Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus.Although the use of aggressive immunosuppression has improved both patient and renal survival over the past several decades,the optimal treatment of LN remains challenging.The therapeutic strategy and progress for patients with lupus nephritis are based on the accumulative evidences of the medicine,and must be personalized according to the patient condition.This paper discusses established and newer treatment options for LN.We also emphasize the challenges in the day-to-day management of lupus nephritis in the clinical practice.

Objective To study the clinical characteristics and the influencing factors of hypertension in IgA nephropathy(IgAN)patients with normal renal function.Methods From 2002 to 2006,a total of 507 idiopathic IgAN patients with normal renal function(eGFR≥90 mL/min)confirmed by renal biopsy were treated in the First Affiliated Hospital of Sun Yat-sen University.The patients were divided into a hypertension group(n=93)and a normal group(n=414)according to the BP levels.Univariate and multivariate logistic regression analysis were used to analyze the relationship between the hypertension and the clinical characteristics.Results We found that 18.3%(93/507)of the IgAN patients had hypertension,with hypertension as the main symptom in some cases.Univariate analysis showed that male sex,older age,higher BMI,elevated level of triglyceride and cholesterol were the clinical risk factors for hypertension in IgAN patients(P

ObjectiveByreportinga fatalcaseof severelupusnephritis(LN) complicated with invasive aspergilluspneumonia and meningitis and reviewing the associated literatures,to provide a way of early diagnosis andproper management for the patients suffering from systemic lupus erythematosus(SLE) and invasive fungus infection(IFI).MethodsThe onset,diagnosis and treatment course of the disease were described and associated literatures werereviewed to analyze and summary the diagnostic methods,common pathogenic bacteria and predisposing factors of SLE patients with IFI.ResultsApplication of IFI guideline for cancer patients and those undergoing hematopoietic stem cell transplantation could be helpful in the early diagnosis and treatment of SLE patients complicated with IFI.The most common pathogen of SLE patient suffering from IFI was cryptococcus neoformans and aspergillus,not candida albicans.The mainpredisposingfactorswerehighlupusactivityandimmunosuppressant.Conclusions Guideline of IFI for cancer patients and those undergoing hematopoietic stem cell transplantation is also helpful for the SLE patients complicated with IFI.The most common pathogens of IFI in SLE patients are cryptococcusneoformansand aspergillus.The predisposing factors are high lupus activity and immunosuppressant.

Objective To investigate the long?term effect of nerve?spring radical hysterectomy( NSRH) on anorectal function after radical hysterectomy. Methods Fifty?six cases of uterine cervical carcinoma patients who met the criteria were selected for the study and were randomly divided into RH group and NSRH group. Defecation functional and anorectal manometry were compared at 1 year after surgery. Results There were 2 patients were excluded both in the two groups, and 26 cases were included in the follow up of each group. Compared with RH group, NSRH group had a lower constipation and chronic diarrhea incidence ( 2 (7. 7%),8(30. 8%);1(3. 8%),6(23. 1%);χ2=4. 457,4. 127P<0. 05),a better self?evaluation bowel func?tion(no significant change:10(38. 5%),5(19. 2%);poor:7(26. 9%),3(11. 5%);very poor:9(34. 6%),18 (69. 2%);χ2=6. 267,P=0. 044;P<0. 05),a higher level of maximal anal squeeze pressure((132. 7±43. 6) mmHg,(119. 5±45. 3) mmHg;t=2. 116,P<0. 05),a lower level of threshold perception of distension((38. 6 ±10. 5) mmHg,(45. 8±12. 4) mmHg;t=2. 326,P<0. 05) and threshold perception of evacuative stimulus ((78. 3±33. 2) mmHg,(90. 6±40. 9) mmHg;t=2. 208,P<0. 05). Conclusion RH may cause more serious long?term anorectal dysfunction,while NSRH help to protect defecation function.

Objective To explore the effect of Numb on tubular epithelial-to-mesenchymal transition (EMT) in rat proximal epithelial cells. Methods NRK52E cells were treated with different concentrations of recombinant human transforming growth factor-β1 (TGF-β1) (0, 1, 5, 10, 15, 20 μg/L) for 48 h or 10 μg/L TGF-β1 for different times (0, 24, 48, 72 h) in vitro. The expressions of E-cadherin, a-smooth muscle actin(α-SMA) and Numb in NRK 52E cells were detected by RT-PCR, Western blot and immunofluorescence staining. Meanwhile Numb siRNA oligo was transfected into NRK 52E cells with lipofectamine before TGF-β1 treatment, then Western blot was applied to detect the protein expression of E-cadherin, α-SMA and Numb in NRK52E cells. Results TGF-β1 could induce EMT in NRK52E cells in dose- and time-dependent manner. During the progress of TGF-β1-induced EMT, the protein expression of Numb in 5, 10, 15, 20 μg/L group was 1.33 folds (P=0.024), 1.39 folds (P=0.035), 1.45 folds (P=0.025), 1.51 folds (P=0.000) respectively as compared to 0 μg/L group. Likewise, the protein and mRNA expression of Numb in 24 h, 48 h, 72 h group was 1.48 folds (P=0.046) and 1.56 folds (P=0.012), 1.54 folds (P=0.011) and 1.82 folds (P=0.008), 1.79 folds (P=0.028) and 1.82 folds (P=0.002) respectively as compared to 0 h group. Moreover, large amount of Numb was accumulated in the cytoplasm. Down-regulation of Numb expression by siRNA transfection did not influence the basal expression of E-cadherin and α-SMA in NRK 52E cells, but attenuated the progression of EMT in NRK52E cells induced by TGF-β1. The up-regulation of α-SMA protein was reduced to 18.1% (P=0.004) while the down-regulation of E-cadherin protein was reversed to 2.19 folds (P=0.004). Conclusion Numb can promote EMT in rat proximal epithelial cells.

Objective To investigate the clinical and pathological characteristics of IgA nephropathy (IgAN) with macrohematuria (MH).Method 1512 consecutive patients with biopsyproven IgAN diagnosed from January 2006 to December 2011 were enrolled,and divided into MH group and control group respectively,according to whether there existed episodes of MH before renal biopsy.The clinical and pathological characteristics were compared between two groups.Patients in MH group were then divided into three groups according to the interval from the last episode of MH to renal biopsy to clarify the concomitant clinicopathological changes associated with occurrence of MH.Results The rate of MH in history was 22.1％.MH group patients had significantly lower serum creatinine,slighter proteinuria,lower prevalence of hypertension and heavier microhematuria than control group (all P ＜ 0.001).The prebiopsy durations were similar in two groups (P=0.627).In MH group,chronic pathological indicators,including global/segmental sclerosis,tubule atrophy/interstitial fibrosis were all slighter (all P＜ 0.001),whereas activity indicators,including necrosis lesions,crescents and mesangial proliferation were all more severe compared with control group (all P ＜ 0.05).Those who underwent renal biopsy within 30 days of the last episode of MH had more severe proteinuria and microhematuria,higher prevalence of necrosis lesions,more severe crescents formation,and endothelial proliferation (all P ＜ 0.05).Conclusions IgAN patients with MH in history have relatively milder clinical and chronic pathological manifestations,however more active pathological changes especially in those who suffer episode of MH recently.

Objective To develop a nomogram for the use of predicting renal outcomes of Chinese lupus nephritis (LN) patients.Methods From January 1,2005 to October 1,2015,513 patients with biopsy-proven LN in the First Affiliated Hospital of Sun Yat-Sen University were enrolled into this study.Renal outcomes were defined as end-stage renal disease or doubling of serum creatinine.Demographic characteristics,laboratory data,and pathologic data were recorded and included for analysis.Nomograms were designed using multivariate Cox proportional hazards regression to predict the non-outcome renal survival in 5 and 8 year according to the Akaike information criterion (AIC) and continuous reclassification net improvement (cNRI).Predictive accuracy and discriminative ability of the models were determined by concordance index (C-index) and calibration curve.Results During a median follow up of 48 (24,71) months,44 patients (8.58％) reached the endpoint.1-year,5-year and 8-year non-outcome renal survival were 97.57％,92.89％,79.89％ respectively.According to multivariate Cox regression,four nomograms including index for baseline renal function,pathologic severity,and response to treatment were designed.The best model,within which included eGFR was lower than 30 ml · min-1 · (1.73 m2)-1(HR=4.44,95％ CI 2.16-9.13,P ＜ 0.01),percentage of global glomerulosclerosis was higher (HR=12.28,95％CI 3.58-42.13,P ＜ 0.01) and partial remission occurred after 6-month induction treatment (HR=9.16,95％ CI 4.71-17.82,P ＜ 0.01) demonstrated good discrimination to predict 5-year and 8-year non-outcome renal survival [C-index,0.80(95％CI 0.81-0.91),0.76(95％CI 0.68-0.85),respectively].The nomogram based on above model also performed good calibration.Conclusion The nomogram based on patients' baseline eGFR,percentage of global glomerulosclerosis,and treatment reaction after 6-month induction therapy can accurately predict 5-year and 8-year non-outcome renal survival in Chinese lupus nephritis patients.

OBJECTIVE:To establish the method for the determination of mildronate in human plasma and urine,and to study the pharmacokinetic characteristics in healthy volunteers. METHODS:After precipitating plasma and urine sample,LC-MS/MS method was adopted. Dikma Diamonsil C18 column was used with mobile phase consisted of methanol-water(containing 0.2% for-mic acid,0.3% ammonium acetate)(31∶69,V/V)at the flow rate of 0.6 ml/min. ESI was adopted in MRM mode,by using nega-tive ion. The ion for quantitative analysis were m/z 147.10→58.20 (mildronate) and m/z 152.00→110.10 (internal standard,acet-aminophen). The pharmacokinetic parameters of mildronate with single administration and multiple administration were calculated by using DAS 2.1 software and compared. RESULTS:The linear range of mildronate in plasma were 0.02-20 ng/ml(r=0.999 3) and in urine were 0.05-40 ng/ml(r=0.998 2). The lowest limits of quantitation were 0.02 and 0.05 ng/ml. Precision and recovery met the requirements of biological specimen determination,and endogenous impurities hadn’t effect on the determination. The main pharmacokinetics parameters of low-dose,medium-dose and low-dose(250,500,750 mg)of mildronate in plasma with single ad-ministration were as follows:t1/2 were(3.39±0.81),(5.52±0.57)and(5.32±0.96)h;tmax were(0.80±0.45),(1.38±0.43)and (1.10±0.36)h;cmax were(4.17±1.46),(8.08±1.04)and(15.04±1.86)ng/ml;AUC0-36 h were(24.55±5.81),(45.50±7.07)and (85.60 ± 13.09)ng·h/ml. In the dose range,cmax,AUC0-36 h h had a linear relationship with dose (R2 were 0.974 5 and 0.968 3). The main pharmacokinetic parameters of low-dose of mildronate with multiple administration after keeping stable were as follows:cmin was(0.28 ± 0.10)ng/ml;AUCs was(38.78 ± 4.18)ng·h/ml;cs was(1.62 ± 0.17)ng/ml;DF was(3.81 ± 1.14);t1/2 was(6.17 ± 1.46)h;tmax was(1.20 ± 0.33)h;cmax was(6.46 ± 1.96)ng/ml;AUC0-36 h was(40.33 ± 4.65)ng·h/ml;accumulation factor of cmax and AUC were(1.73±0.90)and(1.64±0.40). Compared with single administration,t1/2,cmax and AUC of mildronate with multiple admin-istration after keeping stable all changed,and tmax had no signifi-cant difference. After single administration,26 h accumulative excretion rate of those groups were (0.004 009 ± 0.001 1)%, (0.004 026±0.001 01)% and(0.003 858±0.000 68)% respec-tively. CONCLUSIONS:Established method is sensitive,accurate and specific,and suitable for the determination of mildronate concentration in human plasma and urine and pharmacokinetics study. Mildronate capsule shows certain accumulation effect in healthy volunteers,and linear pharmacokinetic characteristics.

AIM: To investigate the association of gene polymorphism at position 196 of tumor necrosis factor receptor Ⅱ (TNFRⅡ) with systemic lupus erythematosus (SLE) in Chinese, and establish recombinant retroviral vector to analyze the function of the TNFRⅡ 196M/R. METHODS: The genotype at position 196 of TNFRⅡ was determined by PCR-RFLP in 106 SLE patients and 119 healthy controls in china. Human TNFRⅡ196M cDNA were amplified by PCR and cloned into PMD18-T vector. Then, PMD18-TNFRⅡ196R was induced by site-directed mutagenesis. The recombinant T vector, PMD18-TNFRⅡ196M and PMD18-TNFRⅡ196R, were subcloned into retroviral vector PLXSN. Both normal and variant were transfected into rat mesangial cell. The effects of TNF? on production of sTNFRⅡ and IL-6 were study by ELISA. RESULTS: (1) The frequency of TNFRⅡ196R allele was significantly higher than those in controls (35.2% vs 14.3%, P

AIM: To investigate the effect of 4.25%peritoneal dialysis solution (PDS) on CD40 expression in rat peritoneal mesothelial cells so as to reveal the potential mechanisms by which CD40-CD40 ligand (CD40L) interaction may be involved in the inflammation of peritoneal membrane. METHODS: Rat peritoneal mesothelial cells (MC) were harvested from the peritoneal cavity and maintained under defined in vitro conditions. Expression of CD40 on MC under normal culture or stimulation with 4.25%PDS or 4.25%PDS+IFN-? was detected by RT-PCR and FACS analyses. After activation of CD40 on MC with CD40 mAb, the expression of intercellular adhesion molecule-1 (ICAM-1) on MC was analyzed by FCAS. RESULTS: MC cultured in vitro expressed CD40 constitutively. 4.25%PDS markedly up-regulated the expression of CD40 mRNA and its protein. The expression of CD40 mRNA and its protein following stimulation with 4.25%PDS+IFN-? was significantly higher than 4.25%PDS alone. The expression of ICAM-1 on MC was significantly increased after activation of CD40 with CD40mAb.CONCLUSIONS: MC functionally express CD40. The up-regulated CD40 expression on MC following stimulation with 4.25%PDS may play an important role in local peritoneal defense mechanisms and may be involved in the chronic inflammatory process of the peritoneum.