Key advances in the clinical studies of ANCA-associated vasculitis / 医学研究生学报

Anti-neutrophil cytoplasmic antibodies( ANCA)-associated vasculitis ( AAV) has various clinical symptoms, thus various treatment schemes were used in clinics.To date, there has been no validated diagnostic criteria or treatment guideline for AAV.There are three aspects to be considered when assessing the treatment with AAV patients:staging of disease, distinction between disease activity and chronic damages, and quality of life ( QOL) .This review focuses on the latest classification of vasculitis, the rela-tion between disease stages and its severity, the importance of distinguishing active diseases from permanent damages, the therapeutic choices and the management of complications.

Preliminary clinical observation of multi-target therapy for the treatment of ANCA-associated vasculitis with renal involvement / 医学研究生学报

Objective The treatment of anti-neutrophil cytoplasmic antibodies ( ANCA) associated vasculitis ( AVV) such as mycophenolate mofetil ( MMF ) can improve the remission rate, however, it also results in high recurrence rate and high incidence of adverse reaction related to the treatment.The article was to observe the clinical efficacy and safety of multi-target therapy ( MT ) in the treatment of AAV with renal involvement. Methods Retrospective observation was made on 7 AVV patients treated with multi-target therapy in our department from June 2009 to October 2013.The pa-tients (1 male, 6 females) aged from 21 to 54 years were accompa-nied with renal damage and serum creatinine (SCr≤3 mg/dL).All patients had positive myelopeeroxidase-ANCA (MPO-ANCA), high-grade proteinuria and hematuria.4 patients had elevated SCr (1.47-2.94 mg/dL) with EGFR90 mL/min in 2 patients and EGFR60 mL/min) .At the end of follow-up, the EGFR expres-sion was normal in 4 patients, 60-90 mL/min in 1 patient and less than 60 mL/min in 2 patients, without end stage renal disease. ANCA level turned to normal in 3 patients and significantly decreased in 4 patients.No patients had adverse reaction, died, or re-lapsed during the follow-up. Conclusion MT is effective in the control of renal activities of AVV patients with mild or moderate re-nal function damage.It attributes to great improvement of renal function and urine protein, as well as good tolerance.However, pro-spective study is required to confirm the efficacy of this new therapy.

DNA damage caused by suicide gene therapy system under Tet-On regulation in breast cancer cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect and molecular mechanism of DNA damage caused by suicide gene therapy system HSV-TK/GCV under Tet-On regulation in human breast cancer cell line MCF-7 infected by recombinant adeno-associated virus (rAAV).@*METHODS@#We used comet assay to detect the effect of HSV-TK/GCV suicide gene regulation system on MCF-7 DNA damage, and analyzed the expression change of relative DNA damage response active genes and proteins with RT-PCR and Western blot.@*RESULTS@#Compared with other control groups, the comet assay showed that MCF-7 cells with HSV-TK/GCV treatment had obvious comet tails, and the expression level of DNA damage response active genes and proteins changed obviously in the HSV-TK/GCV treatment group,such as ATM, p53 and p27,but CyclinE and CDK2 did not change.@*CONCLUSION@#DNA damage on MCF-7 cells is resulted from HSV-TK/GCV in suicide gene therapy system through a p53-dependent signal pathway, causing cell cycle arrest and cell death.

Neuroform stent-assisted coil embolization for the treatment of intracranial wide-necked aneurysms / 介入放射学杂志

Objective To discuss the technique of Neuroform stent-assisted coil embolization for the treatment of intracranial wide-necked aneurysms and to evaluate its clinical efficacy and complications.Methods Neuroform stent-assisted technique was used for coil embolization treatment in 31 patients with intracranial wide-necked aneurysms, all aneurysms were ruptured and the patients suffered from subarachnoid hemorrhage (SAH). Of the total 43 aneurysms, 39 were wide-necked and 4 were narrow-necked. Results Thirty-five stents were inserted in 31 patients. The stents were implanted in both internal carotid arteries in 3 patients and in both middle cerebral arteries in one patient, Intra-arterial embolization with coils was successfully performed in 41 of 43 aneurysms. Intraoperative hemorrhage occurred in 2 patients, which probably resulted from the rupture of middle cerebral artery branch due to microwire damage. The cerebral isehemic symptom happened in 1 patient with posterior communicating artery aneurysm due to the shifting of the coil from the original site to M2 segment of middle cerebral artery. During a follow-up period of 24.7 months in average, neither death nor recurrent hemorrhage occurred in 29 cases. Twenty-eight patients were in good living condition and the remaining one patient showed obvious disturbance of neural function.Conclusion For the treatment of intracranial wide-necked aneurysms, intra-arterial coil embolization with Neuroform stent-assisted technique is a safe and effective clinical therapy. It can effectively broaden the extent of indications in treating intracranial aneurysms by using interventional technique.

The structure, expression and function prediction of DAZAP2, a down-regulated gene in multiple myeloma / 基因组蛋白质组与生物信息学报·英文版

In our previous studies, DAZAP2 gene expression was down-regulated in untreated patients of multiple myeloma (MM). For better studying the structure and function of DAZAP2, a full-length cDNA was isolated from mononuclear cells of a normal human bone marrow, sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open reading frame) as the NM_014764 from human testis and the D31767 from human cell line KG-1. Phylogenetic analysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughout evolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occurs as a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2 gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic location of human chromosome in Genbank, though no genetic abnormalities of MM have been reported on Chromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mouse Prtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuated distribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identified signaling pathways to regulate proliferation and differentiation of plasma cells.

Current treatment of Henoch-Schonlein purpura nephritis / 医学研究生学报

Henoch-Schonlein purpura nephritis(HSPN) is the common secondary glomerulonephritis.Patients with HSPN have various therapeutic reaction and prognosis owing to their varied clinical manifestations or histological changes,and accordingly different therapeutic regimens should be supplied.Patients with severe HSPN should be given active treatment.This article reviews the current treatment of HSPN.

Microvascular disease in progressive renal disease / 医学研究生学报

The role of the microvascular disease in progressive renal disease is not well understood .This review presents evidence that progressive renal disease is characterized by a progressive lose of the microvasulature. And presents the factors that induce the lose of the microvasculature. Try to find out (agents) which may represent a novel therpeatic approach for slowing the renal disease.

Studies on correlation among genetic polymorphism of glutathione S-transferases and serum creatinine levels in end stage renal disease patients / 医学研究生学报

Objective: To study the correlation among genetic polymorphism of glutathione S-transferases (GST) T1, M1 and serum creatinine levels,as well as intact parathyroid hormone (PTH) levels in the end stage of renal disease(ESRD). Methods: 118 blood samples of ESRD and 133 of healthy control had been enrolled, and simultaneously the patients' serum creatinine (SCr), blood uria nitrogen (BUN), serum calcium and serum phosphorus were recorded. Polymerase chain reaction (PCR) had been employed to determine the genotypes of GST and immunoradiometric assay was used to determine PTH levels. Results: The distribution frequencies of dual null GST T1 and M1(A), null GST T1 and functional M1 (B), functional T1 and null GST M1(C) and dual functional GST T1 and M1(D) were 16.9%, 11.0%, 44.9%, 27.1% in ESRD and 14.4%, 10.8%, 46.7%, 28.1% in the healthy control, respectively. There was no difference between the two groups (P=0.945); Mean SCr levels of A was higher than that of B (P=0.047) and C (P=0.007) group in ESRD. Conclusion: Distributions of GST Genotypes had no difference among ESRD and healthy control groups; SCr level of dual null GST T1 and M1 (A) was higher than single null GST (B and C) in ESRD. GST may played some roles in metabolism of poisons and protecting cells from the attack of toxic substances.

Pathological demography of native patients in a nephrology center in China / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To analysis the pathological demography in Chinese patients undergoing renal biopsy from our nephrology center.</p><p><b>METHODS</b>Between January 1979 and October 2000 in Jinling Hospital, Nanjing, China, 10,002 attempts of percutaneous renal were performed in patients with renal disease from 33 provinces of China. The pathological classifications were made according to the WHO criteria of 1982 for renal pathology or the modified WHO criteria of 1995 by a panel of pathologists and nephrologists during routine clinical-pathological rounds. The pathological demography between those specimens collected from 1979 - 1989 and those from 1990 - 1999 was compared.</p><p><b>RESULTS</b>The mean age of the 10,002 subjects undergoing renal biopsy was 31.4 +/- 13.0 years (ranging from 1 to 78 years), with a male to female ratio of 1.3:1; for the 592 renal transplant recipients, the mean age was 37.5 +/- 9.1 years (ranging from 16 to 66 years), with a male to female ratio of 2.36:1. Primary glomerular diseases (PGD) accounted for 71% of the total patients undergoing renal biopsies, secondary glomerular nephritis (SGN) 23%, tubular-interstitial diseases 3.2%, unclassified renal diseases 1.3%, hereditary and congenital renal diseases 1.0%, end stage renal diseases 0.96%, and recently realized or rare renal diseases 0.15%. IgA nephropathy (IgAN) was the most frequent pathological pattern (40%) of PGD, followed by mesangial proliferative lesion (MsPL) (30%), membranous nephropathy (MN) (10%), and focal segmental glomerulosclerosis (FSGS) (6%). Lupus nephritis (LN) was the most pathology common seen (74%) in SGN. During the 22 years of the study period, there was a steady increase in patients with SGN discovered during pathological evaluation of renal disorders. A rise in prevalence was found in IgA nephropathy, MN (both P < 0.001), crescentic glomerulonephritis (P < 0.0001), anti-GBM disease, and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura related renal damages (both P < 0.001). There was a decrease in endocapillary proliferative glomerulonephritis (P < 0.001) and IgM nephropathy (IgMN) (P < 0.01) from 1990 - 1999 as compared to 1979 - 1989. Infrequent renal pathological entities were also diagnosed in this group, including Niemann Pick disease, Fabry's disease, POEMS syndrome, and lipoprotein glomerulonephropathy.</p><p><b>CONCLUSIONS</b>This is the largest series of renal biopsy data in China, and therefore may reflect the demographic picture of renal diseases in this country. Changes in prevalence of renal pathological entities were reflected in this group of patients over the last 22 years. In primary glomerular diseases, IgA nephropathy is still the most frequently observed pathological pattern. In SGN, LN appeared the most often. Increased prevalence was found in anti-GBM nephritis and HUS/TTP.</p>

Clinical spectrum of diffuse crescentic glomerulonephritis in Chinese patients / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate retrospectively the incidence, distribution of primary disease and clinicopathologic characteristics of diffuse crescentic glomerulonephritis (DCGN) in Chinese patients.</p><p><b>METHODS</b>One hundred and seventy-two consecutive patients diagnosed as having DCGN out of 9828 cases of non-transplanting renal biopsies over sixteen years, were studied. DCGN is categorized into three types according to immunopathologic characteristics. The incidence of this disease, its primary diseases, clinical characteristics and serum antineutrophil cytoplasmic antibodies (ANCAs) were analyzed.</p><p><b>RESULTS</b>The distribution of patients among the three classifications was 8.7% type I, 68.6% type II and 22.7% type III. Clinically, the majority of patients (69.8%) presented rapidly progressive glomerulonephritis (RPGN), but 30.2% manifested a chronic nephritic syndrome or chronic renal failure. In terms of related conditions, 93% were anemic, 61.6% had hypertension, 50.6% oliguria, 45.3% nephrotic syndrome, 43% uremic syndrome and 39.5% displayed gross hematuria. Those patients who were positive in serum for ANCAs had predominantly type III DCGN. Two cases with anti-GBM-antibody crescentic glomerulonephritis and three with lupus nephritis were also positive for ANCAs in serum.</p><p><b>CONCLUSION</b>DCGN is not rare in Chinese patients. A majority of patients in our study presented with RPGN, but 30.2% manifested a chronic renal failure. Lupus patients with DCGN that were positive for ANCAs had more severe vasculitic lesions.</p>

Cyclosporine A in treatment of membranous lupus nephropathy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN).</p><p><b>METHODS</b>Twenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg x kg(-1) x d(-1) for 3 months, with a 1 mg x kg(-1) x d(-1) reduction every month and then maintained at a dosage of 2 mg x kg(-1) x d(-1). The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of < 0.4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement > 50% of baseline value and a serum albumin value of 30 - 35 g/L, without SLE activity. No response was defined as having a Upr decrement < 50% of baseline value and > 2.0 g/d, or as a deterioration of renal function, or as having active SLE.</p><p><b>RESULTS</b>One patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6 - 36 months (mean 16.8 +/- 8.4 months). The mean starting dosage of CsA was 4.7 +/- 0.5) mg x kg(-1) x d(-1) and the trough level of the whole blood CsA was 248 +/- 110) micro g/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17.4% (3rd month), 21.7% (6th month), 40% (12th month), 88.9% (18th month) and 100% (24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the patients after withdrawing CsA for 4 - 24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6 - 24 months.</p><p><b>CONCLUSIONS</b>CsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment.</p>

Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To make an open label prospective trial for comparing the therapeutic effects of mycophenolate mofetil (MMF) vs cyclophosphamide (CYC) pulse therapy on patients with diffuse proliferative lupus nephritis (DPLN).</p><p><b>METHODS</b>Forty-six patients with biopsy proven active DPLN were enrolled in this study. Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d (MMF Group). Another 23 cases received conventional intermittent CYC pulse therapy (CYC Group). Supplemental steroid treatment was offered in the same manner to both groups. The age, sex distribution and severity of renal damage were matched in two groups. Therapeutic effects were evaluated at the end of six-month treatment. Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time.</p><p><b>RESULTS</b>MMF therapy was more effective in reducing proteinuria and hematuria. A 50% reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6% and 91.3% patients in the MMF Group, while only 47.8% and 65.2% in the CYC Group. MMF was more effective in inhibiting autoantibody production (especially anti-dsDNA antibody) and in decreasing serum cryoglobulin levels. Pathologically, the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis, and less microthrombi, less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group. Adverse reactions related to the treatment included gastrointestinal symptoms 26.1% and 43.5% in the MMF and CYC Groups respectively, infection 17.4% in the MMF group and 30.4% in the CYC group.</p><p><b>CONCLUSION</b>MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study.</p>

The Effect of Multiple Myeloma Tumor-associated Gene MYEOV2 on NIH/3T3 Cells Growth / 中国医师杂志

Objective To analyze the influence of multiple myeloma tumor-associated gene MYEOV2 on NIH/3T3 cells growth. Methods The recombinant plasmid, pcDNA3.1(+)/MYEOV2, was constructed and subsequently transfected into NIH/3T3 cells by liposome. The positive clones of the transfected NIH/3T3 cells were obtained by G418 selection. RT-PCR was used to detecte the expression of MYEOV2 gene in the cells. Fluorescence-activated cell sorting (FACS) and cell grow curve drawing were applied to analyze the influence of MYEOV2 gene on NIH/3T3 cells proliferation. Results The cell clones stably expressing MYEOV2 gene were obtained. FACS analysis showed that the percentage of S phase cell of pcDNA3.1(+)/MYEOV2-transfected cells, pcDNA3.1(+) -transfected cells and non-transfected cells was 30.9%, 20.1% and 16.1%, respectively, and the difference of sphase cell percentage between pcDNA3.1(+)/MYEOV2-transfected cells and the other two groups of cells was significant (P

Effects of mycophenolate mofetil on patients with pauci-immune crescentic glomerulonephritis / 中国实用内科杂志

Objective To compare the effect,relapse rate and outcomes between mycophenolate mofetil(MMF)and pulse intravenous cyclophosphamide(CTX)in the induction therapy of pauci-immune crescentic glomerulonephritis(PICGN)in Chinese.Methods A total of 44 patients who had PICGN[16 male,28 female,age(46.8?13.7)y],of whom 25 patients were ANCA positive,were enrolled in this study.All patients had renal involvement with ≥50% crescent formation prior to the study and received either MMF treatment(MMF group,n=22)or intermittent CTX pulse therapy(CTX group,n=22).The patients in both groups also received methylprednisolone(MP)pulse therapy followed by oral prednisone.General conditions,clinicopathological findings,remission rate,relapse rate,and outcomes were compared.All the patients were followed up until June 2005,with an average follow-up of 8～60(Med 27)months in the MMF group,and 6～72(Med 29)months in the CTX group.Results No significant difference was found between MMF group and CTX group in general conditions,base parameters of clinical and pathological findings.The remission rate at the 12th month in MMF and CTX group was 90.9% and 72.7% respectively.The complete remission rate in MMF group(59.1%)was significantly higher than that of the CTX group(27.3%)(P

Clinicopathologic study in 152 patients with class V lupus nephritis / 中华肾脏病杂志

Objective To investigate the clinical characteristics and outcome of the subgroups of class V lupus nephritis (LN) . Methods 152 patients with class V LN proven by renal biopsy were classified into 2 subgroups according to the 1995 WHO modified classification of LN. Class Va (61 patients) referred to pure membranous glomerulonephritis. Class Vb (91 patients) referred to diffuse membranous glomerulonephritis with superimposed mesangial widening and/or mild to moderate hypercellularity, withdeposition of immune complex in the mesangial region. 488 patients with class Ⅳ LN in the same period werechosen as control. The clinical manifestations, serology examination, transformation of histopathological pattern and prognosis were compared between patients with class Va and class Vb. Results The incidence of hypertension, anemia in patients with class Vb were higher than that in class Va significantly (38. 5% vs 21. 3% , 72. 5% vs 52. 5% respectively, P

THE SIGNIFICANCE OF URINARY INTERLEUKIN—6 IN PATIENTS WITH IgA NEPHROPATHY / 中华肾脏病杂志

Cytokines may play an important role in the development of IgA Nephropathy(IgAN). In this study, the levels of Interleukin—6(IL—6)activity in the urine and serum from 21 patients with IgAN were measured by using IL—6 dependent cell line, 7TD. IL—6 activities were detectable in both urine and serum in patients with IgAN(IL—6 detectable rate 47.6% and 25% respectively), while it was undetectable in normal volunteers. There was no correlationship between urinary and serum IL—6 activities. Also, we found that patients with elevated urinary IL—6 activity had heavy proteinuria and severe glomerular and tubular—interstitial histological changes. The results suggest that the measurement of IL—6 is useful in evaluating the degree of glomerular and interstitial damage in patients with IgAN.

Effects of extract from Narcissus tazettavar. chinensis on proliferation and apoptosis of human multiple myeloma cell line ARH-77 / 中草药

Objective To study the effects of extract from Narcissus tazetta var. chinensis on proliferation and apoptosis of human multiple myeloma cell line ARH-77. Methods The survival rate of cells were tested by MTT assay when cells were affected by 1.25, 2.5, 5, 10, 20 ?g/mL of the extract for 3 d. After being induced by 10 ?g/mL of the extract for 3 d, apoptotic cells were observed with fluorescence stain; changes of he csll cycle were analyzed by Flow Cytometry; the number and shape of nucleolar organizer region (NOR) were tested by AgNOR assay and submicroscopic structure were observed by transmission electron microscope. Results The extract from N. tazetta var. chinensis could significantly inhibit the proliferation and reduce the survival rate of ARH-77 cells (P