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.

How to realize the control of limb movement and apply it to intelligent robot systems at the level of cerebellar cortical neurons is a hot topic in the fields of artificial intelligence and rehabilitation medicine. At present, the cerebellar model usually used is only for the purpose of controlling the effect, borrowing from the functional mode of the cerebellum, but it ignores the structural characteristics of the cerebellum. In fact, in addition to being used for controlling purposes, the cerebellar model should also have the interpretability of the control process and be able to analyze the consequences of cerebellar lesions. Therefore, it is necessary to establish a bionic cerebellar model which could better express the characteristics of the cerebellum. In this paper, the process that the cerebellum processes external input information and then generates control instructions at the neuron level was explored. By functionally segmenting the cerebellum into homogeneous structures, a novel bionic cerebellar motion control model incorporating all major cell types and connections was established. Simulation experiments and force feedback device control experiments show that the bionic cerebellar motion control model can achieve better control effect than the currently widely used cerebellar model articulation controller, which verifies the effectiveness of the bionic cerebellar motion control model. It has laid the foundation for real brain-like artificial intelligence control.
Arm ; Artificial Intelligence ; Bionics ; Cerebellum ; Humans ; Motion

Objective By comparing the medical complaints and disputes between the two tertiary general hospitals in Beijing and Lhasa, this paper proposed on how to build a harmonious doctor-patient relationship.Methods A study of annual reports of these two hospitals analyzed descriptively patient complaint rate, rate of medical disputes registered for court jurisdiction, makeup of medical disputes, and their solutions.Results In 2016, the patient complaint rate, and rate of medical disputes registered for court jurisdiction were 3.5/10 000 and 12.4/10 000 respectively, much higher than 0.8/10 000 and 1.1/10 000 of the Lhasa counterpart hospital.A significant gap was also found in the makeup of medical disputes, their solutions, and role of hospital leadership between the two hospitals.Conclusions Beijing is recommended to appoint hospital leader on duty, to assist in handling medical complaints and disputes, and ease doctor-patient contradictions.Lhasa is recommended to improve the medical dispute handling mechanism, improve medical service competency and management.

Objective To evaluate the dual blood supply of lung adenocarcinoma and squamous cell carcinoma using dualinput perfusion CT.Methods A total of 40 patients confirmed with lung cancer pathologically underwent CT perfusion (CTP) scanning.The pulmonary flow (PF),bronchial flow (BF),perfusion index (PI,PI=PF/[PF+BF])and tumor volume,location were measured and recorded by 2 experienced radiologists.The differences in CTP parameters between lung adenocarcinomas and squamous cell carcinomas,the central lung cancers and peripheral lung cancers were analyzed.The correlation between the tumor volume and CTP parameters was analyzed.Interobserver agreements were assessed with intraclass correlation coefficient (ICC).Results The average of PF,BF and PI of all 40 cases was (54.26± 21.07)ml/ (min · 100 ml),(64.41±22.06)ml/(min · 100 ml) and (43.38±16.07)％,respectively.Tumor histology was consistent with adenocarcinomas in 23 cases and squamous cell carcinomas in 17 cases,lung adenocarcinomas showed lower PI than that of squamous cell carcinomas (t=-2.196,P=0.034).There were 17 peripheral lung cancers and 23 central lung cancers,and the PI of the peripheral lung cancers was higher than that of the central lung cancer (t=2.305,P=0.027).No statistically significant differences were found for BF and PF between two types of lung cancers and central lung cancers and the peripheral cancers (all P＞0.05).Tumor volume was negatively associated with PI (r =-0.39,P=0.01).Good agreement was found between the two observers,the ICC for BF,PF and PI was 0.97,0.93 and 0.91,respectively.Conclusion Dual-input CTP technique can be used to evaluate the differences of blood supply between different pathological types and locations of lung cancer,with PI depending both on tumor size and location.

Objective · To explore the change of metabolomic profiling after erlotinib (anepithelial growth factor receptor tyrosine kinase inhibitor)resistance of lung adenocarcinoma cells (PC9-ER), and find the differential metabolome associated witherlotinib resistance. Methods · Metabolic profiling of PC9-ER cells and homologous parent PC9 cells was acquired by the ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The data were analyzed by multi-dimensional statistical methods, such as partial least squares projection to latent structures-discriminant analysis (PLS-DA), to select and identify differential metabolites associated with erlotinib resistance. Results · A total of 14 differential metabolites were identified in PC9-ER cells. Seven up-regulated metabolites included N-acetylspermidine, phosphatidylethanolamine, AMP, pantothenic acid,proline, glutamate, and histidine, while seven down-regulated metabolites included citrulline, phosphorylcholine, glutathione, cysteinylglycine, glutathione oxidized, NAD, and S-adenosylmethionine, mainly participating in glutathione metabolism, glutamate metabolism, ammonia recycling, and protein biosynthesis. Conclusion · Metabolic profiling of erlotinib-resistant lung adenocarcinoma cells was changed. The information of differential metabolites associated with erlotinib resistance could provide clues for new resistance mechanisms and potential metabolism-related drug targets.

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.