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Ying Pei Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Rui Wang School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Wanyu Chen Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Shulin Yi Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Chen Huang Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Shaochan Liang School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Hongying Cao School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Yifei Xu Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China

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Bo Tan Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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Background

Similar to the high-fat diet (HFD), the high-glycemic diet (HGD) contributes to the development and progression of type 2 diabetes mellitus (T2DM). However, the effect of HGD on gastrointestinal motility in T2DM and its underlying mechanisms remain unclear.

Methods

Thirty C57BL/6J mice were randomly designated into the normal-feeding diet (NFD) group, HFD group, and HGD group. The plasma glucose, plasma insulin, and gastrointestinal motility were examined. Meanwhile, the tension of isolated colonic smooth muscle rings was calculated, and the gut microbiota was analyzed by 16s rDNA high-throughput sequencing.

Result

After 16 weeks of HGD feeding, obesity, hyperglycemia, insulin resistance, and constipation were observed in HGD mice. Autonomic contraction frequency of the colonic neuromuscular system and electrical field stimulation-induced contractions were reduced in HGD mice. On the contrary, neuronal nitric oxide synthase activity and neuromuscular relaxation were found to be enhanced. Finally, gut microbiota analysis revealed that Rhodospirillaceae abundance significantly increased at the family level in HGD mice. At the genus level, the abundance of Insolitispirillum increased remarkably, whereas Turicibacter abundance decreased significantly in HGD mice.

Conclusion

HGD induced constipation in obese diabetic mice, which we speculated that it may be related to neuromuscular dysmotility and intestinal microbiota dysbiosis.

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Kuang Hung Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Bo-Ching Lee Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Po-Ting Chen Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Kao-Lang Liu Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Chin-Chen Chang Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
Department and Graduate Institute of Forensic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

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Vin-Cent Wu Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Yen-Hung Lin Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Context

Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA.

Objective

To evaluate the influence of ACS on image–adrenal venous sampling (AVS) correlation and the postoperative results.

Methods

This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image–AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis.

Results

Sixty-five patients (26.4%) had ACS. The image–AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26–4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954–271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004–0.339), P = 0.004).

Conclusion

PA patients with ACS have higher image–AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.

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Haojie Zhang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yuke Cui Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Ruihua Dong Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, School of Public Health, Fudan University, Shanghai, China

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Wen Zhang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Shihan Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Heng Wan Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Chi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yuying Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Chunfang Zhu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Bo Chen Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, School of Public Health, Fudan University, Shanghai, China

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Ningjian Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yingli Lu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Background

Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.

Methods

A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.

Results

In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.

Conclusion

The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

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Bo Zhu Department of Obstetrics and Gynecology, Assisted Reproduction Unit, Sir Run Run ShawHospital, Zhejiang University School of Medicine Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, Zhejiang, China
Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Yumei Chen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Fang Xu Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Xiaolu Shen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Xuanyu Chen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Jieqiang Lv Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Songying Zhang Department of Obstetrics and Gynecology, Assisted Reproduction Unit, Sir Run Run ShawHospital, Zhejiang University School of Medicine Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, Zhejiang, China

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Background

Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of β cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and β-cell function in polycystic ovary syndrome (PCOS).

Methods

PCOS mouse model was established by injection of DHEA. Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice.

Results

PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in β cells, which in turn impaired proinsulin maturation and secretion. Blocking this process could significantly relieve ER stress and apoptosis and improve insulin homeostasis.

Conclusion

ER stress activated by androgens excess in PCOS contributes to β cell dysfunction and hyperinsulinemia.

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Xiaojie Wang Center for Clinical Epidemiology and Methodology (CCEM), Guangdong Second Provincial General Hospital, Guangzhou, China

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Zhiyuan Chen Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada

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Ziyi Li Center for Clinical Epidemiology and Methodology (CCEM), Guangdong Second Provincial General Hospital, Guangzhou, China

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Bo Chen Department of Endocrinology, Guangdong Second Provincial General Hospital, Guangzhou, China

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Yong Qi Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, China

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Guowei Li Center for Clinical Epidemiology and Methodology (CCEM), Guangdong Second Provincial General Hospital, Guangzhou, China
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada

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Jonathan D Adachi Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
Department of Medicine, McMaster University, Hamilton, Canada

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Background

Several epidemiological studies have demonstrated the risk factors for fall, while few studies investigated the association between frailty and risk of fall in diabetic patients aged ≥45 years.

Methods

In this multicity observational study, participants with type 2 diabetes aged ≥45 years were enrolled. Frailty status was measured by a frailty index (FI) of deficit accumulation. We used multivariable regression models to examine the relationship between frailty and fall in diabetic patients, and further investigated the associations between frailty and fall in varied subgroups.

Results

A total of 2049 participants with type 2 diabetes were identified in our study. Our results showed a per-s.d. and a per-0.01 increment of FI were associated with an increased risk of fall, with a fully adjusted OR of 1.89 (95% CI: 1.50, 2.38), 1.06 (95% CI: 1.04, 1.09), respectively. The effects were magnified when frailty was considered as dichotomous, with an OR of 3.08 (95% CI: 2.18, 4.34). In further subgroup analyses, we found that the females, the older, rural residents, individuals with no sitting toilet, people with poor balance performance and those in poor health status were susceptible to fall. Especially, for the risk of fall in the older, a per-s.d. increase of FI corresponded to an OR of 2.46 (95% CI: 1.68, 3.62). When frailty was regarded as a binary variable, the effect increased to 4.62 (95% CI: 2.54, 8.38) in the older subgroup.

Conclusion

Frailty was associated with a higher risk of fall in people with type 2 diabetes, and the effects were higher in vulnerable groups. This evidence suggested that more attention should be paid to vulnerable groups for fall prevention.

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Victor Jing-Wei Kang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Bo-Ching Lee Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Jia-Zheng Huang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Vin-Cent Wu Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Hung Lin Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chin-Chen Chang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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TAIPAI group
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

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Zhengrong Jiang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Linghong Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lijun Chen Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Jingxiong Zhou Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Bo Liang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Xuefeng Bai Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lizhen Wu Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Huibin Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Background

Graves’ disease is a common autoimmune disease. Cytokines and their signalling pathways play a major part in the pathogenesis of Graves’ disease; however, the underlying mechanism needs to be clarified.

Aims

The aim of this study was to explore whether circular RNAs participate in the immunological pathology of Graves’ disease via cytokine-related signalling pathways.

Methods

Bioinformatics analysis was performed to identify differentially expressed circular RNAs and their targets and associated pathways. A total of three patients with Graves’ disease and three sex- and age-matched healthy controls were enrolled for validation with microarray analysis and real-time quantitative PCR (qPCR). An additional 24 patients with Graves’ disease and 24 gender- and age-matched controls were included for validation by real-time fluorescent qPCR. Flow cytometry and CCK8 assays were used to detect the apoptotic and proliferative levels of Jurkat cells (T lymphocytes) with the silenced expression of circRNA. ELISA was performed to detect the growth and apoptosis-related proteins. The competition mechanism of endogenous RNA was explored by real-time fluorescence qPCR.

Results

A total of 366 significantly differentially expressed circular RNAs were identified in the Graves’ disease group compared to healthy controls. The level of hsa_circ_0090364 was elevated in Graves’ disease patients and positively correlated with thyroid-stimulating hormone receptor antibodies. Further analyses suggested that hsa_circ_0090364 may regulate the JAK-STAT pathway via the hsa-miR-378a-3p/IL-6ST/IL21R axis to promote cell growth.

Conclusions

These results provide novel clues into the pathophysiological mechanisms of Graves’ disease and potential targets for drug treatment.

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