Objective To investigate the mechanism of HSP90 inhibitor AUY-922 reversing the resistance of human neuroblastoma cells to the second generation ALK inhibitor TAE684. Methods The effect of AUY-922 on the proliferation of human neuroblastoma cells SH-SY5Y and KELLY carrying ALK F1174L gene was detected by MTT method. The effect of AUY-922 on cell cycle of SH-SY5Y and KELLY cells was detected by flow cytometry. The effects of AUY-922 on cyclin Cdc2, ALK protein and downstream signal pathways p-Akt, p-Erk, p-stat3 in SH-SY5Y and KELLY cells were detected by Western blot. Results AUY-922 could significantly inhibit the proliferation of SH-SY5Y and KELLY cells, and the IC₅₀ were about 0.30 μmol/L and 0.12 μmol/L, respectively. AUY-922 could induce cell cycle arrest of SH-SY5Y and KELLY cells in G₂/M phase in a dose-dependent manner. AUY-922 could degrade Cdc2 and ALK proteins in SH-SY5Y and KELLY cells in a dose-dependent manner, and reduce the levels of p-Akt, p-Erk and p-stat3. Conclusion The reversal effect of HSP90 inhibitor AUY-922 on drug resistance of human neuroblastoma to ALK inhibitor may be related to its induction of G₂/M cell cycle arrest, the degradation of ALK protein and the inhibition of downstream signal pathway.

Objective To investigate the value of renal CT volumetric texture analysis with machine learning radiomics in assessment of pathological grade of clear cell renal cell carcinoma(ccRCC). Methods Thirty-four biopsy-confirmed ccRCC subjects who had four-phase CT scanning (NC:non-contrast, CM: Corticomedullary, N: Nephrographic, E: Excretory) were collected retrospectively from June 2013 to October 2017 for the study.Non-rigid registration was performed on multi-phase CT images in reference to CM-phase.Each lesion was segmented on CM-phase CT images using our in-house volumetric image analysis platform,"3DQI".A set of fifty-nine volumetric textures,including histogram,gradient,gray level co-occurrence matrix(GLCM),run-length(RL),moments,and shape,was calculated for each segment lesion in each phase as parameters for the training/testing of Random Forest (RF) classifier. Four groups according to pathological Fuhrman grade on a scaleⅠtoⅣ,these tumors were then divided into low(Ⅰ+Ⅱ) and high grade ( Ⅲ + Ⅳ) groups. Feature selection was performed by Boruta algorithm. A 10-fold cross-validation method was applied to validate the RF performance by receiver operating characteristic (ROC) curves analysis to determine the diagnostic accuracy of the model. Results Subjects were divided into four groups by Fuhrman grade on a scaleⅠtoⅣ:3 cases gradeⅠ,19 cases gradeⅡ,8 cases gradeⅢand 4 cases gradeⅣ.In CM-phase,kurtosis and long-run-emphasis(RLE)were selected the most important textures for ccRCC staging among 59 features. The area under curve (AUC) of ROC was 0.88 (79% sensitivity and 82% specificity)by using kurtosis and RLE textures.The mean values of kurtosis and RLE were(-20.00±22.00)×10-2and(3.00±0.40)×10-2for low group,whereas(31.00±32.00)×10-2and(5.00± 0.02)×10-2for high group.Within the mean±SD range of statistics,radiomics can distinguish between low and high grade tumors.In multi-phase analysis,three most important features were selected among 236(59× 4) textures: kurtosis (CM-phase), GLCM homogeneity I (HOMO 1) (E-phase), and GLCM homogeneity 2 (HOMO2)(E-phase).The mean values of HOMO 1(E-phase)and HOMO 2(E-phase)were(19.00±0.03)× 10-2and(11.00±0.02)×10-2for low group,whereas(22.00±0.03)×10-2and(14.00±0.02)×10-2for high group. The AUC was 0.92(93% sensitivity and 87% specificity)by using these three textures. Conclusion This study has demonstrated that renal CT volumetric texture analysis with machine learning radiomics could preoperative accurately perform cancer staging for ccRCC.

Objective:To explore the application of games combined with speech training in rehabilitation care for language development retardation in high-risk children aged 2 to 5 years.Methods:Totally 190 high-risk children aged 2 to 5 years with language development retardation admitted from January 2016 to December 2018 in Luzhou People's Hospital were selected by convenient sampling, and divided into observation group ( n=95) and control group ( n=95) according to the random number table. Children in the control group received conventional speech training, while children in the observation group received speech training combined with games for 6 months. The effects of rehabilitation training were observed in the two groups, and the speech development quotient of the children was evaluated using the Gesell Developmental Schedules (GDS) . The satisfaction rate to rehabilitation of parents of two groups were compared. Results:After 6 months of training, the effective rates of rehabilitation training were 86.32% (82/95) in the observation group and 73.68% (70/95) in the control group, and the difference was statistically significant ( P<0.05) . The GDS scores were (60.36±8.25) in the observation group and (56.67 ± 7.84) in the control group, and the difference was statistically significant ( P<0.05) . The satisfaction rate of parents of children in the observation group on rehabilitation effect, service attitude, professional skills, and humane care were higher than those in the control group, and the differences between the two groups were statistically significant ( P<0.05) . Conclusions:In high-risk children aged 2 to 5 years with language development retardation, speech training combined with games can improve children's speech development quotient and promote their rehabilitation.

Objective To investigate the safety,feasibility and clinical application effect of upper arm totally implantable venous access port (TIVAP) inserted by the combination of oncologists and nurses in patients with tumor.Methods A total of 34 patients,who needed long-term transfusion treatment,were included in this study with upper arm TIVAP from March 2017 and December 2017.There were 20 males and 14 females.The median age was 63 (35 ～ 83) years.Upper arm TIVAP was implanted by both doctors and nurses into the patients with tumor,and the TIVAP related success rate,complications and patients satisfaction were recorded.Results 34 patients all succeeded in TIVAP implantation with the operation success rate of 100％.The average operation time was about 40 minutes (30 to 60 minutes) from the disinfecting cloth to the end of the suture.The operations of all patients were successful.After the operation two patients died of cancer progression,one patient had soft tissue infection around capsular bag,None of the patients had other complications such as blocked infusion,catheter shift,port reversal,and so on,and the incidence of complication was 2.94％ (1/34).Conclusions Upper arm TIVAP has the advantages of safe puncture,shorter operation time,few intra-operative and post-operative complications and higher feasibility for operation by both oncologist and nurse,which can supplement the limitations and deficiencies of the chest wall port and PICC in a certain extent,therefore is a good choice for clinical application.