Maternal dietary copper deficiency induces cardiomyopathy and liver injury in mice by activating autophagy.

Maternal nutritional deficiencies during pregnancy result in birth defects and elevate the risk of cardiovascular diseases and metabolic diseases. Accumulating evidence suggests that deficiency of copper, a fundamental trace element involved in several pivotal physiological processes, promotes the onset of multiple diseases, notably heart and liver diseases. Yet, exploration into the effects of maternal copper deficiency (CuD) on offspring is still limited. In this study, we hypothesized that maternal CuD induced cardiomyopathy and liver injury in offspring through the activation of autophagy. We established a maternal CuD mouse model by feeding pregnant C57BL/6 mice with a CuD diet until the end of the experiment. Echocardiography, histological analysis, western blotting, and quantitative polymerase chain reaction were performed on offspring at postnatal day 14. We found that maternal CuD caused growth retardation and early postnatal death in the offspring. Furthermore, our results revealed that CuD induced cardiac systolic dysfunction, cardiac hypertrophy, hepatic steatosis, and liver injury. Moreover, higher expression of LC3 and lower expression of p62 were observed in the heart tissues and liver tissues of CuD mice compared with the control group, indicating that CuD induced autophagy activation. In conclusion, maternal CuD caused severely deleterious effects on the heart and liver of the offspring via activating autophagy.

Research trends between diabetes mellitus and bariatric surgery researches: Bibliometric analysis and visualization from 1998 to 2023.

This study conducted a bibliometric analysis using the Web of Science Core Collection (WOSCC) to explore the relationship between diabetes mellitus and bariatric surgery (BS) from January 1985 to August 2023. No publications were found between 1985 and 1998. However, from 1998 to 2023, a total of 9,496 English articles were identified, accumulating 291,289 citations (241,563 excluding self-citations) and achieving an H-Index of 197. Leading contributors to the field were the United States, China, and Italy. Noteworthy authors in this area of research included Philip R. Schauer, Wei-Jei Lee, and Carel W. le Roux. The major journals that featured this research were 'Obesity Surgery,' 'Diabetes Care,' and 'Surgery for Obesity and Related Diseases.' The most highly cited article focused on lifestyle, diabetes, and cardiovascular risks 10 years after BS, emphasizing the significant attention given to the nutritional, cardiac, and general internal medicine impacts of diabetes and BS. The increase in research output during the review period indicates a growing interest in the relationship between diabetes and BS, providing a valuable reference for future studies in this evolving field.

Assessment of transient elastography in diagnosing MAFLD and the early effects of sleeve gastrectomy on MAFLD among the Chinese population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. METHODS: In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. RESULTS: Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5 kPa, 8.3 kPa, and 10.4 kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. CONCLUSION: In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.

Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus.

AIM: Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram. METHODS: In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model. RESULTS: Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability. CONCLUSION: The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

Novel diagnostic biomarkers of oxidative stress, immune- infiltration characteristics and experimental validation of SERPINE1 in colon cancer.

BACKGROUND: Colon cancer (CC) is a prevalent malignant tumor that affects the colon in the gastrointestinal tract. Its aggressive nature, strong invasiveness, and rapid progression make it a significant health concern. In addition, oxidative stress can lead to the production of reactive oxygen species (ROS) that surpass the body's antioxidant defense capacity, causing damage to proteins, lipids, and DNA, potentially promoting tumor development. However, the relationship between CC and oxidative stress requires further investigation. METHODS: We collected gene expression data and clinical data from 473 CC patients from The Cancer Genome Atlas (TCGA) dataset. Additionally, we obtained 433 oxidative stress genes from Genecards ( https://www.genecards.org/ ). Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients. To validate the models, we utilized data from the Gene Expression Omnibus (GEO) database. We assessed the accuracy of the models through various techniques, including the creation of a nomogram, receiver operating characteristic curve (ROC) analysis, and principal component analysis (PCA). The Cytoscape program was utilized to identify hub genes among differentially expressed genes (DEGs) in tumor patients using the TCGA dataset. Subsequently, we conducted survival analysis, clinical relevance analysis, and immune cell relevance analysis for the intersected genes obtained by combining the hub genes with the genes from the predictive models. Moreover, we investigated the mRNA expression and potential functions of these intersected genes using a range of experimental approaches. RESULTS: In both the TCGA and GSE17538 datasets, patients classified as high-risk had significantly shorter overall survival compared to those in the low-risk group (TCGA: p < 0.001; GSE17538: p = 0.010). As a result, we decided to further investigate the role of SERPINE1. Our survival analysis revealed that patients with high expression of SERPINE1 had a significantly lower probability of survival compared to those with low expression (p < 0.05). Additionally, our clinical correlation analysis showed a significant relationship between SERPINE1 expression and T, N, and M stages, as well as tumor grade. Furthermore, our immune infiltration correlation analysis demonstrated notable differences in multiple immune cells between the high- and low-expression groups of SERPINE1. To validate our findings, we conducted experimental tests and observed that knocking down SERPINE1 in colon cancer cells resulted in significant reductions in cell viability and proliferation. Interestingly, we also noticed an increase in oxidative stress parameters, such as ROS and MDA levels, while the levels of reduced GSH decreased upon SERPINE1 knockdown. These findings suggest that the antineoplastic effect of silencing SERPINE1 may be associated with the induction of oxidative stress. CONCLUSION: In conclusion, this study introduces a new approach for the early diagnosis and treatment of CC, and further exploration of SERPINE1 could potentially lead to a significant advancement.

Uncovering the pathogenesis of obesity complicated with papillary thyroid carcinoma via bioinformatics and experimental validation.

This study aimed to investigate the common molecular mechanism between obesity and papillary thyroid cancer (PTC), the most common pathological type of thyroid cancer. In this study, we obtained gene expression datasets for obesity (GSE151839) and PTC (GSE33630) from the Gene Expression Omnibus (GEO). We used the Perl program and R software to identify differentially expressed genes (DEGs) and common genes, perform GO function and KEGG pathway enrichment analysis, construct a protein-protein interaction (PPI) network, identify hub genes, and perform transcription factors (TFs) analysis. After undergoing validation in external datasets and in vitro experiments, common targets for both diseases were ultimately identified. A total of 23 genes that were differentially expressed (DEGs) between obesity and papillary thyroid carcinoma (PTC) were identified in our study. Among these DEGs, 17 genes were up-regulated while 6 genes were down-regulated. Then the top ten key genes were identified from the PPI network using cytoHubba and MCODE plug-in. Further evidence from external datasets revealed that MMP9, MNDA, TNC, and CHIT1 were identified as hub genes for both diseases. The study utilized Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) to perform an enrichment analysis of TFs. This analysis identified ELF4 and STAT3 as common TFs for both diseases. Additionally, in vitro experiments were conducted to further analyze the clinical significance and biological functions of these TFs. The identification and investigation of hub genes and their corresponding TFs that regulate abnormalities in obesity and PTC can enhance our comprehension of the underlying connection between these two diseases, thus leading to the development of novel diagnostic approaches.

Bibliometric and Correlation Analysis of Bariatric Surgery Researches in Asia-Pacific from 2000 to 2021.

INTRODUCTION: Bariatric surgery has grown in popularity over the past two decades, especially in the Asia-Pacific. Correspondingly, researchers' interest in this field has also increased. This study aims to perform a bibliometric analysis of publications from Asia-Pacific represented by the International Federation for the Surgery of Obesity and Metabolic Disorders Asia-Pacific Chapter (IFSO-APC) and investigate the relevant factors that might affect the publications. METHODS: The search terms for bariatric surgery were searched in Web of Science focusing on the period 2000-2021. Bibliometric analysis was performed after screening the search results. Univariate and multivariate regression analyses were performed on the number of publications and corresponding indicators obtained from official agencies. RESULTS: A total of 9,547 publications in IFSO-APC were retrieved, of which China had the largest number with 2,782 publications. Authors and journals with major contributions were listed. The authors' or affiliations' cooperation networks mainly were limited to domestic. "Bariatric surgery" was the most frequent keyword with 2,063 times and also the largest cluster. "Morbid obesity" was the strongest citation bursts. Multivariate analysis found that the number of publications in each country/region was associated with body mass index ≥25 kg/m2, gross domestic product, and total population. CONCLUSION: Generally, Asia-Pacific represented by IFSO-APC scientific publications on bariatric surgery has grown significantly in the last two decades, but cooperation between countries/regions should be strengthened. "Morbid obesity" is the focus and frontier of research in this field.

Co-construction of oxygen doping and van der walls heterojunction in O-CB/ZnIn2S4 promoting photocatalytic production and activation of H2O2 for the degradation of antibiotics.

The in situ production of H2O2 by photocatalysis have shown a sustainable strategy for water remediation, but the peroxide evolution capacity are still unsatisfactory. Herein, we ingeniously design oxygen-doped carbon black/zinc indium sulfide (O-CB/ZnIn2S4) composites for photocatalytic production and activation of H2O2 to degrade antibiotics. The rich oxygen dopants and van der walls heterojunction between O-CB and ZnIn2S4 promoted charge transfer, oxygen adsorption and reduction for peroxide generation. The optimized O-CB/ZnIn2S4-2 composites exhibited ultrahigh H2O2 production rate (1985 µmol/g/h) in pure water (pH=7) without sacrificial reagents and aeration assistance, which was 2 times, 3 times, and 12 times higher than CB/ZnIn2S4-2, ZnIn2S4 and O-CB, respectively. Additionally, O-CB/ZnIn2S4-2 composites exhibited considerable amount of OH of 30 µmol/L in 60 min, which was originated from the reduction of innergenerate-H2O2 by photogenerated electrons and direct photolysis. The degradation and quenching experiments shows that the innergenerate-H2O2 contributed to the rapid degradation and deep mineralization of tetracycline antibiotics(tetracycline, oxytetracycline, chlortetracycline hydrochloride). Moreover, intermediates analysis and toxicity estimation further confirm the significant mineralization and toxicity decrease during the degradation of oxytetracycline by O-CB/ZnIn2S4-2. The work provides deep insights into the crucial role of dopants and heterojunction in promoting H2O2 production and activation.

Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.

Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity.

BACKGRUOUND: MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed. METHODS: We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared. RESULTS: Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM. CONCLUSION: We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

Construction of a Prognostic Model for Predicting Colorectal Cancer Prognosis and Response to Immunotherapy Based on Cuproptosis-Associated lncRNAs.

Colorectal cancer (CRC) is a common and highly lethal gastrointestinal malignancy. Immunotherapy has shown positive efficacy in the treatment of CRC; however, only a minority of patients benefit from immunotherapy. The aim of this study is to construct a cuproptosis-related lncRNA (CRLs) risk score model to predict the prognosis and immune infiltration of CRC patients. Firstly, we synthetically analyzed 19 cuproptosis-related genes (CRGs) from CRC samples derived from the TCGA and obtained 33 CRLs that were significantly associated with prognosis. Next, we defined three cuproptosis modification patterns via consensus clustering analysis (C1, C2, and C3). Further analysis showed that there were significant differences in the abundance of B cells, NK cells, fibroblasts, monocytes, CD8+ cells, bone marrow dendritic cells, and cytotoxic lymphocytes in different clusters. In addition, the LASSO regression screened out 6 individual CRLs (AC009315.1, PLS3-AS1, ZEB1-AS1, AC007608.3, AC010789.2, and AC010207.1) closely related to the prognosis of CRC. We found that the low-risk group had better survival prognoses in patients. Furthermore, the high-risk group had lower immune scores and exhibited lower CD8+ T cell infiltration. Moreover, the low-risk group had lower immune exclusion, immune dysfunction and TIDE scores than the high-risk group. Interestingly, the lncRNAs in our risk model were positively associated with most immune checkpoints. CD274 (PD-L1), CTLA4, and HAVCR2 (TIM3) were positively correlated with risk scores. Moreover, MSI-H patients had lower risk scores than MSI-L patients, and IPS scores were significantly higher in the low CRLs score group. In conclusion, we constructed a novel risk score model with6 lncRNAs related to cuproptosis, which may be a potential biomarker for evaluating the prognosis and immune treatment for CRC.

Determination of weight loss effectiveness evaluation indexes and establishment of a nomogram for forecasting the probability of effectiveness of weight loss in bariatric surgery: a retrospective cohort.

BACKGROUND: The purpose of this research was to determine the index that contributes the most to assessing the effectiveness of weight loss 1 year following bariatric surgery and to implement it as the clinical outcome to develop and confirm a nomogram to predict whether bariatric surgery would be effective. METHODS: Patient information was extracted from the Chinese Obesity and Metabolic Surgery Database for this retrospective study. The most contributing weight loss effectiveness evaluation index was created using canonical correlation analysis (CCA), and the predictors were screened using logistic regression analysis. A nomogram for estimating the likelihood of effectiveness of weight loss was constructed, and its performance was further verified. RESULTS: Information was obtained for 540 patients, including 30 variables. According to the CCA, ≥25 percentage total weight loss was found to be the most correlated with patient information and contribute the most as a weight loss effectiveness evaluation index. Logistic regression analysis and nomogram scores identified age, surgical strategy, abdominal circumference, weight loss history, and hyperlipidemia as predictors of effectiveness in weight loss. The prediction model's discrimination, accuracy, and clinical benefit were demonstrated by the consistency index, calibration curve, and decision curve analysis. CONCLUSIONS: The authors determined a 25 percentage total weight loss as an index for weight loss effectiveness assessment by CCA and next established and validated a nomogram, which demonstrated promising performance in predicting the probability of effectiveness of weight loss in bariatric surgery. The nomogram might be a valuable tool in clinical practice.

Regulatory role of atrial natriuretic peptide in brown adipose tissue: A narrative review.

Atrial natriuretic peptide (ANP) has been considered to exert an essential role as a cardiac secretory hormone in the regulation of hemodynamic homeostasis. As the research progresses, the role of ANP in the crosstalk between heart and lipid metabolism has become an interesting topic that is attracting the interest of researchers. The regulation of ANP in lipid metabolism shows favorable effects, particularly the activation of brown adipose tissue (BAT). The complex regulatory network of ANP on BAT has not been fully outlined. This narrative review critically evaluated the existing literature on the regulatory effects of ANP on BAT. In general, we have summarized the expression of ANP and its receptors in various human tissues, analyzed the progress of research on the relationship between the ANP and BAT, and described several potential pathways of ANP to BAT. Exogenous ANP, natriuretic peptide receptor C (NPRC) deficiency, cold exposure, bariatric surgery, and cardiac or renal insufficiency could all contribute to BAT expression by increasing circulating ANP levels.

A Novel Nomogram and Online Calculator for Predicting the Risk of Obesity Hypoventilation Syndrome in Bariatric Surgery Candidates.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is frequently misdiagnosed and undertreated, increasing the risk of perioperative complications. We aimed to determine the predictors of OHS and to develop and validate a novel nomogram and online calculator for identifying patients at risk of OHS in bariatric surgery candidates. METHODS: We retrospectively analyzed the data of patients undergoing bariatric surgery between March 2017 and June 2020. Predictors were identified using univariate and multivariate analyses to establish the nomogram. The discriminative ability, calibration, and clinical value of the nomograms were tested using C-statistics, calibration plots, and decision curve analysis. The nomogram was internally validated using bootstrap resampling. RESULTS: A total of 577 patients were enrolled, and OHS was presented in 17.9% (103/577). Body mass index (BMI) (odds ratio [OR], 1.11; 95% confidence interval (CI), 1.04-1.18; p = 0.001), neck circumference (OR, 1.09; 95% CI, 1.01-1.18; p = 0.035), type 2 diabetes (T2D) (OR, 2.02; 95% CI, 1.17-3.45; p = 0.011), serum bicarbonate (OR, 1.47; 95% CI, 1.30-1.67; p < 0.001), and C-reactive protein (CRP) (OR, 1.03; 95% CI, 1.01-1.06; p = 0.017) were independent risk factors for OHS and incorporated to develop the nomogram. The nomogram revealed good discrimination, with a C-index of 0.830 (95% CI: 0.784-0.876) (0.8227 through internal validation), and good calibration. Decision curve analysis further confirmed the nomogram's clinical usefulness. CONCLUSIONS: The novel nomogram and online calculator provided an excellent preoperative individualized prediction of OHS in patients undergoing bariatric surgery, hereby potentially assisting clinicians and surgeons in the early detection and intensive monitoring of OHS.

A Retrospective Evaluation of Pregnancy Outcomes Following Bariatric Surgery: A Single-Center Experience.

Background: Bariatric and metabolic surgery (BMS) is an effective treatment for obesity and its complications, but its effect on pregnancy outcomes is inconclusive. The present study aimed to investigate women's pregnancy status and outcomes as well as the impact of pregnancy intervals after BMS. Methods: The menstrual cycle and fertility status of women who underwent BMS in our centre between July 2010 and January 2021 were retrospectively analyzed and followed up until one-year post-delivery. The pregnancy outcomes after BMS were observed, including changes in weight, pregnancy interval, pregnancy complications, weight and health status of the newborn (premature birth, admission to neonatology, or deformity). Results: We identified 31 women who were successfully conceived after BMS. There were statistical differences in weight and menstrual status before and post-operation (P < 0.05), and 77.97% of them had remission or recovery of obesity-related comorbidities. Eighteen patients delivered successfully after BMS, but there were still 12 cases of spontaneous abortion and 1 case of induced abortion. The abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years (P = 0.045). Of the women who delivered successfully, 5 had pregnancy-specific complications, including gestational diabetes mellitus and hypertensive disorder of pregnancy. However, the growth and development of the newborn are normal since the birth follow-up. Conclusion: The present results suggest that the abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years. It is recommended that postoperative patients avoid pregnancy until their weight is stable to reduce the risk of adverse pregnancy outcomes.

Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex.

Copper deficiency has emerged to be associated with various lipid metabolism diseases, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms that dictate the association between copper deficiency and metabolic diseases remain obscure. Here, we reveal that copper restoration caused by hepatic ceruloplasmin (Cp) ablation enhances lipid catabolism by promoting the assembly of copper-load SCO1-LKB1-AMPK complex. Overnutrition-mediated Cp elevation results in hepatic copper loss, whereas Cp ablation restores copper content to the normal level without eliciting detectable hepatotoxicity and ameliorates NAFLD in mice. Mechanistically, SCO1 constitutively interacts with LKB1 even in the absence of copper, and copper-loaded SCO1 directly tethers LKB1 to AMPK, thereby activating AMPK and consequently promoting mitochondrial biogenesis and fatty acid oxidation. Therefore, this study reveals a mechanism by which copper, as a signaling molecule, improves hepatic lipid catabolism, and it indicates that targeting copper-SCO1-AMPK signaling pathway ameliorates NAFLD development by modulating AMPK activity.

Accuracy of Oxygen Saturation Measurements in Patients with Obesity Undergoing Bariatric Surgery.

BACKGROUND: We aimed to determine the magnitude, direction, and influencing factors of the concordance between arterial oxygen saturation (SaO2) and peripheral capillary oxygen saturation (SpO2) in patients with obesity undergoing bariatric surgery, supporting the measurement of SaO2 and SpO2 in key populations. METHODS: Patients with obesity undergoing bariatric surgery from 2017 to 2020 were included. Preoperative SpO2 and SaO2 were collected. Linear correlation and multiple linear regression analyses were performed to characterize the relationships between body mass index (BMI), age, and sex with pulse oximetry and arterial blood gas (ABG) parameters. Bland-Altman analysis was applied to determine the concordance between SpO2 and SaO2 and the limits of this concordance. RESULTS: A total of 134 patients with obesity undergoing bariatric surgery were enrolled. SaO2 was negatively associated with BMI (p < 0.0001) and age (p = 0.006), and SpO2 was negatively associated with BMI (p = 0.021) but not with age. SpO2 overestimated SaO2 in 91% of patients with a bias of 2.05%. This bias increased by 203% in hypoxemic patients compared with nonhypoxemic patients (p < 0.0001). The bias was 1.3-fold higher (p = 0.023) in patients with a high obesity surgery mortality risk score (OS-MRS) than in those with low or intermediate scores. CONCLUSION: Compared with SpO2, preoperative SaO2 can more accurately reflect the real oxygen saturation in patients with obesity undergoing bariatric surgery, especially for those with BMI ≥ 40 kg/m2, age ≥ 40 years, and high OS-MRS. ABG analysis can provide a more reliable basis for accurate and timely monitoring, ensuring the perioperative safety of susceptible patients.

Obesity hypoventilation syndrome in bariatric surgery patients: an underestimated disease.

BACKGROUND: Obesity is a known risk factor for obesity hypoventilation syndrome (OHS). However, study on the prevalence and clinical characteristics of OHS among bariatric surgery patients is scarce. OBJECTIVES: To investigate the prevalence of OHS in bariatric surgery patients and to identify its related predictors. SETTING: The study was conducted at a bariatric surgery center in a tertiary university hospital. METHODS: A cross sectional analysis was performed in the patients undergoing bariatric surgery between March 2017 and January 2020. Anthropometric, laboratory, pulmonary function, blood gas analysis, and polysomnographic data was collected and analyzed. RESULTS: Of 522 patients, the overall prevalence of OHS was 15.1%, with men (22.8 %) having a greater frequency than women (9.4%) (P < .001). The prevalence increases with obesity severity, from 4.1% in those with body mass index (BMI) <35 kg/m2 to 39.1% in those with BMI ≥50 kg/m2. Of 404 patients with obstructive sleep apnea (OSA), OHS was present in 17.3%, with 9.8% in mild OSA, 10.0% in moderate OSA, and 27.3%in severe OSA. Only 11.4% of patients diagnosed with OHS had no OSA. On logistic regression, BMI (odds ratio [OR]: 1.10; 95% confidence interval [CI], 1.01-1.21; P = .033), neck circumference (OR: 1.15; 95% CI, 1.03-1.28; P = .014), serum bicarbonate (OR: 1.39; 95% CI, 1.20-1.61; P = .000), C-reactive protein (CRP) (OR: 1.04; 95% CI, 1.00-1.07; P = .034) were independently associated with OHS. CONCLUSION: In bariatric surgery patients, OHS presented a high prevalence, especially in men. Higher levels of BMI, neck circumference, serum bicarbonate, and CRP indicated higher risk of OHS.

TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states.

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiological fasting and feeding.

Endophilin A2-mediated alleviation of endoplasmic reticulum stress-induced cardiac injury involves the suppression of ERO1α/IP3R signaling pathway.

Cardiac injury upon myocardial infarction (MI) is the leading cause of heart failure. The present study aims to investigate the role of EndoA2 in ischemia-induced cardiomyocyte apoptosis and cardiac injury. In vivo, we established an MI mouse model by ligating the left anterior descending (LAD) coronary artery, and intramyocardial injection of adenoviral EndoA2 (Ad-EndoA2) was used to overexpress EndoA2. In vitro, we used the siRNA and Ad-EndoA2 transfection strategies. Here, we reported that EndoA2 expression was remarkably elevated in the infarct border zone of MI mouse hearts and neonatal rat cardiomyocytes (NRCMs) stimulated with oxygen and glucose deprivation (OGD) which mimicked ischemia. We showed that intramyocardial injection of Ad-EndoA2 attenuated cardiomyocyte apoptosis and reduced endoplasmic reticulum (ER) stress in response to MI injury. Using siRNA for knockdown and Ad-EndoA2 for overexpression, we validated that knockdown of EndoA2 in NRCMs exacerbated OGD-induced NRCM apoptosis, whereas overexpression of EndoA2 attenuates OGD-induced cardiomyocyte apoptosis. Mechanistically, knockdown of EndoA2 activated ER stress response, which increases ER oxidoreductase 1α (ERO1α) and inositol 1, 4, 5-trisphosphate receptor (IP3R) activity, thus led to increased intracellular Ca2+ accumulation, followed by elevated calcineurin activity and nuclear factor of activated T-cells (NFAT) dephosphorylation. Pretreatment with the IP3R inhibitor 2-Aminoethoxydiphenylborate (2-APB) attenuated intracellular Ca2+ accumulation, and pretreatment with the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or the calcineurin inhibitor Cyclosporin A (CsA) inhibited EndoA2-knockdown-induced NRCM apoptosis. Overexpression of EndoA2 led to the opposite effects by suppressing ER-stress-mediated ERO1α/IP3R signaling pathway. This study demonstrated that EndoA2 protected cardiac function in response to MI via attenuating ER-stress-mediated ERO1α/IP3R signaling pathway. Targeting EndoA2 is a potential therapeutic strategy for the prevention of postinfarction-induced cardiac injury and heart failure.