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Jian Gong School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, China

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Yinjuan Lv School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, China

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Yuhao Meng Hubei University of Chinese Medicine, Wuhan, China

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Weiheng Zhang Hubei University of Chinese Medicine, Wuhan, China

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Xiaocui Jiang Hubei University of Chinese Medicine, Wuhan, China

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Min Xiao Laboratory Animal Center, Hubei University of Chinese Medicine, Wuhan, China

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Prenatal stress can lead to the programming of the neuroendocrine system in male offspring, disrupting the hypothalamic testicular axis and adversely affecting the reproductive health of male offspring. This study aimed to determine the long-term effects of prenatal stress on the KISS1 system in male offspring and the effects on reproductive function in male offspring. Sixteen pregnant females were divided into a prenatal control group (PC, n = 8) and a prenatal stress group (PS, n = 8). The PS group was modeled with chronic unpredictable mild stress (CUMS) from day 1 of gestation to full-term delivery. Differences between the two groups in various maternal parameters, including glucocorticoid secretion, litter size, and the effects of male offspring birth weight, the KISS1 system, and reproductive function, were determined. Male offspring of PS dams had lower birth weights compared to prenatal controls.KISS1 gene expression is reduced at birth and in adult PS offspring, and its receptor KISS1-R protein is similarly reduced in PS offspring at birth and adulthood. In adulthood, PS male offspring show significantly reduced sex hormone production, altered testicular morphology, reduced maturation of their supporting cells, and decreased expression of connexin 43 (CX43), leading to an altered sperm microenvironment and reduced sperm quality. In conclusion, prenatal stress leads to adverse changes in the KISS1 system in male offspring and decreased reproductive function.

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Lukas Plachy Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Petra Dusatkova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Klara Maratova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Shenali Anne Amaratunga Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Dana Zemkova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Vit Neuman Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Stanislava Kolouskova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Barbora Obermannova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Marta Snajderova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Zdenek Sumnik Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Jan Lebl Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Stepanka Pruhova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Because the causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled in the study. Their median age was 11.2 years, pre-treatment height was −3.2 s.d., and maximal stimulated GH was 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 had central hypothyroidism, ten had hypogonadotropic hypogonadism, and three had central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with clinical suspicion of a specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without a detected causal variant after the first-tier testing or with no suspicion of a specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving the OTX2 gene). The remaining 6 children had causative genetic variants in the GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated the cause of CPHD in a fifth of the patients. Moreover, our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD.

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Mohamed Hssaini Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco
Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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Sana Abourazzak Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Ihsane El Otmani Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Morocco

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Mohamed Ahakoud Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Amina Ameli Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Laila Bouguenouch Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Hicham Bekkari Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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Background

Differences/disorders of sex development (DSD) encompass a wide range of conditions. Their clinical spectrum and etiological diagnosis have not been reported in Moroccan patients.

Aims

The study aims to highlight the clinical spectrum, etiological diagnosis, and management of patients with DSD.

Subjects and methods

This is a retrospective study of all patients diagnosed with DSD under the age of 18 years, who were referred to the Pediatric Endocrinology Department and the Medical Genetics Laboratory at HASSAN II University Hospital of Fez between June 2018 and June 2023.

Results

Out of 57 patients, 54.4% (n = 31) were diagnosed with 46,XX DSD, the most common type, while 45.6% (n = 26) had 46,XY DSD. Patients with 46,XX DSD presented earlier than those with 46,XY DSD, at a median age of 0.08 years and 0.96 years, respectively. The most commonly reported complaint was atypical genitalia. At the first presentation, the sex of rearing was already assigned to 26 males and 27 females. All patients with 46,XX DSD were diagnosed with congenital adrenal hyperplasia (CAH) at a median age of diagnosis of 0.92 years. Of these, 11 patients were raised as males. Disorders of androgen action or synthesis were more common in XY patients (69.2%). The consanguinity rate was 46.5%, and there were 19 cases with a positive family history, with 10 siblings having died.

Conclusion

DSD are not rare in Morocco. Overall, CAH remains the most frequent DSD etiology. Molecular genetic analyses are needed to determine the accurate etiological distribution of DSD, especially in XY patients.

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Danzhou Fang D Fang, Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Shiying Li S Li, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Yirui Wang Y Wang, Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Yue Chen Y Chen, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China

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Gengbiao Yuan G Yuan, Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Maohua Rao M Rao, Department of nuclear medicine,the second affiliated hospital of chongqing medical university, Chongqing, 400010, China

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Objective: Hyperthyroidism, a prevalent endocrine disorder, can lead to complications such as liver failure due to the liver's essential role in thyroid hormone metabolism. The study aimed to elucidate the respective contributions of 131I or/and ALSS in managing hyperthyroidism alongside liver failure.

Methods: A retrospective analysis was carried out on 74 patients diagnosed with severe liver failure in the context of Graves' disease. Patients were categorized into three groups: Group A (n=34) received 131I treatment, group B (n=17) underwent 131I and ALSS treatment, and group C (n=24) received ALSS treatment alone.

Results: Throughout the treatment period, the liver function indexes in all groups exhibited a decline trend. The thyroid function of group A and group B treated with 131I was significantly improved compared with that before treatment. There was no significant change in thyroid function in group C. After the correction of hyperthyroidism, significant improvements were observed in the liver function of individuals in group A and B, particularly with more noticeable amelioration compared to group C. After two months of treatment, the efficacy rates for the three groups were 79.41%, 82.35%, and 60.87% respectively. Mortality rates of the three groups were 5.88%,17.65% and 36% (p<0.01). Group B, receiving both 131I and ALSS treatments, exhibited a lower mortality rate than group C.

Conclusion: In cases of severe liver failure accompanied by hyperthyroidism, prompt administration of 131I is recommended to alleviate the adverse effects of hyperthyroidism on liver function and facilitate a conducive environment for the recovery of liver functionality.

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Salma R Ali S Ali, Department of Child Health, University of Glasgow, Glasgow, G51 4TF, United Kingdom of Great Britain and Northern Ireland

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Melissa Gardner M Gardner, Paediatrics, University of Michigan Medical School, Department of Pediatrics Ann Arbor, US 48109-0624, Michigan, United States

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Yiqiao Xin Y Xin, University of Glasgow, Glasgow, United Kingdom of Great Britain and Northern Ireland

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Stuart O’Toole S O’Toole, Department of Paediatric Surgery, Royal Hospital for Children, Glasgow, United Kingdom of Great Britain and Northern Ireland

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Martyn Flett M Flett, Department of Paediatric Surgery, Royal Hospital for Children, Glasgow, United Kingdom of Great Britain and Northern Ireland

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Boma Lee B Lee, Department of Paediatric Surgery, Royal Hospital for Children, Glasgow, United Kingdom of Great Britain and Northern Ireland

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Mairi Steven M Steven, Department of Paediatric Surgery, Royal Hospital for Children, Glasgow, United Kingdom of Great Britain and Northern Ireland

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David E. Sandberg D Sandberg, Pediatrics, Univ Michigan, Ann Arbor, United States

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S. Faisal Ahmed S Ahmed, University of Glasgow, Glasgow, United Kingdom of Great Britain and Northern Ireland

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Background: There is a paucity of information on health-related quality of life (HRQoL) outcomes in parents and children with conditions affecting sex development. The objective of this study was to develop short forms of HRQoL questionnaires which consist of a 63-item and 25-item parent self-report (PSR) and parent proxy-report (PPR), respectively, optimising use in routine clinic settings.

Methods: Short questionnaires were developed following exploratory factor analysis using raw data from 132 parents. Long and short PSRs were completed by 24 parents of children with conditions affecting sex development with median age of 3.6 years (range 0.1, 6.6); 21 (88%) were boys and 11 (46%) had proximal hypospadias. A subset of 19 parents completed long and short PPRs.

Results: Item selection based on factor loadings of >0.8 and expert consultation, produced short PSR and PPRs containing 16 and 7 items, respectively. There was no statistically significant difference in 11 out of 12 (92%) scales on the PSR and 4 out of 5 (80%) scales on the PPR when comparing short and long questionnaire scores. Short and long questionnaires took <1 minute and 5 minutes for completion, respectively. Eighteen parents (75%) reported that the time taken to complete short questionnaires was acceptable; 10 (42%) preferred short questionnaires. Ten (42%) versus 6 (25%) stated a preference for completing short versus long questionnaires.

Conclusion: Short versions were largely representative of the long questionnaires and are acceptable to evaluate psychosocial distress in young children and their caregivers. Further psychometric validation of short forms is warranted.

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Shanhong Li Department of Medical Informatics, Medical School of Nantong University, Nantong, Jiangsu Province, China

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Jincheng Tao Department of Medical Informatics, Medical School of Nantong University, Nantong, Jiangsu Province, China
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

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Jie Tang Department of Medical Informatics, Medical School of Nantong University, Nantong, Jiangsu Province, China

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Yanting Chu Department of Medical Informatics, Medical School of Nantong University, Nantong, Jiangsu Province, China

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Huiqun Wu Department of Medical Informatics, Medical School of Nantong University, Nantong, Jiangsu Province, China

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The global burden of controlling and managing diabetes mellitus (DM) is a significant challenge. Despite the advancements in conventional DM therapy, there remain hurdles to overcome, such as enhancing medication adherence and improving patient prognosis. Digital therapeutics (DTx), an innovative digital application, has been proposed to augment the traditional disease management workflow, particularly in managing chronic diseases like DM. Several studies have explored DTx, yielding promising results. However, certain concerns about this innovation persist. In this review, we aim to encapsulate the potential of DTx and its applications in DM management, thereby providing a comprehensive overview of this technique for public health policymakers.

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Yi Wang Y Wang, Department of Endocrinology, Genetics and Metabolism , Beijing Children's Hospital Capital Medical University, Beijing, China

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Yingying Xu Y Xu, Department of Pediatrics, Sun Yat-Sen University, Guangzhou, China

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Rongrong Xie R Xie, Department of Endocrinology, Children’s Hospital of Soochow University, Suzhou, China

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Bing Yan Cao B Cao, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Yuan Ding Y Ding, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Jiayun Guo J Guo, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Xiaoqiao Li X Li, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Xiaolin Ni X Ni, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Zheng Yuan Z Yuan, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital Capital Medical University, Beijing, China

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Linqi Chen L Chen, Department of Endocrinology, Children’s Hospital of Soochow University, Suzhou, China

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Liyang Liang L Liang, Department of Pediatrics, Sun Yat-Sen University, Guangzhou, China

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Chunxiu Gong C Gong, Department of Endocrinology, Genetics and Metabolism, Capital Medical University, Beijing, 100054, China

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Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations.

Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into Groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in Group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups.

Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among Groups 1–3, the rates of cardiovascular manifestations were NA vs. 12.8% vs. 81.2%; gastrointestinal disturbances were 11.4% vs. 8.5% vs. 62.5%; strabismus was 25.7% vs. 12.8% vs. 62.5%; sleep disturbance was NA vs. 6.4% vs. 50.0%; and abnormal pain threshold was NA vs. 10.6% vs. 25.0% (all p<0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (p<0.01).

Conclusions: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

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Hui Li Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Peng Wu Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Background

Epigenetics, which involves regulatory modifications that do not alter the DNA sequence itself, is crucial in the development and progression of thyroid cancer. This study aims to provide a comprehensive analysis of the epigenetic research landscape in thyroid cancer, highlighting current trends, major research areas, and potential future directions.

Methods

A bibliometric analysis was performed using data from the Web of Science Core Collection (WOSCC) up to 1 November 2023. Analytical tools such as VOSviewer, CiteSpace, and the R package ‘bibliometrix’ were employed for comprehensive data analysis and visualization. This process identified principal research themes, along with influential authors, institutions, and countries contributing to the field.

Results

The analysis reveals a marked increase in thyroid cancer epigenetics research over the past two decades. Emergent key themes include the exploration of molecular mechanisms and biomarkers, various subtypes of thyroid cancer, implications for therapeutic interventions, advancements in technologies and methodologies, and the scope of translational research. Research hotspots within these themes highlight intensive areas of study and the potential for significant breakthroughs.

Conclusion

This study presents an in-depth overview of the current state of epigenetics in thyroid cancer research. It underscores the potential of epigenetic strategies as viable therapeutic options and provides valuable insights for researchers and clinicians in advancing the understanding and treatment of this complex disease. Future research is vital to fully leverage the therapeutic possibilities offered by epigenetics in the management of thyroid cancer.

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Shuqi Li S Li, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Chenye Shi C Shi, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Haifu Wu H Wu, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Hongmei Yan H Yan, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Mingfeng Xia M Xia, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Heng Jiao H Jiao, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Yang He Y He, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Ming Zhong M Zhong, Department of Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai, China

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Wenhui Lou W Lou, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Xin Gao X Gao, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Hua Bian H Bian, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Xinxia Chang X Chang, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement.

Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using non-targeted metabolic liquid chromatography-mass spectrometry (LC-MS) method.

Results: During the 1, 3, and 6 months postoperative follow-up, the BMI, HOMA-IR, liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement and liver fat content reduction.

Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

Open access
Agata Hanna Bryk-Wiązania Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Mari Minasyan Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Alicja Hubalewska-Dydejczyk Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Aleksandra Gilis-Januszewska Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Objective

Cushing’s syndrome (CS) is associated with an 18-fold greater risk of venous thromboembolism (VTE). We aimed to identify factors which provoke VTE among patients with CS and VTE and to describe the anticoagulant regimen used in these cases.

Methods

In this retrospective observational study, patients included in the European Registry on CS (ERCUSYN) in Krakow center, Poland, were followed for the occurrence of VTE and anticoagulant treatment. We identified factors provoking VTE according to the International Society of Thrombosis and Hemostasis (ISTH), along with factors included in the Padua score and CS-VTE score.

Results

Of the 128 patients followed for a median of 4.3 years, there were nine patients who experienced ten VTE episodes (prevalence of 7.8% and incidence of 13.4 per 1000 patient-years). All VTEs were classified as provoked according to the ISTH guidance, predominantly due to the transient major and minor (50% and 20%, respectively) factors, while they were less commonly due to persistent (30%) factors. In 2/9 patients, we could not identify any risk factor for VTE according to the Padua score, while in 2/6 patients according to the CS-VTE score. Patients were mostly anticoagulated with vitamin K antagonists (4/8 patients), followed by direct oral anticoagulants (3/8) and low-molecular-weight heparin (1/8). The median duration of anticoagulation was 2.75 years and exceeded beyond the primary treatment in 28% of episodes provoked by transient factors.

Conclusion

Further, multicenter studies are required to create a validated thrombotic risk score and guidelines regarding VTE treatment in CS patients.

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