CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects and can enhance the anti-cancer activity of cancer treatments. CpG ODN directly induced the activation and maturation of plasmacytoid dendritic cells, stimulated the secretion of Th1-type cytokines, and enhanced the differentiation of B cells into antibody-secreting plasma cells. CpG oligodeoxynucleotides as vaccine adjuvants can enhance both the humoral and cellular responses to antigens in some clinical trails. CpG ODN was applied in several clinical trials as an adjuvant of tumor vaccine. CpG ODN alone had anti-tumor activity and had synergistic effects with other anti-tumor therapies including monoclonal antibodies, chemotherapy, radiotherapy, cytokines, etc. Compared with standard regimen, in the phase Ⅲ clinical trial CpG ODN did not prolong the median survival time and induced severe adverse reaction in the treatment of ⅢB-Ⅳ stage non-small cell lung cancer. But CpG ODN had definite anti-cancer activity in other clinical trials. The safety and efficacy of CpG ODN in anti-tumor therapy needs to be further verified in clinic.

Objective To investigate the prevalence of BK virus(BKV) infection in renal transplant recipients and the methods for its clinical diagnosis and treatment.Methods The urine and blood samples of 64 renal transplant recipients were taken for the BKV cytological and PCR tests.Five clinical factors were investigated to find the etiologic risks of BKV infection in renal transplant recipients.Four BKV infected recipients received experimental treatment.Results The occurrence of urine decoy cell,BKV viruria and viremia in all patients was(28.7 %),(17.2 %) and(6.3 %),respectively.The occurrence of urine decoy cell in serum creatinine(SCR) level elevated recipients was higher than that in SCR stable recipients(P=(0.04)).No significant relationships were found between the five clinical factors(gender,age,induction therapy,acute rejection episode,renal function after transplantation) and the occurrence of urine decoy cell,viruria and viremia.Ganciclovir treatment showed effective in four BKV infected recipients.Conclusions BKV monitoring is necessary for those recipients with evaluated SCR levels after renal transplantation.BKV viremia test can be used as a screening test.The efficacy of ganciclovir in the treatment of BKV infection should be further investigated.

Objective To investigate the adjunctive therapeutic effects and safety of intravenous immunoglobin (IVIG) for treating pneumonia following kidney transplantation.Methods Sixteen cases of pulmonary infection after kidney transplantation were divided into two groups.Twenty-eight cases were subjected to IVIG therapy (0.2 g·kg-1 ·day-1) for 7-10 days besides the standard specific anti-bacterial,anti-fungal,and anti-virus treatment and regular immunosuppressive regimen with dose adjustment (IVIG group),and the control group was only treated with standard specific anti-pathogen therapy.The incidence and mortality ofsevere pulmonary infection,levels of serum IgG,T lymphocyte subsets,and creatinine in the two groups were observed.Results The effective power of IVIG group and control group was 100 ％ and 93.75 ％ (P＜0.05).The incidence of severe pneumonia in IVIG and control groups was 0 and 12.5％,respectively (P＜0.05),with the mortality being 0 and 6.25％,respectively (P＜ 0.05).The levels of serum IgG were significantly increased in IVIG group as compared with that before treatment and in control group.There were no significant adverse reactions associated with IVIG infusion.Conclusion As an adjunctive therapy,IVIG treatment for pulmonary infection can reduce the incidence of severe pulmonary infection and mortality after kidney transplantation,further increase the survival rate of patients after kidney transplantation.

Objective To investigate the influence of immunosuppression strategy optimization on the outcomes of the renal transplant recipients in the last decades. Methods Data from 404 renal transplant recipients from Jan. 1st, 2001 to Dec. 31st, 2010 were analyzed retrospectively. The patients were divided into early transplant group (n = 260) and late transplant group (n= 144). The change of immunosuppression strategy included a low dose antithymoglobin (ATG) induction, a quick corticosteroid reduction and mycophenolate mofetil therapeutic monitoring with calcineurin inhibitor minimization. Recipients' gender,age, donor type, induction therapy, immunosuppression regime, occurrences of biopsy-proven acute rejection (BPAR), severe pulmonary infection and patient/allograft survival were compared between groups. A Cox regression model was used to investigate the factors that influenced the allograft survival. Results The follow-up rate was 98. 3 % in this study. The median follow-up period was 65 month (1-112 months). The proportion of ATG induction in late transplant group was significantly higher than in early transplant group (78. 5 % versus 31. 9 %, P<0. 01). The severe pulmonary infection rate was lower in late transplant group, while the BPAR rate was comparable between two groups. The allograft survival rate was significantly higher in late transplant group. Severe pulmonary infection was correlated with patient/allograft survival in Cox regression model. Conclusion The improvement of outcome in renal transplant recipients in our center is related to the optimization of immunosuppression strategy that reduces the severe pulmonary infection rate with no increase in BPAR.

Objective To investigate the efficacy and adverse reactions of half-dose glucocorticosteroid and cytoxan,combined with leflunomide for the treatment of lupus nephritis (LN) of MRL/lpr mice,and provide experimental evidences for LN therapy.Methods Twenty-eight 10-week-old MRL/lpr mice were randomly divided into four groups:Group A,blank control group; Group B,classical control group; Group C,full-dose control group; Group D,half-dose treatment group,with 7 mice in each group.The therapeutic efficacy and side reactions in the four groups were observed and compared before and 12 weeks after treatment.Statistical analysis was conducted with one-way ANOVA,q test and Pearson's correlation analysis.Results The serum anti-double stranded DNA (anti-dsDNA) antibody titers (0.43±0.16,0.32±0.09,0.44± 0.18,1.95±0.19) U/ml,serum creatinine level (1.63±0.63,0.40±0.23,0.82±0.21,10.86±2.17) mg,24-hour urine protein excretion level (71±8,60±5,68±3,121±10) μmol/L and renal pathological changes in group B,C,D were significantly improved than those of the group A (P＜0.05) after 12 weeks treatment.There was no significant difference in the efficacy between group B,C,and D (P＞0.05).The incidence of adverse reactions in group D was significantly lower than that in other groups (P＜0.05).Conclusion Multi-target therapy,such as half-dose prednisone and CTX,combined with leflunomide can effectively control lupus disease activity with less side effects.This regimen is cheap,safe and effective for the treatment of LN in MRUL/lpr mice.This study has provided animal evidences for this multi-target therapy for LN.

Objective To analyze the histological underestimation of stereotactic core needle biopsy (SNCB).and tO attract clinicians' attention.Methods SNCB was performed in 146 patients with 179 lesions from September 2000 to June 2005.and 21 lesions were underestimated histologically.0f 21 nonpalpable breast lesions(NPBL).6 lesions were diagnosed as BI-RADS nl,12 8S BI-RADS Ⅳ,3 as BI-RADS V according to BI-RADS before biopsy.Mammography showed 16 lesions with calicification, 2 cases with masses,1 case with asymmetry density and 2 cases with stellate sign.Results Eleven lesions diagnosed as fibrocystic disease with atypical ductal hyperplasia by biopsy were proved to be ductal carcinoma in situ (DCIS)in 7 lesions and early infiltration in 4 lesions by pathology.3 lesions diagnosed as severe atypical hyperplasia by biopsy were finally proved to be 1 carcinoma in situ and early infiltration in 2 lesions by pathology.3 lesions diagnosed as DCIS by biopsy were invasive carcinoma.4 lesions diagnosed papillary lesions by biopsy and finally were 1 carcinoma in situ,1 early infiltration,1 infiltrating ductal carcinoma and l intraductal papillary adenocarcinoma.Conclusion The histological underestimation of SCNB Was related to the stereotactic location technology,lesion and doctor'S understanding,the radiologist should master the biopsy skills.

Objective To explore the matrix effect on cyclosporine A (CsA) test by fluorescence polarization immunoassay (FPIA) and enzyme-multiplied immunoassay technique (EMIT), explain the discrepancy of external quality control results between these two methods and find the corrective action.Methods One hundred whole blood samples with various concentrations were adopted and CsA levels were detected by FPIA and EMIT.The results were compared with each other.Moreover, the influence of residual metal ions upon immunoreactions was assessed by adding Cu2+ and Zn2+.The effect of non-whole blood matrix on extraction efficiency for quality control materials and CsA calibrator was evaluated by adding identical volume of Hb-rich reagents followed with re-extraction.Results There is good correlation between results measured with FPIA(X) and EMIT(Y) methods ( Y=0.926 8X -8.115,R2 =0.996 9).Neither FPIA nor EMIT was affected by residual metal ions ( P ＞ 0.05 ). Non-whole blood matrix decreased the extraction efficiency of two methods, but it could be corrected by supplementation of the Hb-rich reagents (≥30 g/L).Conclusions Non-whole blood matrix may be the main reason for the inconsistent results measured by FPIA and EMIT methods.It could be corrected by using Hb-rich reagents.In addition,we should consider the influence of low lib on CsA test,espocially for organ transplant patients with lower Hb ( ＜30 g/L).

Objective To investigate the relationship between the polymorphism of human multidrug resistance 1 gene(MDR1)polymorphism and early MMF pharmacokinetics.Methods Twenty-eight Chinese primary renal transplant recipients were emrolled.On day 14 post-transplant,patients took the MMF orally on fast.Whole blood samples(2 ml)were obtained at the following time points:predose(G0)and 0.5,1,1.5,2,4,6,8,10 and 12 h(C0.5,C1,C1.5,G2,C4,C6,C8,C10,C12,respectively)postdose during the dosing interval.The MPA plasrna concentration was assayed by high performance liquid chromatography (HPLC).Pharmacokinetie parameters were determined by WINNOLIN 3.1.Three major single nucleotide polymorphisrrls(SNP),C1236 T,G2677 T/A,C3435 T of MDR1 were analyzed by PCR-RFLP.Pharmacokinetie parameters of MPA were compared between different MDR1 genotype and haplotype groups.Ailele frenqueneis were also compared in high(MPA area under concentratation-time curve 0～12 h,frequencies of 1236 TT,2677 TT/AA,3435 TT in three major MDR1 SNP positions,exons 12,21 and 26,were 0.368,0.184 and 0.211,respectively.MPA AUC was significantly higher in 1236 TT group than in 1236 CC/CT group(65.36±11.51 vs 53.33±13.77,P=0.032).On C1236 T SNP,TT genotype frequency showed significant difference between MPA high and low exposure groups(66.7%vs 15.4%,P=0.013,OR=2.526).T allele frequency was marginally higher in MPA high exposure group than that in low exposure group(83.3%vs 53.3%,P=0.072).Conclusion TT genotype on 1236 of MDR1 indicates a risk of early high exposure to MPA in Chinese renal transplant patients given by oral MMF,

Objective To investigate role of N-(30,40-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) in mediating the negative immune regulation by indoleamine 2,3-dioxygenase in mice skin transplantation.Method The mice skin transplant model was established.T lymphocytes were isolated from mice splenocytes,and serum was collected.ELISA was applied to detect the IL-2 and IFN-γ concentrations in culture supernates of mice spleen lymphocytes and serum.Flow cytometry was applied to examine the phenotypes of T lymphocytes and RT-PCR to analyze the IDO mRNA transcription.Results T lymphocyte proliferation was significantly decreased by 3,4-DAA and the concentrations of IL-2 and IFN-γ were apparently decreased in 3,4-DAA group as compared with those in control group.The percentages of CD3 +,CD4 + and CD8 + T lymphocytes were lower,and the percentage of CD4 + CD25 + T lymphocytes was higher in 3,4-DAA disposal group than in control group,but there was no significant difference.IDO mRNA expression showed obvious increase in 3,4-DAA group as compared with control group.Conclusion 3,4-DAA can up-regulate the IDO expression to induce the increasing metabolism of tryptophan,subsequently inhibiting T cell proliferation and showing specific property of negative immune regulation.

To explore the effect of different processing methods and conditions of coumarin and volatile compounds in Angelica Dahuricae Radix and their change regularity, in order to optimize and establish appropriate drying methods and conditions. After being cleaned, fresh Angelica Dahuricae Radix herbs were baked, sun-dried, shade-dried, sun-dried after sulfur-fumigation, dried by quick-lime embedding, freeze-dried, microwave-dried. Finally, 24 groups of samples were obtained after being mashed and passing through the 60-mesh screen. The HPLC-PDA method was adopted to simultaneously determine the content of coumarin compounds. The GC-MS method was used to determine the content of volatile compounds. The principal component analysis (PCA) was made on the standardized analysis results for the 24 groups of samples processed with different drying methods. According to the PCA results, the comprehensive scores of coumarin and volatile compounds in Angelica Dahuricae Radix herbs processed with different methods in the order from high to low were that unpeeled and dried by quicklime embedding > unpeeled and dried with hot-air at 100 degrees C > unpeeled and dried with hot-air at 40 degrees C > peeled and infrared-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 40 degrees C > peeled and sun-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 100 degrees C > peeled and microwave-dried > peeled and dried with hot-air at 80 degrees C > unpeeled and sun-dried > unpeeled and dried with sulfur-fumigation > peeled and dried with sulfur-fumigation > unpeeled and dried with hot-air at 120 degrees C > unpeeled and freeze-dried > unpeeled and infrared-dried > peeled and dried with hot-air at 120 degrees C > peeled and freeze-dried > peeled and dried by quicklime embedding > unpeeled and dried with hot-air at 80 degrees C > peeled and shade-dried > unpeeled and shade-dried > unpeeled and microwave-dried. According to the findings, different drying processing methods have certain impacts on the content coumarin and volatile compounds in Angelica Dahuricae Radix herbs. The traditional method of drying by quicklime embedding is recommended as the optimum origin processing method of Angelica Dahuricae Radix, which is followed by the method for being peeled and dried with hot-air at 100 degrees C.
Angelica ; chemistry ; Coumarins ; analysis ; Desiccation ; methods ; Gas Chromatography-Mass Spectrometry ; Hot Temperature ; Principal Component Analysis ; Volatile Organic Compounds ; analysis