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Normoalbuminuric diabetic kidney disease

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 310-318 doi: 10.1007/s11684-017-0542-7

摘要:

Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus (DM) patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease (NADKD) or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.

关键词: diabetes     diabetic kidney disease     normoalbuminuria     renal impairment    

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

《医学前沿(英文)》 2020年 第14卷 第3期   页码 293-304 doi: 10.1007/s11684-019-0715-7

摘要: Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocin-induced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

关键词: netrin-1     VEGF-165     UNC5B     angiogenesis     diabetic kidney disease    

Identification of differentially expressed miRNAs associated with chronic kidney disease–mineral bone

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 378-385 doi: 10.1007/s11684-017-0541-8

摘要:

The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD–mineral bone disorder (CKD–MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD–MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational analyses were performed with the imputed microRNA regulation based on weighted ranked expression and putative microRNA targets (IMRE) method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD–MBD. TLR4 levels were significantly downregulated, whereas pri-miR-146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.

关键词: chronic kidney disease     microRNA     mineral bone disorder     uremia    

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

《医学前沿(英文)》 2011年 第5卷 第3期   页码 288-293 doi: 10.1007/s11684-011-0127-9

摘要: Haemorheological abnormalities have been described in diabetes mellitus, as well as in non-alcoholic fatty liver disease (NAFLD). However, the relationship between the changes in liver fat content and haemorheology is unknown. The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes. The serum biochemical markers, such as fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), liver enzymes, lipid profiles, and haemorheological properties, were examined. IHLC was quantified using proton magnetic resonance spectroscopy ( H-MRS) scanning of the liver. A significant correlation was observed between IHLC and whole blood viscosity at high, middle, and low shear rates. IHLC also positively correlated with haematocrit, the reduced whole blood viscosity at low and middle shear rates, and the erythrocyte aggregation index. Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD. In summary, haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

关键词: diabetes mellitus     type 2     haemorheology     non-alcoholic fatty liver disease    

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

《医学前沿(英文)》 2020年 第14卷 第5期   页码 642-650 doi: 10.1007/s11684-019-0719-3

摘要: This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR<30 mg/g, =136, NA), microalbuminuria (UACR at 30–300 mg/g, =132, MA), and clinical albuminuria (UACR>300 mg/g, =122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects ( <0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR ( <0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

关键词: type 2 diabetes mellitus     diabetic kidney disease     miR-154-5p     urinary albumin to creatinine ratio    

Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 386-392 doi: 10.1007/s11684-017-0574-z

摘要:

Kidney damage is common in patients with diabetes mellitus (DM). However, whether the type of kidney damage can be reliably diagnosed using clinical data alone remains unclear. Predictive factors for diabetic nephropathy (DN) outcomes are also poorly understood. In this study, the clinical manifestations of 111 cases of biopsy-proven DN were described, and the clinical and pathological parameters of patients with different DN outcomes were compared. Results showed that long DM duration (>10 years in 32.4% of patients), severe proteinuria (62.2%), and renal dysfunction (estimated glomerular filtration rate [eGFR]<60 mL/(min·1.73 m2)) (52.3%) did not accurately indicate whether the condition of these patients progressed to DN. Hematuria (48.6%) failed to specify either DN or nondiabetic renal disease. Diabetic retinopathy (78.4%) was a crucial complication in patients with DN. Kaplan–Meier analysis revealed that the renal survival of 53 patients who were diagnosed with DN and were followed up was not significantly associated with glomerular classification (P>0.05). Cox’s regression analysis demonstrated that renal survival time was significantly influenced by sex (b= 1.394, P= 0.038), hematuria (b= 0.036, P= 0.029), and eGFR (b= −0.039, P= 0.002) but was not significantly affected by age, 24 h urinary protein excretion, or glomerular classification (P>0.05). In conclusion, the clinical characteristics of DN vary, and renal biopsy is necessary to determine renal damage patterns. Sex, hematuria, and the eGFR may affect DN outcomes, whereas the glomerular classification may not.

关键词: diabetic nephropathy     clinical characteristics     renal biopsy     outcomes    

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

《医学前沿(英文)》 doi: 10.1007/s11684-023-1019-5

摘要: Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词: sleep     physical activity     chronic kidney disease     isotemporal substitution     behavioral pattern    

Hyperglycemic memory in diabetic cardiomyopathy

《医学前沿(英文)》 2022年 第16卷 第1期   页码 25-38 doi: 10.1007/s11684-021-0881-2

摘要: Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.

关键词: diabetes     diabetic cardiomyopathy     hyperglycemic memory    

Successful kidney transplantation in highly sensitized patients

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 80-85 doi: 10.1007/s11684-011-0115-0

摘要:

Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panel-reactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novoproduction of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.

关键词: Kidney transplantation     desensitization    

Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

《化学科学与工程前沿(英文)》 2023年 第17卷 第3期   页码 298-306 doi: 10.1007/s11705-022-2212-9

摘要: Herein, a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method. The carbon dots-based sensor (CA-CDs) exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00. Notably, the fluorescence sensor has a reversible response to pH change. Finally, the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice. Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice, while the pH value in liver of diabetic mice was almost the same as that of the normal mice. The present study provides a simple analytical method for pH detection suitable for in vivo.

关键词: carbon dots     two-photon imaging     pH     diabetic mice    

Mechanisms of “kidney governing bones” theory in traditional Chinese medicine

null

《医学前沿(英文)》 2014年 第8卷 第3期   页码 389-393 doi: 10.1007/s11684-014-0362-y

摘要:

Studies conducted by our group on the mechanism of “kidney governing bones” theory in traditional Chinese medicine (TCM) are reviewed in this paper. Conclusions can be summarized as follows. (1) Neuroendocrine-immune network (NIN)-osteoclast regulatory pathway OPG-RANKL-RANK is one of the mechanisms of “kidney governing bones.” Although kidney-reinforcing therapy is regarded as one of the holistic regulatory mechanisms of the body, characteristic holistic regulation in TCM can be reflected through nonselective regulation of the NIN during kidney reinforcement therapy, which can be used to treat osteoporosis through microadjustments in the microenvironment of the bone marrow. (2) Marrow exhaustion in TCM, which is the state wherein lipocytes in the bone marrow increase whereas other cells decrease, serves as the pathogenesis of osteoporosis brought about by failure of the “kidney governing bones.” (3) The kidney in TCM can be regarded as a complex system comprising multiple functional units in the body, including the unit “governing bones.” Kidney deficiency refers to a deficiency in only one or more units of the kidney system and not the whole system itself, which explains the kidney-reinforcing effect of many herbs; some herbs can treat osteoporosis, but some cannot. Although both classified as kidney-reinforcing agents, the former can resolve failure of the “kidney governing bones” unit while the latter regulates the failure of other units in the kidney system. Despite the current understanding on “kidney governing bones” theory, the mechanism of “kidney governing bones” remains complicated and unresolved. Thus, further studies in this area are warranted.

关键词: kidney governing bones     kidney deficiency     marrow     osteoporosis     neuroendocrine-immune network     osteoclast regulatory pathway    

Risk factors of prognosis after acute kidney injury in hospitalized patients

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 393-402 doi: 10.1007/s11684-017-0532-9

摘要:

The risk factors, especially laboratory indicators, of prognosis after acute kidney injury (AKI) remain unclear. We conducted a retrospective survey of Chinese People’s Liberation Army General Hospital from January 1, 2012 to December 31, 2012 according to the AKI diagnosis standard issued by Kidney Disease Improving Global Outcomes. The epidemiological features and factors influencing hospital mortality and renal function recovery were evaluated through logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387 suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%, respectively. Multivariate logistic regression analysis revealed that high AKI stage, age greater than 80 years, neoplastic disease, low cardiac output, increased white blood cell count, and decreased platelet count and serum albumin levels were the risk factors affecting the mortality of AKI patients. Conversely, body mass index between 28 and 34.9 was a protective factor. Increased AKI stage, tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors of renal function recovery upon discharge. In addition to traditional risk factors, white blood cell count, platelet count, albumin, and BMI were the predictors of the mortality of AKI patients. No laboratory indicators were found to be the risk factors of renal function recovery in AKI patients.

关键词: acute kidney injury     risk factors     prognosis    

Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要:

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词: diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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

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    

White blood cell count and the incidence of hyperuricemia: insights from a community-based study

Jian Liu, Pingyan Shen, Xiaobo Ma, Xialian Yu, Liyan Ni, Xu Hao, Weiming Wang, Nan Chen

《医学前沿(英文)》 2019年 第13卷 第6期   页码 741-746 doi: 10.1007/s11684-017-0579-7

摘要: Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). The relationship between HUA and white blood cell (WBC) count remains unknown. A sampling survey for CKD was conducted in Sanlin community in 2012 and 2014. CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR of 60 mL/(min·1.73 m ). HUA was defined as serum uric acid>420 µmol/L in men and>360 µmol/L in women. This study included 1024 participants. The prevalence of HUA was 17.77%. Patients with HUA were more likely to have higher levels of WBC count, which was positively associated with HUA prevalence. This association was also observed in participants without CKD, diabetes mellitus, hyperlipidemia, or obesity. Multivariate logistic regression analysis showed that WBC count was independently associated with the risk for HUA in male and female participants. Compared with participants without HUA, inflammatory factors such as high-sensitivity C-reactive protein, tumor necrosis factor-α and interleukin 6 increased in participants with HUA. Hence, WBC count is positively associated with HUA, and this association is independent of conventional risk factors for CKD.

关键词: white blood cell count     hyperuricemia     chronic kidney disease     inflammation    

标题 作者 时间 类型 操作

Normoalbuminuric diabetic kidney disease

null

期刊论文

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

期刊论文

Identification of differentially expressed miRNAs associated with chronic kidney disease–mineral bone

null

期刊论文

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

期刊论文

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

期刊论文

Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

null

期刊论文

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

期刊论文

Hyperglycemic memory in diabetic cardiomyopathy

期刊论文

Successful kidney transplantation in highly sensitized patients

null

期刊论文

Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

期刊论文

Mechanisms of “kidney governing bones” theory in traditional Chinese medicine

null

期刊论文

Risk factors of prognosis after acute kidney injury in hospitalized patients

null

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

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

YU Xiaofang, XU Xialian, YE Zhibin

期刊论文

White blood cell count and the incidence of hyperuricemia: insights from a community-based study

Jian Liu, Pingyan Shen, Xiaobo Ma, Xialian Yu, Liyan Ni, Xu Hao, Weiming Wang, Nan Chen

期刊论文