BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.

This article systematically summarizes the theoretical framework, training content, training methods, and evaluation tools of TeamSTEPPS curriculum, and explores its application status and future research directions in nursing clinical training and college teaching, in order to provide a basis for further promoting this curriculum in nursing clinical training and college teaching in China.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Objective To explore the correlation between childhood trauma and plasma adiponectin levels in patients with depression.Methods A total of 121 patients with depression and 39 healthy controls(control group)were enrolled.Childhood trauma questionnaire(CTQ-SF)was used to assess the experience of childhood abuse and neglect,and the patients with depression were divided into trauma group(n=53)and non-trauma group(n=68)according to the CTQ-SF score.The 17-item Hamilton depression scale-17(HAMD17)and the Hamilton anxiety scale(HAMA)were used to evaluate the severity of depression and anxiety symptoms,respectively.Plasma adiponectin levels of subjects were measured by enzyme-linked immunosorbent assay.Results The plasma adiponectin level of trauma group[3.82(2.44,4.92)μg/mL]was significantly lower than that of non-trauma group[4.64(2.98,6.43)μg/mL,P=0.01]and the control group[6.29(4.54,7.51)μg/mL,P＜0.01].The plasma adiponectin level of non-trauma group was lower than that of the control group(P＜0.01).Correlation analysis showed that plasma adiponectin level in patients with depression was negatively correlated with childhood trauma(r=-0.34,P＜0.01).Multivariate linear regression analysis showed that plasma adiponectin level was negatively correlated with childhood trauma scores in patients with depression(β=-0.05,P＜0.01).Conclusions Patients with depression who have experienced childhood trauma have lower plasma levels of adiponectin,and childhood trauma may be associated with decreased plasma adiponectin levels in patients with depression.

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.

OBJECTIVE：To optimi ze the ratio of four comp onents of Compound renshen jianti formulation （Panax ginseng ， Dioscorea oppositifolia ，Lycium barbarum fruit，Alpinia oxyphylla ），and to investigate its anti-fatigue activity and acute toxicity. METHODS：The water extract of Compound renshen jianti formulation was prepared by water extraction ，concentration and decompression drying. By single factor tests ，using weight-bearing swimming time as index ，the effects of four factors were investigated，such as the amount of P. ginseng ，D. oppositifolia ，L. barbarum fruit，A. oxyphylla . On the basis of single factor tests，using comprehensive score of weight-bearing swimming time ，serum urea nitrogen content ，liver glycogen content and AUC of blood lactate after exercise as index ，the formulation was optimized by Box-Behnken response surface method. The mice was divided into blank control group （water），positive control group （Renshen hongjingtian capsules ，0.135 g/kg）and compound low-dose，medium-dose and high-dose groups [the optimal ratio of Compound renshen jianti formulation extract （called“optimal compound formulation ”for short ）4.08，8.16，12.24 g/kg，by crude drug] ，intragastric administration of drug or distilled water 20 mL/kg，once a day ，for consecutive 30 d. The weight-bearing swimming time ，the contents of serum urea nitrogen ，liver glycogen and blood lactate AUC after exercise were used to optimize its anti-fatigue activity of optimal compound formulation. The comprehensive score was calculated based on the measured data of mice in the compound formulation middle-dose group ， and the difference between it and the theoretical prediction value was compared. The mice were given optimal compound formulation intragastrically （total dose 16.00 g/kg， by extract）. The general state ， body mass change ， toxic characteristics and death of mice were observed and recorded for 14 days. Median lethal dose （LD50）and maximum tolerated dose （MTD）were measured. RESULTS ：The optimal formulation ratio of Compound renshen jianti formulation included that P. ginseng 1.5 g，D. oppositifolia 10 g，L. barbarum fruit 10 g，A. oxyphylla 3 g. Results of anti-fatigue activity validation test showed that the optimal compound formulation could significantly prolonged weight-bearing swimming time ，reduced serum content of urea nitrogen ，blood lactate content and its AUC （except for low-dose group ），while significantly increased the content of liver glycogen （P＜0.05 or P＜0.01）. Average comprehensive score of medium-dose group was 96.95，which was only 0.06％ different from the theoretical prediction value of 97.01. The results of acute toxicity test showed that there was no death in mice. The oral MTD of the optimal compound formulation was more than 15 g/kg，which was non-toxic. CONCLUSIONS ：The optimal Compound renshen jianti formulation has effective anti-fatigue activity of mice ，and has no significant toxic effect.

Objective:To analyze the reform of improving the teaching effects of nursing college students' practical training.Methods:Cluster sampling method was used to select 396 nursing college students in a higher nursing school as the research objects, with 197 in experimental group and 199 in control group. Self-directed learning was adopted in practical teaching of surgical nursing in the students in experimental group, and traditional surgery teaching was adopted in control group. Self-rating scale of self-directed learning (SRSSDL) was used every 3 months during the period. The students' self-directed learning ability was measured dynamically, and the scores of practical examination and course satisfaction were compared between the two groups. The data were statistically analyzed by repeated measures analysis of variance and independent sample t-test using SPSS 17.0.Results:The scores of repeated measurement of SRSSDL in the experimental group were higher than those in the control group ( F=16.237, P=0.016). Except for the common surgical instruments module ( P=0.056), the scores of practical training examination in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.01 for the operating room nursing module, P=0.005 for the wound nursing module, P<0.01 for the enterostomy nursing module). The students' satisfaction with the overall curriculum in the experimental group was higher than that in the control group. Conclusion:Self-directed learning in the teaching of nursing practice can effectively enhance comprehensive ability and quality of students based on self-directed learning ability, and improve the teaching effect of practical training courses.

PURPOSE: Colorectal cancer (CRC) is the third most common cancer in China and poses high morbidity and mortality. In recent years, increasing evidence has indicated that microRNAs played important functions in the occurrence and development of tumors. The purpose of this study was to identify the biological mechanisms of miR-362 in CRC. MATERIALS AND METHODS: Quantitative real-time PCR was carried out to assess the expression of miR-362 and SIX1. The Kaplan-Meier method was employed to evaluate the 5-year overall survival of CRC patients. The proliferative and invasive abilities of CRC cells were assessed by MTT and transwell assays. RESULTS: miR-362 was significantly decreased in CRC tissues and cell lines, compared to the normal tissues and normal cells. A significant connection was confirmed between the overall survival of 53 CRC patients and low expression of miR-362. Downregulation of miR-362 inhibited the proliferation and invasion through binding to the 3′-UTR of SIX1 mRNA in CRC. Additionally, we discovered that SIX1 was a direct target gene of miR-362 and that the expression of miR-362 had a negative connection with SIX1 expression in CRC. SIX1 could reverse partial functions in the proliferation and invasion in CRC cells. CONCLUSION: miR-362 may be a prognostic marker in CRC and suppress CRC cell proliferation and invasion in part through targeting the 3′-UTR of SIX1 mRNA. The newly identified miR-362/SIX1 axis provides insight into the progression of CRC.
Cell Line ; Cell Proliferation ; China ; Colorectal Neoplasms ; Down-Regulation ; Humans ; Methods ; MicroRNAs ; Mortality ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

Objective To investigate the effect of prenatal stress (PS) at different pregnant time on emotion and cognition of adult offspring rats.Methods Twelve healthy female Sprague Dawley (SD) rats were randomly divided into control group(CON,n=4),the early pregnancy group(PS1,the 1～ 7 days of pregnancy,n=4) and the late pregnancy group(PS3,the 15 ～ 21 days of pregnancy,n=4).The pregnant rats were exposed to single-prolonged stress(SPS) on gestational day 7 or 15 respectively,except control group.The offspring were measured every weekend from 1-7 week after birth.At the eighth weekend,the sucrose intake (anhedonia) and Morris water maze (MWM) were performed to assess depression-like behavior and spatial learning and memory.Results The body weight of the first to seventh weeks after birth showed that there was a statistically significant difference among the three groups (F=28.207,P＜0.01),and there was a significant difference in time effect (F=1 041.546,P＜0.01).The body weight of two PS groups was significantly lower than those of control group(P＜0.05).The body weight of PS3 was lower than that of PS1 significantly(P＜0.05).Sucrose preference:PS3((27.70± 19.31) ％) were reductive on sucrose consumption than CON significantly((66.93±19.67) ％)(P＜0.05)while PS1 ((89.80±6.79) ％) increased in sucrose consumption compared with the CON significantly(P＜0.05).MWM:in training stage the difference of average avoid latency was existed in the three groups of the first 5 days(F=11.121,P＜0.01).Similarly,there was a significant difference in measure time(F=91.327,P＜0.01),the escape latency of the PS3 was decreased,while PS1 was significantly increased compared with CON;in testing stage,PS3 ((54.50±4.64) s,(53.21±4.45)) showed a significant increase in the duration in target site and numbers of times across the target site compared with CON((32.24±.4.17) s,(31.68±4.00)) (P＜0.05).Conclusion The acceptance of stress in the late pregnancy may lead to depression like behavior in the adult offspring and also enhance the learning and memory ability.And acceptance of stress in early pregnancy can cause impairment of learning and memory ability in adult offspring rats.

Objective To compare the results of TEOAE and DPOAE in the same population of normal newborns, to provide information on choosing appropriate screening tools.Methods A two-steps protocol was taken with the first screening during the first 48 to 72 hours of birth and rescreened from one to two months old if the newborns failed the first screening.For each step of screening, TEOAE and DPOAE were performed simultaneously using AccuScreen hearing screening instrument (Madsen-GN Otometrics, Taastrup, Denmark).A total of 1 062 normal newborns (F/M=508/554) delivered in Peking Union Medical College Hospital were enrolled in this research for the first screening.Infants who failed either TEOAE or DPOAE screening in the first screening were referred to a second screening.Among them, 135 performed both DPOAE and TEOAE in the second step.The newborns who failed the second screening would receive ABR when they were 3 months old.Results In the first screening,the failure rate for TEOAE was 11.0% (117/1 062) and 13.7% (145/1 062) for DPOAE.In the second screening step, the failure rates were 17.8% (24/135) and 20.7% (28/135) for TEOAE and DPOAE, respectively.Chi-square and Fisher's test showed that the failure rates of DPOAE were significant higher than TEOAE for both steps (P<0.001).The agreements between TEOAE and DPOAE were 96.0% and 95.6% for the first and second steps respectively, and the kappa values were 0.817 and 0.857.As to the average time taken to accomplish the screening for one ear, TEOAE was 24±25 s and DPOAE was 40±34 s during the first screening;in the rescreening, TEOAE was 52±41 s and DPOAE was 73±62 s.Paired-t tests showed that the differences between DPOAE and TEOAE testing time were statistically significant (P=0.000) in both screening steps.Finally, 7 newborns (10 ears) were diagnosed conductive hearing loss(except 1 ear was sensorineural hearing loss).Conclusion As a screening tool, TEOAE got lower refer rates and took less time than DPOAE implicating TEOAE a better screening tool for normal neonates.