Objective To evaluate the effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients.Methods Between March 2007 and March 2011,a total of 60 patients undergoing consecutive kidney transplantation with asymptomatic arteriovenous fistula were divided randomly into two groups: arteriovenous fistula closure group,and non-arteriovenous fistula closure group.By using echocardiography,the changes in CO,CI,EF,LVEDV and LVMI were analyzed.Results At 12th month after transplantation,the values of CO,LVEDV and LVMI were significantly lower than those before transplantation (P＜0.05).The value of CI also showed a tendency to decrease (P＞0.05),and the value of EF was increased significantly (P＜0.05).At 6th month after arteriovenous fistula closure (18 months after transplantation),the values of CO,CI,LVEDV and LVMI were significantly lower than those before arteriovenous fistula closure (12 months after transplantation) (P＜0.05),and the value of EF was increased significantly (P＜0.05),but the values of CO,CI,EF,LVEDV and LVMI remained unc(b)anged in controls (P＞0.05).At 18th month after transplantation,the values of CO (4.4 ±0.8 L/min),CI [3.0 ± 0.8 L·min-1·m-2],LVEDV (110.0 ± 17.4 ml) and LVMI (114.7 ± 42.5g/m2) in trial group were significantly lower than the values [CO: 5.1 ± 0.9 L/min,CI: 3.5 ± 1.0L·min-1·m-2,LVEDV: 121.4±19.3 mL,LVMI: 138.4±44.1 g/m2] in controls (P＜0.05),and the value of EF (75.2％ ± 7.4％ vs.70.5％ ± 8.2％) significantly higher (P＜005).Conclusion In both groups,kidney transplantation benefits significantly the regression of cardiac mass,cardiac index and left ventricular dimensions,but closure of asymptomatic AVF induces more significant regression.

Objective To evaluate the effect of diammonium glycyrrhizinate extracted from the Chinese traditional medicine licorice root on the growth of human hair follicles cultured in vitro,and to detect the expression of wnt/β-catenin signaling pathway-related molecules.Methods Isolated hair follicles were cultured with diammonium glycyrrhizinate at different concentrations of 0.1,0.01,0.001 and 0.000 1 μmol/L for 10 days,and the hair follicles cultured in Williams' E medium without diammonium glycyrrhizinate served as a control group.The length of hair follicles was measured under a microscope every day,the morphologic changes of hair follicles were observed,and photos were taken.Immunofluorescence assay was performed to assess the proliferation of hair matrix cells,as well as to determine the expression of β-catenin,glycogen synthase kinase 3β (GSK3β),phosphorylated GSK3β (p-GSK3β) and lymphoid enhancer factor-1 (Lef1) in the Wnt/β-catenin signaling pathway.Statistical analysis was carried out by repeated-measures analysis of variance and one-way analysis of variance.Results As repeated-measures analysis of variance showed,only 0.01 μmol/L diammonium glycyrrhetate showed significantly promotive effect on the growth of hair follicles compared with the medium alone (P ＜ 0.05),and there were no significant differences in the length of hair follicles between the other concentration groups and the control group.Compared with the control group,the transition to the catagen phase of human hair cycle was delayed in the 0.01-μmol/L diammonium glycyrrhetate group,while it did not change in the other diammonium glycyrrhetate groups and control group.Immunofluorescence assay showed that the number of ki67-positive hair matrix cells was obviously increased in the 0.1-,0.01-,0.001-μmol/L diammonium glycyrrhizinate groups compared with the control group,while there was no difference between the 0.000 1-μmol/L diammonium glycyrrhizinate group and the control group.One-way analysis of variance revealed that the expression of β-catenin,p-GSK3β and Lef1 significantly differed among all the groups (F =12.604,16.65,15.266 respectively,P ＜ 0.05),while no significant difference in the expression of GSK3β was found among these groups (F =1.472,P ＞ 0.05).Least significant difference (LSD)-t test revealed that the expre-ssion of β-catenin,p-GSK3β and Lef1 in the hair matrix cells was significantly higher in the 0.1-,0.01-,0.001-μmol/L diammonium glycyrrhizinate groups than in the control group (all P ＜ 0.05),but there was no significant difference between the 0.000 1-μmol/L diammonium glycyrrhizinate group and the control group (P ＞ 0.05).Conclusion Diammonium glycyrrhetate at the concentration of 0.01 μmol/L shows markedly promotive effect on the in vitro growth of hair follicles,and can increase the proliferative activity of hair matrix cells and delay the transition to the catagen phase,which may be associated with the activation of Wnt/β-catenin signaling pathway.

Objective To analyze the correlation between the status of the donation after brain and cardiac death (DBCD)donors and postoperative recovery of the organ function in the liver and renal transplant recipients.Methods The assessment data and organ protection measures of 12 DBCD donors admitted to the Organ Transplantation Center in Sichuan Provincial People’s Hospital from August 2011 to November 2013 were retrospectively analyzed.The parameters of postoperative recovery of 12 liver and 22 renal transplant recipients were also assessed.The correlation between the parameters of the donors and postoperative recovery of the liver and renal transplant recipients was statistically analyzed.Results Among 12 liver transplant recipients,1 patient had primary non-function (PNF)(1 /12,8%)and 11 cases developed delayed graft function (DGF) after renal transplantation (11 /22,50%).Intensive care unit (ICU)period,liver function,maintaining systolic blood pressure (SBP),blood coagulation function,blood glucose level and electrolyte (Na +/K +) were significantly correlated with postoperative recovery of the liver and kidney function in the recipients (all in P <0.05 ).Age,cause of brain death,maintaining diastolic blood pressure (DBP),activated partial thromboplastin time (APTT)and pH of arterial blood gas (ABG)were associated with postoperative recovery of the liver function.Total bilirubin and white blood cell count (WBC)were correlated with postoperative recovery of kidney function.Conclusions DBCD donors cater to the specific conditions in China.The incidence of postoperative PNF in liver recipients is relatively low whereas and the incidence of DGF after renal transplantation is relatively high.Assessment of the DBCD donors and organ protection measures should be specifically taken to enhance the clinical efficacy of liver and renal transplantation from DBCD donors.

Objective:To analyze the outcome of 15 cases with refractory systemic lupus erythematosus (SLE) treated with Belimumab, and evaluate the safety and efficacy of the therapy.Methods:A retrospective and real-world clinical research method was adopted.Fifteen children with confirmed refractory SLE and complete follow-up data were selected from the Department of Rheumatology, Beijing Children′s Hospital from April 1, 2020 to March 31, 2022.By comparing the changes of clinical symptoms, auxiliary examination results, SLE disease activity index (SLEDAI-2000) and Physician′s Global Assessment (PGA) scores as well as adverse events in different treatment periods (before treatment, 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatment), the safety and effectiveness of Belimumab treatment were all recorded.The counting data was expressed in percentage, the measurement data meeting the normal distribution was expressed in Mean±SD, and the two samples of measurement data were compared by t-test, P<0.05 means significant differences. Results:The ratio of male to female was 3∶2, and the onset age was (7.93±4.99) years; The basic treatment time was 4 months to 5 years and 1 month.There were 8 cases with lupus nephritis (LN), 2 cases suffering from hypocomplementemia for more than 1 year, 2 cases with central nervous system involvements, 2 cases complicated with antiphospholipid syndrome and 1 case with early-onset SLE.Of 8 LN cases, 1 case was complicated with neuropsychiatric lupus (NPLE) and distal femoral head infarction of both knees, and 3 cases were complicated with lumbar compression fractures and hip infarction.All patients were treated with regular traditional therapy to induce remission.During the maintenance period, the disease activity maintained at light to moderate levels, and it was difficult to reduce glucocorticoid.At baseline, SLEDAI-2000 score was 4-13, and PGA score was 1-2.50.Basic treatment includes glucocorticoids combined with immunosuppressants (Cyclosporine, Mycophenolate Mofetil, Leflunomide tablets) and antimalarial drugs, and Cyclophosphamide and/or Tripterygium Wilfordii were used at the same time according to the damage of target organs.The drug safety after intravenous injection of Belizumab showed that one patient in this group had respiratory tract infection symptoms 4 weeks after treatment; Another patient had a slight increase of alanine aminotransferase 8 weeks after treatment, and recovered to normal symptomatic treatment.No drug-related adverse reactions were found in the other 13 patients.After 4 weeks of treatment, the score of SLEDAI-2000 and PGA compared with the baseline level, and the difference was statistically significant (SLEDAI-2000 P=0.002; PGA P=0.006). There was no clinical recurrence.One patient with familial chilblain like lupus erythematosus showed significant improvement in rash 2 weeks after treatment, and low fever accompanied by increased rash 8 weeks after treatment; After 16 weeks of treatment, the body temperature was normal and the rash basically subsided. Conclusions:Belimumab is clinically effective in the treatment of refractory childhood SLE, with no serious adverse events reported.However, its long-term efficacy and safety need to be further studied by multi-center and long-term research with a large sample size.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.