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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    

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Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

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《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    

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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    

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Normoalbuminuric diabetic kidney disease

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《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    

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improves glycometabolism and ameliorates insulin resistance by regulating the PI3K/Akt pathway in KKAy mice

Xiaoqing Li, Xinxin Li, Genbei Wang, Yan Xu, Yuanyuan Wang, Ruijia Hao, Xiaohui Ma

《医学前沿（英文）》 2018年 第12卷 第6期   页码 688-696 doi: 10.1007/s11684-018-0662-8

摘要：

Xiao Ke Qing (XKQ) granule has been clinically used to treat type 2 diabetes mellitus (T2DM) for 10 years in Chinese traditional medication. However, its mechanisms against hyperglycemia remain poorly understood. This study aims to investigate XKQ mechanisms on diabetes and diabetic liver disease by using the KKAy mice model. Our results indicate that XKQ can significantly reduce food and water intake. XKQ treatment also remarkably decreases both the fasting blood glucose and blood glucose in the oral glucose tolerance test. Additionally, XKQ can significantly decrease the serum alanine aminotransferase level and liver index and can alleviate the fat degeneration in liver tissues. Moreover, XKQ can ameliorate insulin resistance and upregulate the expression of IRS-1, PI3K (p85), p-Akt, and GLUT4 in the skeletal muscle of KKAy mice. XKQ is an effective drug for T2DM by ameliorating insulin resistance and regulating the PI3K/Akt signaling pathway in the skeletal muscle.

关键词： XKQ     type 2 diabetes mellitus     KKAy mice     PI3K/Akt pathway     diabetic liver disease    

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Non-genetic mechanisms of diabetic nephropathy

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《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    

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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    

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Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 301-305 doi: 10.1007/s11684-013-0283-1

摘要：

Systemic inflammatory response following myocardial ischemia-reperfusion injury (IRI) to a specific organ may cause injuries. Ischemic post-conditioning (IPostC) has emerged as a promising method for myocardial protection against IRI both in experimental and in clinical settings. Enhancement of endogenous nitric oxide (NO) is one of the major mechanisms by which IPostC confers cardioprotection. However, the sensitivity of the diabetic heart to IPostC is impaired and the underlying mechanism is unknown. Adiponectin (APN) is an adipocyte-derived plasma protein with anti-diabetic and anti-inflammatory properties. Plasma levels of APN are decreased in obese subjects and in patients with type 2 diabetes. APN supplementation has been shown to increase NO production and attenuate myocardial IRI in normal (non-diabetic) animals. However, the effect of APN on myocardial injury in diabetic subjects, especially its potential in restoring the sensitivity of the diabetic heart to IPostC has not been investigated. In the current paper, we discussed the possible reasons why the myocardium of diabetic subjects loses sensitivity to IPostC and also highlighted the potential effectiveness and mechanism of APN in restoring IPostC cardioprotection in diabetes. This review proposes to conduct studies that may facilitate the development of novel and optimal therapies to enhance cardioprotection in patients with severe diseases such as diabetes.

关键词： adiponectin     ischemic post-conditioning     ischemia reperfusion injury     diabetes    

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Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its

HUANG Hongying, LIU Guangchao, QI Yijun, DU Yaowu, CHEN Jugao, MA Yuanfang

《医学前沿（英文）》 2008年 第2卷 第2期   页码 186-190 doi: 10.1007/s11684-008-0035-9

摘要： The aim of this study is to explore inhibitory activity of Bifidobacterium adolescent combined with cisplatin on the growth of melanoma (B16) in mice and the underlying mechanism. C57 mice were inoculated with B16 cancer cells to construct mouse model of melanoma and treated with bifidobacterium adolescent combined with cisplatin. Ratios of inhibitory activity on the growth of melanoma (B16) were calculated. Pathology changes of the tumor were observed by HE staining. B16 cell cycles were examined on a flow cytometer. Lymphocyte proliferation was measured with MTT assay and the T-cell subset was measured by double marked fluorescence. When bifidobacterium of 10 cfu/L was injected, the ratio of inhibitory activity on the growth of melanoma (B16) reached 54%, which was similar to that of cisplatin group. The ratio of inhibitory activity reached 74.45% when the mice were treated by bifidobacterium combined with cisplatin. HE staining shows that bifidobacterium inhibited B16 cell proliferation and enhanced the cisplatins killing activity on B16 cells. The results of flow cytometry demonstrated that B16 cell proliferation was arrested at G stage after treatment with bifidobacterium. The B16 cell proliferation was arrested at S stage after treatment with cisplatin. The CD4+ percentage increased and the difference was significant compared with the normal group after treatment with bifidobacterium, indicating that T-cell immune activity was enhanced. Treatment with bifidobacterium combined with cisplatin can enhance the inhibitory activity on the growth of melanoma (B16) of cisplatin. The mechanism of the inhibitory activity on B16 cell proliferation is correlated with the enhanced immune activity in mice.
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Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating

《医学前沿（英文）》 2021年 第15卷 第5期   页码 750-766 doi: 10.1007/s11684-021-0839-4

摘要： Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

关键词： particulate matter 2.5     sirtuin 2     p65     airway inflammation     bronchial hyperresponsiveness     triptolide    

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Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 490-498 doi: 10.1007/s11684-016-0470-y

摘要：

This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugate vaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DNA technology. A total of 15 young mice aged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another 15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid (TT) vaccine. Furthermore, the third group of 15 young mice was inoculated with phosphate buffer saline as control. The immunized mice were inoculated with pneumococcus in the middle ear. Results showed that IgG antibody responses against both the PsaA protein and Hib polysaccharide were observed in the Hib-PsaA group. However, no statistical difference was observed in the titer of IgG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. The elimination rate of pneumococcus and the inflammation of the middle ear showed the effectiveness of protective immunity against otitis media caused by pneumococcus. Our results suggest that the Hib polysaccharide can be successfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugate vaccine can induce both anti-PsaA and anti-Hib immune responses in young mice and elicit effective protection against acute otitis media caused by pneumococcus.

关键词： conjugate vaccine     pneumococcal surface adhesin A     Hemophilus influenzae b     immunogenicity     otitis media    

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Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX

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《医学前沿（英文）》 2016年 第10卷 第2期   页码 212-218 doi: 10.1007/s11684-016-0438-y

摘要：

Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5×1011 and 1×1011 virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.

关键词： hemophilia B     AAV8     hFIX     gene therapy    

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Zinc homeostasis in the metabolic syndrome and diabetes

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《医学前沿（英文）》 2013年 第7卷 第1期   页码 31-52 doi: 10.1007/s11684-013-0251-9

摘要：

Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

关键词： zinc     zinc transporters     metallothionein     diabetes     diabetic complications     insulin resistance     antioxidant    

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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    

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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 86-93 doi: 10.1007/s11684-011-0118-x

摘要：

Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

关键词： adeno-associated virus     angiogenesis     gene transfer     ischemia     middle cerebral artery occlusion     netrin-1    

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标题 作者 时间 类型 操作

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

期刊论文

Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

null

期刊论文

Hyperglycemic memory in diabetic cardiomyopathy

期刊论文

Normoalbuminuric diabetic kidney disease

null

期刊论文

improves glycometabolism and ameliorates insulin resistance by regulating the PI3K/Akt pathway in KKAy mice

Xiaoqing Li, Xinxin Li, Genbei Wang, Yan Xu, Yuanyuan Wang, Ruijia Hao, Xiaohui Ma

期刊论文

Non-genetic mechanisms of diabetic nephropathy

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

Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic

null

期刊论文

Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its

HUANG Hongying, LIU Guangchao, QI Yijun, DU Yaowu, CHEN Jugao, MA Yuanfang

期刊论文

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating

期刊论文

Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate

null

期刊论文

Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX

null

期刊论文

Zinc homeostasis in the metabolic syndrome and diabetes

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

Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral

null

期刊论文