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Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

《医学前沿（英文）》 2009年 第3卷 第2期   页码 204-210 doi: 10.1007/s11684-009-0039-0

摘要： To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy upon chronic allograft nephropathy (CAN) of rats, male Lewis (LEW, RT11) rats received male Fisher (F344, RT11v1) renal allografts. The recipients were divided into three groups: (1) empty control group; (2) vector control group; (3) gene therapy group. All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation. Morphometric analysis was used to determine the fibrosis of grafts. Immunohistochemistry was used to detect the expression of E-Cadherin, Vimentin, TβR I and the infiltration of CD4 T lymphocyte, CD8 T lymphocyte and ED-1 monocytes. Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 in serum. The grafts in the control group and vector control group showed CAN. There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I. In the gene therapy group, the fibrosis was ameliorated and fewer T lymphocytes and ED-1 monocytes infiltrated in the interstitium. There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats. Compared with the empty control group, the expression of TGF-β1 in the gene therapy group was down-regulated. Adanti-ERK2 gene therapy protects the renal allograft and attenuates graft fibrosis, which may be correlated with a decreased renal tubular epithelial mesenchymal transition, a decreased infiltration of CD4 T lymphocyte, CD8 T lymphocytes and ED-1 monocytes in renal interstitium, and the down-regulated TGF-β1 expression.

关键词： anti-ERK2     renal transplantation     epithelial mesenchymal transition     chronic allograft nephropathy    

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Mechanism of arterial remodeling in chronic allograft vasculopathy

Qichang Zheng, Shanglong Liu, Zifang Song

《医学前沿（英文）》 2011年 第5卷 第3期   页码 248-253 doi: 10.1007/s11684-011-0149-3

摘要： Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term survival of grafts even though therapeutic strategies have improved considerably in recent years. CAV is characterized by concentric and diffuse neointimal formation, medial apoptosis, infiltration of lymphocyte or inflammatory cells, and deposition of extracellular matrix both in arteries and veins. Recent studies have shown that stem cells derived from the recipient contribute to neointimal formation under the regulation of chemokines and cytokines. Arterial remodeling in allografts eventually causes ischemic graft failure. The pathogenesis is multi-factorial with both immunologic and non-immunological factors being involved. The immunological factors have been discussed extensively in other articles. This review focuses mainly on the arterial remodeling that occurs in 3 layers of vessel walls including intimal injury, accumulation of smooth muscle-like cells in the neointimal, medial smooth muscle cell apoptosis, adventitial fibrosis, and deposition of extracellular matrix.

关键词： transplantation     chronic rejection     neointimal     immunology     arterial remodeling     allograft vasculopathy    

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Relationship between Th17 cells and allograft rejection

Zhikun ZHENG MM, Jinsong LI MD, Ke JIANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 491-494 doi: 10.1007/s11684-009-0066-x

摘要： Thl7 cells, a special kind of auxiliary type T cells, can secrete IL-17A, IL-17F, IL-21, IL-22, etc., as a newly discovered T-cell subset in recent years. As a different subset from the Thl and Th2 cells, Th17 cells play an important role in the development of a variety of autoimmune diseases. A current study shows that the IL-6 inflammatory response of the organization in combination with the occurrence of TGF-β can induce the differentiation of Thl7 cells. IL-23 can promote the production of IL17, as well as participate in amplification and maintenance of the survival of IL-l7 generating cells. In this process, STAT3 and ROR-γt are key transcription factors for the growing of Thl7 cells. As our knowledge on Th17 family members is rapidly growing and changing, it will be important to specify their involvement in the induction and regulation of allograft rejection in animal models as well as in clinical settings. Herein, we review the key features of Th17 cells and discuss their potential relevance to transplantation immunity.

关键词： TH17 cells     regulation     allograft     rejection    

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DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

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《医学前沿（英文）》 2016年 第10卷 第4期   页码 507-516 doi: 10.1007/s11684-016-0475-6

摘要：

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown the ethnic-specific association between certain human leukocyte antigen (HLA) alleles and IgAN susceptibility. This study was designed to explore the relationship between HLA-DQB1 alleles and disease susceptibility and clinical manifestations of patients with IgAN in southern Han Chinese. A PCR sequence-based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients and 229 healthy subjects. Clinical data were collected from each patient at the time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and healthy subjects. High frequency of HLA-DQB1*060101 and low frequency of HLA-DQB1*030101 were observed in IgAN patients compared with healthy controls. Further stratification analysis revealed that the frequency of DQB1*060101 was significantly higher in patients with urine protein≥1.0 g/24 h than in patients with urine protein<1.0 g/24 h. In combination with our previous DRB1 results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101-DQB1*020101 was significantly lower (OR= 0.194, Pc = 0.016) compared with healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a potential predictor of high-risk IgAN susceptibility in Chinese Han population.

关键词： DQB1     human leukocyte antigen (HLA)     IgA nephropathy     haplotype     association study    

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Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

Hanyu Zhu, Bo Fu, Yong Wang, Jing Gao, Qiuxia Han, Wenjia Geng, Xiaoli Yang, Guangyan Cai, Xiangmei Chen, Dong Zhang

《医学前沿（英文）》 2019年 第13卷 第5期   页码 618-625 doi: 10.1007/s11684-018-0620-5

摘要： This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group ( = 248) and non-MN group ( = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

关键词： multiparameter analysis     diagnosis     model     membranous nephropathy    

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New perspective on the natural course of chronic HBV infection

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 129-134 doi: 10.1007/s11684-014-0339-x

摘要：

Chronic hepatitis B virus (HBV) infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen (HBeAg) seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

关键词： hepatitis B virus     chronic HBV infection     natural course     hepatitis B     seroconversion    

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Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

《医学前沿（英文）》 2007年 第1卷 第3期   页码 308-311 doi: 10.1007/s11684-007-0059-6

摘要： In patients with chronic renal failure, whether they have had hemodialysis or not, the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with normal kidney function. The detection of tumor markers is extensively used for the diagnosis of corresponding tumors. It has been recently shown that some tumor markers are higher in patients with chronic kidney disease (CKD) than in the normal population. The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA, CA, CA, AFP, CA, CA, CYFRA, NSE, SCC-Ag, PSA, and fPSA. The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study. The 232 non-dialysis patients were divided into three groups according to their Ccr. In group 1, Ccr was ≤25 mL/min. In group 2, Ccr was between 25 and 50 mL/min. In group 3, Ccr was ≥50 mL/min. The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups. Nine tumor markers in 37 uremic patients were tested. For comparison, 37 non-dialysis patients with similar Ccr of the same age and gender served as controls. There existed significant differences in serum levels of CEA, CA, CYFRA, NSE, and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr. There were no significant differences among the three groups in the serum concentrations of CA, AFP, CA, CA, PSA and fPSA. The serum levels of CA and NSE were significantly higher (199, CYFRA, NSE, CA and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP, CA, CA, PSA and fPSA were as valuable as they were in patients with normal kidney function. Hemodialysis further increased the serum level of CA and NSE.

关键词： CKD     non-dialysis     valuable     detection     chronic    

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Acupuncture is ineffective for chronic low back pain? A critical analysis and rethinking

Xuqiang Wei, Baoyan Liu

《医学前沿（英文）》 2021年 第15卷 第5期   页码 767-775 doi: 10.1007/s11684-020-0785-6

摘要： Acupuncture is a promising treatment for relieving pain and improving lower back function in clinical practice. However, evidence from randomized clinical trials (RCTs) remains controversial. Most RCTs conclude that acupuncture procedures for chronic low back pain (CLBP) had no significant difference in efficacy and belonged to placebo. We carefully reviewed and analyzed the methodology and implementation of sham acupuncture in RCTs. Controversial evidence of acupuncture for CLBP is only a microcosm of the evaluation methodological limitation of acupuncture. Inappropriate selection of sham acupuncture controls, rigorous RCT research models, and incorrect interpretation of results may contribute to negative evidence. Evaluating and disregarding the holistic efficacy of acupuncture with an explanatory RCT model based on evaluation drugs may be unwise. Moreover, sham acupuncture is often proven to be non-inert, unreasonable, and with low fidelity. Pitfalls of the explanatory RCT model and sham acupuncture design should be avoided. Establishing a new evaluation system that is in line with the clinical characteristics of acupuncture and obtaining high-quality evidence are difficult but promising tasks.

关键词： chronic low back pain     sham acupuncture     acupuncture     methodology     therapeutic evaluation    

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Vaccine therapies for chronic hepatitis B: can we go further?

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 17-23 doi: 10.1007/s11684-014-0313-7

摘要：

Chronic hepatitis B is a major health burden worldwide. In addition to the recent progress in antiviral treatment, therapeutic vaccination is a promising new strategy for the control of chronic hepatitis B. On the basis of the major specific and non-specific immune dysregulations and defects in chronic hepatitis B patients, this paper presents the peptide and protein-based, DNA-based, cell-based, and antigen-antibody-based therapeutic vaccines, which have undergone clinical trials. The advantages, disadvantages, and future perspectives for these therapeutic vaccines are discussed.

关键词： chronic hepatitis B     therapeutic     antigen-antibody complexes     DNA     vaccine    

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Perceived resource support for chronic illnesses among diabetics in north-western China

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《医学前沿（英文）》 2016年 第10卷 第2期   页码 219-227 doi: 10.1007/s11684-016-0441-3

摘要：

A high level of social support can improve long-term diabetes self-management. Support from a single source has been evaluated. This study aims to analyze support from multiple and multilevel sources for diabetic patients by using the Chronic Illness Resources Survey (CIRS). Factors influencing the utilization of the CIRS were also evaluated. A total of 297 patients with diabetes were investigated using the CIRS and Perceived Diabetes Self-management Scale in Shihezi City, China. Descriptive statistics were used to explain demographic variables and scores of the scales. Factors affecting the utilization of chronic illness resources were determined through univariate analysis and then examined by multivariate logistic regression analysis. Of the 297 diabetic patients surveyed, 67% failed to reach the standard (more than 3 points) of utilizing chronic illness resources. Moreover, utilization of chronic illness resources was positively moderately correlated with self-management of diabetes (r = 0.75, P <0.05). According to the multivariate logistic regression analysis, age (OR, 3.42; 95%CI, 1.19–9.84) and monthly income (OR, 5.27; 95%CI, 1.86–14.90) were significantly positively associated with the CIRS score. Individuals with high school (OR, 2.61; 95%CI, 1.13–6.05) and college (OR, 3.02; 95%CI, 1.13–8.04) degrees obtained higher scores in the survey than those with elementary school education. Results indicated that utilization of resources and support for chronic illness self-management, particularly personal adjustment and organization, were not ideal among diabetics in the communities of north-western China. Improved utilization of chronic illness resources was conducive for proper diabetes self-management. Furthermore, the level of utilization of chronic illness resources increased with age, literacy level, and monthly income.

关键词： chronic illness resources survey     diabetes     community     north-western China    

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Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 271-276 doi: 10.1007/s11684-009-0054-1

摘要： The aim of this paper is to investigate the relationship between hepatitis B virus (HBV) DNA levels during the course and the progression to cirrhosis with chronic hepatitis B. A total of 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 were followed up for a median of 28 months. Compared with the patients without cirrhosis, the patients progressed to cirrhosis were older and with higher HBV-DNA levels at end point. However, there was no significant difference in cirrhosis progression between different HBV-DNA groups at baseline ( = 0.531). Kaplan-Meier analysis showed higher HBV-DNA level at endpoint had increasing risk of cirrhosis ( = 0.019). The results of Cox model indicated that HBV-DNA levels at endpoint, stage of fibrosis, negative hepatitis B e antigen, and γ-glutamyl transpeptidase at baseline were independent risk factors of cirrhosis. The relative risk ratios were 1.898, 1.918, 8.976, and 1.006, respectively. Progression to cirrhosis in chronic hepatitis B patients is correlated with HBV-DNA levels during follow-up.

关键词： hepatitis B     chronic     viral load     liver cirrhosis    

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Advances in some common chronic liver diseases

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 127-128 doi: 10.1007/s11684-014-0341-3

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Overview on acute-on-chronic liver failure

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《医学前沿（英文）》 2016年 第10卷 第1期   页码 1-17 doi: 10.1007/s11684-016-0439-x

摘要：

Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.

关键词： liver failure     chronic liver failure     acute-on-chronic liver failure     diagnosis     prognosis     treatment    

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allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 304-311 doi: 10.1007/s11684-015-0400-4

摘要：

In the tyrosine kinase inhibitor (TKI) era, imatinib is the first-line therapy for patients with chronic myeloid leukemia (CML) in chronic or accelerated phase. Although second-generation TKIs (TKI2), including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 (n?=?33) and allo-HSCT (n?=?60) groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 (36.7%), 35 (58.3%), and 3 (10%) patients underwent allo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients (100%) achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate (42.9% vs. 86.4%, P = 0.002), 5-year event-free survival rate (14.3% vs. 76.1%, P<0.001), and 5-year progression-free survival (28.6% vs. 78.1%, P<0.001) than those in the allo-HSCT group. Multivariate analysis showed that male sex and TKI2therapy were predictors of poor overall survival, whereas hemoglobin<100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patients with CML in accelerated phase.

关键词： chronic myeloid leukemia     imatinib     dasatinib     nilotinib     allogeneic hematopoietic stem cell transplantation    

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Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 135-144 doi: 10.1007/s11684-014-0331-5

摘要：

Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.

关键词： chronic hepatitis B     epidemiology     prevention     treatment    

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标题 作者 时间 类型 操作

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

期刊论文

Mechanism of arterial remodeling in chronic allograft vasculopathy

Qichang Zheng, Shanglong Liu, Zifang Song

期刊论文

Relationship between Th17 cells and allograft rejection

Zhikun ZHENG MM, Jinsong LI MD, Ke JIANG MD,

期刊论文

DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

null

期刊论文

Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

Hanyu Zhu, Bo Fu, Yong Wang, Jing Gao, Qiuxia Han, Wenjia Geng, Xiaoli Yang, Guangyan Cai, Xiangmei Chen, Dong Zhang

期刊论文

New perspective on the natural course of chronic HBV infection

null

期刊论文

Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

期刊论文

Acupuncture is ineffective for chronic low back pain? A critical analysis and rethinking

Xuqiang Wei, Baoyan Liu

期刊论文

Vaccine therapies for chronic hepatitis B: can we go further?

null

期刊论文

Perceived resource support for chronic illnesses among diabetics in north-western China

null

期刊论文

Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

期刊论文

Advances in some common chronic liver diseases

null

期刊论文

Overview on acute-on-chronic liver failure

null

期刊论文

allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic

null

期刊论文

Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China

null

期刊论文