficiency of treatment.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Biopsy ; CD56 Antigen ; metabolism ; DNA-Binding Proteins ; metabolism ; Gene Deletion ; Humans ; Keratin-7 ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Small Cell Lung Carcinoma ; genetics ; metabolism ; pathology ; Synaptophysin ; metabolism ; Transcription Factors

Humans ; Retroperitoneal Neoplasms ; pathology ; Rhabdomyosarcoma ; pathology

Abdominal Pain ; etiology ; Acute Pain ; etiology ; Child ; Humans ; Lymphoma ; complications

Objective:To detect the expressions of survivin, galectin-3 and thyroid peroxidase in papillary thyroid microcarcinoma ( PTMC) and cancer adjacent normal tissue to explore the clinical significant.The correlations between the expressions of survivin,Gal-3 and TPO with BRAFV600E gene mutation in PTMC were analyzed.Methods: The expressions of survivin,Gal-3 and TPO were measured by immunohistochemical ( IHC ) method in 56 cases of PTMC tissue and adjacent normal tissue; BRAFV600E mutation was detected by PCR amplification and subsequently sequencing.Chi square test was used to analyse the relation in the expression rates of survivin,Gal-3 and TPO and BRAFV600E gene mutation.Results:The survivin and Gal-3 were strongly expressed but TPO was negatively expressed.The survivin and Gal-3 were negative in adjacent normal tissues but TPO was expressed.There were sig-nificant differences in the expression rates of survivin, Gal-3 and TPO between PTMC tissue and adjacent normal tissue (all P<0.001).The BRAFV600E mutation rate (32.1%) and the expression rates of survivin,Gal-3 and TPO in PTMC tissue were found to be positively related to lymph node metastases (P=0.009,P=0.025,P=0.007,P=0.008),and negatively related to gender and age (all P>0.05).There were no correlation was found between the expressions of survivin,Gal-3,TPO and the BRAFV600E gene mutation in PTMC(all P>0.05).Conclusion: The strong expressions of survivin and Gal-3,the mild expression of TPO and BRAF mutation may be important in the development of PTMC,and the detection of BRAFV600E gene mutation and the expressions of survivin, Gal-3 and TPO could be used to the judgment of pathogenetic condition and prognostic outcomes.

Objective To observe therapeutical effects of gastric bypass on non-obese type 2 diabetes patients.Methods From June 2008 to April 2010,data of 47 patients with both gastric lesions and non-obese type 2 diabetes mellitus undergoing gastric bypass in the Institute of General Surgery were studied.The patients were divided into 3 groups according to the operation type:total stomach resection plus Roux-en-Y anastomosis ( n =20),partial stomach resection plus Roux-en-Y anastomosis(n =13)and Billroth Ⅱ gastrectomy(n =14).They were followed for 6 months after surgery.Level of body mass index (BMI),fasting blood glucose (FBG) and GLP-1 was measured before operation and on the 1 st week,2nd week,1 st month,3rd month,and 6th month after operation.The level of glycosylated hemoglobin was measured before operation and on the 3rd and 6th month after operation.The prognosis of the patients on the 6th month after surgery was evaluated.Results Compared with preoperative level,FBG level in all the 3 groups significantly decreased on the 1 st week after surgery and maintained a similar level during the follow-up period (P ＜ 0.01 ).GLP-1 level was elevated after operation (P ＜0.01 or P ＜ 0.05).On the 3rd and 6th month after operation,glycosylated hemoglobin level in all the 3 groups significantly decreased (P ＜ 0.01 or P ＜ 0.05 ).The change of the above parameters was greater in groups undergoing Roux-en-Y anastomosis than in Billroth Ⅱ group(P ＜ 0.05 ).The control rate of T2DM for Billroth Ⅱ,partial stomach resection plus Roux-en-Y anastomosis and total stomach resection plus Roux-en-Y anastomosis was 78.5％(11/14),100％ (13/13) and 100％ (20/20)respectively on the 6th month after surgery,indicating Roux-en-Y gastric bypass had better effect of blood glucose control than Billroth Ⅱ (P ＜ 0.05 ).Postoperative BMI decreased significantly in all groups (P ＜ 0.05) and there was no statistical difference between all the groups (P ＞ 0.05 ).Conclusions All groups of gastric bypass are effective in terms of glucose control.Roux-en-Y gastric bypass is more effective than Billroth Ⅱ on diabetes control and its therapeutic effect is independent of weight loss.