Objective:To establish O-(2-[ 18F]fluoroethyl)- L-tyrosine( 18F-FET) PET radiomics features-based model and investigate its predictive efficacy for isocitrate dehydrogenase type 1 (IDH1) genotyping in untreated gliomas. Methods:From November 2017 to February 2019, 58 pathologically confirmed glioma patients (36 males, 22 females; age (41.8±15.1) years) with preoperative 18F-FET PET/CT imaging in Huashan Hospital, Fudan University were retrospectively enrolled. PyRadiomics software package was used to extract 105 radiomics features. Least absolute shrinkage and selection operator (LASSO) algorithm with 5-fold cross-validation was used to build the logistic regression model. And radiomic scores (RS) of each lesion were calculated according to their weighted coefficients. The area under the receiver operating characteristic (ROC) curve was used for evaluating the predictive efficacy for IDH1 prediction. The predictive efficacies of radiomics model and traditional semi-quantitative parameters including tumor-to-background ratio (TBR; maximum TBR (TBR max), mean TBR (TBR mean), peak TBR (TBR peak)), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU), were compared by Delong test. Results:Seven radiomics features including maximum 2-dimensional (2D) diameter slice, first order_maximum, first order_range, gray level co-occurrence matrix (GLCM)_joint energy, GLCM_inverse variance, gray level dependence matrix (GLDM)_dependence entropy and GLDM_large dependence low gray level emphasis were selected for the LASSO regression model building and RS calculation. ROC analysis results showed that the predictive accuracy of RS for IDH1 genotyping (mutation, n=20; wild-type, n=38) was 81.0%(47/58), with sensitivity of 65.0%(13/20), specificity of 89.5%(34/38), and area under curve (AUC) of 0.842, respectively. The traditional 18F-FET semi-quantitative parameter TLU ranked the second regarding the diagnostic performance, with accuracy of 60.3%(35/58), sensitivity of 85.0%(17/20), specificity of 47.4%(18/38), and AUC of 0.661( z=3.426, P<0.01). Conclusion:Radiomics analysis based on 18F-FET PET images can improve the predictive efficacy for IDH1 genotyping in untreated adult glioma patients.

Objective To investigate the role of autophagy in radiation-induced death response of human nasopharyngeal carcinoma cells.Methods MTT method was used to detect cell viability of CNE-2 cells in different time after irradiation.Clonogenic survival assay was used to evaluate the effect of autophagy inhibitor (chloroquine phosphate) and autophagy inductor (rapamycin) on radiosensitivity of nasopharyngeal carcinoma cells.Cell apoptosis was assessed by flow cytometry.The expressions of LC3 and P62 were measured with Western blot.Cell ultrastructural analysis was performed under an electron microscope.Results Irradiation with 10 Gy induced a massive accumulation of autophagosomes accompanied with up-regulation of LC3-Ⅱ expression in CNE-2 cells.Compared with radiation alone,chloroquine phosphate (CDP) enhanced radiosensitivity significantly by decreasing cell viability (F =25.88,P ＜ 0.05),autophagic ratio (F =105.15,P ＜ 0.05),and LC3-Ⅱ protein level(F =231.68,P ＜0.05),while up-regulating the expression of P62 (F =117.52,P ＜ 0.05).Inhibition of autophagy increased radiation-induced apoptosis (F =143.72,P ＜ 0.05).Rapamycin (RAPA) also significantly decreased cell viability,but increased autophagic ratio and LC3-Ⅱ protein level while down-regulated the expression of P62.Induction of autophagy increased radiation-induced apoptosis(F =167.32,P ＜ 0.05).Conclusions Blockage of autophagy with CDP could enhance radiosensitivity in human nasopharyngeal carcinoma cells,suggesting that inhibition of autophagy could be used as an adjuvant treatment to nasopharyngeal carcinoma.

OBJECTIVE:To study the bioequiavailability of two sertraline hydrochloride formulations in healthy volunteers.METHODS:A randomized, crossover study of 22 healthy volunteers receiving single oral dose of 50mg sertraline hydrochloride solution(test preparation) or sertraline hydrochloride tablets(comparator preparation) was conducted and the blood concentrations determined by LC/MS/MS.RESULTS: The pharmacokinetic parameters for the test sertraline and the comparator sertraline were as follows:t1/2 were (27.3?5.2)h and (26.3?3.0)h,respectively;Cmax were(9.56?2.49)?g?L-1 and(9.43?2.91)?g?L-1,respectively;tmax were(5.18?1.47)h and(6.00?1.07)h,respectively;AUC0～108 were(329?112)?g?h?L-1 and (297?111)?g?h?L-1,respectively;AUC0～∞ were(354?127)?g?h?L-1 and (316?122)?g?h?L-1,respectively.There were no significant differences in main pharmacokinetics parameters between the 2 preparations,except in tmax from analysis of variance and one-side & two-sides t tests.The relative bioavailability of the test sertraline was(115.5?26.7)%.CONCLUSION:These two sertraline hydrochloride formulations are bioequivalent.

OBJECTIVE: To study the bioequivalence of tegaserod maleate dispersible tablets in healthy volunteers.METHODS: A single oral dose of 6mg test or reference preparations of tegaserod maleate was given to 22 healthy volunteers in a randomized crossover study.The plasma concentrations of tegaserod were determined by LC/MS/MS assay.RESULTS: The main pharmacokinetic parameters of test and reference products were as follows: tmax(0.86? 0.22) and(1. 01? 0.24) h;Cmax(2.21? 0.69) and(2.05? 0.64) ng? mL1;AUC0～ 17(6.35? 2.48) and(6.47? 1.99) ng? h? mL-1,AUC0～ ∞(6.69? 2.59) and(6.70? 2.03) ng? h? mL-1,respectively.The relative bioavailability of test to reference preparation was(98.2? 22.1) %.CONCLUSION: The reference preparation and the test preparation are bioequivalent.

BACKGROUND:Transverse acetabular fracture often involves the damage of anterior and posterior columns of acetabulum. The most popular fixation of the anterior and posterior columns needs the combined anterior and posterior approach. Big trauma is not conducive to patient’s recovery after surgery. Limited incision or percutaneous minimaly invasive lag screw placement can reduce soft tissue injuries, but the strength of the fixation lacks of biomechanical verification. OBJECTIVE: To compare different types of fixations for transverse acetabular fracture, explore the appropriate fixation options that can achieve effective fixation and reduce tissue injury by combing with repair approach and the condition of soft tissue. METHODS: The fourth generation of synthetic semi-pelvic sawbones was set as a template to establish a model of acetabular transverse fracture using finite element analysis. Five different fixation options were used to fix the transverse acetabular fracture. The magnitudes of anterior and posterior displacement of transverse fracture were compared to assess the stability of different options under a simulated condition of incomplete weight bearing stand. RESULTS AND CONCLUSION:The motion at anterior column was minimal when fixed by anterior column locking plate + posterior column screw and the minimum displacement at posterior column was the fixation of anterior column screw + posterior column locking plate. Both of the motions of these two fixations were less than the reconstruction plate fixation respectively. The worst fixation was the anterior column and posterior column lag screw fixation with the largest displacement. The anterior column locking plate + posterior column screw, accomplished by single approach, could not only reduce surgical trauma, but also has a stronger stability. Moreover, this fixation option is effective method to place posterior column lag screw under direct vision and reduce the difficulty of screw implantation.

Objective:To investigate the effects of hematopoietic progenitor kinase 1 (HPK1) overexpression by construction of lentiviral vector on the proliferation and apoptosis of breast cancer MCF-7 and MDA-MB-231 cells,and to elucidate its possible mechanism.Methods:The cells were infected with the lentivirus overxpressing HPK1,and the MCF-7-HPK1 and MDA-MB-231-HPK1 cell lines were stably expressed HPK1;each cell line was divided into three experimental groups:blank group (untreated),control group (empty vector) and HPK1-overexpression group.The expression levels of HPK1 mRNA and protein in breast cancer cells in each group were detected by RTPCR and Western blotting methods,respectively.The cell proliferation rate was detected by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry.Transwell assay was used to analyze the cell migration ability.Western blotting method was used to measure the expression levels of caspase 3,PTEN,MMP-9,MMP-2,Ki-67and HPK1 proteins.Results:Compared with blank groups and control groups,the expression levels of HPK1 mRNA and protein in the both cell lines in HPK1 overexpression groups were significantly up-regulated (P＜0.05),the proliferation rates were significantly decreased (P＜0.05) and the apoptotic rates were significantly increased (P＜0.05),the number of cells crossing matrigel was significantly reduced (P＜0.05),the cell cycle of MCF-7 was blocked in G1 phase (P＜0.05),the expression levels of caspase 3 and PTEN proteins in HPK1 overexpression group were significantly increased (P＜0.05),and the expression levels of MMP-2 and MMP-9 proteins were significantly decreased (P＜0.05).Conclusion:HPK1 overexpression can inhibit the proliferation and migration of MCF-7 and MDA-MB-231 cells and induce apoptosis,which may be related to the up-regulation of caspase 3 and PTEN and down-regulation of MMP-9,MMP-2 and Ki-67.

Objective:To preliminarily explore the effects of tumor treating fields (TTF) arrays on the dose distribution in the treatment of Glioblastoma (GBM) using combined radiotherapy and concurrent TTF.Methods:EDR2 and MatriXX plate ionization chamber were employed to measure the absorbed doses of tissues at different depths (< 1 mm, 3 mm, 5 mm, 1 cm, 1.5 cm, 3 cm, 5 cm, 10 cm, and 15 cm) in the case that TTF arrays and latex-free foam were attached and not attached on the surface. Then the absorbed doses were calculated, compared, and analyzed. For the volumetric arc therapy (VMAT) of 10 GBM patients, deep dose verification was performed using the Sun Nuclear ArcCheck 3D dose verification system and the D99%, Dmean, and D1% of tumors and OARs were assessed. Results:The surface dose increased by 173% in the case that TTF arrays and latex-free foam were attached to the surface compared with the case of the surface with nothing attached. The surface dose increased by 61.7% due to the attachment of low-density latex-free foam. The dose deviation gradually decreased with an increase in the depth and stabilized (about 4%) at a depth of greater than 1.5 cm. As indicated by the VMAT verification result, the D99%, Dmean, and D1% of PTV and CTV decreased by 1.1%-1.2% and the Dmean and D1% of OARs (i.e., brainstem, pituitary gland, optic chiasma, optic nerve, eyeball, and eye crystal) decreased by 0.7%-1.5% in the case that TTF array and latex-free foam were attached on the surface compared with the case the surface with nothing attached. Conclusions:The combined radiotherapy and concurrent TTF in the GBM treatment will lead to a slight reduction of the absorbed doses of targets and OARs but a significant increase in the absorbed doses of the scalp. Therefore, it is recommended that the scalp doses should be reduced as far as possible in the design of the radiation treatment plan to reduce the adverse reactions on the scalp of GBM patients.

When Escherichia coli CICIM B0013-030 (B0013, ack-pta, pps, pflB) was used for D-lactate production, succinate and acetate were the main byproducts (as much as 11.9 and 7.1% the amount of lactate respectively). In order to decrease the byproduct levels, we inactivated succinate and acetate synthesis in B0013-030. Two recombinant plasmids containing mutation cassettes of frdA::difGm and tdcDE::difGm respectively were constructed first. The mutation cassettes were used to delete the target genes on the chromosomal by Red recombination. Subsequently, the antibiotic resistance gene was excised from the chromosomal by Xer recombination. Thereby, mutants B0013-040B (B0013-030, frdA) and B0013-050B (B0013-040B, tdcDE) were produced. D-lactate producing abilities of the engineered strains were tested both in shake flasks and in bioreactors using two-phase fermentation (aerobic growth and anaerobic fermentation) with glucose as the sole carbon source. When fermentation was carried out in shake flasks, inactivation of frdA in B0013-030 to produce B0013-040B reduced succinate accumulation by 80.8%. When tested in a 7-liter bioreactor, B0013-040B accumulated 114.5 g/L D-lactate of over 99.9% optical purity. However, 1.0 g/L succinate and 5.4 g/L acetate still remained in the broth. Further inactivation of tdcD and tdcE genes in B0013-040B to produce B0013-050B decreased acetate and succinate accumulation to 0.4 g/L and 0.4 g/L respectively, and lactate titer was as much as 111.9 g/L (tested in the 7-liter bioreactor). In lightof the lower byproduct levels and high lactate production, strain B00 13-050B may prove useful for D-lactate production.
Acetates ; metabolism ; Escherichia coli ; genetics ; metabolism ; Fermentation ; Genetic Engineering ; Lactic Acid ; biosynthesis ; Metabolic Networks and Pathways ; genetics ; Mutation ; Plasmids ; genetics ; Succinic Acid ; metabolism

OBJECTIVE: To investigate the effects of LCL161, a Smac mimetic, on the proliferation and apoptosis in hepatocellular carcinoma cells and the underlying mechanisms. 
 METHODS: The effect of LCL161 on the cell viability of HepG2 and SMMC7721 cells was measured by MTT assay. The effect of LCL161 at lower concentrations on the proliferation in hepatocellular carcinoma (HCC) cells was detected by colony formation assay. Apoptosis was assessed by flow cytometry with PI staining. The mitochondrial membrane potential was measured by JC-1 staining. The expression of PARP, p-Akt, cIAP1 and XIAP protein was analyzed by Western blot.
 RESULTS: LCL161 displayed notable antiproliferative activity on HCC cells at the concentrations of 1-16 μmol/L (P<0.01), with IC50 values of 4.3 and 4.9 μmol/L for HepG2 and SMMC7721 cells, respectively, after treatment for 48 h. LCL161 at lower concentrations obviously inhibited the colony formation of HCC cells. LCL161 induced significant apoptosis in HCC cells (P<0.01), and resulted in the apoptotic rate at (1.5±0.8)% or (1.8±0.6)% , (15.2±2.8)% or (12.2±2.4)%, (28.7±3.0)% or (22.4±2.7)%, (34.6±2.3)% or (30.2±2.4)% for HepG2 cells or SMMC7721 cells at the concentration of 0, 2, 4 or 8 μmol/L, respectively. The result of JC-1 staining indicated that the mitochondrial membrane potential of HCC cells was reduced by LCL161. In addition, LCL161 promoted the cleavage of PARP, down-regulated the protein expression of p-Akt, and degraded cIAP1.
 CONCLUSION LCL161 possesses significant anti-proliferative activity and pro-apoptotic action in HepG2 and SMMC7721 cells, which might be correlated with reduction in mitochondrial membrane potential, down-regulation of p-Akt and degradation of cIAP1.
Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; Down-Regulation ; Hep G2 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Liver Neoplasms ; Membrane Potential, Mitochondrial ; drug effects ; Proto-Oncogene Proteins c-akt ; genetics ; Thiazoles ; pharmacology ; Ubiquitin-Protein Ligases ; metabolism ; X-Linked Inhibitor of Apoptosis Protein