Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment:A phase 2 clinical trial

BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.

Effectiveness and safety of human umbilical cord-mesenchymal stem cells for treating type 2 diabetes mellitus

BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.

Nurses’ knowledge, perceptions, and behaviors regarding antineoplastic drugs:the mediating role of protective knowledge

Objective:To explore the relationships between Chinese nurses’knowledge,perceptions,and attitudes and their behavior and actual implementation of safety measures when handling antineoplastic drugs(ADs)in their daily work.Methods:This was a multisite study conducted in 8 public hospitals in China.A self-administered questionnaire was sent to par ticipants querying the degree of contact with ADs.The hypothesized relations were explored using structural equation modelling via the bootstrap method.Mediation analysis was applied to explore the mediating role of protective knowledge regarding AD exposure on the associations among protective training,using warning labels,and using protective masks.Results:A total of 305 nurses were enrolled.The average age of all par ticipants was 30.2(standard deviation[SD]:6.2)years.Nurses who had received protective training for AD exposure were more likely to use labels for ADs after age,body mass index(BMI),length of service,marital status,education,and department were controlled as covariates.The bias-corrected bootstrap of 95%confidence interval(CI)indicated that protective knowledge significantly mediated(23.4%)the association between protective training and using labels(indirect effect=0.202,95%CI:0.009,0.495);the proportion of mediation was 23.4%.Protective knowledge significantly mediated the association between protective training and using protective masks(indirect effect=0.157,95%CI:0.048,0.325);the propor tion of mediation was 27.2%.Conclusions:The findings of this study have provided baseline information on the current state of Chinese nurses’perceptions,knowledge,and preventive behaviors toward ADs as the crisis is happening.Training is also recommended to improve nurses’perceptions of the risks associated with ADs.

Self-assembly multifunctional DNA tetrahedron for efficient elimination of antibiotic-resistant bacteria

Antibiotic resistance is a major challenge in the clinical treatment of bacterial infectious diseases.Herein,we constructed a multifunctional DNA nanoplatform as a versatile carrier for bacteria-specific delivery of clinical antibiotic ciprofloxacin(CIP)and classic nanoantibiotic silver nanoparticles(AgNP).In our rational design,CIP was efficiently loaded in the self-assembly double-bundle DNA tetrahedron through intercalation with DNA duplex,and single-strand DNA-modified AgNP was embedded in the cavity of the DNA tetrahedron through hybridization.With the site-specific assembly of targeting aptamer in the well-defined DNA tetrahedron,the bacteria-specific dual-antibiotic delivery system exhibited excellent combined bactericidal properties.With enhanced antibiotic accumulation through breaking the out membrane of bacteria,the antibiotic delivery system effectively inhibited biofilm formation and promoted the healing of infected wounds in vivo.This DNAbased antibiotic delivery system provides a promising strategy for the treatment of antibiotic-resistant infections.

巴曲酶灌注联合肝动脉化疗栓塞治疗原发性肝癌的临床初步研究(英文)

Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization(TACE).Methods:Forty patients with PHC were randomized into experimental group(transcatheter arterial perfusion of batroxobin combined with TACE treatment,20 patients) and control group(TACE alone group,20 patients).The patients were followed up and the data were recorded,compared and analyzed.Results:(1) Compared with the control group,the FIB level in the experimental group was significantly decreased at the first month after treatment(P < 0.05).(2) The baseline of the tumor was shortened in both groups after the treatment.There was a significant difference between the two groups at different time intervals(P < 0.05).(3) After the treatment,there was a significant difference of progression-free survival(PFS) levels between the two groups(t =2.877,P < 0.05).(4) The incidence of metastasis were 5.0%(1/20) in both groups at 6 months after treatment,and that after one year was 10.0%(2/20) in the experimental group and 25.0%(5/20) in the control group.However,the difference was not significant(χ2 = 0.693,P > 0.05).Conclusion:Batroxobin can rapidly and effectively decrease the FIB level of the PHC cases.Therefore it may be used as an effective and safe adjuvant drug for the treatment of primary hepatic carcinomas.Transcatheter arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone therapy.It could be taken as a new therapeutic regimen in the PHC treatment.