Publications by authors named "Yuemin Sun"

26 Publications

  • Page 1 of 1

Survey on sodium and potassium intake in patients with hypertension in China.

J Clin Hypertens (Greenwich) 2021 Sep 25. Epub 2021 Sep 25.

Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Sodium and potassium intake in hypertensive patients in China is not clear. The authors aimed to investigate the distribution of sodium and potassium intake in hypertensive patients in China, and to analyze the relationship between sodium and potassium intake and blood pressure. The study was performed in 130 hospitals from 23 provinces across China from 2016 to 2019. Finally, 9501 hypertensive patients average aged 54 years were included. 24 h urinary sodium and potassium excretion were measured. Distribution of urinary electrolytes were described according to age, gender and region. The association between urinary electrolytes and blood pressure was analyzed by multivariate linear regression. Hypertensive patients exhibited an average 24 h urinary sodium and potassium excretion of 156.7 ± 81.5 mmol/d and 39.2 ± 20.2 mmol/d (equivalent to sodium chloride of 9.2 g/d, potassium chloride of 2.9 g/d), sodium/potassium ratio (median) of 4.14 (2.92,5.73). Urinary electrolytes were lower in women than men (sodium: 171.1 vs 138.7, p < .05; potassium: 40.3 vs 37.7, p < .05), in the elderly than in the younger (sodium: 168.7 vs 139.9, p < .05; potassium: 39.5 vs. 37.5, p < .05). For every 1 unit of Na/K ratio increase, blood pressure increased by 0.46/0.24 mmHg. Blood pressure was 2.75/1.27 mmHg higher in quartile 4 than quartile 1 of Na/K. It remains high sodium and low potassium for hypertensive patients in China. Decreased sodium, Na/K ratio and increased potassium may help for blood pressure management.
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http://dx.doi.org/10.1111/jch.14355DOI Listing
September 2021

Perioperative Electroacupuncture Can Accelerate the Recovery of Gastrointestinal Function in Cancer Patients Undergoing Pancreatectomy or Gastrectomy: A Randomized Controlled Trial.

Evid Based Complement Alternat Med 2021 31;2021:5594263. Epub 2021 Mar 31.

State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

The effect of perioperative acupuncture on accelerating gastrointestinal function recovery has been reported in colorectal surgery and distal gastrectomy (Billroth-II). However, the evidence in pancreatectomy and other gastrectomy is still limited. A prospective, randomized controlled trial was conducted between May 2018 and August 2019. Consecutive patients undergoing pancreatectomy or gastrectomy in our hospital were randomly assigned to the electroacupuncture (EA) group and the control group. The patients in the EA group received transcutaneous EA on Bai-hui (GV20), Nei-guan (PC6), Tian-shu (ST25), and Zu-san-li (ST36) once a day in the afternoon, and the control group received sham EA. Primary outcomes were the time to first flatus and time to first defecation. In total, 461 patients were randomly assigned to the groups, and 385 were analyzed finally (EA group,  = 201; control group,  = 184). Time to first flatus (3.0 ± 0.7 vs 4.2 ± 1.0, < 0.001) and first defecation (4.2 ± 0.9 vs 5.4 ± 1.2, < 0.001) in the EA group were significantly shorter than those in the control group. Of patients undergoing pancreatectomy, those undergoing pancreaticoduodenectomy and intraoperative radiation therapy (IORT) surgery benefitted from EA in time to first flatus ( < 0.001) and first defecation ( < 0.001), while those undergoing distal pancreatectomy did not ( =0.157, =0.007) completely. Of patients undergoing gastrectomy, those undergoing total gastrectomy and distal gastrectomy (Billroth-II) benefitted from EA ( < 0.001), as did those undergoing proximal gastrectomy (=0.015). Patients undergoing distal gastrectomy (Billroth-I) benefitted from EA in time to first defecation (=0.012) but not flatus (=0.051). The time of parenteral nutrition, hospital stay, and time to first independent walk in the EA group were shorter than those in the control group. No severe EA complications were reported. EA was safe and effective in accelerating postoperative gastrointestinal function recovery. Patients undergoing pancreaticoduodenectomy, IORT surgery, total gastrectomy, proximal gastrectomy, or distal gastrectomy (Billroth-II) could benefit from EA. This trial is registered with NCT03291574.
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http://dx.doi.org/10.1155/2021/5594263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026294PMC
March 2021

Lobaplatin in Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer: Safety and Efficacy Profiles.

Cancer Manag Res 2020 29;12:5141-5146. Epub 2020 Jun 29.

Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China.

Objective: This study aims to evaluate the safety and efficacy of lobaplatin in prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer.

Methods: Advanced gastric cancer patients who underwent radical gastric resection and/or prophylactic HIPEC were systematically reviewed in our department from January 2016 to June 2017. All enrolled patients were grouped in either HIPEC or non-HIPEC groups. Clinical data were collected and analyzed.

Results: A total of 129 patients were enrolled with 61 cases in the HIPEC group and 68 in the non-HIPEC group. The two groups were well balanced in terms of clinical characteristics. In patients of the HIPEC group, three suffered leakage from the duodenal stump or anastomosis, one suffered abnormal bleeding and two were found to have abnormal routine blood tests; no significant difference in adverse events between groups, however, was noted ( > 0.05) and most patients recovered uneventfully. During follow-up, peritoneal recurrence was significantly less among HIPEC patients ( = 0.029), with only three suffering peritoneal recurrence, as compared to 12 non-HIPEC patients. In addition, the estimated illness-specific 3-year disease-free survival rate was significantly higher in the HIPEC group as compared to the non-HIPEC group (89.4% vs.73.9%; = 0.031).

Conclusion: Lobaplatin in prophylactic HIPEC is safe for advanced gastric cancer patients after treatment by radical resection and can effectively improve illness-specific 3-year disease-free survival.
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http://dx.doi.org/10.2147/CMAR.S249838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334017PMC
June 2020

NLR-A Simple Indicator of Inflammation for the Diagnosis of Left Ventricular Hypertrophy in Patients with Hypertension.

Int Heart J 2020 Mar 14;61(2):373-379. Epub 2020 Mar 14.

Department of Cardiology, Tianjin Medical University General Hospital.

We aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), brain natriuretic peptide (BNP), and left ventricular hypertrophy (LVH) in hypertension.

Methods: This study included 386 patients with hypertension. Mann-Whitney U test and multivariate binary logistic regression analysis were used to investigate the relationship between NLR, CRP, BNP, and LVH in patients with hypertension, as well as compare the levels of NLR, CRP, and BNP in the four configurations. Receiver operator characteristic (ROC) curve was used to compare the diagnostic efficacy of NLR, CRP, and BNP on LVH.

Results: The NLR and CRP and BNP levels of the LVH group were significantly higher than those of the non-LVH group. In the multivariate logistic regression analysis, NLR as well as age, BMI, and SBP were associated with LVH. In addition, in patients with eccentric and concentric hypertrophy, the NLR and CRP and BNP levels were higher than those of the normal left ventricular geometry and concentric remodeling groups. The cutoff values of NLR, CRP, and BNP obtained by ROC curve were 2.185, 2.205, and 283.45, respectively, for the prediction of LVH.

Conclusions: NLR is independently associated with LVH in patients with hypertension, and this is consistent with the diagnostic efficacy of CRP and BNP, which may be a simple and convenient indicator for judging LVH.
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http://dx.doi.org/10.1536/ihj.19-138DOI Listing
March 2020

Clinicopathological Characteristics and Prognosis of Proximal and Distal Gastric Cancer during 1997-2017 in China National Cancer Center.

J Oncol 2019 13;2019:9784039. Epub 2019 Jun 13.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: The prognostic relevance of gastric tumor location has been reported and debated. Our study was conducted to examine the differences in clinicopathological features, prognostic factors, and overall survival (OS) between patients with proximal gastric cancer (PGC) and distal gastric cancer (DGC).

Patients And Methods: Patients with PGC or DGC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1997-2017. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models.

Results: We reviewed 16,119 cases of gastric cancer patients, including 6,479 of PGC and 9,640 of DGC. PGC patients presented as older patients (61.5 versus 56.4 years, 0.001) and more males (82.9% versus 68.2%, <0.001). Compared with DGC, PGC was more likely to be in later pT stage (pT3 and pT4, 65.0% versus 52.8%, <0.001) and lymph node metastasis (54.8% versus 50.9%, <0.001). In univariate analysis, PGC patients had a worse survival outcome in stage I (Hazard ratio [HR] = 2.04, 95% CI: 1.42-2.94) but a better prognosis in stage IV (HR = 0.85, 95% CI: 0.73-0.98) when compared to DGC patients. However, multivariate analysis demonstrated that PGC was not an independent predictor for poor survival (HR = 1.07, 95% CI: 1.00-1.14). Results from multivariate analysis also revealed that pT4, lymph node metastasis, distant metastasis, no gastrectomy, and Borrmann IV were independent predictors associated with poor survival for both PGC and DGC patients. Additional prognostic factors for PGC patients included underweight (BMI < 18.5) (HR = 1.29, 95% CI: 1.06-1.58), linitis plastica (HR = 2.13, 95% CI: 1.25-3.65), and overweight (23 ≤ BMI <27.5) (HR = 0.80, 95% CI: 0.71-0.90). During the 20-year study period, the 5-year OS increased significantly for both PGC and DGC, with the increase rate of 91.7% and 67.7%, respectively.

Conclusion: In China, PGC significantly differed from DGC in clinicopathological characteristics and prognostic factors. However, there was no significant relationship between survival outcome and gastric tumor location.
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http://dx.doi.org/10.1155/2019/9784039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595386PMC
June 2019

Zinc improves mitochondrial respiratory function and prevents mitochondrial ROS generation at reperfusion by phosphorylating STAT3 at Ser.

J Mol Cell Cardiol 2018 05 30;118:169-182. Epub 2018 Mar 30.

Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Serine 727 (Ser) phosphorylation of STAT3 plays a role in the regulation of mitochondrial respiration. This study aimed to test if zinc could regulate mitochondrial respiration through phosphorylation of STAT3 at Ser in the setting of ischemia/reperfusion in the heart. Under normoxic conditions, treatment of isolated rat hearts with ZnCl increased cytosolic STAT3 phosphorylation at Ser followed by phospho-STAT3 translocation to mitochondria. In isolated rat hearts subjected to 30 min regional ischemia followed by 20 min of reperfusion, ZnCl given 5 min before the onset of reperfusion also increased mitochondrial phospho-STAT3. ZnCl enhanced ERK phosphorylation and PD98059 reversed the effect of ZnCl on STAT3 phosphorylation. ZnCl improved the mitochondrial oxidative phosphorylation at reperfusion. This effect was abolished by STAT3S727A, a mutant in which Ser is replaced with alanine, in H9c2 cells subjected to hypoxia/reoxygenation. In addition, ZnCl increased the mRNA level of the complex I subunit ND6, which was also reversed by STAT3S727A. Moreover, ZnCl attenuated mitochondrial ROS generation and dissipation of mitochondrial membrane potential (ΔΨm) at reoxygenation through Ser phosphorylation. Finally, ZnCl suppression of succinate dehydrogenase (SDH) activity upon the onset of reperfusion was nullified by the Ser mutation. In conclusion, zinc improves cardiac oxidative phosphorylation and inhibits mitochondrial ROS generation at reperfusion by increasing mitochondrial STAT3 phosphorylation at Ser via ERK. The preservation of ND6 mtDNA and the inhibition of SDH activity may account for the role of STAT3 in the beneficial action of zinc on the mitochondrial oxidative phosphorylation and ROS generation at reperfusion.
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http://dx.doi.org/10.1016/j.yjmcc.2018.03.019DOI Listing
May 2018

Anthropometric Indices Predict the Development of Hypertension in Normotensive and Pre-Hypertensive Middle-Aged Women in Tianjin, China: A Prospective Cohort Study.

Med Sci Monit 2018 Mar 30;24:1871-1879. Epub 2018 Mar 30.

Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China (mainland).

BACKGROUND The aims of this study were to investigate the relationship between optimal anthropometric indices and their cut-off values and the incidence of hypertension in a cohort of middle-aged women in China. MATERIAL AND METHODS A cohort of 812 women, aged between 40-70 years were recruited between May 2011 and June 2013. An ideal baseline blood pressure was defined as <120/80 mmHg; pre-hypertension was 120-139/80-89 mmHg; hypertension was ≥140/≥90 mmHg. Anthropometric measurements included waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), and waist-height ratio (WHtR). The cohort was divided into an ideal blood pressure group (Group 1) and a pre-hypertensive group (Group 2). Two-year follow-up blood pressure measurements were performed. Receiver-operating characteristic (ROC) curve analysis determined the optimal anthropometric indices and cut-off values for developing hypertension. RESULTS At two-year follow-up, hypertension developed in 9.0% (n=31) in Group 1 and 32.3% (n=121) in Group 2. Logistic regression analysis showed that in both groups, women in the highest quartile for WC, BMI, WHR, and WHtR had a significantly increased risk of developing hypertension compared with the lowest quartile (P<0.05). ROC curve area under the curve (AUC) for these anthropometric indices were greater in Group 1, and for WC in Groups 1 and 2, with the optimal cut-off values greater in Group 1. CONCLUSIONS In a cohort of middle-aged women in China, anthropometric indices of obesity were predictive of the development of hypertension during a two-year follow-up period.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892460PMC
http://dx.doi.org/10.12659/msm.908257DOI Listing
March 2018

Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the setting of hypoxia/reoxygenation in cardiac cells.

Free Radic Res 2018 Jan 19;52(1):80-91. Epub 2017 Dec 19.

a Department of Physiology and Pathophysiology , Tianjin Medical University , Tianjin , China.

Zinc plays a role in autophagy and protects cardiac cells from ischemia/reperfusion injury. This study aimed to test if zinc can induce mitophagy leading to attenuation of mitochondrial superoxide generation in the setting of hypoxia/reoxygenation (H/R) in cardiac cells. H9c2 cells were subjected to 4 h hypoxia followed by 2 h reoxygenation. Under normoxic conditions, treatments of cells with ZnCl increased both the LC3-II/LC3-I ratio and GFP-LC3 puncta, implying that zinc induces autophagy. Further experiments showed that endogenous zinc is required for the autophagy induced by starvation and rapamycin. Zinc down-regulated TOM20, TIM23, and COX4 both in normoxic cells and the cells subjected to H/R, indicating that zinc can trigger mitophagy. Zinc increased ERK activity and Beclin1 expression, and zinc-induced mitophagy was inhibited by PD98059 and Beclin1 siRNA during reoxygenation. Zinc-induced Beclin1 expression was reversed by PD98059, implying that zinc promotes Beclin1 expression via ERK. In addition, zinc failed to induce mitophagy in cells transfected with PINK1 siRNA and stabilized PINK1 in mitochondria. Moreover, zinc-induced PINK1 stabilization was inhibited by PD98059. Finally, zinc prevented mitochondrial superoxide generation and dissipation of mitochondrial membrane potential (ΔΨ) at reoxygenation, which was blocked by both the Beclin1 and PINK1 siRNAs, suggesting that zinc prevents mitochondrial oxidative stress through mitophagy. In summary, zinc induces mitophagy through PINK1 and Beclin1 via ERK leading to the prevention of mitochondrial superoxide generation in the setting of H/R. Clearance of damaged mitochondria may account for the cardioprotective effect of zinc on H/R injury.
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http://dx.doi.org/10.1080/10715762.2017.1414949DOI Listing
January 2018

Effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma mortality: A retrospective cohort study consisting of 1783 patients.

Sci Rep 2017 08 29;7(1):9572. Epub 2017 Aug 29.

Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

The effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma (PDAC) mortality are contradictory. Individuals who were diagnosed as PDAC and hospitalized at the China National Cancer Center between January 1999 and January 2016 were identified and included in the study. Ultimately, 1783 consecutive patients were included in the study. Patients were categorized as never, ex-drinkers/smokers or current drinkers/smokers. Hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Compared with never drinkers, the HRs were 1.25 for ever drinkers, 1.24 for current drinkers, and 1.33 for ex-drinkers (trend P = 0.031). Heavy drinking and smoking period of 30 or more years were positive prognostic factors for PDAC. For different smoking and alcohol drinking status, only subjects who are both current smokers and current drinkers (HR, 1.45; 95% CI, 1.03-2.05) were associated with reduced survival after PDAC compared to those who were never smokers and never drinkers. Patients who are alcohol drinkers and long-term smokers before diagnosis have a significantly higher risk of PDAC mortality. Compared to those who neither smoker nor drink, only patients who both smokers and drinkers were associated with reduced survival from PDAC.
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http://dx.doi.org/10.1038/s41598-017-08794-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574975PMC
August 2017

The relationship between S-adenosylhomocysteine and coronary artery lesions: A case control study.

Clin Chim Acta 2017 Aug 4;471:314-320. Epub 2017 Jul 4.

Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

The role of homocysteine (Hcy) in the pathogenesis of coronary artery disease (CAD) is controversial, as decreased Hcy levels have not demonstrated consistent clinical benefits. Recent studies propose that S-adenosylhomocysteine (SAH), and not Hcy, plays a role in cardiovascular disease (CVD). We aimed to assess the relationship between plasma SAH and coronary artery lesions. Participants (n=160; aged 40-80years) with chest pain and suspected CAD underwent coronary angiography (CAG) for assessment of coronary artery stenosis, and were assigned to either the atherosclerosis (AS) or CAD group. Plasma SAH and S-adenosylmethionine (SAM) concentrations were measured and the association between coronary artery lesions and SAH was assessed. SAH levels were significantly higher in the CAD group (23.09±2.4nmol/L) than in the AS group (19.2±1.5nmol/L). While the AS group had higher values for SAM/SAH (5.1±0.7 vs. 4.1±1.1), levels of SAM, Hcy, folate, and vitamin B12 were similar in the two groups. Coronary artery lesions were associated with SAH (β=11.8 [95% CI: 5.88, 17.7, P<0.05]. Plasma SAH concentrations are independently associated with coronary artery lesions among patients undergoing coronary angiography. Plasma SAH might be a novel biomarker for the early clinical identification of CVD.
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http://dx.doi.org/10.1016/j.cca.2017.07.001DOI Listing
August 2017

Association of microalbuminuria with diabetes is stronger in people with prehypertension compared to those with ideal blood pressure.

Nephrology (Carlton) 2018 Jul;23(7):690-696

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Aim: Microalbuminuria (MA) has been demonstrated as a biomarker for microvascular dysfunction. This study is aimed to evaluate the association of glycaemic status with MA in prehypertensive and ideal BP subjects and to evaluate the interaction between glycaemic and blood pressure status as risk factors for MA prevalence.

Methods: 1059 subjects aged 40-70 with non-hypertension who were recruited from six districts of Tianjin were divided into a prehypertensive group (622 cases) and an ideal blood BP group (437 cases). Subjects of the prehypertensive group and the ideal BP group were divided respectively into three subgroups: normoglycaemia subgroup, prediabetes subgroup and diabetes subgroup. The prevalence of MA in the above three subgroups of subjects with prehypertension and ideal BP were assessed. We performed a statistical analysis for interaction test between glycaemia and BP status on microalbuminuria in the overall study sample by a multivariate logistic regression model. The association of glycaemic status (defined as normoglycaemia, prediabetes, and diabetes) with MA was evaluated separately in prehypertensive and ideal BP subjects.

Results: Results showed that the prevalence of MA in both prehypertensive and ideal BP groups rose with the increasing of classification of glycaemic level of subgroups (32.6%, 18.3%, 14.8% vs. 23.1%, 16.2%, 13.4%), the differences in prehypertensive group were statistically significant (Pearson χ = 15.24, P < 0.001). The ORs (95% CI) of MA were 1.25 (0.86-1.83) for prediabetes and 2.56 (1.62-4.03) for diabetes in the fully adjusted model. There was no interaction between prediabetes and BP status regarding MA (P = 0.237) but we found a significant interaction between diabetes and BP status (P < 0.001). In the prehypertensive group, multivariate logistic regression models showed that the diabetes subgroup had a significant association with MA, and the adjusted odds ratio of the diabetes subgroup to the normoglycaemia subgroup was 2.68 (95%CI 1.54-4.67) (P < 0.001). However, there was no significant association of glycaemic status with MA in the ideal BP group. Stratified analysis by a multivariate logistic regression model in the whole study population showed that people with both prehypertension and diabetes had the highest risk of MA (adjusted OR = 2.50, 95%CI 1.16-5.36; P = 0.019), compared with those with ideal BP and normoglycaemia (reference group).

Conclusions: Our findings suggest that there was a statistically significant association between diabetes and microalbuminuria only in prehypertensive subjects. In addition, our study highlights the interaction between prehypertension and diabetes as a risk factor for MA.
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http://dx.doi.org/10.1111/nep.13082DOI Listing
July 2018

The Relationship Between Serum Zinc Levels, Cardiac Markers and the Risk of Acute Myocardial Infarction by Zinc Quartiles.

Heart Lung Circ 2018 Jan 12;27(1):66-72. Epub 2017 Mar 12.

Department of Cardiology, Tianjin Medical University General Hospital, China. Electronic address:

Background: Zinc is one of the most important microelements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and cardiac markers, and the risk of acute myocardial infarction (AMI) by zinc quartiles.

Methods: We enrolled a total of 529 patients and measured their serum zinc levels and cardiac markers. We performed further studies after dividing subjects into four groups according to their concentrations of zinc by quartile to clarify the relationship between zinc levels and risk of increased acute myocardial infarction prevalence rate.

Results: We observed that there was a significant inverse linear relationship between zinc and Lg(creatine kinase) (p=0.011), Lg(creatine kinase-MB) (p=0.002) and Lg(cardiac troponin T) (p=0.045). In addition, the acute myocardial infarction prevalence rates were 28.8%, 24.8%, 20.5%, and 18.2% by patients with zinc quartiles, respectively. Multivariate logistic regression analysis showed that the odds ratio between the lowest and highest zinc quartile groups was 1.92 (1.019-3.604) (p<0.05).

Conclusions: The present study revealed a relationship between serum zinc levels in that zinc levels were significantly inversely correlated with serum creatine kinase (CK), creatine kinase-MB (CKMB) and cardiac troponin T (cTnT) levels. Furthermore, we found that the prevalence rate of acute myocardial infarction decreased with increasing zinc quartiles.
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http://dx.doi.org/10.1016/j.hlc.2017.01.022DOI Listing
January 2018

Adenosine A receptor activation ameliorates mitochondrial oxidative stress upon reperfusion through the posttranslational modification of NDUFV2 subunit of complex I in the heart.

Free Radic Biol Med 2017 05 20;106:208-218. Epub 2017 Feb 20.

Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070, China. Electronic address:

While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion. NECA prevented mitochondrial structural damage, decreases in respiratory control ratio (RCR), and collapse of mitochondrial membrane potential (ΔΨm). Both the adenosine A receptor antagonist SCH58261 and A receptor antagonist MRS1706 inhibited the action of NECA. NECA reduced mitochondrial proteins carbonylation, HO, and superoxide generation at reperfusion, but did not change superoxide dismutase (SOD) activity. In support, the protective effects of NECA and Peg-SOD on ΔΨm upon reperfusion were additive, implying that NECA's protection is attributable to the reduced superoxide generation but not to the enhancement of the superoxide-scavenging capacity. NECA increased the mitochondrial Src tyrosine kinase activity and suppressed complex I activity at reperfusion in a Src-dependent manner. NECA also reduced mitochondrial superoxide through Src tyrosine kinase. Studies with liquid chromatography-mass spectrometer (LC-MS) identified Tyr118 of the NDUFV2 subunit of complex 1 as a likely site of the tyrosine phosphorylation. Furthermore, the complex I activity of cells transfected with the Y118F mutant was increased, suggesting that this site might be a negative regulator of complex I activity. In support, NECA failed to suppress complex I activity at reperfusion in cells transfected with the Y118F mutant of NDUFV2. In conclusion, NECA prevents mitochondrial oxidative stress by decreasing mitochondrial superoxide generation through inhibition of complex I via the mitochondrial Src tyrosine kinase. Phosphorylation of Tyr residue in NDUFV2 subunit may account for the inhibitory effect of NECA on complex I.
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http://dx.doi.org/10.1016/j.freeradbiomed.2017.02.036DOI Listing
May 2017

Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer: Retrospective cohort study, 7-year experience with 247 patients at the National Cancer Center in China.

Medicine (Baltimore) 2016 Sep;95(38):e4861

Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, China National Cancer Center, Beijing, China School of Public Health, Yale University, New Haven, CT.

To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT.A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center.Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47-0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32-0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04-0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment.Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044898PMC
http://dx.doi.org/10.1097/MD.0000000000004861DOI Listing
September 2016

Zinc Levels in Left Ventricular Hypertrophy.

Biol Trace Elem Res 2017 Mar 25;176(1):48-55. Epub 2016 Jul 25.

Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.

Zinc is one of the most important trace elements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and left ventricular hypertrophy (LVH). A total of 519 patients was enrolled and their serum zinc levels were measured in this study. We performed analyses on the relationship between zinc levels and LVH and the four LV geometry pattern patients: normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH. We performed further linear and multiple regression analyses to confirm the relationship between zinc and left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). Our data showed that zinc levels were 710.2 ± 243.0 μg/L in the control group and were 641.9 ± 215.2 μg/L in LVH patients. We observed that zinc levels were 715 ± 243.5 μg/L, 694.2 ± 242.7 μg/L, 643.7 ± 225.0 μg/L, and 638.7 ± 197.0 μg/L in normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH patients, respectively. We further found that there was a significant inverse linear relationship between zinc and LVM (p = 0.001) and LVMI (p = 0.000) but did not show a significant relationship with RWT (p = 0.561). Multiple regression analyses confirmed that the linear relationship between zinc and LVM and LVMI remained inversely significant. The present study revealed that serum zinc levels were significantly decreased in the LVH patients, especially in the eccentric LVH and concentric LVH patients. Furthermore, zinc levels were significantly inversely correlated with LVM and LVMI.
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http://dx.doi.org/10.1007/s12011-016-0808-yDOI Listing
March 2017

Efficacy and safety of fenofibrate as an add-on in patients with elevated triglyceride despite receiving statin treatment.

Int J Cardiol 2016 Oct 29;221:832-6. Epub 2016 Jun 29.

Department of Cardiology, Jinshan Hospital Fudan University, 1508 Longhang Road, Shanghai 201508, China.

Background: Since the withdrawal of cerivastatin, statin-fibrate combination therapy has been questioned in China due to safety concern. The objective of this study was to evaluate the efficacy and safety profile of fenofibrate as an add-on in patients with dyslipidemia despite receiving statin therapy.

Methods: This was a prospective, multi-center, single-arm, open-label study conducted in Chinese dyslipidemia patients with high CV risk. Fenofibrate (200mg daily) was added to the existing statin treatment for 8weeks. Lipid profile and safety parameters were measured and compared between baseline and after the treatment. Five hundred and six subjects were enrolled from 28 sites from 14 cities nationwide across China.

Results: After 8weeks of fenofibrate treatment, the mean blood triglyceride level decreased to 1.77mmol/L (38.1% reduction vs. 3.00mmol/L at the baseline; p<0.01). Mean high-density lipoprotein cholesterol (high density lipoprotein cholesterol) was increased to 1.22mmol/L (by 17.4% from 1.07mmol/L at the baseline; p<0.01). No case of severe muscle damage (defined as elevated creatine kinase over 5 times of upper limit of normal (ULN) or rhabdomyolysis was observed.

Conclusion: In statin-treated patients with high CV risk who had elevated triglyceride, adding fenofibrate could improve lipid profile with acceptable safety profiles.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.234DOI Listing
October 2016

Association of self-reported sleep duration and hypertension: Results of a Chinese prospective cohort study.

Clin Exp Hypertens 2016;38(6):514-9. Epub 2016 Jul 8.

a Department of Cardiology , Tianjin Medical University General Hospital , Tianjin , China.

Objectives: To examine the association of self-reported sleep duration and hypertension using the data from Tianjin China.

Methods: Participants aged 40-70 years without hypertension were recruited with a stratified cluster sampling method across six districts of Tianjin, China. Information regarding their sociodemographic and lifestyle-related characteristics was gathered by questionnaires. After 2 years of follow-up, the second physical examination was taken on the same crowd.

Results: During the 2-year period, 874 subjects (221 men, 653 women) were successfully contacted. Multivariate logistic regression was used to analyze the relationship between the frequency of incident hypertension after the 2-year follow-up and sleep duration according to age groups. Among the younger age group (40-<55 years), a short sleep duration (≤ear h) was associated with a significantly higher risk of hypertension compared with sleeping for 7-8 h in unadjusted analyses (OR: 3.15 [95% CI: 1.04-9.54]). In a model after adjustment for the impact factors, a significant difference was also found in the frequency of incident hypertension.

Conclusions: In our study, a short sleep duration (≤sho h) is a significant risk factor for hypertension in younger subjects, with no association among older subjects.
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http://dx.doi.org/10.3109/10641963.2016.1163367DOI Listing
December 2016

Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma.

Tumour Biol 2016 Feb 15;37(2):2333-9. Epub 2015 Sep 15.

Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Science, Beijing, 100021, China.

This study investigated the correlation between the expression of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and the prognosis of gastric carcinoma patients. A total of 156 paired tumor and matched normal samples were collected from patients of gastric carcinoma who underwent surgical resection. The expression of PDK1 was analyzed by real-time quantitative PCR and immunohistochemistry method. Potential correlation between PDK1 protein expression and the clinicopathological characteristics was determined by chi-square test and Spearman correlation analysis. The influence of PDK1 expression on 5-year survival rate and survival length was determined by Kaplan-Meier analysis. The expression of PDK1 mRNA and protein were significantly higher in tumor samples comparing to those in adjacent normal samples (paired t test, P = 0.007). Immunohistochemical staining results indicated that PDK1 protein level was positively correlated with infiltration (P = 0.006). However, no associations with age, sex, clinical stage, lymph node metastasis, and distant metastasis were observed (P > 0.05). The 5-year survival rate was 20.1 and 63.4 % of the patients with high and low expression level of PDK1, respectively (P < 0.05). The median survival length was 32.5 months (95 % CI 22.8-37.6) for patients with high level of PDK1 and 63.1 months (95 % CI 52.3-64.7) for patients with low level of PDK1 (×2 = 20.153, P < 0.05). Kaplan-Meier survival curves demonstrated that elevated expression of PDK1 was an independent negative prognostic factor of gastric carcinoma (P<0.05). Our study indicated that PDK1 might serve as a candidate pro-oncogene and a potential prognostic biomarker for gastric carcinoma.
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http://dx.doi.org/10.1007/s13277-015-4024-8DOI Listing
February 2016

Elevated Serum Level of Interleukin 17 in a Population With Prehypertension.

J Clin Hypertens (Greenwich) 2015 Oct 3;17(10):770-4. Epub 2015 Jul 3.

Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.

Cytokines play an important role in the pathogenesis of hypertension. The authors hypothesized that interleukin 17 (IL-17) might contribute to the prehypertensive state. This study evaluated the relationship between serum levels of IL-17 and prehypertension. A total of 394 participants were enrolled, after excluding for hypertension or treated hypertension, and divided into two groups (optimal blood pressure [BP] and prehypertension) based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification of BP. Optimal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg. Prehypertension was defined as systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg. IL-17A levels were determined by enzyme-linked immunosorbent assay. The mean serum IL-17 concentration in the prehypertension group was significantly higher than in the optimal BP group. The cohort was divided into quartiles Q1 (≤3.5 ng/L), Q2 (3.60 to 6.10 ng/L), Q3 (6.20 to 10.00 ng/L), and Q4 (≥10.10 ng/L) based on IL-17 levels. The Q2 to Q4 groups had increasing odds ratios for having prehypertension compared with the Q1 group. Elevated serum IL-17 was accompanied by a rise in systolic BP. Thus, increased serum IL-17 levels are associated with prehypertension.
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http://dx.doi.org/10.1111/jch.12612DOI Listing
October 2015

[Application value of core needle biopsy technique in the pathological diagnosis of locally advanced pancreatic cancer].

Zhonghua Yi Xue Za Zhi 2015 Apr;95(14):1093-5

Department of Abdominal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing 100021, China; Email:

Objective: To explore the application value of core needle biopsy technique in the pathological diagnosis of locally advanced pancreatic cancer patients.

Methods: During April 2007 to April 2014, retrospective analysis was conducted for 36 patients of locally advanced pancreatic cancer to summarize the clinical data of core needle biopsy technique. And the relevant data included clinical features, pathological findings and puncture-related complications. Regular postoperative follow-ups were conducted.

Results: All received pathological examination of core needle biopsy. And the pathological diagnoses were pancreatic cancer (n=29), pancreatic neuroendocrine tumors (n=2) and chronic pancreatitis (n=5). During the follow-ups, liver metastasis was pathologically confirmed postoperatively at Months 4 and 6 months among 5 chronic pancreatitis patients. The remainder was followed up for over 12 months. There was neither change in size nor metastasis. One case was diagnosed at Peking Union Hospital as autoimmune pancreatitis while another 2 cases had a clinical diagnosis of chronic pancreatitis. The accuracy of core needle puncture was 94.4%. There were 2 cases of postoperative pancreatic fistula in class A. Bleeding complication was absent.

Conclusion: The application of core needle biopsy technique is both safe and effective in the pathological diagnosis of locally advanced pancreatic cancer.
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April 2015

Does elevated serum uric acid level predict the hypertension incidence? A Chinese prospective cohort study.

Clin Exp Hypertens 2015 28;37(6):498-504. Epub 2015 Apr 28.

a Department of Cardiology , Tianjin Medical University General Hospital , Tianjin , China and.

Background And Aims: Hyperuricemia is an independent risk factor for hypertension. This study aims to investigate whether SUA predicts 2-year incidence of hypertension in population with pre-hypertension and ideal blood pressure in Tianjin, China.

Methods And Results: In this population-based prospective study, we analyzed 608 subjects (455 women) aged 40-70 with non-hypertension (SBP < 140 mmHg and DBP < 90 mmHg) who were recruited with stratified cluster sampling method across six districts of Tianjin in 2011-2012. Participants were divided into pre-hypertensive group (group P) and ideal blood pressure group (group I) according to their first physical examination. After 2 years follow-up, the second physical examination was taken on the same crowd. The 2-year hypertension incidence rate in group P (35.6%) was higher than that of group I (8.3%) (p < 0.05). In group P, the hypertension incidence rate increased with the increase of SUA quartiles. Multivariate logistic regression analysis showed that the odd ratio (OR) between the highest SUA quartile group and the lowest SUA quartile group in group P were 2.02 (1.04-3.92), 3.34 (1.10-10.04) in men and 2.43 (1.08-5.45) in women (p < 0.05). However, there is no significant correlation between SUA and the risk for hypertension incidence in group I. Multiple linear regression showed that the SBP increased 0.017 mmHg with the increasing of 1 μmol/L deviation of SUA in group P.

Conclusions: SUA levels predict SBP elevation and hypertension incidence in population with pre-hypertension, however, do not predict the DBP elevation in pre-hypertensive population as well as change of BP in ideal blood pressure population.
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http://dx.doi.org/10.3109/10641963.2015.1013121DOI Listing
August 2016

Prognostic value of plasma galectin-3 levels in patients with coronary heart disease and chronic heart failure.

Int Heart J 2015 May 23;56(3):314-8. Epub 2015 Apr 23.

Department of Cardiology, Tianjin Medical University General Hospital.

In this study, we evaluated the prognostic value of plasma galectin-3 levels in patients with coronary heart disease (CHD) and chronic heart failure (HF) and selected 261 CHD patients who were consecutively admitted to our hospital. The enrolled chronic HF patients included HF patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Patients without HF served as the control group. Galectin-3 and B-type natriuretic peptide (BNP) levels were determined and the primary endpoint was the composite of all-cause mortality and rehospitalization with 12-month follow-up. Plasma galectin-3 levels were higher in HF patients compared with non-HF patients (P < 0.001). Receiver operating characteristic (ROC) analyses for diagnosis of HF showed that galectin-3 had the greatest area under the curve (AUC) of 0.756 (P < 0.001), with an optimal cutoff of 10.8 ng/mL, yielding a sensitivity of 81.7% and a specificity of 61.7%. Follow-up ROC analyses of galectin-3 for outcome prediction showed an optimal cutoff of 17.8 ng/ mL, yielding a sensitivity of 97.3% and a specificity of 77.6%. Galectin-3 yielded an AUC of 0.899 (P < 0.001), whereas the AUC of BNP was 0.633 (P = 0.022). Galectin-3 led to an AUC of 0.931 (P < 0.001) for HFpEF and an AUC of 0.882 (P < 0.001) for HFrEF. Cox proportional hazards regression analysis revealed that galectin-3 was an independent prognostic predictor for chronic HF, especially for HFpEF patients (RR: 1.231, 95% CI: 1.066-1.442). In summary, plasma galectin-3 levels were increased in CHD HF patients and were an independent predictor of all-cause mortality and rehospitalization. In HFpEF patients galectin-3 levels correlated stronger with outcomes than in HFrEF patients.
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http://dx.doi.org/10.1536/ihj.14-304DOI Listing
May 2015

High prevalence of metabolic syndrome in a middle-aged and elderly population with prehypertension in Tianjin.

Clin Exp Hypertens 2015 12;37(5):369-74. Epub 2014 Dec 12.

Department of Cardiology, Tianjin Medical University General Hospital, Tianjin Medial University , Tianjin , China.

Background: Prehypertension has been reported as being correlated with future cardiovascular risk and end-organ damage in middle-aged and elderly persons, and also playing an important role in metabolic syndrome (MetS). The association between prehypertension and MetS has rarely been reported among urban adults in Tianjin, China.

Methods: In this cross-sectional study, a total of 1176 participants aged 40-70 years (524 males and 652 females) were enrolled after excluding participants with hypertension or treated hypertension. Participants were divided into two groups [optimal blood pressure (BP) and prehypertension] based on the classification of BP from the JNC-7. The definition of MetS was as per the International Diabetes Federation standard. An adjusted logistic regression model was used to assess relationships between prehypertension and MetS.

Results: The prehypertension group had a significantly higher odds ratio (OR) than the optimal BP group for abnormal waist circumference (WC), fasting plasma glucose (FPG) and triglycerides (TG). In addition, the prehypertension group had a higher OR (3.12; 95% confidence interval 2.34-4.18) for having MetS after adjusting for potential confounders.

Conclusions: The risk of having MetS was significantly associated with prehypertension in middle-aged and elderly persons in Tianjin. Stricter control of BP in this age group is warranted.
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http://dx.doi.org/10.3109/10641963.2014.977487DOI Listing
August 2016

Association of cardiometabolic risk profile with prehypertension accompany hyperhomocysteinaemia.

Clin Exp Hypertens 2015 22;37(3):218-22. Epub 2014 Jul 22.

Department of Cardiology, Tianjin Medical University General Hospital , Tianjin , People's Republic of China.

Background: Study suggested that elevated homocysteine showed a multiplicative effect on cardiovascular diseases in hypertensive subjects. It was reported that elevated homocysteine level was independently associated with increased arterial stiffness in prehypertensives. It remains unclear whether prehypertensives combined with elevated homocysteine have adverse cardiovascular risk factors. We aimed to compare cardiometabolic risk profile between prehypertensives with hyperhomocysteinaemia and those without either condition.

Methods: Plasma total homocysteine and risk profile were determined among 874 Chinese non-hypertension individuals in Tianjin. They were subdivided into four groups: prehypertension with hyperhomocysteinaemia (≥10 μmol/L), prehypertension with normal homocysteine (<10 μmol/L), normotension with hyperhomocysteinaemia, normotension with normol homocysteine, respectively.

Results: In 874 participants, 22.5% of them were male, mean age was 56.8 years. In multiple comparisons, after adjustment for age, gender, smoking, alcohol, exercise, education prehypertensives had higher body mass index (BMI) and high sensitive C reactive protein (hs-CRP) than normotensives (p < 0.05, respectively); Only prehypertensive subjects with hyperhomocysteinaemia had higher triglyceride and serum uric acid compared to normotensive subjects, and lower HDL cholesterol than normotensives with normal homocysteine (p < 0.05, respectively). However, the significance of higher hs-CRP, uric acid and lower HDL cholesterol were abolished when further adjustment was made for BMI.

Conclusion: The combination of prehypertension and hyperhomocusteinaemia increases the likelihood of having adverse cardiometabolic risk profile. Strict lipid management and weigh control may be needed in prehypertensives with elevated homocysteine.
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http://dx.doi.org/10.3109/10641963.2014.939276DOI Listing
January 2016

Detecting diabetic risk using the oral glucose tolerance test in Chinese patients with hypertension: a cross-sectional study.

Hypertens Res 2014 Jan 17;37(1):82-7. Epub 2013 Oct 17.

Department of Hypertension and endocrinology, Daping Hospital of Chongqing, Chongqing, China.

To analyze the clinical significance of the oral glucose tolerance test (OGTT) in the assessment of abnormal glucose metabolism in Chinese patients with hypertension. In this cross-sectional study of 10,173 hypertensive adult patients from eight sites in China, data on patient, clinical and disease characteristics were collected, and fasting plasma glucose (FPG) levels were measured. A subset of 5322 patients also underwent an OGTT. Abnormal glucose metabolism (impaired glucose regulation (IGR) or diabetes mellitus (DM)) was detected in 31.1% of the 10,173 patients by FPG testing and in 67% of the 5322 patients by OGTT. OGTT increased the detection rate by 35.8%. Patients with FPG levels ≥5.6 and ≥6.1 mmol l(-1) had the mean OGTT 2-h plasma glucose levels of 8.79 and 9.68 mmol l(-1), respectively. Compared with normoglycemic patients, those with IGR or DM had higher rates of total proteinuria (normoglycemic 15.8% vs. IGR 22.1% vs. DM 33.7%, P<0.001), a lower absolute estimated glomerular filtration rate (eGFR; in ml min(-1) per 1.73 m(2)) (82.9 vs. 80.77 vs. 79.74, P=0.06) and a higher prevalence of cardiovascular disease (normoglycemic 17.6% vs. IGR/DM 13.8%, P<0.001). Abnormal abdominal circumference, eGFR ≤60 ml min(-1) per 1.73 m(2), and proteinuria were independently associated with abnormal glucose metabolism (IGR or DM). Hypertensive patients who are diabetic or at risk of diabetes are at greater risk of renal damage and cardiovascular disease than those who are normoglycemic. It is insufficient to assess the glucose metabolism status of Chinese hypertensive patients using only FPG testing; the use of OGTT can increase the detection rate by 35.8%. Patients whose FPG levels were <5.6 mmol l(-1) may be found to have abnormal glucose metabolism after an OGTT.
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http://dx.doi.org/10.1038/hr.2013.126DOI Listing
January 2014

Derlin-1 is overexpressed on the tumor cell surface and enables antibody-mediated tumor targeting therapy.

Clin Cancer Res 2008 Oct;14(20):6538-45

Department of Cell and Molecular Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.

Purpose: Tumor targeting therapy is one of the most promising strategies for anticancer treatment. Derlin-1 has been reported to participate in misfolded protein dislocation and integrates into the endoplasmic reticulum (ER) membrane to survey for such protein aggregates. We elucidate herein that Derlin-1 can leak to the plasmalemma from the ER in tumor cells and may have clinical application as a novel cancer target in the hope of developing a new tumor targeting therapy.

Experimental Design: The cell surface expression of Derlin-1 was shown by immunofluorescence analysis of nonpermeabilized cells and Western blotting of fractional proteins of tumor cells. Derlin-1 expression in cancerous tissues was also shown by immunohistochemistry. Biodistribution analysis and gamma-scintigraphic imaging were done using (125)I-labeled Derlin-1 targeting antibody in isogenic mice models. Finally, tumor-bearing mice were treated by the anti-Derlin-1 polyclonal antibody and monoclonal antibodies.

Results: Derlin-1 was expressed on various tumor cell surfaces and adopted a homodimer conformation. Robust cytoplasmic and membrane expression of Derlin-1 was detected in various types of human cancers tissues but was not correlated with any clinicopathologic features of pancreatic cancer. Derlin-1 directed antibodies specifically targeted to colon tumors and significantly suppress tumor growth in isogenic mice.

Conclusions: These preclinical data show that Derlin-1 protein is a functional molecular target expressed on the tumor cell surface and is a candidate therapeutic target that may be translated into clinical applications.
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http://dx.doi.org/10.1158/1078-0432.CCR-08-0476DOI Listing
October 2008
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