AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal / 中国辐射卫生

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Role of complement in radiation-induced lung injury / 中国辐射卫生

@#<b>Objective</b> To investigate the role of complement in radiation-induced lung injury in mice after chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy. <b>Methods</b> C57BL/6 mice underwent chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy, followed by observation for the inflammatory reaction of the lung tissue in the early stage (within 15 d) and pulmonary fibrosis in the later stage (30 and 180 d). Enzyme-linked immunosorbent assay was used to measure the levels of C2, C3a, C4, and C5b-9 in the lung tissues at 1, 3, 7, 15, 30, and 180 d after irradiation. The expression of complement mRNA in BEAS-2B cells after irradiation was determined using RT-PCR. <b>Results</b> Radiation-induced lung injury in micepresented as inflammatory response in the early stage and fibrosis in the late stage. Complement C2, C4, and C5b-9 complexes were increased in the early period (3 or 7 d) after irradiation (<i>P</i> < 0.05), which might be associated with the inflammatory response induced by irradiation. During 3 to 180 d, complement C3a was significantly higher in the irradiated mice than in the control mice, suggesting a close relationship between C3a and radiation-induced lung injury. The irradiated cells showed increased mRNA expression of C2 and C3, with no changes in the mRNA levels of C4 and C5. <b>Conclusion</b> Different complement proteins have varying responses to radiation-induced lung injury, among which C3a is closely related to radiation-induced lung injury, suggesting that regulating C3a and its receptors may be a new way to prevent and treat radiation-induced lung injury.

Antigen presentation and T cell activation by dendritic cells in radiation damage / 中国辐射卫生

@#<b>Objective</b> To explore dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the <i>in vitro</i> cell co-culture technology to simulate the <i>in vivo </i>microenvironment of the lung tissue. <b>Methods</b> ⁶⁰Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4⁺ and CD8⁺ T cells. <b>Results</b> ⁶⁰Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4⁺ and CD8⁺ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. <b>Conclusion</b> Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.

A novel diffusion-weighted imaging-based posterior circulation score for prediction of futile recanalization in acute basilar artery occlusion / 中华神经科杂志

Objective:To develop a novel posterior circulation score (PCS) based on pretreatment diffusion-weighted imaging (DWI) for predicting futile recanalization (FR) of acute basilar artery occlusion (BAO) after endovascular therapy (EVT).Methods:A prospectively registered consecutive cohort of BAO patients treated with EVT in Beijing Tiantan Hospital, Capital Medical University during a six-year period was reviewed. This novel DWI-based PCS (DWI-PCS) was calculated according to the characteristics of acute infarction at four sites (pons, midbrain, thalamus and cerebellum), with a normal score of 0 point and a full score of 16 points. FR was defined as the occurrence of poor outcome (modified Rankin Scale score>3) at 90 days despite successful recanalization (modified Thrombolysis In Cerebral Infarction ≥ 2b) at final angiogram after EVT. The independent association of DWI-PCS with FR was evaluated by multivariable Logistic regression, and the predictive discrimination of DWI-PCS was measured by the area under the receiver operating characteristic (ROC) curve. Additionally, the effects of DWI-PCS on FR in different subgroups stratified by age, time window, stroke severity and etiology were explored.Results:Of 109 patients in this study, 48 (44.0%) suffered from FR. The multivariable Logistic analysis showed that DWI-PCS was significantly associated with FR (adjusted OR=1.31, 95% CI 1.07-1.62, P=0.01). The ROC curve analysis demonstrated that the area under the curve of DWI-PCS for predicting FR was 0.74 (95% CI 0.65-0.83), and the optimal cut-off value was ≥ 3 points (sensitivity 0.75, specificity 0.66, accuracy 0.70). Finally, the effects of DWI-PCS on FR were not found to be different across all subgroups ( P>0.10 for all interactions). Conclusions:The novel DWI-PCS may be a valid and reliable predictor of FR in BAO patients treated with EVT. Nevertheless, external validation with blinded outcome is still needed to confirm its performance before clinical application.

Research progress in diagnosis and treatment of post-traumatic stress disorder / 中华全科医师杂志

Post-traumatic stress disorder (PTSD) is a mental disorder characterized by hyperarousal, flashback and avoidance behavior after experiencing traumatic events. This article reviews the diagnostic criteria, pathogenesis and treatment options of this disease.

Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention / 대한뇌졸중학회지

Background@#and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. @*Methods@#Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. @*Results@#Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. @*Conclusions@#There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Discussion on the conflict of interests in the achievements transformation in hospitals / 中华医院管理杂志

With the constant growth of national investment in science and technology, biomedical scientific and technological achievements keep mushrooming. Hospitals, as a powerful force in high-tech research and development, experimental translation and industrialization of biomedicine research, play an important role in the transfer and translation of scientific and technological achievements. This paper analyzed the conflicts of interest in the achievements translation in hospitals, and considered that conflicts of interest are widespread in practice. Under the background of encouraging innovation and promoting the achievements translation, projects with conflicts of interest should be carried out in hospitals conditionally. While reducing the conflicts of interest, the achievements translation should be done properly.

Discussion on the conflict of interests in the achievements transformation in hospitals / 中华医院管理杂志

With the constant growth of national investment in science and technology,biomedical scientific and technological achievements keep mushrooming.Hospitals,as a powerful force in high-tech research and development,experimental translation and industrialization of biomedicine research,play an important role in the transfer and translation of scientific and technological achievements.This paper analyzed the conflicts of interest in the achievements translation in hospitals,and considered that conflicts of interest are widespread in practice.Under the background of encouraging innovation and promoting the achievements translation,projects with conflicts of interest should be carried out in hospitals conditionally.While reducing the conflicts of interest,the achievements translation should be done properly.

Interfering with glutathione S-transferase P1 induces lung cell damage under irradiation conditions / 中华放射肿瘤学杂志

Objective To investigate the association and mechanism between glutathione S-transferase P1(GSTP1) and radiation-induced lung injury.Methods Two effective GSTP1 siRNAs were designed and synthesized.The normal lung epithelial cell line BEAS-2B cells were transfected with GSTP1 siRNA (experimental group,siRNA-1,siRNA-2) and negative control siRNA (negative control group,NC).Western blot was performed to detect the expression levels of GSTP1 protein and EMT-related proteins.CDNB was adopted to evaluate the activity of GSTs.DCFH-DA probe was used for incubation.Flow cytometry was conducted to detect the median fluorescence intensity (MFI) and cellular apoptosis.Annexin-v/PI staining was utilized for incubation.MTT assay was performed to measure the proliferation of BEAS-2B,and the growth curve was drawn based on the results.Results After radiation,compared with the NC group,the ROS level and MFI were significantly higher in experimental group (6774.66±399.60 vs.8759.00±256.96 vs.9967.67±735.11,P＜0.05).In the experimental group,the percentage of cellular apoptosis was remarkably higher than that in the NC group (12.3± 1.16 vs.17.38± 1.65 vs.22.88± 1.20,P＜0.05).MTT assay demonstrated that the OD values in the experimental group were significantly lower than that in the NC group everyday.Further more,the level of EMT process is higher in the experimental group.Conclusions Interfering with the GSTP1 expression in lung epithelial cells can increase the intracellular ROS level,increase the percentage of cellular apoptosis,and reduce the cell proliferation rate following γ-radiation.Besides,it can also promote the epithelial mesenchymal transition in lung epithelial cells.The down-regulation of GSTP1 protein expression level probably aggravates the radiationinduced lung cell injury and promotes the epithelial mesenchymal transition.

Specialized division of labor system in effect evaluation of clinical research / 中华医学科研管理杂志

Objective To establish a specialized division of labor system for cerebrovascular disease clinical research and verify the effectiveness of specialized division of labor system in the management of cerebrovascular disease clinical research.Methods Using Delphi method to establish the specialized division of labor system of clinical research,identify personnel responsibilities,access mechanism and access standards.Compare two clinical studies that using and not using this system in terms of clinical research management efficiency,effectiveness of the clinical research progress and quality control.Results Specialized division of labor system can reduce the time spent for research design and preparation,improve the research progress and data integrity,reduce the protocol deviation and the loss of subject follow up.Conclusions Specialized division of labor system can improve the efficiency of clinical research management and improve the research progress and quality.

The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE / 中华内科杂志

Objective Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results A total of 59 (1.9％) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95％CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04;95％CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05;95％CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

Evaluation of functional departments′ position values at a general hospital in Beijing / 中华医院管理杂志

Objective To assess the relative value of individual positions in the functional departments of a general hospital in Beijing,for reference of improving the salary allocation system and fine management of human resources.Methods The expert consultation method and International Position Evaluation system were used to quantitatively assess the tasks,work difficulty,size of responsibility and the qualifications required for every.Results A total of 38 experts contributed to this research which studied 140 positions including all functional departments of this hospital.The department having the most positions is the finance department(17)and the least is the Youth League committee(1).The position scoring the highest(805)was the director of medical affairs department;that scoring the lowest(263)was the food and beverage service positions of the diet and nutrition department.There was an evident turning point at score 547.Conclusions Functional departments′ position setting of this hospital proves reasonable,and the assessment scoring can reflect the value of the position in related dimensions.The result can be used as reference indexes for the hospital to perfect its human resource management system and improve the remuneration precision.

Hospital recruitment indicator system:a competence theory based applied research / 中华医院管理杂志

The paper presented the competence theory,and its application in the current hospital recruitment in China.Based on existing studies,the authors proposed a competence-based hospital recruitment indicator system and measurement approach,consisting of 15 level-1 indicators and 16 level-2 indicators.They also named the merits of such a system compared to conventional ones as evidenced in practice.On such basis the paper proposed to further improve such a system and mechanism,as well as the quantitative research and empirical study of the competence indicator system.

Analysis of in-hospital delay factors of influencing intravenous thrombolytic therapy in patients with acute ischemic stroke / 中国脑血管病杂志

Objective To investigate the influencing factors of in-hospital delay using alteplase for intravenous thrombolytic therapy in patients with acute ischemic stroke.Methods From January 2006 to May 2015,220 consecutive patients with acute ischemic stroke admitted to the Department of Neurology,Tangshan Gongren Hospital Affiliated to North China University of Science and Technology were enrolled retrospectively.They all received alteplase for intravenous thrombolytic therapy.Their mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 16±8.According to door-to-needle time (DNT),they were divided into either a delay group (DNT >60 min;n=151) or a non-delay group (DNT ≤60 min;n=69).The baseline data,laboratory tests,onset-to-door (OTD) time,imaging,and etiology classification of trial of org 10172 in acute stroke treatment (TOAST) of both groups were recorded.Univariate analysis was performed on both groups,and further multivariate logistic analysis was performed.Results (1) The proportion of the past history of transient ischemic attack,blood glucose level on admission,time from onset to hospital in the non-delay group were significantly higher than those of the delay group.There were significant differences between the two groups (43.5%[30/69] vs.3.3%[5/151],7.9±3.0 mmol/L vs.6.9±2.1 mmol/L,95±53 min vs.80±34 min,all P0.05).(2) Multivariate Logistic regression analysis showed that the risks of patients with the past history of transient ischemic attack (OR,0.330,95%CI 0.109-0.998,P=0.046),elevated blood glucose levels on admission (OR,0.775,95%CI 0.657-0.914,P=0.005),prolonged onset-to-door time (OR,0.648,95%CI 0.504-0.831,P=0.013),internal carotid artery lesions (OR,0.192,95%CI 0.038-0.960,P=0.044) for occurring in-hospital delay after thrombolysis were low.Systolic pressure on admission(OR,1.275,95%CI 1.091-1.491,P=0.027)and cardioembolism(OR,3.892,95%CI 1.661-9.112,P=0.006) for occurring in-hospital delay after thrombolysisin were high.Conclusion The patients with past history of transient ischemic attack,higher blood glucose,prolonged onset-to-door time,and having internal carotid artery lesions may be cause the attention of family members and doctors,and were less prone to having thrombolytic in-hospital delay,whereas those with higher systolic blood pressure on admission and cardioembolism were prone to having in-hospital delay.

Association between hemoglobin concentration and stroke severity on admission in ischemic stroke with-out diabetes / 中国综合临床

Objective To evaluate the association between hemoglobin concentration and stroke severity on admission in ischemic stroke without diabetes. Methods Based on the China National Stroke Registry,the information of acute stroke patients were collected by trained research coordinators and investigators with the methods of review clinical records or interview. Demography, disease history, behavior and habits, hemoglobin concentration,and NIHSS score on admission were collected in this study. The iIncluded patients with the integri?ty of the information of non diabetes,3 h to the hospital,no gastrointestinal bleeding and Hb concentration and NIHSS score at admission. Hemoglobin concentration was classed according to quintiles and the outcome was grouped into ≤3 and >3 groups. The method of logistic regression was used to explore the association between hemoglobin and NIHSS. Results A total of 1 419 individuals was included in this study,including 883 males and 536 females. The mean age was 67. 24±12. 46 years old and the proportion of NIHSS>3 was 67. 51% (958/1419). With respect to non?minor stroke (NIHSS>3),the odds rations and 95% confident intervals of patients with hemoglobin ≤121. 0 g/L(Q1),>122. 1-≤132. 0 g/L(Q2),>141. 0-≤152. 0 g/L(Q4),≥152. 1 g/L (Q5) were 1. 84(95%CI 1. 21-2. 79,P=0. 004),1. 24(95%CI 0. 83-1. 86,P=0. 294),1. 32(95%CI 0. 88-1. 96,P=0. 178) ,1. 52( 95%CI 1. 01-2. 28,P=0. 044) respectively,compared with hemoglobin between 132. 0 and 141. 0 g/L( Q3) . Conclusion Stroke severity is associated with lower and higher hemoglobin concentration in acute ischemic stroke without diabetes.

Disciplines converging management practice at a research hospital / 中华医院管理杂志

The paper introduced the concept and background ofdisciplines convergingmanagement,holding that this management philosophy can encourage dialogues among disciplines in a holist concept.It is believed that with an innovative mechanism in the management and operation,such converging has initially proven its value,promoting disciplines from high refinement to coordination and synergy,supporting research hospitals in development.

To Write The Medical Research Contract From The Angle of Funding Management / 中华医学科研管理杂志

Medical research contract is an important part of business between medical research organizations.It is the official document identifying the right and obligations of respective medical research organizations during research activities.It is the legal basis,and is also on the basis of research expenditure.Therefore,it is very important to improve ability of the contract writing in research management.Composing a sound medical research contract has significant importance in research activities.This paper explored the remarkable issues when composing a medical research contract from the respective of management of funding,including how to make the contract more fair,rational,rigorous and legal.

Procedures and Key Points of Ethical Review for Research Protocols / 中华医学科研管理杂志

By introducing the stage management of ethics review for medical research protocols,this paper try to explain the submission requirement,the review procedures,the key points for focusing on,and analyze the issues found in ethical reviewing of research protocols,help to guide the procedures of ethical review,as well as improve the supervision of ethical review for research protocols.

Effects of different concentrations and different duration of sevoflurane anesthesia on cognitive function in mice / 中华麻醉学杂志

Objective To evaluate the effects of different concentrations and different duration of sevoflurane anesthesia on cognitive function in mice.Methods Fifty adult male C57BL/6 mice,weighing 20-24 g,aged 10 weeks,were randomly divided into 5 groups (n =10 each) using a random number table:control group (group C),1.3％ sevoflurane inhaled for0.5 h group (group S1),1.3％ sevoflurane inhaled for 2.0 h group (group S2),2.5％ sevoflurane inhaled for 2.0 h group (group S3),and 2.5％ sevoflurane inhaled for 4.0 h group (group S4).At 2 weeks after anesthesia,Morris water maze test was performed,and the escape latency and frequency of crossing the original platform were recorded.After the end of the test,the mice were sacrificed,and brains were removed to detect the expression of 2B subunit-containing N-methyl-D-aspartate receptors (NR2B) and activated caspase-3 in the hippocampus.Results Compared with group C,the escape latency was significantly shortened,and the frequency of crossing the original platform was increased in S1-3 groups,and the escape latency was prolonged,and no significant change was found in the frequency of crossing the original platform in group S4.Compared with group C,the expression of NR2B in hippocampal tissues was up-regulated in S1-4 groups,and the expression of activated caspase-3 in hippocampal tissues was up-regulated in S3 and S4 groups.Conclusion The reason for different effects of sevoflurane anesthesia on cognitive function is related to the concentration and duration in mice.