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      • KCI등재

        Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

        Hua-Xing Huang,Liang-Lan Shen,Hai-Yan Huang,Li-Hua Zhao,Feng Xu,Dong-Mei Zhang,Xiu-Lin Zhang,Tong Chen,Xue-Qin Wang,Yan Xie,Jian-Bin Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.6

        Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients.Methods: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD.Results: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD.Conclusion: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

      • Refining and Validating a Two-stage and Web-based Cancer Risk Assessment Tool for Village Doctors in China

        Shen, Xing-Rong,Chai, Jing,Feng, Rui,Liu, Tong-Zhu,Tong, Gui-Xian,Cheng, Jing,Li, Kai-Chun,Xie, Shao-Yu,Shi, Yong,Wang, De-Bin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

        The big gap between efficacy of population level prevention and expectations due to heterogeneity and complexity of cancer etiologic factors calls for selective yet personalized interventions based on effective risk assessment. This paper documents our research protocol aimed at refining and validating a two-stage and web-based cancer risk assessment tool, from a tentative one in use by an ongoing project, capable of identifying individuals at elevated risk for one or more types of the 80% leading cancers in rural China with adequate sensitivity and specificity and featuring low cost, easy application and cultural and technical sensitivity for farmers and village doctors. The protocol adopted a modified population-based case control design using 72, 000 non-patients as controls, 2, 200 cancer patients as cases, and another 600 patients as cases for external validation. Factors taken into account comprised 8 domains including diet and nutrition, risk behaviors, family history, precancerous diseases, related medical procedures, exposure to environment hazards, mood and feelings, physical activities and anthropologic and biologic factors. Modeling stresses explored various methodologies like empirical analysis, logistic regression, neuro-network analysis, decision theory and both internal and external validation using concordance statistics, predictive values, etc..

      • KCI등재

        Five-Year Follow-Up Results of a Randomized Controlled Trial Comparing Bipolar Plasmakinetic and Monopolar Transurethral Resection of the Prostate

        Chang-Ying Xie,Xing-Huan Wang,Guang-Bin Zhu,Xiang-Bin Liu 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.4

        Purpose: To report the 5-year follow-up results of a randomized controlled trial comparing bipolar transurethral resection of the prostate (TURP) with standard monopolar TURP for the treatment of benign prostatic obstruction (BPO). Materials and Methods: A total of 220 patients were randomized to bipolar plasmakinetic TURP (PK-TURP) or monopolar TURP (M-TURP). Catheterization time was the primary endpoint of this study. Secondary outcomes included operation time, hospital stay, as well as decline in postoperative serum sodium and hemoglobin levels. All patients were assessed preoperatively and followed-up at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Parameters assessed included quality of life, transrectal ultrasound, serum prostate-specific antigen level, postvoid residual urine volume, maximum urinary flow rates (Qmax), and International Prostate Symptom Score. Patient baseline characteristics, perioperative data including complications, and postoperative outcomes were compared. Complication occurrence was graded according to the modified Clavien classification system. Results: PK-TURP was significantly superior to M-TURP in terms of operation time, intraoperative irrigation volume, resected tissue weight, decreases in hemoglobin and sodium, postoperative irrigation volume and time, catheterization time, and hospital stay. At 5 years postoperatively, efficacy was comparable between arms. No differences were detected in safety outcomes except that the clot retention rate was significantly greater after M-TURP. Conclusion: Our results indicate that PK-TURP is equally as effective in the treatment of BPO, but has a more favorable safety profile in comparison to M-TURP. The clinical efficacy of PK-TURP is long-lasting and comparable with M-TURP.

      • KCI등재

        Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

        Sen-Ling Feng,Hai-Bin Luo,Liang Cai,Jie Zhang,Dan Wang,Ying-Jiang Chen,Huan-Xing Zhan,Zhi-Hong Jiang,Ying Xie 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

        Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinicalcancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediatedby ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrateswere carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. Theexpressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cellxenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation ofABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPaseand reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 bindingsite which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 anddocetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizingeffect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXTtreatment significantly suppressed the growth of drug-resistant tumors without increase in toxicitywhen compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvantchemotherapy, which encourages further pharmacokinetic and clinical studies.

      • KCI등재

        Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

        Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

      • SCIESCOPUSKCI등재

        Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

        Feng, Sen-Ling,Luo, Hai-Bin,Cai, Liang,Zhang, Jie,Wang, Dan,Chen, Ying-Jiang,Zhan, Huan-Xing,Jiang, Zhi-Hong,Xie, Ying The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

        Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

      • β-elemene Induces Caspase-dependent Apoptosis in Human Glioma Cells in vitro through the Upregulation of Bax and Fas/FasL and Downregulation of Bcl-2

        Li, Chen-Long,Chang, Liang,Guo, Lin,Zhao, Dan,Liu, Hui-Bin,Wang, Qiu-Shi,Zhang, Ping,Du, Wen-Zhong,Liu, Xing,Zhang, Hai-Tao,Liu, Yang,Zhang, Yao,Xie, Jing-Hong,Ming, Jian-Guang,Cui, Yu-Qiong,Sun, Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

        Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

      • KCI등재

        Modeling of low viscosity oil-water annular flow in horizontal and slightly inclined pipes: Experiments and CFD simulations

        Yi-Xin Pan,Hong-Bing Zhang,Rong-Hua Xie,Xing-Bin Liu,Min Wang 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.10

        To characterize the effect of pipe inclination, low viscosity, flow rate and inlet water cut on annular flow pattern, a low viscosity oil-water two-phase annular flow in horizontal and slightly inclined (+1o, +3o and +5o) pipes with diameter of 20 mm has been experimentally investigated. A modified VOF model based on the CFD software package FLUENT was used to predict the in-situ oil fraction and pressure drop. The experimental data indicate that annular flow appears at a medium-high water cut. The slip ratio increases with flow rate increase but decreases with increasing water cut. The changes are more significant as the degree of inclination increases. Pressure drop is strongly dependent on flow rate, as it increases rapidly as inlet flow rate increase. Good agreement between the experimental data and calculated results of slip ratio and pressure drop was obtained.

      • Low Expression of Tyrosine-protein Phosphatase Nonreceptor Type 12 is Associated with Lymph Node Metastasis and Poor Prognosis in Operable Triple-negative Breast Cancer

        Wu, Min-Qing,Hu, Pan,Gao, Jie,Wei, Wei-Dong,Xiao, Xiang-Sheng,Tang, Hai-Lin,Li, Xing,Ge, Qi-Dong,Jia, Wei-Hua,Liu, Ren-Bin,Xie, Xiao-Ming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

        Background: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associated with breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breast cancer has not been clearly identified. Patients and Methods: 51 triple-negative breast cancer (TNBC) patients and 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were included in this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. Results: High PTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status (p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group was associated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox regression analysis. Conclusion: These findings provide evidence that low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognostic biomarker in TNBC patients.

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