A clinical scoring model based on Gd-EOB-DTPA enhanced MRI predicting microvascular invasion in hepatocellular carcinoma: a multicenter study / 中华放射学杂志

Objective:To establish a clinical diagnostic scoring model for preoperative predicting hepatocellular carcinoma (HCC) microvascular invasion (MVI) based on gadolinium-ethoxybenzyl-diethylenetriamine pentacetic acid (Gd-EOB-DTPA) enhanced MRI, and verify its effectiveness.Methods:From January 2014 to December 2020, a total of 251 cases with pathologically confirmed HCC from Tianjin First Central Hospital and Jilin University First Hospital were retrospectively collected to serve as the training set, while 57 HCC patients from Tianjin Medical University Cancer Hospital were recruited as an independent external validation set. The HCC patients were divided into MVI positive and MVI negative groups according to the pathological results. The tumor maximum diameters and apparent diffusion coefficient (ADC) values were measured. On the Gd-EOB-DTPA MRI images, tumor morphology, peritumoral enhancement, peritumoral low intensity (PTLI), capsule, intratumoral artery, intratumoral fat, intratumoral hemorrhage, and intratumoral necrosis were observed. Univariate analysis was performed using the χ 2 test or the independent sample t-test. The independent risk factors associated with MVI were obtained in the training set using a multivariate logistic analysis. Points were assigned to each factor according to the weight value to establish a preoperative score model for predicting MVI. The receiver operating characteristic (ROC) curve was used to determine the score threshold and to verify the efficacy of this scoring model in predicting MVI in the independent external validation set. Results:The training set obtained 98 patients in the MVI positive group and 153 patients in the MVI negative group, while the external validation set obtained 16 patients in the MVI positive group and 41 patients in the MVI negative group. According to logistic analysis, tumor maximum diameter>3.66 cm (OR 3.654, 95%CI 1.902-7.018), hepatobiliary PTLI (OR 9.235, 95%CI 4.833-16.896) and incomplete capsule (OR 6.266, 95%CI 1.993-9.345) were independent risk factors for MVI in HCC, which were assigned scores of 3, 4 and 2, respectively. The total score ranged from 0 to 9. In the external validation set, ROC curve analysis showed that the area under the curve of the scoring model was 0.918 (95%CI 0.815-0.974, P=0.001). When the score>4 was used as the threshold, the accuracy, sensitivity, and specificity of the model in predicting MVI were 84.2%, 81.3%, and 85.4%, respectively. Conclusions:A scoring model based on Gd-EOB-DTPA-enhanced MRI provided a convenient and reliable way to predict MVI preoperatively.

BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells / 中国药理学与毒理学杂志

mTOR is commonly activated in human cancer and an attractive therapeutic target.Its activation is caused primarily by oncogenic mutations in RAS/RAF/MAPK and PI3K/AKT pathways, which cooperate to promote cancer progression and therapeutic resistance. mTOR inhibitors induce growth suppression and death receptor/FADD-dependent apoptosis in colon cancer cells and xeno-grafts. Using a panel of BRAFV600E and WT colorectal cancer cell lines and in vitro selected resistant culture, and xenograft models, we demonstrate here that BRAFV600E confers resistance to mTOR inhibitors. Everolimus treatment disrupts the S6K1-IRS-2/PI3K negative feedback loop, leading to BRAFV600E-dependent activation of ERK and Mcl-1 stabilization in colon cancer cells, which in turn blocks the crosstalk from the death receptor to mitochondria. Co-treatment with inhibitors to Mcl-1, PI3K, RAF or MEK restores mTOR inhibitor-induced apoptosis by antagonizing Mcl-1 or abrogating pERK/Mcl-1 elevation in BRAFV600E cells. Our findings provide a rationale for genotype-guided patient stratification and potential drug combinations to prevent or mitigate undesired activation of survival pathways induced by mTOR inhibitors.

Explicit physical self and its correlation with their implicit physical self in college students / 中国心理卫生杂志

Objective:To investigate the relationship between explicit and implicit physical self among contemporary college students.Methods:A total of 485 college students were recruited,with 264 male students,221 female students,266 junior students,219 senior students,189 students in the urban areas and 296 students in the rural areas.The Adolescents'Physical Self Scale (APS) was used to measure their explicit physical self.The Implicit Association Tests were designed to examine implicit physical self of 50 college students,who were selected from 485 college students by isometric random sampling.Results:The difference were significant among the five dimensions of college students' APS scores (P ＜ 0.001).The average scores of college students' appearance,sexual attractiveness were the highest,while the average score of body flaws was the lowest.Male students scored higher in five APS dimensions than female students (Ps ＜ 0.05).Senior students scored higher in the appearance,movement characteristics,figure and body flaws than junior students (Ps ＜0.05).Students in the urban areas scored higher in the appearance,movement characteristics,figure and body flaws than the students in the rural areas(Ps ＜ 0.05).There was no significant correlation between explicit and implicit physical self (P ＞ 0.05).The scores of relative separation index of movement characteristics were lower in male students than in female students (Z =2.45,P ＜ 0.05).The scores of relative separation index of body flaws were lower in the urban ones than in the rural ones (Z =3.14,P ＜ 0.01).Conclusion:It suggests that separation phenomenon exists between explicit and implicit physical self and the separation phenomena is distinct among the students of different genders or from different areas.

Discussing of Mental Rehabilitation of Children with Disability under ICF Theory and Practice / 中国康复理论与实践

@#Objective To discuss the mental rehabilitation of disabled children under International Classification of Functioning, Disabil-ity and Health (ICF). Methods The target, the organization of work team, environment support and the core problems of disabled children's mental rehabilitation were discussed based on the concept of ICF. Results The goal of mental rehabilitation was to recover the mental func-tion of disabled children. The multidisciplinary team should include medicine, psychology, education, social work and so on. Supportive en-vironments such as professional workers, families, communities, partner and barrier-free environment were the effective means of disabled children's mental rehabilitation. Respect and equality were the precondition of disabled children's mental rehabilitation, and positive atten-tion should be the working attitude. Conclusion ICF-CY can provide a new perspective and framework for the mental rehabilitation of dis-abled children.

Implications of World Report on Disability to Services of Rehabilitation for Persons with Disabilities in China / 中国康复理论与实践

@#World Report on Disability discussed the current situation of persons with disabilities, health care, rehabilitation, support and assistance, barrier-free environment, education, employment, and relevant policy recommendations, adhering to the spirit of Convention on the Rights of Persons with Disabilities, using the International Classification of Functioning, Disability and Health as its theoretical structure.Based on the report, this article discussed the revelations to services of rehabilitation for persons with disabilities and their problems,which were advocating new concepts of rehabilitation services, using multidisciplinary rehabilitation model, and strengthening construction of talents in services of rehabilitation.

Resistance of leukemia KG1a cells with positive N-cadherin in phase G(0) against killing activity of VP16 / 中国实验血液学杂志

Drug resistance is an important character of leukemic stem cells. To explore the mechanism of the chemotherapy resistance of N-cadherin positive leukemia cells, the quiescent state of N-cadherin positive leukemia cells was determined by flow cytometry and the relationship of G(0) phase cell ratio with the chemotherapy resistance was analyzed. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio and the sensitivity of cells to VP16 were determined. Finally the quiescent state and drug resistance properties of KG1a cells were determined after inhibiting N-cadherin-mediated cell-cell interaction by EGTA treatment. The results showed that the G(0) phase cell ratio in N-cadherin positive KG1a cells was higher than that in N-cadherin negative KG1a cells. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio was decreased significantly and the sensitivity of KG1a cells to VP16 increased. Following EGTA treatment for 24 hours, the G(0) phase cell ratio decreased and the drug-sensitivity was enhanced significantly. It is concluded that N-cadherin-mediated adhesion keeps N-cadherin positive leukemia cells in quiescent state of G(0) phase, thus protect these leukemia cells against VP16 chemotherapy.

Proportion of CD34(+)CD38(-) cell population in bone marrow of patients with de novo AML as prognostic factor of complete remission at first course of induction chemotherapy / 中国实验血液学杂志

This study was to investigate the relationship between the CD34(+)CD38(-) cell population and its proportion in G(0) phase of de novo AML non-M(3) at diagnosis and the clinical and experimental characteristics. The flow cytometry was used to detect the expression of the cell surface antigen CD34 and CD38 in the bone marrow mononuclear cells (MNC) of the AML non-M(3) at diagnosis and investigate the cell cycle of the subpopulations, and then the relationships between the proportion of CD34(+)CD38(-)cell population and its G(0) state and the complete remission (CR) rate after the first induction chemotherapy was analyzed. The results showed that the proportion of the CD34(+)CD38(-) cell population and its G(0) phase had no relationship with the karyotypes and WBC count at new diagnosis and the Flt3/ITD status, but correlate with the blasts in the bone marrow after the first course induction chemotherapy. The proportion of the CD34(+)CD38(-) cells in patients who have visible blasts in the bone marrow at day 7 after completion of the first course induction chemotherapy was (12.47 ± 26.26)%, but the counterparts was (2.62 ± 7.20)% in the group of patients whose bone marrow had no visible blasts (p = 0.031). The proportion of the CD34(+) cell population in patients who had visible blasts in the bone marrow at day 1 after completion of the first course induction chemotherapy was (17.40 ± 21.20)%, yet the proportion of the CD34(+) cell populations was (5.64 ± 6.96)% in the patients who had no visible blasts in the bone marrow (p = 0.001). The proportion of the CD34(+)CD38(-) cell populations in the patients who achieved CR after the first course induction chemotherapy was (2.51 ± 9.72)%, which was lower than the proportion (24.92 ± 27.04%) of the non-CR patients (p = 0.001). Furthermore, the proportion (1.60 ± 4.82%) of the CD34(+)CD38(-) cell population in the AML non-M(2b) CR patients was more obviously lower than that in the non-CR patients (p < 0.001). In univariate analysis, whether or not achieved CR after the first course induction chemotherapy correlated with age (p = 0.022), the proportion of the CD34(+)CD38(-) cell population (p = 0.008) and the proportion of the visible blasts in the bone marrow at day 7 after induction therapy (p = 0.011). Multivariate analysis showed that only the proportion of the CD34(+)CD38(-) cells had correlation tendency with CR rate. It is concluded that the proportion of the CD34(+)CD38(-) cells in bone marrow of de novo AML non-M(3) is a prognostic factor to anticipate the CR rate of the first course for induction therapy.

HIGH-PERFORMANCE LIQUID CHROMATOGRATHY ASSAY FOR NIFEDIPINE IN BIOLOGICAL FLUIDS AND KINETICS OF NIFEDIPINE METABOLISM BY HUMAN LIVER MICROSOMES / 重庆医科大学学报

A high-performance liquid chromatographic method was developed to determine nifedipine in biological fluids, by using ultraviolet detection at 240 nm.Phenacetin was chosen as internal standard.A Nova-Pak C18(4 um, 3.9?150mm) was employed with methanol-water (68:32) as mobile phase. Nifedipine was extracted by ethyl acetate with a percentage of recovery about 95.3?1.0%. The limit of detection of this method for nifedipine was 4 ng for an injection volume of 20 ul. One major metabolite was formed from nifedipine after incubation with human liver microsom-es, the NADPH generating system was needed in this metabolic ptocess. Km and Vmax measured by nifedipine disappearance from roicrosomal incubation mixture were 58.0 umol/L and 1.51 nmol/mg/min, respectively