Publications by authors named "Chaonan Zhu"

19 Publications

  • Page 1 of 1

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

JAMA Oncol 2021 Aug 5. Epub 2021 Aug 5.

The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Nanjing, China.

Importance: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed.

Objective: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer.

Design, Setting, And Participants: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021.

Interventions: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone.

Main Outcomes And Measures: The primary end point was the 2-year overall survival rate using intention-to-treat analysis.

Results: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group.

Conclusions And Relevance: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT02813967.
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http://dx.doi.org/10.1001/jamaoncol.2021.2705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343504PMC
August 2021

Amorphous Selenium Nanoparticles Improve Vascular Function in Rats With Chronic Isocarbophos Poisoning via Inhibiting the Apoptosis of Vascular Endothelial Cells.

Front Bioeng Biotechnol 2021 24;9:673327. Epub 2021 Jun 24.

School of Pharmacy, Xinxiang Medical University, Xinxiang, China.

Aim: This study aimed to investigate the preventive effect and possible mechanism of amorphous selenium nanoparticles (A-SeQDs) on isocarbophos induced vascular dysfunction.

Methods: A-SeQDs was made by auto redox decomposition of selenosulfate precursor. Male rats were given isocarbophos (0.5 mg/kg/2 days) by intragastric administration for 16 weeks to induce vascular dysfunction. During the course, A-SeQDs (50 mg/kg/day) was added to the water from week 5. Then, the rats were killed to observe and test the influence of A-SeQDs on the vascular dysfunction induced by isocarbophos. Finally, human umbilical vein endothelial cells (HUVECs) were treated with 10% DMEM of isocarbophos (100 μM) for 5 days to detect the related indexes. Before the use of isocarbophos treatment, different drugs were given.

Results: A-SeQDs could reduce total carbon dioxide, MDA, VCAM-1, ICAM-1, IL-1, and IL-6 while increasing oxygen saturation, NO content, and SOD activity in rats. A-SeQDs also resulted in relatively normal vascular morphology, and the expression of sodium hydrogen exchanger 1 (NHE1) and caspase-3 decreased in rats. Furthermore, in HUVECs treated with isocarbophos, A-SeQDs maintained mitochondrial membrane potential, inhibited the cleaved caspase-3 expression, and released cytochrome c from mitochondria to cytosol.

Conclusion: A-SeQDs can inhibit the apoptosis of HUVECs through the mitochondrial pathway, and effectively treat the impairment of vascular endothelial function caused by isocarbophos, which is NHE1-dependent.
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http://dx.doi.org/10.3389/fbioe.2021.673327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266299PMC
June 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 08 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

Deep learning for predicting subtype classification and survival of lung adenocarcinoma on computed tomography.

Transl Oncol 2021 Aug 1;14(8):101141. Epub 2021 Jun 1.

Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, No. 37 Guo Xue Alley, Chengdu 610041, China. Electronic address:

Objectives: The subtype classification of lung adenocarcinoma is important for treatment decision. This study aimed to investigate the deep learning and radiomics networks for predicting histologic subtype classification and survival of lung adenocarcinoma diagnosed through computed tomography (CT) images.

Methods: A dataset of 1222 patients with lung adenocarcinoma were retrospectively enrolled from three medical institutions. The anonymised preoperative CT images and pathological labels of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive adenocarcinoma (IAC) with five predominant components were obtained. These pathological labels were divided into 2-category classification (IAC; non-IAC), 3-category and 8-category. We modeled the classification task of histological subtypes based on modified ResNet-34 deep learning network, radiomics strategies and deep radiomics combined algorithm. Then we established the prognostic models in lung adenocarcinoma patients with survival outcomes. The accuracy (ACC), area under ROC curves (AUCs) and C-index were primarily performed to evaluate the algorithms.

Results: This study included a training set (n = 802) and two validation cohorts (internal, n = 196; external, n = 224). The ACC of deep radiomics algorithm in internal validation achieved 0.8776, 0.8061 in the 2-category, 3-category classification, respectively. Even in 8 classifications, the AUC ranged from 0.739 to 0.940 in internal set. Further, we constructed a prognosis model that C-index was 0.892(95% CI: 0.846-0.937) in internal validation set.

Conclusions: The automated deep radiomics based triage system has achieved the great performance in the subtype classification and survival predictability in patients with CT-detected lung adenocarcinoma nodules, providing the clinical guide for treatment strategies.
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http://dx.doi.org/10.1016/j.tranon.2021.101141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184655PMC
August 2021

Discovering the role of VEGF signaling pathway in mesendodermal induction of human embryonic stem cells.

Biochem Biophys Res Commun 2021 05 20;553:58-64. Epub 2021 Mar 20.

Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Basic Clinical Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Human embryonic stem cells (hESCs) have the unique feature of unlimited self-renewal and differentiation into derivatives of all three germ layers in human body, providing a powerful in vitro model for studying cell differentiation. FGF2, BMP4 and TGF-β signaling have been shown to play crucial roles in mesendodermal differentiation of hESCs. However, their underlying molecular mechanisms and other signaling pathways potentially involved in mesendodermal differentiation of hESCs remain to be further investigated. In this study, we uncover that VEGF signaling pathway plays a critical role in the mesendodermal induction of hESCs. Treating hESCs with Lenvatinib, a pan-inhibitor of VEGF receptors (VEGFRs), impedes their mesendodermal induction. Conversely, overexpression of VEGFA165, a major human VEGF isoform, promotes the mesendodermal differentiation. Similar to the VEGFR inhibitor, MEK inhibitor PD0325901 hinders mesendodermal induction of hESCs. In contrast, overexpression of ERK2, an intrinsically active ERK2 mutant, markedly reduces the inhibitory effect of the VEGFR inhibitor. Thus, the MEK-ERK cascade plays an important role for the function of VEGF signaling pathway in the mesendodermal induction of hESCs. All together, this study identifies the critical role of VEGF signaling pathway as well as potential crosstalk of VEGF signaling pathway with other known signaling pathways in mesendodermal differentiation of hESCs.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.036DOI Listing
May 2021

Epigallocatechin-3-gallate ameliorates glucolipid metabolism and oxidative stress in type 2 diabetic rats.

Diab Vasc Dis Res 2020 Nov-Dec;17(6):1479164120966998

College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China.

Aims: The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM).

Main Methods: Male Sprague-Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining.

Key Findings: A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes.

Significance: EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.
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http://dx.doi.org/10.1177/1479164120966998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919214PMC
January 2021

A double-edged sword: the association of daytime napping duration and metabolism related diseases in a Chinese population.

Eur J Clin Nutr 2021 02 20;75(2):291-298. Epub 2020 Oct 20.

Chronic Disease Research Institute, the Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Some studies have suggested that daytime napping may increase the risk of type 2 diabetes. However, limited data have revealed the association between nap duration and other metabolic diseases. Data from the baseline survey of Lanxi Cohort Study, a population-based study of natural residents in Zhejiang Province, China, were used to investigate the relationship between nap duration and metabolic abnormalities.

Methods: A total of 3236 participants underwent a physical examination, laboratory tests, and face to face interview. They were categorized into four groups according to nap duration. Logistic regression models were used to examine the odds ratios (ORs) of napping duration with four metabolism-related diseases. Stratified analysis was further used to explore the interaction effects of gender and age on results.

Results: Compared to the no daytime napping group, people who napped during the daytime for more than 1 h were independently associated with a greater prevalence of diabetes (OR 1.56). Those who napped during the daytime within a half hour showed a lower prevalence of fatty liver, dyslipidemia, and central obesity. To be more specific, those who habitually napped during the daytime for more than 1 h exhibited an increasing prevalence of diabetes among female older than 50 years old. Those who habitually napped during the daytime within a half hour exhibited a decreasing prevalence of fatty liver and dyslipidemia among male <50 years old, and that of central obesity among female <50 years old.

Conclusions: Short daytime napping duration is associate with reduced rate of metabolism-related diseases and may protects people from negative health conditions, whereas long daytime napping duration is associate with higher prevalence of diabetes, which then can be harmful for health.
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http://dx.doi.org/10.1038/s41430-020-00777-2DOI Listing
February 2021

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

J Hepatol 2020 12 21;73(6):1368-1378. Epub 2020 Jul 21.

Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, China.

Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis.

Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686).

Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%.

Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide.

Lay Summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.
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http://dx.doi.org/10.1016/j.jhep.2020.07.025DOI Listing
December 2020

Association between mid-trimester cervical length and risk of spontaneous preterm birth is modified by a prior cervical excisional procedure.

Int J Clin Exp Pathol 2019 1;12(6):2249-2256. Epub 2019 Jun 1.

Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine Hangzhou 310006, China.

To determine whether and how prior cervical excision modifies the association between a short residual mid-trimester cervical length and the risk of spontaneous preterm birth (SPB). This is a retrospective cohort study on spontaneous preterm birth (SPB) in a total of 1875 patients with and without prior cervical excisional procedure (CEP, loop electrosurgical excision procedure or cold knife cone). Adjusting for potential confounders, we conducted a logistic regression analysis, along with a test of interaction between prior history of CEP and cervical length on SPB. Among 1875 women, there were 274 patients who experienced preterm birth (33.9%). Risk of SPB is significantly associated with age, BMI, cervical length (CL), gestational week at measurement of CL by ultrasonography, multipara, history of preterm birth, fertilization (IVF) and CEP. Moreover, a test of interaction indicated a close association between risk of SPB and CL, which was modified by history of prior CEP. We identified a CL cutoff value of 2.8 cm at which the risk of SPB in patients with prior CEP was identical to the risk in patients without prior CEP. Given the same CLs which were less than 2.8 cm, prior CEP patients presented a higher risk of preterm birth than non-CEP ones. In contrast, given the same CLs which were more than 2.8 cm, prior CEP patients presented lower risk of preterm birth than non-CEP ones. Association between mid-trimester cervical length and risk of SPB was modified by a prior cervical excisional procedure. In patients with prior CEP compared to those without, there was an increased risk of SPB at CL < 2.8 cm and a decreased risk of SPB at CL > 2.8 cm.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949615PMC
June 2019

Sex-dependent prolongation of sciatic nerve blockade in diabetes patients: a prospective cohort study.

Reg Anesth Pain Med 2019 Jul 12. Epub 2019 Jul 12.

Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Introduction: Diabetes may affect the duration of nerve block after regional anesthesia. This study aimed to compare the durations of sensory and motor block in diabetes versus non-diabetes patients after lower limb nerve block and delineate any sex-based differences in the duration of sensory and motor blocks of both diabetes and non-diabetes patients.

Methods: This prospective single-blinded cohort study recruited 86 patients who underwent unilateral lower extremity surgery; 52 patients were non-diabetic and 34 were diabetic. Each patient received an ultrasound-guided nerve stimulator-assisted subgluteal sciatic nerve block with 0.75% ropivacaine. Duration of sensory block was assessed with the Semmes-Weinstein monofilament test, and duration of motor block was assessed with dorsal and plantar flexion of the foot.

Results: The sensory and motor block durations of diabetes patients were significantly prolonged versus non-diabetes patients (19.8±6.0 hours vs 15.6±5.1 hours; p<0.05) and (19.5±8.1 hours vs 14.8±5.7 hours, p=0.005), respectively. The durations of sensory and motor block were comparable between male diabetes and non-diabetes patients, but they were significantly longer in female diabetes patients. Multiple regression analysis further revealed that, after adjustment for age and preoperative sensory threshold, diabetes, fasting plasma glucose and HbA1c levels were significantly associated with sensory and motor blocks. Sex analysis showed the association was only present in female diabetes patients, not male diabetes patients.

Conclusion: The durations of sensory and motor block are significantly prolonged after subgluteal sciatic nerve block in diabetes patients. Furthermore, the prolonged nerve blockade is present only in diabetes women, not diabetes men.

Trial Registration Number: NCT02482831.
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http://dx.doi.org/10.1136/rapm-2019-100609DOI Listing
July 2019

Association of Intraoperative Hypotension with Acute Kidney Injury after Noncardiac Surgery in Patients Younger than 60 Years Old.

Kidney Blood Press Res 2019 29;44(2):211-221. Epub 2019 Mar 29.

Center of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, China,

Background/aims: Intraoperative hypotension (IOH) may be associated with surgery-related acute kidney injury (AKI). However, the duration of hypotension that triggers AKI is poorly understood. The incidence of AKI with various durations of IOH and mean arterial pressures (MAPs) was investigated.

Materials: A retrospective cohort study of 4,952 patients undergoing noncardiac surgery (2011 to 2016) with MAP monitoring and a length of stay of one or more days was performed. The exclusion criteria were a preoperative estimated glomerular filtration (eGFR) ≤60 mL min-1 1.73 m2-1, a preoperative MAP less than 65 mm Hg, dialysis dependence, urologic surgery, age older than 60 years, and a surgical duration of less than 60 min. The primary exposure was IOH, and the primary outcome was AKI (50% or 0.3 mg dL-1 increase in creatinine) during the first 7 postoperative days. Multivariable logistic regression was used to model the exposure-outcome relationship.

Results: AKI occurred in 186 (3.76%) noncardiac surgery patients. The adjusted odds ratio for surgery-related AKI for a MAP of less than 55 mm Hg was 14.11 (95% confidence interval: 5.02-39.69) for an exposure of more than 20 min. Age was not an interaction factor between AKI and IOH.

Conclusion: There was a considerably increased risk of postoperative AKI when intraoperative MAP was less than 55 mm Hg for more than 10 min. Strict blood pressure management is recommended even for patients younger than 60 years old.
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http://dx.doi.org/10.1159/000498990DOI Listing
December 2019

Associations of Body Composition with Blood Pressure and Hypertension.

Obesity (Silver Spring) 2018 10 27;26(10):1644-1650. Epub 2018 Sep 27.

Chronic Disease Research Institute, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.

Objective: The present study investigated the associations of body composition, including skeletal muscle and fat mass, with blood pressure (BP) and hypertension.

Methods: Data from 3,130 participants aged 18 to 80 years were analyzed. Body composition and total skeletal muscle (TSM) were measured or calculated based on dual-energy x-ray absorptiometry. Multivariate linear and logistic regression models were used to analyze the associations of TSM, body fat percentage, android to gynoid fat ratio, and leg and arm lean body mass (LBM) with BP and hypertension. The Wald test was used to estimate the differences in the coefficients.

Results: TSM indices, body fat percentage, and android to gynoid fat ratio were significantly associated with higher odds ratio for prehypertension and hypertension, except for TSM/weight, after controlling for potential confounders. The standardized beta coefficients of arm LBM indices for systolic and diastolic BP were higher than relevant indices of leg LBM.

Conclusions: Different indices of TSM, especially in arm LBM, were all positively associated with elevated BP, prehypertension, and hypertension in Chinese adults, after considering potential confounding factors, including body fat and fat distribution. Future longitudinal studies are warranted to confirm our findings.
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http://dx.doi.org/10.1002/oby.22291DOI Listing
October 2018

Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling.

Cell Death Dis 2018 09 11;9(9):924. Epub 2018 Sep 11.

Basic Clinical Research Center, Renji Hospital, Department of Histology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, 200025, Shanghai, China.

Trophoblast lineages, precursors of the placenta, are essential for post-implantation embryo survival. However, the regulatory network of trophoblast development remains incompletely understood. Here, we report that Cited1, a transcription coactivator, is a robust inducer for trophoblast-like state from mouse embryonic stem cells (ESCs). Depletion of Cited1 in ESCs compromises the trophoblast lineage specification induced by BMP signaling. In contrast, overexpression of Cited1 in ESCs induces a trophoblast-like state with elevated expression of trophoblast marker genes in vitro and generation of trophoblastic tumors in vivo. Furthermore, global transcriptome profile analysis indicates that ectopic Cited1 activates a trophoblast-like transcriptional program in ESCs. Mechanistically, Cited1 interacts with Bmpr2 and Smad4 to activate the Cited1-Bmpr2-Smad1/5/8 axis in the cytoplasm and Cited1-Smad4-p300 complexes in the nucleus, respectively. Collectively, our results show that Cited1 plays an important role in regulating trophoblast lineage specification through activating the BMP signaling pathway.
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http://dx.doi.org/10.1038/s41419-018-0991-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134011PMC
September 2018

Erratum to: A Single Nucleotide Polymorphism in the FADS1 Gene is Associated with Plasma Fatty Acid and Lipid Profiles and Might Explain Gender Difference in Body Fat Distribution.

Lipids Health Dis 2017 05 13;16(1):89. Epub 2017 May 13.

Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, Zhejiang, 310058, China.

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http://dx.doi.org/10.1186/s12944-017-0479-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429941PMC
May 2017

A Single Nucleotide Polymorphism in the FADS1 Gene is Associated with Plasma Fatty Acid and Lipid Profiles and Might Explain Gender Difference in Body Fat Distribution.

Lipids Health Dis 2017 Mar 31;16(1):67. Epub 2017 Mar 31.

Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, Zhejiang, 310058, China.

Background: Genotyping of the rs174547 polymorphism in the fatty acid desaturase 1 gene (FADS1) shows that it is associated with the FA composition of plasma phospholipids and lipid metabolic indices among several ethnic groups. However, this association requires further confirmation in the Chinese population, and little is known about the effect of polymorphisms in fatty acid-related genes on body fat distribution.

Methods: Anthropometric measurements of 951 Chinese adults aged 18-79 were obtained and body fat distribution was estimated using dual-energy X-ray absorptiometry. The FA composition of plasma phospholipids was measured by gas chromatography. Multiple linear regression assessed whether the rs174547 genotype was associated with FA composition, body fat distribution, and metabolic traits in additive, dominant, and recessive models.

Results: The rs174547 C minor allele was associated with a higher proportion of linoleic acid, lower arachidonic acid and docosahexaenoic acid, as well as lower delta-6-desaturase and delta-5-desaturase activity. Female C allele carriers had lower android fat percentages and lower levels of low-density lipoprotein-cholesterol, while male C allele carriers had lower gynoid fat percentages and higher triglyceride after adjusting for age, income, BMI, behavioral risk factors, and regional fat percentages.

Conclusion: An association of FADS1 rs174547 with the FA composition of plasma phospholipids was identified among this Chinese adult population. The association with body fat distribution and lipid metabolic indices differed between men and women, which might explain sexual differences in body fat distribution and lipid metabolism.
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http://dx.doi.org/10.1186/s12944-017-0459-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374576PMC
March 2017

Application of melatonin-loaded poly(N-isopropylacrylamide) hydrogel particles to reduce the toxicity of airborne pollutes to RAW264.7 cells.

J Colloid Interface Sci 2017 Mar 22;490:181-189. Epub 2016 Nov 22.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address:

The adverse effect of airborne PM2.5 pollutes on human beings and the environment, most likely due to heavy metal leaching, has received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of PM2.5 pollutes. In this study, the heavy metal content of PM2.5 pollutes around Zhejiang university were firstly identified. Their cytotoxicity was confirmed, by inducing significantly enhanced intracellular reactive oxygen species level. Poly(N-isopropylacrylamide) (PNIPAM) submicron hydrogel particles with tunable crosslinking densities and thermo-responsive swelling/shrinking properties were then prepared by adjusting the crosslinking density. Anti-oxidant drug melatonin (MLT) was encapsulated into the obtained PNIPAM nanogel particles with the drug loading efficiency larger than 50%, achieving thermo-responsive drug release profile. The PNIPAM/MLT particles had a strong ability to reduce the cytotoxicity to Raw264.7 cells induced by the extractant of PM2.5 pollutes, as well as to suppress the intracellular reactive oxygen species (ROS) level and secretion of tumor necrosis factor alpha (TNF-α), especially when the cells were treated under 25°C for 3h after ingestion of the PNIPAM/MLT particles. This concept-proving study demonstrates the potential to use the thermo-responsive PNIPAM/MLT particles to suppress the toxicity of airborne PM2.5 pollutes, which is a paramount requirement for human health.
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http://dx.doi.org/10.1016/j.jcis.2016.11.075DOI Listing
March 2017

Truncal and leg fat associations with metabolic risk factors among Chinese adults.

Asia Pac J Clin Nutr 2016 Dec;25(4):798-809

Obesity and Body Composition Research Center, Chronic Disease Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China. Email:

Background And Objectives: To examine the associations of regional body fat distribution with metabolic risk factors among Chinese.

Methods And Study Design: Truncal fat (TF) and leg fat (LF) were measured by dualenergy X-ray absorptiometry (DXA) among 947 adults, and abdominal visceral fat (VAT) and subcutaneous fat (SAT), upper leg SAT were measured by magnetic resonance image (MRI) among 103 adults during 2008-2013. Metabolic risk factors included fasting blood glucose, total triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and metabolic syndrome (MetS).

Results: TF showed adverse effect while LF showed beneficial effect on metabolic risk factors, and all these effects were independent of body mass index (BMI) (mostly p<0.01). Individuals with higher TF and lower LF experienced the highest risk of MetS compared to other subgroups of combination of TF and LF (all p<0.05). Abdominal VAT was positively associated with risk of MetS (men: odds ratio (OR)=4.45, 95% confidence interval (CI): 1.18, 16.8; women: OR=6.54, 95% CI: 1.08, 39.6) and serum triglyceride (men: beta (β)=0.379, 95% CI: 0.090, 0.667; women: β=0.700, 95% CI: 0.327, 1.07). Upper leg SAT showed an opposite association with most metabolic factors compared to abdominal SAT and VAT, however, the association was not statistically significant.

Conclusion: TF and LF showed opposite effects on metabolic risk factors among Chinese adults. Abdominal VAT, but not abdominal SAT, was positively associated with serum triglyceride and risk of MetS. Future studies are warranted to examine the potential mechanism of the opposite effects between TF and LF on metabolic risk factors among Chinese.
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http://dx.doi.org/10.6133/apjcn.092015.35DOI Listing
December 2016

FeO/BSA particles induce osteogenic differentiation of mesenchymal stem cells under static magnetic field.

Acta Biomater 2016 12 16;46:141-150. Epub 2016 Sep 16.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address:

Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (FeO/BSA) particles were prepared, which showed a spherical morphology with a diameter below 200 nm, negatively charged surface, and tunable magnetic property. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field, resulting in almost twice intracellular amount of the particles within 21 d compared to that of the magnetic field free control. Uptake of the FeO/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a static magnetic field, as evidenced by elevated alkaline phosphatase (ALP) activity, calcium deposition, and expressions of collagen type I and osteocalcin at both mRNA and protein levels. Therefore, uptake of the FeO/BSA particles brings significant influence on the differentiation of MSCs under magnetic field, and thereby should be paid great attention for practical applications.

Statement Of Significance: Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (FeO/BSA) particles with a diameter below 200nm, negatively charged surface, tunable FeO content and subsequently adjustable magnetic property were prepared. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field. Uptake of the FeO/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a constant static magnetic field, while the magnetic particles and external magnetic field alone do not influence significantly the osteogenic differentiation potential of MSCs regardless of the uptake amount. The results demonstrate a potential magnetic manipulation method for stem cell differentiation, and also convey the significance of careful evaluation of the safety issue of magnetic particles in real an application situation.
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http://dx.doi.org/10.1016/j.actbio.2016.09.020DOI Listing
December 2016
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