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.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

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.

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.

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 observe the clinical efficacy of hyperbaric oxygen（HBO）combined with infliximab in the treatment of ulcerative colitis and explore its possible action mechanism.Methods:A total of 50 patients with ulcerative colitis were randomly divided into treatment group（26 cases）and control group（24 cases）. The treatment group was given HBO combined with infliximab，while the control group was given infliximab alone. Both groups were treated for 30 weeks.Results:The comprehensive efficacy，infliximab response rate，and trough level of the maintenance period（from the 3rd to the 5th injection）in the treatment group were significantly higher than those of the control group with statistically significant differences，respectively［92.3% vs. 66.7%， P<0.05；92.3% vs. 66.7%， P<0.01；（1.32±0.26）μg/ml vs.（0.74±0.22）μg/ml， P<0.01］；and the treatment group could significantly improve the levels of CD4 + and CD4 +/CD8 +，reduce the levels of CD8 +，TNF-α，IL-6，and CRP（ P<0.05）. Conclusion:HBO combined with infliximab in the treatment of ulcerative colitis can significantly improve the response rate of infliximab and enhance the curative effect，which may be achieved by inhibiting the proliferation of T lymphocyte and reducing the release of inflammatory factors.

Objective:To observe the clinical efficacy of hyperbaric oxygen（HBO）combined with infliximab in the treatment of ulcerative colitis and explore its possible action mechanism.Methods:A total of 50 patients with ulcerative colitis were randomly divided into treatment group（26 cases）and control group（24 cases）. The treatment group was given HBO combined with infliximab，while the control group was given infliximab alone. Both groups were treated for 30 weeks.Results:The comprehensive efficacy，infliximab response rate，and trough level of the maintenance period（from the 3rd to the 5th injection）in the treatment group were significantly higher than those of the control group with statistically significant differences，respectively［92.3% vs. 66.7%， P<0.05；92.3% vs. 66.7%， P<0.01；（1.32±0.26）μg/ml vs.（0.74±0.22）μg/ml， P<0.01］；and the treatment group could significantly improve the levels of CD4 + and CD4 +/CD8 +，reduce the levels of CD8 +，TNF-α，IL-6，and CRP（ P<0.05）. Conclusion:HBO combined with infliximab in the treatment of ulcerative colitis can significantly improve the response rate of infliximab and enhance the curative effect，which may be achieved by inhibiting the proliferation of T lymphocyte and reducing the release of inflammatory factors.

Objective:To observe the effect of computerized cognitive remediation therapy(CCRT) in the patients with mild cognitive impairment (MCI).Methods:A randomized, single-blinded clinical study was carried out from the April to June in 2019. 46 patients who met MCI criteria were randomly allocated into a CCRT group ( n=24) and a control group ( n=22). In CCRT group, the CCRT was conducted five times a week (30 minutes each time) for a total of 8 weeks (40 times), while a natural observation was performed in the control group. All the subjects were assessed by the Mini-Mental State Examination(MMSE) and the Montreal Cognitive Assessment(MoCA) before and after the treatment. The Wilcoxon test in the paired rank-sum test of two related samples was used to evaluate the effect of CCRT on MCI before and after the intervention, and the Mann-Whitney U test in the rank-sum test of two independent samples was used to compare the differences in MMSE and MoCA scores between the two groups. Results:Before treatment, there were no statistically significant differences in MMSE, MoCA total scores and each factor between the CCRT group and the control group ( P>0.05). A total of 21 patients in CCRT group completed CCRT treatment. After 8 weeks of treatment, the difference between two groups in the total score of MMSE ( Z=-2.83), attention and calculation( Z=-2.58), time orientation( Z=-2.00) and visual spatial function ( Z=-2.45) scores were higher than those before the treatment ( P<0.05); the difference between two groups in MoCA total score ( Z=-3.40), visual space and executive function( Z=-3.41), attention ( Z=-3.09) were higher than those before the treatment ( P<0.05). Conclusion:CCRT may improve the cognitive function of MCI patients, especially the attention and visuospatial functions.

Objective:To observe the effect of computerized cognitive remediation therapy(CCRT) in the patients with mild cognitive impairment (MCI).Methods:A randomized, single-blinded clinical study was carried out from the April to June in 2019. 46 patients who met MCI criteria were randomly allocated into a CCRT group ( n=24) and a control group ( n=22). In CCRT group, the CCRT was conducted five times a week (30 minutes each time) for a total of 8 weeks (40 times), while a natural observation was performed in the control group. All the subjects were assessed by the Mini-Mental State Examination(MMSE) and the Montreal Cognitive Assessment(MoCA) before and after the treatment. The Wilcoxon test in the paired rank-sum test of two related samples was used to evaluate the effect of CCRT on MCI before and after the intervention, and the Mann-Whitney U test in the rank-sum test of two independent samples was used to compare the differences in MMSE and MoCA scores between the two groups. Results:Before treatment, there were no statistically significant differences in MMSE, MoCA total scores and each factor between the CCRT group and the control group ( P>0.05). A total of 21 patients in CCRT group completed CCRT treatment. After 8 weeks of treatment, the difference between two groups in the total score of MMSE ( Z=-2.83), attention and calculation( Z=-2.58), time orientation( Z=-2.00) and visual spatial function ( Z=-2.45) scores were higher than those before the treatment ( P<0.05); the difference between two groups in MoCA total score ( Z=-3.40), visual space and executive function( Z=-3.41), attention ( Z=-3.09) were higher than those before the treatment ( P<0.05). Conclusion:CCRT may improve the cognitive function of MCI patients, especially the attention and visuospatial functions.