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Peiwen Zheng School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Fan Wang Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China

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Hui Li Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, China

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Hanlu Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Mengtong Li School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haozheng Ma School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Jue He School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Li Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Yanlong Liu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haiyun Xu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Objective

This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism.

Methods

A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed.

Results

Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers.

Conclusion

These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

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Hui Long Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Yanhong Nie Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Li Wang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Yong Lu Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Yan Wang Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Yijun Cai Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Zhen Liu Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Miaomiao Jia Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Qifeng Lyu Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Qiang Sun Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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AMH as a promising predictor of ovarian response has been studied extensively in women undergoing assisted reproductive technology treatment, but little is known about its prediction value in monkeys undergoing ovarian stimulation. In the current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years received 699 ovarian stimulation cycles. Serum samples were collected for AMH measure with enzyme-linked immunosorbent assay. It was found that serum AMH levels were positive correlated with the number of retrieved oocytes (P < 0.01) in the first, second and third stimulation cycles. In the first cycles, area under the curve (ROCAUC) of AMH is 0.688 for low response and 0.612 for high response respectively, indicating the significant prediction values (P = 0.000 and P = 0.005). The optimal AMH cutoff value was 9.68 ng/mL for low ovarian response and 15.88 ng/mL for high ovarian response prediction. In the second stimulation cycles, the significance of ROCAUC of AMH for high response rather than the low response was observed (P = 0.001 and P = 0.468). The optimal AMH cutoff value for high ovarian response was 15.61 ng/mL. In the third stimulation cycles, AMH lost the prediction value with no significant ROCAUC. Our data demonstrated that AMH, not age, is a cycle-dependent predictor for ovarian response in form of oocyte yields, which would promote the application of AMH in assisted reproductive treatment (ART) of female cynomolgus monkeys. AMH evaluation would optimize candidate selection for ART and individualize the ovarian stimulation strategies, and consequentially improve the efficiency in monkeys.

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Chenghao Piao Department of Radiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Xiaojie Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Shiqiao Peng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Xinyu Guo Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Hui Zhao Department of Laboratory Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Li He Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yan Zeng Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Fan Zhang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Kewen Zhu Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yiwei Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Objective

Gestational diabetes mellitus (GDM) is characterized by glucose intolerance during gestation. It is associated with a series of maternal and foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and autoimmune diseases has been recently discovered. The aim of this study was to evaluate whether IL-34 participates in the pathogenesis of GDM.

Method

A total of 120 women were enrolled in this study, which included 60 GDM patients and age- and sex-matched healthy pregnant women. The expression of IL-34 in serum, cord blood and placental tissues was analysed by ELISA and Western blot assays. The association between IL-34 levels and clinical features was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rmIL-34) on apoptosis and pancreatic β cell function.

Results

We found that IL-34 expression is highly increased in serum, cord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentrations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic β cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inhibited pancreatic β cell function and cell viability, while CSF-1R inhibitor blocked this effect.

Conclusion

IL-34 plays a crucial role in the development of GDM by targeting CSF-1R, insulin production and β cell function.

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Ju-shuang Li Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Tao Wang Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Jing-jing Zuo Center on Clinical Research, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Cheng-nan Guo Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Fang Peng Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Shu-zhen Zhao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Hui-hui Li Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Xiang-qing Hou Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yuan Lan Center on Clinical Research, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
Department of Ophthalmology, Pingxiang People’s Hospital of Southern Medical University, Pingxiang, Jiangxi, China

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Ya-ping Wei Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

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Chao Zheng The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Guang-yun Mao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical Unviersity, Wenzhou, Zhejiang, China
Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
Center on Clinical Research, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Diabetic retinopathy (DR), the most common microvascular complication of diabetes and leading cause of visual impairment in adults worldwide, is suggested to be linked to abnormal lipid metabolism. The present study aims to comprehensively investigate the relationship between n-6 polyunsaturated fatty acids (PUFAs) and DR. This was a propensity score matching based case–control study, including 69 pairs of DR patients and type 2 diabetic patients without DR with mean age of 56.7 ± 9.2 years. Five n-6 PUFAs were determined by UPLC-ESI-MS/MS system. Principle component regression (PCR) and multiple conditional logistic regression models were used to investigate the association of DR risk with n-6 PUFAs depending on independent training and testing sets, respectively. According to locally weighted regression model, we observed obvious negative correlation between levels of five n-6 PUFAs (linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid and arachidonicacid) and DR. Based on multiple PCR model, we also observed significant negative association between the five n-6 PUFAs and DR with adjusted OR (95% CI) as 0.62 (0.43,0.87). When being evaluated depending on the testing set, the association was still existed, and PCR model had excellent classification performance, in which area under the curve (AUC) was 0.88 (95% CI: 0.78, 0.99). In addition, the model also had valid calibration with a non-significant Hosmer–Lemeshow Chi-square of 9.44 (P = 0.307) in the testing set. n-6 PUFAs were inversely associated with the presence of DR, and the principle component could be potential indicator in distinguishing DR from other T2D patients.

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Jintao Hu Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Qingbo Chen Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Xiao Ding Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Xin Zheng Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Xuefeng Tang Department of Pathology, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Song Li Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Hui Yang Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China

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Objective

Many cancer cells cannot survive without exogenous glutamine (Gln); however, cancer cells expressing glutamine synthetase (GS) do not have this restriction. Previous metabolomics studies have indicated that glutamine metabolism is altered during pituitary tumorigenesis. However, the main role of Gln in pituitary adenoma (PA) pathophysiology remains unknown. The aim of this study was to evaluate the expression of GS and the main role of Gln in human PAs.

Methods

We used cell proliferation assay and flow cytometry to assess the effect of Gln depletion on three different pituitary cell lines and human primary PA cells. We then investigated the expression level of Gln synthetase (GS) in 24 human PA samples. At last, we used LC-MS/MS to identify the differences in metabolites of PA cells after the blockage of both endogenous and exogenous Gln.

Results

PA cell lines showed different sensitivities to Gln starvation, and the sensitivity is correlated with GS expression level. GS expressed in 21 out of the 24 human PA samples. Furthermore, a positive p53 and ki-67 index was correlated with a higher GS expression level (P < 0.05). Removal of both endogenous and exogenous Gln from GS-expressing PA cells resulted in blockage of nucleotide metabolism and cell cycle arrest.

Conclusions

Our data indicate that GS is needed for PA cells to undergo proliferation during Gln deprivation, and most human PA cells express GS and might have a negative response to exogenous Gln depletion. Moreover, Gln is mainly responsible for nucleotide metabolism in the proliferation of GS-expressing pituitary tumor cells.

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Chengnan Guo Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yixi Xu Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yange Ma Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Xin Xu Wenzhou Medical University, Wenzhou, Zhejiang, China

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Fang Peng Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Hui-hui Li Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Dongzhen Jin Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Shu-zhen Zhao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Zhezheng Xia Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Mengyuan Lai Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Mingzhu Che Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Ruogu Huang Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yanan Wang Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Depeng Jiang Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, Canada

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Chao Zheng The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Guangyun Mao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China

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Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with glutamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pairs of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were determined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnaire, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regression models. The adjusted odds of DR averagely decreased by 86% (odds ratio (OR): 0.14; 95% CI: 0.06, 0.33) with per interquartile range increase of trehalose. Comparing with the lowest quartile, adjusted OR (95% CI) were 0.20 (0.05, 0.83), 0.14 (0.03, 0.63) and 0.01 (<0.01, 0.05) for participants in the second, third and fourth quartiles of trehalose, respectively. In addition, as compared to their counterparts, T2D patients with lower trehalose (<median) and higher glutamate (≥median) had the highest odds of DR (OR: 36.81; 95% CI: 6.75, 200.61). An apparent super-multiplicative effect of trehalose and glutamate on DR was observed, whereas relative excess risk due to interaction was not significant. The study suggests that trehalose is beneficial to inhibit the occurrence of DR and synergistically decreases the risk of DR with reduced glutamate. Our findings also provide new insights into the mechanisms of DR and further longitudinal studies are required to confirm these findings.

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