AIM　To determine whether ONO-1078 {pranlukast, 4-oxo-8-［p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS　Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO-1078 (0.01, 0.05, 0.10 mg*kg-1), dexamethasone (0.5 mg*kg-1), nimodipine (0.2 mg*kg-1) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty-four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS　ONO-1078, dexamethasone and nimodipine reduced the neurological scores. ONO-1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO-1078 dose-dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION　ONO-1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.

Objective To investigate the effect of swifch from cyclosporine to FK506 on renal allograft outcome after initial acute rejection. Methods Clinical outcome of patients who experienced first acute rejection episode were retrospectively analyzed. After initial acute rejection, 23 patients were switched to FK506-based immunosuppression, and 63 patients continued CsA-based immunosuppression. Demographic data, lipid, serum creatinine, uric acid, incidence of recurrent acute rejection and graft survival were analyzed and compared. Results During one year after anti-rejection therapy, incidence of biopsy-proved recurrent rejection events was significantly lower with FK506 therapy (1/23, 4.35%) compared with CsA therapy (16/63, 25.40%)(P=0.033). 5-year graft survival rate of FK506-based immunosuppression group was higher than that of CsA-based immunosuppression group (100.0% vs 81.4%). Serum uric acid level of FK506-based immunosuppression group from 24 months to 36 months after initial rejection were significantly lower than that of CsA-based immunosuppression group [(265.5 ±147.9) μmol/L, (245.8±88.9) μmol/L vs (428.5±119.3) μmol/L, (441.2±125.3) μmol/L, P<0.01, respectively]. Conclusion Conversion to FK506 therapy can significantly reduce recurrent rejection episode, and decreasing serum uric acid level provides long-term benefits to graft survival.

Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.

Objective To study the effects of CYP3A5 * 1 and CYP3A5 * 3 genotypes on tacrolimus dose requirement.Method We tested archival peripheral blood of 69 kidney recipients for CYP3A5 genotyping by polymerase chain reaction.The dose,blood concentrations and dose-normalized blood concentrations of tacrolimus were measured at 1st and 2nd month after the renal transplantation.Result There were 6 cases of CYP3A5 * 1/* 1 (8.7％),22 cases of CYP3A5 * 1/* 3 (31.9％),and 41 cases of CYP3A5 * 3/* 3 (59.4％).At 1st and 2nd month after the renal transplantation,the carriers of CYP3A5 * 1 genotype had a higher mean tacrolimus dose than CYP3A5 * 3/* 3 genotye (both P＜0.000 1),and those of CYP3A5 * 1 genotype had lower mean tacrolimus concentrations than CYP3A5 * 3/* 3 genotye (P=0.020 8,and P =0.019 1 respectively).Meanwhile,the carriers of CYP3A5 * 1 genotype had lower dose-normalized blood concentrations of tacrolimus than CYP3A5 * 3/* 3 genotye (P＜0.000 1) at 1st month after the renal transplantation,as well as at 2nd month after the renal transplantation (P =0.0191).Hepatic and renal function showed no significant effect on tacrolimus dose adjusted concentration at 1st and 2nd month after transplantation.Gender did not show a significant impact on tacrolimus dose.Conclusion CYP3A5 * 1 carriers needhigher tacrolimus dose than CYP3A5 * 3 homozygote to achieve the target blood concentration.CYP3A5 genotyping is a new approach for detecting tacrolimus dose requirement in kidney recipients.

Objective To analyze the early renal function of donors after nephrectomy.Methods Clinical data of 467 cases of living kidney donors during the period from April,2010 and November,2014 in our center were retrospectively analyzed.Data on serum creatinine (Scr),glomerular filtration rate (GFR),serum uric acid (UA),and urine microproteins before operation and three days,seven days,one month and three months after operation were collected to evaluate the impact of nephrectomy on early renal function after operation for donators.Results Before operation and three days,seven days,one month,three months after operation,the average serum creatinine (Scr) level was (59.9±12.8),(85.8±21.0),(91.2±21.3),(92.8±21.6),(91.0±21.3) μmol/L,respectively; The GFR were (113.5±25.3),(75.1± 17.9),(70.3± 15.2),(68.5± 16.0),(69.5± 15.1) ml/min,respectively; The levels of uric acid were (292.60±79.58),(142.18±55.28),(228.41±66.39),(321.31± 83.72),(346.61±87.21) μmol/L,respectively; All these data above-mentioned after operation reached statistical significance compared with that before operation (P ＜ 0.05).Parameters including urine IgG,urine albumin,urine retinol-binding protein and urine β2-microglobulin post-operation time point were significantly different when compared with relative parameters pre-operation (P ＜ 0.05).Conclusions Nephrectomy has significant influence on GFR,uric acid,and urine microprotein for donors in the early stage after operation.It's worth to evaluate nephrectomy's long-term effect on the renal function of donors in clinical practice.

Objective To evaluate the effects of different strategies on short-and long-term clinical outcomes of renal transplantation in Chinese subjects.Methods 2520 renal transplantations were retrospectively evaluated,including 2490 first renal transplantations and 30 second renal transplantations.Triple-immunosuppressant including cyclosporine A,azathioprine or myeophenolate mofetil(MMF)and prednisone(Pred)was adopted.Patients receiving kidney transplantation were given low dose immunosuppressants since 2000.Immunosuppressants including tacrolimus,MMF and Pred were adopted in some patients since 2000.Risk factors leading to graft loss and patients'death were analyzed.Results Until the cut date of June 30,2009,135 patients lost follow-up,and the follow-up rate was 94.6%.Incidence of acute(within 6 months post-transplantation) rejection was 18% among 2520 patients.Incidence of acute rejection (within 6 months post-transplantation) was 25.7% in panel reactive antibody (PRA) positive patients,significantly higher than 17.0% in PRA negative patients(P<0.05).Incidence of acute rejection within 6 months post-transplantation was 16.9% in HLA mismatches<4 patients,significantly lower than 23.7% in HLA≥4 patients (P<0.01).Total patient/death censored graft 1-,3-,5- and 1O-year survivals were 94.5%/96.0%,91.6%/93.1%,88.5%/90.1% and 81.7%/80.6%,respectively.Acute rejection and immunosuppressant regimen were independent risks for allograft loss.1mmunosuppressant regiment,pulmonary infection,cardio-brain-vessel accident, hepatic failure and tumor were independent risks for patients' death.Conclusion Renal allograft and patient survival appeared to be improved by optimal immunosuppressant regimen,strict HLA match and efficient post-transplant complication prophylaxis.

Objective To investigate the effects of hypomagnesemia on the initial amount of hematoma and patient's condition at hospitalization in elderly patients with intracerebral hemorrhage (ICH).The 90 consecutive hospitalized patients with primary ICH were chosen for prospective cohort study in the Second Hospital of Anhui Medical University from February 2017 to May 2018.Methods Demographic and baseline data of patients were collected,and CT scan,serum magnesium concentration and other laboratory examinations after hospital admission were tested.Ninety patients were divided into two groups:hypomagnesemia group(serum magnesium ＜ 0.75 mmol/L,n =38) and normo-magnesemia group(0.75-1.25 mmol/L,n =52).The impact of serum magnesium level on the patient's initial volume of hematoma and critical condition at admission were analyzed.Results The median value of random blood glucose (7.29 mmol/L vs.6.44 mmol/L)and fibrinogen degradation products(3.43 mg/L vs.1.98 mg/L)were higher in the patients with hypomagnesemia than in the normal magnesium group.The median volume of initial volume of hematoma at admission was larger in patients with hypomagnesemia than in the normal magnesium group (20 cm3 vs.10 cm3).The median value of Glasgow coma scale at admission was lower in patients with hypomagnesemia than in the normal magnesium group(12.5 scores vs.14.0 scores).And their difference was statistically significant(U =-2.663,-2.951,-5.000 and-2.821 respectively,P =0.008,0.003,0.000 and 0.005).The correlation analysis showed that the initial volume of hematoma in patients with intracerebral hemorrhage was negatively correlated with the serum magnesium concentration at admission (r =-0.528,P =0.001).Conclusions Patients with hypomagnesemia has a larger hematoma volume and more serious disease condition.There is a significantly negative correlation between serum magnesium and hematoma volume of ICH.The serum magnesium level may become a predictor of ICH in the future.

Objective:By retrospectively analyzing 6 cases of IgG4-related membranous nephropathy (IgG4-MN), combined with literature review, to explore the clinical and renal pathological characteristics of the disease, and improve clinicians' understanding of the disease.Methods:The data of six patients with biopsy-proven IgG4-MN in the nephrology center of our hospital during April 2017 to January 2021 were collected. At the same time, we reviewed the literature systematically and summarized the clinicopathological characteristics.Results:Six male patients with the age ranged fom 55 to 75 years old were described. Urine protein level was (3.1±2.1) g/24 h, 3 cases (50%) showed nephrotic syndrome and 4 cases (67%) had elevated serum creatinine. The median creatinine level was (103±24) μmol/L. Six cases (100%) had elevated serum immunoglobulin (Ig)E level, and 4 cases (67%) had elevated IgG4. M-type phospholipase A2 receptor (PLA2R) was positive in 1 case (17%) and tubulointerstitial nephritis (TIN) was present in 6 cases. The review of the literature suggested that a total of 49 cases with IgG4-MN were reported, including 6 cases in this report. There were 40 males (40/46, 87%), with a age range of (61±12) years old, 32 cases (32/49, 65%) showed nephrotic syndrome range proteinuria, and the proportion of serum IgG and IgG4 increase was 61%(20/33) and 88% (36/41), respectively, 13 cases (13/15, 87%) had elevated serum IgE level, 47% (14/30) had low-complement C3 and 44%(12/27) had low-complement C4 level. The main organs involved were pancreas (15/37) and lymph nodes (16/37). Renal pathology showed TIN in 74%(36/49). Electron dense deposition was mainly subepithelial deposits. 7%(2/28) were positive for anti-PLA2R antibody in serum, 17%(3/18) were positive for PLA2R in kidney tissue, 6%(1/18) were suspected positive for PLA2R in kidney tissue, and 8%(1/12) were dual positive in blood and kidney tissue.Conclusion:IgG4-MN usually presents with nephrotic range proteinuria or nephrotic syndrome in middle-aged and elderly patients. Most of them are complicated with TIN and other organ involvement. A certain proportion of patients are PLA2R positive in IgG4-MN, and whether it is primary or secondary MN needs further study.

Objective To investigate the risk factors of early neurological deterioration (END) in patients with cerebral infarction induced by symptomatic intracranial artery stenosis.Methods One hundred and eighty-nine cerebral infarction patients with symptomatic intracranial artery stenosis were collected. According to National Institutes of Health Stroke Scale (NIHSS) scores at 72 h of admission minus baseline NIHSS scores, these patients were divided into END group (n=51,≥2) and non-END group (n=138, <2). Clinical data and laboratory results were retrospectively collected. Univariate Logistic regressionwas used to analyze the differences of above data between the two groups, and multivariate Logistic regression was used to analyze the risk factors of END in patients with cerebral infarction induced by symptomatic intracranial artery stenosis.Results There were significant differences between the END group and the non- END group in age ([69.1±10.6] yearsvs.[65.8±10.4] years), baseline NIHSS scores (10.6±4.6vs. 5.1±4.1), intracranial artery stenosis site (anterior circulation, 82.4％％vs. 66.7％), intracranial artery stenosis degree (occlusion, 66.7％vs.44.2％), cholesterol level ([6.7± 1.0] mmol/Lvs. [4.8±0.8] mmol/L) and lymphocyte count ([2.3±2.2]×109/Lvs.[1.5±0.6]×109/L,P< 0.05). Multivariate Logistic regression analysis showed that age (OR=2.411, 95％C1: 1.102-5.273,P= 0.028), intracranial artery occlusion (OR=122, 95％CI: 3.635-4102,P=0.007) and baseline NIHSS scores (OR=2.464, 95％CI: 1.189-5.105,P=0.015) were risk factors for END.Conclusion Patients with symptomatic intracranial artery stenosis induced cerebral infarction, especially those with old age, intracranial artery occlusion or low baseline NIHSS scores, need more attention to avoid END.

Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.