Prevalence and associated factors of vitamin D deficiency after Roux-en-Y gastric bypass: a systematic review and meta-analysis.

OBJECTS: To estimate the prevalence and associated factors of vitamin D deficiency (VDD) after Roux-en-Y gastric bypass (RYGB). METHODS: PubMed, EMBASE, and CENTRAL were searched for relevant records from inception to 17 March 2023, using search terms: vitamin D, vitamin D3, vitamin D deficiency, hypovitaminosis D, gastric bypass, and RYGB. Studies were eligible for inclusion if they provided related data on VDD prevalence after RYGB. RESULTS: Of the 1119 screened studies, 72 studies involving 7688 individuals were enrolled in the final analysis. The prevalence estimates of VDD after RYGB were 42%. Subgroup analyses suggested the pooled prevalence of postoperative VDD was 35% for follow-up duration less than or equal to 1 year, 43% for greater than 1 and less than or equal to 5 years, and 54% for greater than 5 years. Meta-regression showed that VDD prevalence was positively correlated with follow-up time. Also, the prevalence was higher in studies with inadequate vitamin D supplementation than in those with adequate supplementation and in Asia population than in those from South America, Europe, and North America. Other factors associated with high VDD prevalence after RYGB included high presurgical VDD prevalence, noncompliant patients, and black populations. No significant association existed between VDD and alimentary length. CONCLUSION: VDD presented a high prevalence in patients following RYGB. It occurred more frequently with longer postoperative follow-up time. Population-specific vitamin D supplementation measures, targeted treatment for presurgical VDD, improved patient compliance, and periodical follow-ups were necessary to reduce VDD and other adverse outcomes.

Long-Term Results of Bariatric Surgery in Adolescents with at Least 5 Years of Follow-up: a Systematic Review and Meta-Analysis.

OBJECTS: The purpose of this study was to investigate the long-term outcomes of bariatric surgery in adolescents with obesity by including studies with a follow-up of at least 5 years. METHODS: PubMed, EMBASE, and CENTRAL were systematically searched. Studies that met the criteria were included in the analysis. RESULT: We identified 29 cohort studies with a total population of 4970. Preoperative age ranged from 12 to 21 years; body mass index (BMI) ranged from 38.9 to 58.5 kg/m2. Females were the predominant gender (60.3%). After at least 5-year of follow-up, the pooled BMI decline was 13.09 kg/m2 (95%CI 11.75-14.43), with sleeve gastrectomy (SG) was 15.27 kg/m2, Roux-en-Y gastric bypass (RYGB) was 12.86 kg/m2, and adjustable gastric banding (AGB) was 7.64 kg/m2. The combined remission rates of type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension (HTN), obstructive sleep apnea (OSA), and asthma were 90.0%, 76.6%, 80.7%, 80.8%, and 92.5%, (95%CI 83.2-95.6, 62.0-88.9, 71.5-88.8, 36.4-100, and 48.5-100), respectively. Postoperative complications were underreported. Combined with the current study, we found a low level of postoperative complications. Iron and vitamin B12 deficiencies were the main nutritional deficiency complications identified so far. CONCLUSION: For adolescents with severe obesity, bariatric surgery (especially RYGB and SG) is the independent and effective treatment option. After at least 5 years of follow-up, bariatric surgery in adolescents showed a desirable reduction in BMI and significant remission of T2DM, dyslipidemia, and HTN. Surgical and nutrition-related complications still need to be further explored by more long-term studies.

Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway.

The elabela-apelin/angiotensin domain type 1 receptor-associated protein (APJ) system is an important regulator in certain thrombosis-related diseases such as atherosclerosis, myocardial infarction, and cerebral infarction. Our previous reports have revealed that apelin exacerbates atherosclerotic lesions. However, the relationship between the elabela-apelin/APJ system and platelet aggregation and atherothrombosis is unclear. The results of the present study demonstrate that elabela and other endogenous ligands such as apelin-12, -17, and -36 induce platelet aggregation and thrombosis by activating the pannexin1(PANX1)-P2X7 signaling pathway. Interestingly, the diuretic, spironolactone, a novel PANX1 inhibitor, alleviated elabela- and apelin isoforms-induced platelet aggregation and thrombosis. Significantly, two potential antithrombotic drugs were screened out by targeting APJ receptors, including the anti-HIV ancillary drug cobicistat and the traditional Chinese medicine monomer Schisandrin A. Both cobicistat and Schisandrin A abolished the effects of elabela and apelin isoforms on platelet aggregation, thrombosis, and cerebral infarction. In addition, cobicistat significantly attenuated thrombosis in a ponatinib-induced zebrafish trunk model. Overall, the elabela-apelin/APJ axis mediated platelet aggregation and thrombosis via the PANX1-P2X7 signaling pathway in vitro and in vivo. Blocking the APJ receptor with cobicistat/Schisandrin A or inhibiting PANX1 with spironolactone may provide novel therapeutic strategies against thrombosis.

Prevalence of Rhabdomyolysis Following Bariatric Surgery and its Associated Risk Factors: a Meta-Analysis.

PURPOSE: This study aimed to evaluate the prevalence of rhabdomyolysis (RML) following bariatric surgery and potential associated factors. MATERIALS AND METHODS: We systematically searched PubMed, Embase, and CENTRAL for relevant trials from database inception through August 2022. Articles were eligible for inclusion if they reported the prevalence of RML after bariatric surgery and provided at least one of the following outcome indicators: preoperative mean BMI/mean operative time for the included population. RESULTS: Sixteen studies with a total of 1540 patients were analyzed. The mean preoperative age distribution of the included patients was centered between 32.9 and 47.0 years, and the mean preoperative BMI ranged from 42.3 to 60.0 kg/m2. The operative time varied between 126.7 and 403.3 min. The overall pooled crude prevalence of post-bariatric surgery RML was 19.4%. Subgroup analyses showed the pooled prevalence of RML was 8.1% for operative duration > 120 and ≤ 180 min, 32.8% for > 180 and ≤ 240 min, and 47.4% for > 240 min. Meta-regression revealed that operation time was an independent risk factor for developing RML. Besides, BMI > 50 kg/m2 and open Roux-en-Y gastric bypass (RYGB) indicated a higher risk of RML. CONCLUSION: Post-bariatric surgery RML prevalence occurred more frequently with the extension of the operation time. For bariatric subjects with surgery time > 180 min, open RYGB, or BMI > 50 kg/m2, CKP could be routinely measured early to verify the presence of RML and to actively prevent its fatal complications.

Prevalence and associated factors of secondary hyperparathyroidism after Roux-en-Y gastric bypass: A meta-analysis.

This study aimed to investigate the prevalence and factors associated with secondary hyperparathyroidism (SHPT) after Roux-en-Y gastric bypass (RYGB). We searched PubMed, EMBASE, and CENTRAL for relevant studies using search terms gastric bypass, RYGB and hyperparathyroidism. Thirty-four cohort studies with 4331 patients were incorporated into the final meta-analysis. Overall estimates of the prevalence of SHPT following RYGB were 39%. Subgroup analyses indicated the pooled prevalences of SHPT were 25%, 42%, 48%, and 54% for ≤1 year, >1 and ≤5 years, >5 and ≤10 years, and >10 years, respectively, after RYGB. Meta-regression showed that SHPT occurred was positively related to follow-up durations (p = 0.001). Additionally, SHPT prevalence was higher in studies in which calcium and vitamin D supplementation were considered inadequate than in those which were adequate (p = 0.002). SHPT is highly prevalent in individuals with obesity after RYGB. It seems to progress with time after surgery. Routine calcium and vitamin D supplementation post-RYGB together with targeted treatment of vitamin D deficiency, reasonable adjustment of the doses of supplementation with regular follow-up, and improved patient compliance, as well as long-term screening, are necessary to prevent the development of SHPT.

Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

Cardiac hypertrophy is a leading cause of cardiac morbidity and mortality worldwide. Apelin is the endogenous ligand for the G protein-coupled receptor, APJ. Previously, we have revealed that apelin-13 can induce cardiomyocyte hypertrophy by activating the autophagy pathway. However, the precise mechanism through which apelin-13 regulates reticulophagy to participate in cardiomyocyte hypertrophy remains unclear. Herein, we observed that apelin-13-induced cardiomyocyte hypertrophy by activating FAM134B-dependent reticulophagy via the Pannexin-1/P2X7 signal pathway. Furthermore, we found that apelin-13 stimulated the opening of Pannexin-1 hemichannel and increased extracellular ATP (eATP) levels, which activated the P2X7 purinergic receptor. Activation of the Pannexin-1/eATP/P2X7 axis subsequently led to FAM134B-dependent reticulophagy. Moreover, inhibition of the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy reversed apelin-13-induced cardiomyocyte hypertrophy. Based on our present findings, apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

Apelin/APJ signaling activates autophagy to promote human lung adenocarcinoma cell migration.

AIMS: Beclin1(BECN1) is known as an autophagy-related protein and the expression is promoted by apelin in lung adenocarcinoma cells, suggesting that apelin activates autophagy in lung adenocarcinoma. However, the functions of apelin-induced autophagy in lung adenocarcinoma tumorigenesis and deterioration are still unknown. Thus, this study aims to investigate the effects of apelin-induced autophagy on lung adenocarcinoma tumorigenesis and deterioration. MAIN METHODS: Protein expression of exogenous genes were detected by Western blotting analysis. Lung adenocarcinoma cell migration was assessed with cell migration assays. Autophagy was measured with quantification of GFP-LC3 or RFP-GFP-LC3 puncta using fluorescence microscopy in cells by an observed blinded to experimental condition and by western blot analysis of LC3 and p62 in cell lysates as well as autophagy flux. Immunofluorescence staining was performed in human lung adenocarcinoma A549 cells with p-cofilin antibody. The proteins expression in cancer specimens were examined with immunohistochemistry. KEY FINDINGS: Here, we reveal that apelin induces autophagy activation in lung adenocarcinoma. Apelin/APJ regulates BECN1 transcription via HIF1A. Apelin/APJ-activated autophagy promotes lung adenocarcinoma cell migration. Moreover, treatment with autophagy inhibitors significantly decreases apelin/APJ-induced lung adenocarcinoma cell migration. Evaluation of patient samples of lung adenocarcinoma reveals an association between APJ with BECN1 expression and a poor prognosis. SIGNIFICANCE: Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.

Prevalence and characteristics of gastric remnant cancer: A systematic review and meta-analysis.

The incidence and outcomes of GRC remain variable. Minority published researches have paid attention to the characteristics of GRC. This study aimed to make a systematic review and meta-analysis of the prevalence of GRC, with a focus on characteristics and survival rates of GRC. PubMed, EMBASE, and CENTRAL were searched for related clinical studies. Data were pooled using Stata 11.0, and subgroup and sensitivity analyses were performed if necessary and feasible. Moreover, SPSS (version 19.0) was used for comparing the clinical characteristics of GRC. Twenty studies were selected in this meta-analysis. The results indicated that the pooled prevalence of GRC was 2.6% (95% confidence interval (CI), 2.2-3.0%, p = 0.000). European population and American populations have a higher rate of prevalence of GRC than Chinese populations and Japan. There is no significant difference in histology and the TNM stage between the benign group and the malignant group. The five-year survival rate for GRC cases with benign primary gastric diseases is poorer than the primary gastric diseases malignant. Gastric remnant cancer is not a very rare clinical problem, especially for European and American patients. Active treatment and regular follow-up are conductive to increase 5-years survival rate.

Bile acid, glucose, lipid profile, and liver enzyme changes in prediabetic patients 1 year after sleeve gastrectomy.

BACKGROUND: Few articles have studied individuals with prediabetes after sleeve gastrectomy. Bile acid and lipid levels remain inconsistent in postbariatric patients. The purpose of this study was to explore bile acid, glucose, lipid, and liver enzyme changes in patients with different diabetes statuses who underwent sleeve gastrectomy. The impact of bariatric surgery and its potential benefits for prediabetic patients was also discussed. METHODS: A total of 202 overweight and obese patients who underwent bariatric surgery in our hospital between January 2016 and October 2018 were retrospectively reviewed. Patients were divided into prediabetes (n = 32), nondiabetes (n = 144), and diabetes (n = 26) groups and analysed. Glucose and lipid data were collected from medical records at baseline and at each follow-up visit. RESULT: Significant improvements in body weight, glucose and lipid levels, and liver enzymes (P ≤ 0.05) in prediabetic patients were found throughout the first year postoperatively. Improvement in glycaemic control was first seen one month postoperatively, followed by persistent improvement in the next 12 months. Total bile acid (TBA) decreased, which was associated with ALT improvement in prediabetic patients 1-year post-surgery. There were no significant differences in HbA1c, glucose, or triglycerides (TGs) between prediabetic and T2DM patients or between prediabetic and nondiabetic patients at 12 months post-surgery. CONCLUSION: LSG is highly effective at interfering with glucose and lipid levels as well as total bile acid levels in prediabetic patients in the first year postoperatively. Thus, LSG is indeed an alternative for overweight and obese prediabetic patients.

Regulation of the Golgi apparatus via GOLPH3-mediated new selective autophagy.

AIMS: Although previous studies elaborated that selective autophagy was involved in quality control of some organelles, including nucleus, mitochondria, the endoplasmic reticulum and peroxisomes, it remained unclear whether the selective autophagy of the Golgi apparatus (Golgiphagy) existed or not. MAIN METHODS: In this study, H9c2 cells, HUVECs, HA-VSMCs and HEK293T cells were treated with autophagy inducers, Golgi stress inducers and cardiomyocytes hypertrophy stimulators. The Golgiphagy was evaluated by analysing the co-localization of Golgi markers and LC3B. Furthermore, the transmission electron microscope was used to observe the occurrence of Golgiphagy. The co-immunoprecipitation assay was used to evaluate the interaction of GOLPH3 and LC3B. KEY FINDINGS: Results showed that starvation promoted the co-localization of both GM130-positive and TGN46-positive Golgi fragments with LC3B-positive autophagosomes in H9c2 cells, HUVECs, HA-VSMCs and HEK293T cells. Transmission electron microscopy images showed that Golgi apparatus was sequestered into the autophagosomes in the starvation group. Moreover, Golgi stress inducers also facilitated the co-localization of Golgi markers and LC3B in H9c2 cells, HUVECs, HA-VSMCs and HEK293T cells. Furthermore, cardiomyocyte hypertrophy stimulators also triggered the appearance of Golgiphagy in H9c2 cells. Importantly, the co-immunoprecipitation assay indicated endogenous GOLPH3 interacted with LC3B in H9c2 cells, HUVECs, HA-VSMCs. However, knocking down GOLPH3 inhibited the Golgiphagy. SIGNIFICANCE: This study unveiled a new selective autophagy of the Golgi apparatus (Golgiphagy). In addition, GOLPH3 might act as a novel cargo receptor to regulate Golgiphagy. Maintaining homeostasis of the Golgi apparatus via GOLPH3-mediated autophagy was indispensable for cell survival.

Different surgical techniques that influenced internal hernia prevalence rate after laparoscopic roux-en-Y gastric bypass: a retrospective analysis of 331 cases.

BACKGROUND: Internal hernia (IH) is a serious complication following laparoscopic Roux-en-Y gastric bypass (LRYGB), and closure of mesenteric defect has been recommended to reduce this complication. But what kind of material about suture and how to close the mesenteric defects were still controversial. The main aim of this study was to compare the incidence rate of internal hernia after LRYGB between patients with different surgical techniques. METHOD: Three hundred and thirty-one patients underwent LRYGB between June 2004 and December 2017 in one single institute were retrospective analysed. The IH rate was evaluated according to different surgical methods and surgical materials before and 12 months after LRYGB. RESULTS: All the cases were subdivided into three groups based on the suturing method, Roux limb position, and Suture material. The mean follow up time was 36 ± 12 months, and the total incident rate of IH was 1.8% (n = 6). In the six IH cases, the duration of IH occurred time ranged from 1 month to 36 months postoperatively, and for the IH sites, one for intestinal defect, three for transverse mesocolon defect and two Peterson defect respectively. There was a significant difference about IH rate between interrupted suture and running suture groups (p = 0.011), and there were no significant differences between the other two groups. CONCLUSION: Compare with interrupted suture, running suture may prevent IH after LRYGB. Patient's gender, age, body mass index(BMI), glycometabolism condition, and Roux limb position and suture material had no effects on the IH prevalence after LRYGB.

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

Circular RNAs (circRNAs) play an important regulatory role in a variety of human cancers, including gastric cancer. The mechanisms for the circRNAs in gastric cancers are not fully understood. This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proliferation and invasion of gastric cancer cells. Mechanically, hsa_circ_0008035 acted as a sponge for the miR-375 and absorbed its expression, and miR-375 was found to target YBX1 3'-UTR, constructing a hsa_circ_0008035/miR-375/YBX1 axis. Taken together, these findings are evidence that circRNA hsa_circ_0008035 promotes gastric cancer cell proliferation and invasion by regulating miR-375/YBX1.

Ferritinophagy activation and sideroflexin1-dependent mitochondria iron overload is involved in apelin-13-induced cardiomyocytes hypertrophy.

Excess iron accumulation and cardiac oxidative stress have been shown as important mediators of cardiac hypertrophy, whereas it remains largely elusive about the occurrence of mitochondrial iron overload and its significance during cardiac hypertrophy. In the present study, we aim to investigate the role of NCOA4-mediated ferritinophagy and SFXN1-dependent mitochondria iron overload in apelin-13-induced cardiomyocytes hypertrophy. Apelin-13 significantly promotes ferric citrate (FAC)-induced total cellular and mitochondria ion production, as well as mitochondria ROS contents. Mechanistically, apelin-13 effectively induces the expression of SFXN1, a mitochondria iron transporting protein and NCOA4, a cargo receptor of ferritinophagy in dose and time-dependent manner. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. In addition, apelin-13-triggered mitochondria iron overload is reversed by the genetic inhibition of SFXN1 and NCOA4. NCOA4 deficiency via its silencing also interferes with the enhanced expression of SFXN1 evoked by apelin-13. In apelin-13-treated H9c2 cells, the promotion in cell diameter, volume as well as protein contents are obviously suppressed by the knockdown of NCOA4 and SFXN1 with their corresponding siRNAs. Remarkably, the human and murine hypertrophic hearts models, as well as apelin-13-injected mice models, present evident cardiac mitochondrial iron deposition and raised expressions of NCOA4 and SFXN1. Taken together, these results provide experimental evidences that NCOA4-mediated ferritinophagy might be defined as an essential mechanism leading to apelin-13-cardiomyocytes hypertrophy in SFXN1-dependent mitochondria iron overload manners.

PINK1/Parkin-mediated mitophagy promotes apelin-13-induced vascular smooth muscle cell proliferation by AMPKα and exacerbates atherosclerotic lesions.

Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin-13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. In this study, we aimed to investigate the role of mitophagy in apelin-13-induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE-/-) mice. Apelin-13 enhances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time-dependent manner, while is abolished by APJ antagonist F13A. We observe the engulfment of damage mitochondria by autophagosomes (mitophagy) of human aortic VSMC in apelin-13 stimulation. Mechanistically, apelin-13 increases p-AMPKα and promotes mitophagic activity such as the LC3I to LC3II ratio, the increase of Beclin-1 level and the decrease of p62 level. Importantly, the expressions of PINK1, Parkin, VDAC1, and Tom20 are induced by apelin-13. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. Human aortic VSMC transfected with AMPKα, PINK1, or Parkin and subjected to apelin-13 impairs mitophagy and prevents proliferation. Additional, apelin-13 not only increases the expression of Drp1 but also reduces the expressions of Mfn1, Mfn2, and OPA1. Remarkably, the mitochondrial division inhibitor-1(Mdivi-1), the pharmacological inhibition of Drp1, attenuates human aortic VSMC proliferation. Treatment of ApoE-/- mice with apelin-13 accelerates atherosclerotic lesions, increases p-AMPKα and mitophagy in aortic wall in vivo. Finally, PINK1-/- mutant mice with apelin-13 attenuates atherosclerotic lesions along with defective in mitophagy. PINK1/Parkin-mediated mitophagy promotes apelin-13-evoked human aortic VSMC proliferation by activating p-AMPKα and exacerbates the progression of atherosclerotic lesions.

ROS-Autophagy pathway mediates monocytes-human umbilical vein endothelial cells adhesion induced by apelin-13.

Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI. Autophagy flux induced by apelin-13 was inhibited by NAC and catalase but not hydroxychloroquine (HCQ). NAC, catalase, and DPI prevented apelin-13 induced ICAM-1 expression in HUVECs. Rapamycin enhanced MCs-HUVECs adhesion that was reversed by NAC, catalase, and DPI. Down-regulation of beclin1 and LC3 by siRNA blocked MCs-HUVECs adhesion. Apelin-13 induced atherosclerotic plaque and increased NOX4, LC3-II/I expression in ApoE-/-(HFD) mouse model. Our results demonstrated that apelin-13 induced MCs-HUVECs adhesion via a ROS-autophagy pathway.