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Objective:To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV).Methods:Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3).Results:Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, P<0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels ( r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level ( β=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels ( r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level ( β=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a ( r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils ( r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils ( β=0.511, P=0.002). Conclusion:In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.
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Objective:To investigate factors associated with the concentration of hydroxychloroquine (HCQ) and its metabolites in peripheral blood of patients with systemic lupus erythematosus (SLE) who were receiving long-term oral HCQ treatment.Methods:SLE patients who had been taking HCQ for more than 3 months were recruited. Clinical characteristics, laboratory test results and SLE disease activity index (SLEDAI) scores were examined. The concentrations of HCQ and its metabolites from peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Student's-test and Nonpara-metric tests were used to compare quantitative data, Chi-square and Fisher's exact tests were used to analyze qualitative data. Correlation between the test results was assessed by correlation coefficient. Variables with P values less than 0.05 in univariate analysis were entered into a logistic regression model. Results:In total, 191 SLE patients on long-term HCQ treatment were included in the analysis. Medians of HCQ blood concentrations ([HCQ]), desethylhydroxychloroquine (DHCQ) blood concentrations ([DHCQ]), desethylchloroquine (DCQ) blood concentrations ([DCQ]) and bisdesethylchloroquine (BDCQ) blood concentrations ([BDCQ]) were 523.19 (402.63, 677.88) ng/ml, 291.79 (212.30, 432.51) ng/ml, 49.37 (35.00, 73.05) ng/ml, 21.78(14.37, 52.46) ng/ml respectively. On multivariate analysis, weight-adjusted oral HCQ dose [ OR(95% CI)=1.366 (1.053, 1.772) , P=0.019], the course of hydroxychloroquine [ OR (95% CI) =0.991 (0.984, 0.999), P=0.026], estimated glomerular filtration rate [ OR(95% CI)=0.984 (0.971, 0.997), P=0.014] and platelet count [ OR (95% CI)=1.010 (1.005, 1.015), P<0.001] were associated with [HCQ]. [HCQ], [DCQ], [BDCQ], [BDCQ]/[HCQ] were negatively correlated with estimated glomerular filtration rate (eGFR) ( r=-0.20, P=0.006; r=-0.19, P=0.010; r=-0.26, P<0.001; r=-0.15, P=0.044, respectively) after adjusted for age, course of disease, duration of HCQ treatment and weight adjusted HCQ dosage, [DHCQ]/[HCQ] was negatively correlated with the SLEDAI score ( r=-0.16, P=0.027) when the effects of glucocorticoid was controlled, [BDCQ]/[HCQ] among different renal function levels was statistically significant ( H=12.46, P=0.014). Conclusion:The factors associated with HCQ blood concentrations in SLE patients on long-term oral HCQ treatment are weight-adjusted HCQ dosage, duration of hydroxychloroquine intake and renal function. In addition, [BDCQ] is closely correlated with renal function, [DHCQ] is correlated with SLE disease activity.
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Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
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Objective To investigate the risk factors of posttransplantation initial diabetes mellitus(PTDM) and the prognostic impact on living donor renal transplantation recipients.Methods The clinical data of 273 living donor renal transplantation recipients from 2007 to 2013 were retrospectively studied.Recipients were divided into PTDM group and non-PTDM group according to the diagnostic standard.Potential risk factors were analyzed by logistic regression model.The incidence of adverse events were analyzed and compared between the two groups.Recipients and grafts survival (overall and death-censored) rate was analyzed by Kaplan-Meier method.Results During the 5-year follow-up period,62 out of total 273 relative-living recipients were diagnosed as PTDM (22.71％).Six risk factors for PTDM were identified:BMI ≥25 kg/m2 (OR,3.911;95％CI,1.811-8.445),male gender (OR,2.291;95％CI,1.184-4.436),family history of diabetes (OR,3.225;95％CI,1.447-7.186),ARE (OR,4.481;95％CI,1.908-10.522),administration of tacrolimus (OR,3.678;95％CI,1.807-7.483) and impaired fasting glucose (IFG) diagnosed at 1st week posttransplantation (OR,3.925;95 ％ CI,1.997-7.716).The infection rate was significantly higher in PTDM group than in non-PTDM (16.12％ vs.7.11 ％,P =0.045).No significant difference was observed in both patient and graft survival (both overall and death-censored graft survival) rate during the 5-year follow-up period.Conclusion PTDM was associated with multiple risk factors,including male,high BMI,IFG during 1st week after transplantation,ARE,tacrolimus administration and family diabetes history.PTDM increased the infection incidence but did not affect both recipient and allograft survival significantly during the 5-year follow-up period.
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Objective To investigate the effect of recipient's pre-transplant triglyceride (TG) abnormalities on early graft function (EGF) after kidney transplantation.Methods According to the inclusion and exclusion criteria,154 identified living-kidney transplant recipients in the 309 Hospital of Chinese PLA from Jan.2011 to Dec.2014 were enrolled in present study,including 124 males and 30 females,and aged of 31.9 ± 8.4 years.The cohort was divided into two groups:TG normal group (0.40＜TG≤1.70mmol/L,n=107) and TG abnormalities group (TG＞l.70mmol/L or require lipid lowering therapy,n=47).The incidences of poor early graft renal function (PEGF),slow graft function (SGF) and delayed graft function (DGF) were compared between the two groups,and then the serum creatinine (Scr) levels were compared among the patients showing immediate graft function (IGF) at 3rd,7th and 30th day after transplantation.The ROC curve was drawn up taking TG as diagnosis index to explore the optimal cut-offvalue for predicting PEGF,SGF and DGF after transplantation.Results Compared with the TG normal group,the TG abnormalities group showed significantly higher incidence of PEGF and DGF (P＜0.05).Among the IGF patients,the TG abnormalities group showed higher Scr level at the 7th and 30th day after transplantation (P＜0.05).The area under ROC curve (AUC) reflected TG levels for PEGF,SGF and DGF were 0.774,0.704 and 0.818,respectively (P＜0.05).The optimal cut-offvalues were all 1.37mmol/L.Conclusions Recipients with abnormal pre-transplant TG level may have worse EGF after renal transplantation.The risk of developing PEGF,S GF and D GF tends to emerge when pre-transplant TG level is higher than 1.37mmol/L.
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Objective:To investigate the value of amino acid metabolomics in evaluating chemotherapeutic response of patients with ad-vanced breast cancer, the changes in the levels of 32 amino acids in the circulating serum of patients before (baseline) and after the first cycle (prognosis) of chemotherapy were tested. Methods:Seventy-three advanced breast cancer patients with local recurrence and distant metastasis admitted at the Liaoning Cancer Hospital from March 2015 to October 2016 were enrolled. Peripheral blood samples (2 mL) were collected before and after the first cycles of chemotherapy from each patient. Thirty-two amino acids in the se-rum were tested using the ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients were catego-rized into the improvement or deterioration groups, based on the first imaging test after 2-4 cycles of chemotherapy. The changes in amino acids levels were analyzed in different prognosis groups. Results:The levels of the 32 amino acids ranged 3-180000 pmol/L. Compared to their baseline levels, both glycine and L-glutamine increased in the improvement group, but decreased in the deteriora-tion group. Sarcosine was significantly reduced in the improvement group, while differences in its levels were not obvious in the deteri-oration group. L-threonine, taurine, iminodiacetic acid, and L-glutamic acid were increased in both groups. Conclusion:Changes in the serum levels of glycine, sarcosine, and the other amino acids before and after the first cycles of chemotherapy can predict chemothera-peutic response in patients with advanced breast cancer. Amino acid metabolomics may become a potential biomarker for predicting the efficacy of chemotherapy earlier than that of imaging tests, and thereby help improve therapeutic strategies for advanced breast cancer.