Search

Background The functions of liver fatty acid binding protein (FABP1) in the regulation of nonalcoholic fatty liver disease (NAFLD) have been demonstrated. However, it is not fully understood how FABP1 expression is dynamically regulated in metabolic disorders. Previous studies have reported that ubiquitin proteasome-mediated degradation of FABP1 is involved, but the mechanism remains unknown.Methods Dysregulated expression of hepatic FABP1 and Derlin-1 was observed in NAFLD patients. We performed mice hepatic tissue co-immunoprecipitation (IP)-based mass spectrum (MS) assays. Derlin-1 interacts with FABP1 and modifies its ubiquitin status, as confirmed by co-IP. The role of Derlin-1 in lipid deposition was tested using adenovirus-mediated overexpression in C57 mice, Derlin-1 overexpression (Derlin-1-OE), or Derlin-1 knockdown (Derlin-1-KO) HepG2 cells.Results As a subunit of the endoplasmic reticulum-associated degradation complex (ERAD), Derlin-1 is negatively associated with NAFLD patients and interacts with and ubiquitinates FABP1. Derlin-1 suppresses FABP1 protein levels and inhibits lipid deposition through a FABP1-dependent pathway. Additionally, Trim25, an E3 ubiquitin ligase present in the endoplasmic reticulum (ER), is recruited to promote Derlin-1-related polyubiquitylation of FABP1, thereby creating a ubiquitin-associated network for FABP1. Overexpression of Derlin-1 ameliorates hepatic steatosis in both C57 mice and HepG2 cells, and contributes to attenuated weight gain, lower liver weight, and visceral fat mass.Conclusions FABP1, a master enzyme that maintains fatty acid metabolism, undergoes degradation by Derlin-1 through ubiquitin modification. The activation of Derlin-1 in vivo may represent a potential therapeutic strategy for NAFLD.Trial registration: Clinical Trials. gov ID: NCT02118376.

Background: Several studies suggested that depression was associated with poor prognosis following percutaneous coronary intervention (PCI) in coronary heart disease (CHD), whereas other studies showed that there were no associations between depression and poor outcomes. Objectives: Considering these problems, this meta-analysis was conducted to evaluate the relationship between depression and clinical outcomes after PCI. Methods: Articles published before July 2021 were analyzed from the databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI with a random or fixed effects model. Q test and I2 were used to assess heterogeneities between studies. Results: The meta-analysis indicated that depression was associated with a higher risk of major adverse cardiac events (MACE) after PCI with a random effects model (HR = 1.89, 95% CI: 1.33–2.68, I2 = 57.0%, p = 0.023). The study indicated that depression was associated with a higher risk of all-cause mortality after PCI with a fixed effects model (HR = 1.71, 95% CI: 1.43–2.05, I2 = 0.0%, p = 0.756). The study indicated no significant association between depression and risk of repeat revascularization after PCI with a random effects model (HR = 2.10, 95% CI: 0.96–4.58, I2 = 68.9%, p = 0.022). Conclusion: Results indicated that depression is associated with adverse clinical outcomes in CHD patients’ post-PCI. Appropriate mental health check and psychological treatment may be necessary for the prognosis of CHD patients who receive PCI.

Wei Su,1 Cuiling Zhu,1 Xin Zhang,1 Jun Xie,2 Qingxian Gong2 1School of Management Science and Engineering, Shandong University of Finance and Economics, Jinan, Shandong, People’s Republic of China; 2Shunneng Network Technology Limited Company, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Wei Su; Xin Zhang Email suwei@sdufe.edu.cn; zhangxin@sdufe.edu.cnPurpose: Missed appointments in outpatient registration pose challenges for hospital administrators, especially in the context of China’s shortage of medical resources. Previous studies have identified factors that affect healthcare access via traditional appointment systems. Few studies, however, have specifically investigated Internet appointment systems. Therefore, this study explored the key factors related to missed appointments made on the Internet appointment system of a general hospital in Jinan, Shandong Province.Methods: Online appointment data were collected from the outpatient department of a general hospital in Jinan from September 2017 to February 2018. Logistic regression was used to analyze the relative importance of eight variables: gender, age, interval between scheduling and appointment, day of the week, physician’s academic rank, appointment fee, previous missed appointments, and clinical department.Results: A total of 48,777 online appointment records were collected, which included a 15% no-show rate. The key factors associated with no-shows included age, interval between scheduling and appointment, previous missed appointments, and clinical department. No significant relationships were found between no-shows and gender, day of the week, and appointment fee.Conclusion: No-show rates were influenced by many factors. Based on this study’s findings, targeted measures can be taken to decrease no-show frequency and improve medical efficiency.Keywords: online appointments, no-show appointments, influential factors, logistic regression

Purpose Missed appointments in outpatient registration pose challenges for hospital administrators, especially in the context of China's shortage of medical resources. Previous studies have identified factors that affect healthcare access via traditional appointment systems. Few studies, however, have specifically investigated Internet appointment systems. Therefore, this study explored the key factors related to missed appointments made on the Internet appointment system of a general hospital in Jinan, Shandong Province. Methods Online appointment data were collected from the outpatient department of a general hospital in Jinan from September 2017 to February 2018. Logistic regression was used to analyze the relative importance of eight variables: gender, age, interval between scheduling and appointment, day of the week, physician's academic rank, appointment fee, previous missed appointments, and clinical department. Results A total of 48,777 online appointment records were collected, which included a 15% no-show rate. The key factors associated with no-shows included age, interval between scheduling and appointment, previous missed appointments, and clinical department. No significant relationships were found between no-shows and gender, day of the week, and appointment fee. Conclusion No-show rates were influenced by many factors. Based on this study's findings, targeted measures can be taken to decrease no-show frequency and improve medical efficiency.

To investigate the capacity of ultrashort echo time (UTE) T1 mapping to non-invasively assess gadolinium deposition in cortical bone after gadolinium-based contrast agent (GBCA) administration. Twenty-eight New Zealand rabbits (male, 3.0–3.5 kg) were randomly allocated into control, macrocyclic, high-dose macrocyclic, and linear GBCA groups (n = 7 for each group), and respectively given daily doses of 0.9 ml/kg bodyweight saline, 0.3 mmol/kg bodyweight gadobutrol, 0.9 mmol/kg bodyweight gadobutrol, and 0.3 mmol/kg bodyweight gadopentetate dimeglumine for five consecutive days per week over a period of 4 weeks. After a subsequent 4 weeks of recovery, the rabbits were sacrificed and their tibiae harvested. T1 value of cortical bone was measured using a combination of UTE actual flip angle imaging and variable repetition time on a 7T animal scanner. Gadolinium concentration in cortical bone was measured using inductively coupled plasma mass spectrometry (ICP-MS). Pearson’s correlation between R1 value (R1 = 1/T1) and gadolinium concentration in cortical bone was assessed. Bone T1 values were significantly lower in the lower-dose macrocyclic (329.2 ± 21.0 ms, p < 0.05), higher-dose macrocyclic (316.8 ± 21.7 ms, p < 0.01), and linear (296.8 ± 24.1 ms, p < 0.001) GBCA groups compared with the control group (356.3 ± 19.4 ms). Gadolinium concentrations measured by ICP-MS in the control, lower-dose macrocyclic, higher-dose macrocyclic, and linear GBCA groups were 0.04 ± 0.02 μg/g, 2.60 ± 0.48 μg/g, 4.95 ± 1.17 μg/g, and 13.62 ± 1.55 μg/g, respectively. There was a strong positive correlation between R1 values and gadolinium concentrations in cortical bone (r = 0.73, p < 0.001). These results suggest that UTE T1 mapping has the potential to provide a non-invasive assessment of gadolinium deposition in cortical bone following GBCA administration. • Changes in T 1 value related to gadolinium deposition were found in bone after both linear and macrocyclic GBCA administrations. • R 1 relaxometry correlates strongly with gadolinium concentration in cortical bone. • UTE T 1 mapping provides a potential tool for non-invasively monitoring gadolinium deposition in cortical bone.

Cholelithiasis is one of the most prevalent gastroenterological diseases and is characterized by the formation of gallstones in the gallbladder. Both clinical and preclinical data indicate that obesity, along with comorbidity insulin resistance, is a predisposing factor for cholelithiasis. Forkhead box O1 (FoxO1) is a key transcription factor that integrates insulin signaling with hepatic metabolism and becomes deregulated in the insulin-resistant liver, contributing to dyslipidemia in obesity. To gain mechanistic insights into how insulin resistance is linked to cholelithiasis, here we determined FoxO1's role in bile acid homeostasis and its contribution to cholelithiasis. We hypothesized that hepatic FoxO1 deregulation links insulin resistance to impaired bile acid metabolism and cholelithiasis. To address this hypothesis, we used the FoxO1(LoxP/LoxP)-Albumin-Cre system to generate liver-specific FoxO1-knockout mice. FoxO1-knockout mice and age- and sex-matched WT littermates were fed a lithogenic diet, and bile acid metabolism and gallstone formation were assessed in these animals. We showed that FoxO1 affected bile acid homeostasis by regulating hepatic expression of key enzymes in bile acid synthesis and in biliary cholesterol and phospholipid secretion. Furthermore, FoxO1 inhibited hepatic expression of the bile acid receptor farnesoid X receptor and thereby counteracted hepatic farnesoid X receptor signaling. Nonetheless, hepatic FoxO1 depletion neither affected the onset of gallstone disease nor impacted the disease progression, as FoxO1-knockout and control mice of both sexes had similar gallstone weights and incidence rates. These results argue against the notion that FoxO1 is a link between insulin resistance and cholelithiasis.

The role of liver fatty acid-binding protein (FABP1) in obesity is presently unclear. We investigated the association of FABP1 with obesity and the changes noted after laparoscopic sleeve gastrectomy (LSG) in a Chinese population. The cross-sectional analysis included 187 individuals: 65 had normal weight (18.5 ≤ body mass index (BMI)

Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). Hepatic inflammation results from abnormal macrophage activation. We found that FoxO1 links overnutrition to hepatic inflammation by regulating macrophage polarization and activation. FoxO1 was upregulated in hepatic macrophages, correlating with hepatic inflammation, steatosis, and fibrosis in mice and patients with NASH. Myeloid cell conditional FoxO1 knockout skewed macrophage polarization from proinflammatory M1 to the antiinflammatory M2 phenotype, accompanied by a reduction in macrophage infiltration in liver. These effects mitigated overnutrition-induced hepatic inflammation and insulin resistance, contributing to improved hepatic metabolism and increased energy expenditure in myeloid cell FoxO1-knockout mice on a high-fat diet. When fed a NASH-inducing diet, myeloid cell FoxO1-knockout mice were protected from developing NASH, culminating in a reduction in hepatic inflammation, steatosis, and fibrosis. Mechanistically, FoxO1 counteracts Stat6 to skew macrophage polarization from M2 toward the M1 signature to perpetuate hepatic inflammation in NASH. FoxO1 appears to be a pivotal mediator of macrophage activation in response to overnutrition and a therapeutic target for ameliorating hepatic inflammation to stem the disease progression from benign steatosis to NASH.

Bariatric surgery is an effective method for severe obesity and its related comorbidities. This study was performed to explore the alterations of sex hormones and inflammatory markers following laparoscopic sleeve gastrectomy (LSG) among obese Chinese men with acanthosis nigricans (AN). Sixty-five obese men who underwent LSG were enrolled, comprising simple obesity without AN (OB group, n = 20) and obesity with AN (AN group, n = 45). There were 31 healthy male controls with normal body mass index (BMI) included. Anthropometry data, inflammatory markers, sex hormones and metabolic parameters were compared preoperatively and 12 months post-operatively. At baseline, patients in the AN group were associated with more severe metabolic abnormalities than the OB and control groups. Twelve months after surgery, AN patients obtained significant improvement in skin condition and reduction in AN score. BMI, fasting insulin (FINS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), tumor necrosis factor-α (TNF-α) and total testosterone (TT) were significantly changed in both groups, while interleukin (IL)-6, IL-8 and C-reactive protein were changed significantly only in the AN group. Moreover, FINS, HOMA-IR, TT and IL-6 levels were changed more in the AN group than those in the OB group. Multivariate regression analysis revealed that TT increase correlated significantly with reduction in FINS and HOMA-IR in both groups, but correlated with changes in IL-6 only in the AN group. In conclusion, LSG is effective in improving the skin condition of obese men with AN. The increased TT in AN patients correlated with amelioration of inflammatory state in addition to insulin resistance after LSG.

To examine changes in sex hormones after laparoscopic sleeve gastrectomy (LSG) in Chinese obese male patients and their correlation with metabolic parameters including serum uric acid (SUA) A total of 56 obese men with body mass index (BMI) 41.9 ± 5.8 kg/m2 undergoing LSG were selected. Thirty-one healthy men with normal BMI were included as controls. Levels of total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), SUA, and other metabolic indices were compared pre- and 12 months post-LSG. Calculated free testosterone (cFT) was calculated from TT and SHBG using an empirical equation. At baseline, low TT and hyperuricemia (HUA) were common in obese men. Twelve months after LSG, statistically significant reduction in weight, BMI, and glucolipid metabolism indices was noted. SUA levels declined remarkably from 474.9 ± 94.6 to 338.8 ± 81.9 μmol/L and the percentage of HUA decreased from 76.8 to 54.1% (all P

Gestational diabetes mellitus (GDM) is characterized by fasting hyperglycemia and glucose intolerance during pregnancy, but with poorly understood mechanisms. We found that prolactin receptor (Prlr) is markedly upregulated in liver of pregnant female mice. These findings have spurred the hypothesis that hepatic Prlr signaling is pivotal for physiological adaptation of hepatic metabolism to gestation. To address this hypothesis, we generated liver-conditional L-Prlr-KO mice, followed by determination of glucose and lipid metabolism in female L-Prlr-KO vs. age-matched female WT mice prior to and during gestation. Hepatic Prlr depletion did not impact glucose and lipid metabolism in virgin L-Prlr-KO mice. However, pregnant L-Prlr-KO mice developed GDM, as evidenced by the induction of glucose intolerance, fasting hyperglycemia, higher HOMA-IR levels and abnormal glucose-stimulated insulin secretion at gestational day 15.5. We reproduced these findings in female L-Prlr-KO mice in the 1st, 2nd and 3rd pregnancy, with the severity of GDM exacerbated by transient high fat feeding prior to conception in female L-Prlr-KO mice. Hepatic Prlr depletion did not affect litter size, but pups born to L-Prlr-KO mice had significantly lower birth weight. We recapitulated this finding in newborns derived from the 1st, 2nd and 3rd pregnancy in L-Prlr-KO mice. Hepatic Prlr depletion also resulted in increased triglyceride and cholesterol levels in liver, characteristic of nonalcoholic fatty liver disease and consistent with increased insulin resistance in pregnant L-Prlr-KO mice. Multiparous L-Prlr-KO mice developed postpartum prediabetes. Our studies unveiled an unprecedented role of hepatic Prlr signaling in regulating maternal hepatic metabolism to protect against GDM. Disclosure C. Zhu: None. J. Yamauchi: None. C. Pan: None. J. Gao: None. S. Qu: None. R.R. Banerjee: None. H. Dong: None. Funding National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)

To investigate the capacity of ultrashort echo time (UTE) TTwenty-eight New Zealand rabbits (male, 3.0-3.5 kg) were randomly allocated into control, macrocyclic, high-dose macrocyclic, and linear GBCA groups (n = 7 for each group), and respectively given daily doses of 0.9 ml/kg bodyweight saline, 0.3 mmol/kg bodyweight gadobutrol, 0.9 mmol/kg bodyweight gadobutrol, and 0.3 mmol/kg bodyweight gadopentetate dimeglumine for five consecutive days per week over a period of 4 weeks. After a subsequent 4 weeks of recovery, the rabbits were sacrificed and their tibiae harvested. TBone TThese results suggest that UTE T• Changes in T

Aims Osteocalcin contributes to the regulation of endocrine system. However, the association between osteocalcin and ketosis has not been evaluated. We thus aimed to explore the relationship between total osteocalcin and risk of ketosis in type 2 diabetes (T2DM). Materials and methods We identified 6157 diabetes patients from Shanghai Tenth People's Hospital between 1 January 2011 and 1 March 2017. Six hundred eight subjects were enrolled in the retrospective cross-sectional study: 304 T2DM patients with ketosis whose age, gender, and body mass index were matched with 304 T2DM patients without ketosis. A further retrospective nested case-control study was conducted in 252 T2DM patients without ketosis for a mean duration of 21.58 ± 12.43 months to investigate the occurrence of ketosis. Results Osteocalcin levels were negatively correlated with blood ketones (adjusted r = -0.263) and urine ketones (adjusted r = -0.183). The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio [95% CI] = 2.56 [0.80-8.17], 3.71 [0.90-15.29], 10.77 [2.63-44.15], 23.81 [4.32-131.17] per osteocalcin quintile, respectively). Ketosis occurred in 17 of the 252 T2DM patients during follow-up. The Cox regression analysis indicated that osteocalcin was an independent protective factor against development of ketosis (adjusted hazard ratio [95% CI]: 0.668 [0.460-0.971]). Conclusions Total osteocalcin can be used as a predictor of ketosis in T2DM.

The forkhead box O (FoxO) family consists of FoxO1, FoxO3, FoxO4, and FoxO6 transcription factors in mammalian cells. These four FoxO members are encoded by four distinct genes, which are situated on different chromosomes and are ubiquitously expressed in central and peripheral tissues. They share in common a “forkhead box” or “winged helix” domain, a highly conserved structural protein motif that is responsible for binding to chromatin DNA in the nucleus of cells. Their carboxyl domains, which are evolutionarily divergent in amino acid sequences, are responsible for interacting with variable cofactors to enhance or inhibit target gene expression via a trans-activation or trans-repression mechanism. The FoxO transcription factors are instrumental for integrating nutritional and hormonal signaling to key functions in diverse pathways including cell metabolism, proliferation, differentiation, oxidative stress, cell survival and senescence, autophagy, and aging. Genetic mutations in the FoxO genes, accompanied by alteration of FoxO expression and activity in cells, are associated with a variety of diseases including obesity, diabetes and cancer, or with altered lifespan in mammals. Among the four FoxO isoforms, FoxO1 is the best characterized one for its role in mediating the inhibitory effect of insulin or insulin-like growth factor on glucose and lipid metabolism. In this chapter, we provide an in-depth review of FoxO1 in insulin action and carbohydrate metabolism. We will review clinical and preclinical evidence that FoxO1 deregulation, resulting from insulin resistance, contributes to the dual pathogenesis of hyperglycemia and hyperlipidemia in obesity and type 2 diabetes. We will also review the role of FoxO1 in macrophages and its contribution to hepatic inflammation and nonalcoholic fatty liver disease. FoxO1 is viewed as a potential therapeutic target for improving glucose and lipid metabolism. We will discuss the potential therapeutic benefits and possible adverse effects of pharmacological inhibition of FoxO1 activity in insulin-resistant subjects with metabolic diseases.

Background and objective The stomach plays an important role in obesity and obesity-related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. Methods We performed gene microarray and real time-polymerase chain reaction (RT-PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. Results In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co-regulated in both comparisons. Seven differentially expressed genes were validated by RT-PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G-protein coupled receptor biological processes, and primarily participated in the PI3K-Akt and AGE-RAGE signaling pathways. Conclusions Obesity and obesity-related diabetes are associated with important gene expression and pathway alterations in the stomach.

Laparoscopic sleeve gastrectomy (LSG) has proven to be successful in weight reduction but with potential loss of bone mass. Previous studies indicated that bone morphogenetic protein 4 (BMP4) plays an important role in both bone formation and glucose-lipid metabolism. This study aimed to investigate the changes in bone mineral density (BMD), bone metabolic parameters, and serum BMP4 levels in obese Chinese subjects after LSG.Seventy-one obese patients (34 males, age 31.70 ± 9.61 years and 37 females, age 32.80 ± 11.45 years) were enrolled. BMD (at the right hip, femoral neck, and lumbar spine 1-4 (L1-L4)) was measured by dual-energy X-ray absorptiometry, bone metabolic markers, and routine anthropometric/laboratory biochemical parameters at baseline, 3, 6, and 12 months after LSG (abbreviated as 3, 6, and 12 M post-LSG, respectively) were recorded. Serum BMP4 levels were measured by enzyme-linked immunosorbent assay.LSG led to dramatic weight loss with improved glucose-lipid metabolism in all patients. In females, BMD was significantly decreased at the right hip at all time points studied and at the femoral neck at 6 and 12 M post-LSG (P 0.05 or P 0.01). In males, BMD was not significantly changed (all P 0.05). Intriguingly, serum BMP4 levels were reduced slightly at 3 M post-LSG (P = 0.463) and were significantly at 6 M post-LSG (from 75.51 ± 16.54 to 65.40 ± 10.51 pg/mL, P = 0.048) in females, but unchanged in males (all P 0.05). Vitamin D and 25-hydroxy vitamin D were increased in males at 12 M post-LSG (all P 0.05). Osteocalcin was increased in males at all time points studied and in females at 3 and 6 M post-LSG (all P 0.05). Type I collagen was increased in males at 3 and 6 M post-LSG and in females at all the time points studied (all P 0.05).The effect of LSG on BMD differs between genders, decreasing significantly in females while remaining unchanged in males. Moreover, decreased BMP4 levels may partly account for the diminished BMD in obese Chinese female patients after LSG.

The study was designed to examine changes of body fat distribution after laparoscopic sleeve gastrectomy (LSG) in obese male patients and to confirm whether these changes are correlated with increased testosterone. A total of 30 obese male patients with body mass index (BMI) 30–45 kg/m2 were enrolled in this study. Data on demographic characteristics, anthropometry, metabolic parameters, and body fat distribution were collected at baseline and 6 months after LSG. Body fat distribution was assessed by dual-energy X-ray absorptiometry (DXA). Six months after surgery, the BMI of participants (age 33.0 ± 9.5) decreased from 40.2 ± 5.2 to 30.8 ± 4.4 kg/m2, total testosterone increased from 2.4 ± 1.2 to 4.5 ± 1.8 ng/mL, and the percentage of testosterone deficiency in these patients decreased from 82.7 to 23.1%. Fat mass was significantly decreased in all regions, but the loss of fat mass in the android region was more than that in any other body region. After adjusting age and the BMI, the changes in android FM% and gynoid FM% were significantly correlated with an increase in total testosterone concentration (R2 = 0.187, R2 = 0.282, respectively). In obese male patients with BMI 30–45 kg/m2, an increase of total testosterone correlated to the changes in android FM% and gynoid FM% at the sixth month after LSG surgery.

OBJECTIVE To investigate the gut microbiota in healthy volunteers (HVs), patients with overweight (OW), and patients with obesity (OB), including those with acanthosis nigricans (AN) or without AN (N-AN). METHODS Microbial 16S rRNA genes were examined by using pyrosequencing technology and analyzed by using bioinformatics methods. RESULTS Subjects in the OW and OB groups showed severe disturbances in glycemic control, lipid profile, and inflammatory markers (all P

Background Acanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans. Methods A total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis. Results Patients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P

Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P

Liver fatty acid-binding protein (FABP1) is associated with intracellular transportation of fatty acids. However, only few studies indicated the relationship between serum FABP1 and metabolism. This study aimed to investigate the association of FABP1 levels and metabolism factors, and its change with laparoscopic sleeve gastrectomy (LSG) in Chinese. The cross-sectional analysis included a total of 187 subjects, of which 65 were with normal weight (BMI 18-24 kg/m2), 59 with over weight (BMI25-27 kg/m2), and 64 with obesity (BMI≥28 kg/m2). We found FABP1 levels in obese (303±235pg/ml, p In conclusion, serum FABP1 were correlated with obesity and NAFLD, and it might be an important mediator participating in metabolism disorders. Disclosure H. You: None. Z. Lin: None. C. Zhu: None. X. Wen: None. M. Zhang: None. S. Qu: None. Funding National Key Research and Development Program of China (2018YFC1314101); National Natural Science Foundation of China (81700752, 81500687)

Objective: This study was designed to examine changes in body fat distribution after laparoscopic sleeve gastrectomy (LSG) and to confirm whether these changes are correlated with increased testosterone. Methods: A retrospective study was performed in 51 obese female patients with BMI 30-45 kg/m2 who underwent LSG from Shanghai Tenth People’s Hospital, 38 of whom were PCOS patients. The anthropometric indexes, sex hormone and ovarian volume of ultrasound examinations include both sides ovarian volume, mean ovarian volume (MOV) and maximal ovarian volume (MaxOV) were observed preoperative and follow-up at 3 and 6 months after LSG. The metabolic indexes and ovarian volume were compared before and after surgery. Results: Compared with preoperative, PCOS patients' weight, BMI, waist circumference and hip circumference were significantly lower at 3 and 6 months after operation (P Conclusions: TT and cFT decreased and SHBG increased significantly after LSG. MOV shrinked at 6 months after LSG and was no longer different from non-PCOS patients. LSG is not only an important treatment for weight loss, but also improve PCOS and its clinical symptoms effectively in severe obese women. Disclosure J. Gao: None. M. Zhang: None. C. Zhu: None. X. Wang: None. F. Mei: None. S. Qu: None. Funding National Natural Science Foundation of China (81601269)

Background: Hyperuricemia (HUA) and sex hormone imbalance in obese patients can be reversed by bariatric surgery. However, the relationships between changes in serum uric acid (SUA) and sex hormones variations after bariatric surgery is unexplored. We aimed to investigate the correlations between changes in SUA and sex hormones variations after laparoscopic sleeve gastrectomy (LSG) in Chinese obese patients in relation to gender. Methods: We enrolled 133 severely obese patients who underwent LSG in this study. SUA, sex hormones, and relevant metabolic parameters were compared pre- and 12 months post-LSG. Results: At baseline, HUA was more common in males than in females. Twelve months after LSG, significant improvements in BMI and glucolipid metabolic indices were noted. SUA levels and the prevalence of HUA were declined significantly in both gender while the changes in SUA and percentage of SUA variations were significantly greater in females than in males (all P Conclusion: LSG promotes more profound improvement of SUA levels in female obese patients than in males, and SUA reduction after surgery correlated significantly with different sex hormones changes in males and females. Disclosure C. Zhu: None. J. Gao: None. F. Mei: None. X. Wang: None. D. Zhou: None. S. Qu: None. Funding Shanghai Municipal Science and Technology Commission (17DZ1910603); Fundamental Research Funds for the Central Universities (1501219107); National Natural Science Foundation of China (81500650, 81700752, 81570782)

Background Hyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored. Methods In total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels. Results Compared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P

In order to improve the inventory management level of pharmaceutical chain enterprise, drug sales forecasting is needed. Using machine learning SVR model, we forecast the drugs sale amount with a relatively high accuracy. Suppose the sales amount is influenced by promotion strategy, we integrated the promotion factors into the SVR model. Experimental result of drug sales prediction on the real sales data of a large chain drug company S shows that the SVR algorithm integrated with promotion factors get the accuracy rate of 91% and the algorithm can greatly improve the drug sales prediction results compared with traditional time series model.

Osteoporosis is a prevalent but underdiagnosed condition. As compared to dual-energy X-ray absorptiometry (DXA) measures, we aimed to develop a deep convolutional neural network (DCNN) model to classify osteopenia and osteoporosis with the use of lumbar spine X-ray images. Herein, we developed the DCNN models based on the training dataset, which comprising 1616 lumbar spine X-ray images from 808 postmenopausal women (aged 50 to 92 years). DXA-derived bone mineral density (BMD) measures were used as the reference standard. We categorized patients into three groups according to DXA BMD T-score: normal (T ≥ -1.0), osteopenia (-2.5 T -1.0), and osteoporosis (T ≤ -2.5). T-scores were calculated by using the BMD dataset of young Chinese female aged 20-40 years as a reference. A 3-class DCNN model was trained to classify normal BMD, osteoporosis, and osteopenia. Model performance was tested in a validation dataset (204 images from 102 patients) and two test datasets (396 images from 198 patients and 348 images from 147 patients respectively). Model performance was assessed by the receiver operating characteristic (ROC) curve analysis. The results showed that in the test dataset 1, the model diagnosing osteoporosis achieved an AUC of 0.767 (95% confidence interval [CI]: 0.701-0.824) with sensitivity of 73.7% (95% CI: 62.3-83.1), the model diagnosing osteopenia achieved an AUC of 0.787 (95% CI: 0.723-0.842) with sensitivity of 81.8% (95% CI: 67.3-91.8); In the test dataset 2, the model diagnosing osteoporosis yielded an AUC of 0.726 (95% CI: 0.646-0.796) with sensitivity of 68.4% (95% CI: 54.8-80.1), the model diagnosing osteopenia yielded an AUC of 0.810 (95% CI, 0.737-0.870) with sensitivity of 85.3% (95% CI, 68.9-95.0). Accordingly, a deep learning diagnostic network may have the potential in screening osteoporosis and osteopenia based on lumbar spine radiographs. However, further studies are necessary to verify and improve the diagnostic performance of DCNN models.

Objective: Obesity, a state of chronic low grade inflammation, has been reported to be associated with significant alterations of thyroid function. The purpose of this study is to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on thyroid function and its relation with inflammatory changes in severely obese patients. Methods: We performed a retrospective observational study of 128 severely obese patients (61.7% female; age 31.8 ± 10.0 years, BMI 39.4 ± 5.8 kg/m2) submitted to LSG. Patients were subdivided in two groups: euthyroid group and subclinical hypothyroidism (SCH) group. TSH, FT4, anthropometric data, and inflammatory markers were collected pre- and 1, 3, 6, and 12 months post-LSG. Results: The mean percent weight loss at 12 months was 37.2% ± 11.8%. The mean BMI decreased from 39.4 ± 5.8 kg/m2 to 27.1 ± 3.9 kg/m2. Patients with SCH (37.5% of patients) and higher TSH showed higher BMI, HOMA-IR, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) than those in euthyroid group (all P < 0.05). After surgery, TSH levels significantly decreased at 1, 3, 6, and 12 months regardless of thyroid function, which presented more apparent in SCH group. Additionally, we observed marked reduction of IL-6, IL-8, TNF-α, and CRP levels in SCH group, as well as IL-8, TNF-α, and CRP in euthyroid group from baseline by 12 months postoperatively. Moreover, decreased TSH levels correlated significantly with decreased BMI, HOMA-IR, IL-6, and TNF-α at 12 months after LSG. Conclusion: SCH in severely obesity subjects appears to be associated with excess weight, insulin resistance, and elevated inflammatory markers. LSG promotes a decrease of TSH that is significantly greater in patients with SCH, and associated with alleviation of inflammatory status in addition to substantial weight loss and improved insulin resistance after surgery. Disclosure C. Zhu: None. F. Mei: None. J. Gao: None. X. Wang: None. L. Li: None. L. Lu: None. D. Zhou: None. S. Qu: None.

Laparoscopic sleeve gastrectomy (LSG) has been proven successfully in weight reduction but with potential loss of bone mass. Previous studies indicate that bone morphogenetic protein 4 (BMP4) plays an important role both in bone formation and glucose-lipid metabolism. This study aimed to investigate the alteration of bone mineral density (BMD), bone metabolic parameters and serum BMP4 levels in Chinese obese subjects after LSG. Seventy-one obese patients (34 males, age 31.70±9.61 years and 37 females, age 32.80±11.45 years) were enrolled. BMD (at right hip, femoral neck and lumbar spine 1-4 (L1-L4) by dual-energy X-ray absorptiometry), bone metabolic markers and routine anthropometric/laboratory biochemical parameters at baseline, 3, 6 and 12 months after LSG (abbreviated as 3M/6M/12M Post-LSG) were recorded. Serum BMP4 levels were measured by enzyme-link immunosorbent assay. In females, BMD was significantly decreased at right hip at 3M/6M/12M Post-LSG, femoral neck at 6M/12M Post-LSG and L1-L4 at 6M Post-LSG (all P0.05). Intriguingly, serum BMP4 levels were reduced slightly at 3M Post-LSG (P=0.463), and significantly at 6M Post-LSG (from 75.51±16.54pg/ml to 65.40±10.51pg/ml, P=0.048) in females, while unchanged in males (all P>0.05). In all subjects, free calcium but not total calcium was increased at 12M Post-LSG (P=0.028). Vitamin D and 25(OH)VD were increased in males at 12M Post-LSG (all P In conclusion, the change of BMD differs between genders after LSG, significantly decreased in females while unchanged in males. Moreover, the decreased BMP4 levels may partly account for the diminished BMD in Chinese female obese subjects after LSG. Disclosure X. Wang: None. L. Li: None. C. Zhu: None. J. Gao: None. S. Qu: None.

Background: Acanthosis nigricans (AN) is a skin condition commonly often accompanied by insulin resistance and hyperinsulinemia. Patients with AN are prone to diabetes, especially in young obesity. Metformin were usually used to treat these patients. However, reports about the effectiveness of LSG surgery on young obese patients with AN are rare. Objective: The aim of our study was to evaluate the efficacy of LSG surgery on insulin secretion patterns and anthropometric variables for obese patients with AN. Methods: 30 young obese patients with AN were recruited for this study. Before and at 12 months after the LSG surgery, BMI and blood samples were collected. OGTT were used to evaluate the insulin level and its rhythm of secretion. AN extent and AN texture were determined according to the scale developed and validated. Results: For these patients, BMI decreased from 40.98±4.93 kg/m2 to 27.27±4.13 kg/m2 at 12 months after surgery. Along with weight loss, triglycerides and total cholesterol decreased significantly, and high-density lipoprotein cholesterol (HDL-C) increased significantly as of 12 months after surgery. But the change of low-density lipoprotein cholesterol (LDL-C) is not obvious. A significant decrease in insulin resistant (HOMA-IR) was observed. The insulin release curves showed hyperinsulinemia and abnormal rhythm of secretion before surgery. At 12 months after surgery the fasting, 2h postprandial insulin levels and the rhythm of insulin secretion were restored to normal level. But the insulin levels at 30min and 60min were higher than before surgery. The extent of AN for most patients were improved. Only 23.4% patients still were severe (vs. 59.3% before surgery). More than 50% patients were remission. Conclusion: In this study of LSG in obesity patients with AN, we found significant improvements in weight, dyslipidemia, hyperinsulinemia and AN extent. LSG will be a new effective therapeutic approach for young obesity patients with AN. Disclosure C. Qian: None. S. Qu: None. C. Zhu: None. J. Gao: None. F. Mei: None. L. Bu: None.

Background: Uric acid is believed be an important modulator in glucose and lipid metabolism. This study is aimed to estimate the efficacy of laparoscopic sleeve gastrectomy (LSG) on obese patients and find out the relationship of serum uric acid (SUA) to body fat distribution in both male and female of Chinese patients. Methods: A total of 65 obese patients (32 females and 33 males) who underwent LSG were enrolled for this study. Their body composition was measured by dual-energy X-ray absorptiometry (DEXA). The data of anthropometric measurements, glucolipid metabolism and SUA was collected before and 6 months after LSG separately. Results: More significant reduction of SUA was observed in the female group than the male group after LSG (female (17.98±12.72)% vs. male(3.22±15.66)%, p Conclusions: The efficacy of LSG on glycolipid metabolism may be associated with gender-related differences in body fat distribution. Uric acid may be a gendered modulator of glucose and lipid metabolism. Disclosure X. Zhang: None. F. Mei: None. J. Gao: None. X. Cheng: None. L. Bu: None. C. Zhu: None. S. Qu: None.

The aim of the study was to investigate the longitudinal bone mineral density(BMD) and bone metabolic related markers changes in obese patients with acanthosis nigricans (AN) and without AN(OB) after Laroscopic Sleeve Gastrectomy (LSG). 41 obese patients (AN group:n=29,OB group:n=12) were recruited in this study. Areal BMD (aBMD) and lumbar spine volumetric BMD (vBMD)were measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Insulin and markers of bone metabolism including 25-OHD, calcium, intact parathyroid hormone (iPTH), osteocalcin (OC), and type I collagen cross-linked C-terminal telopeptide (CTX) ] were assessed; Insulin area under the curve(AUCins) and HOMA-IR were computed. Results showed that the AN group had a higher fasting serum insulin (42.80±28.52 vs. 22.55±8.94mU/L,p=0.006), AUCins (522.42±280.32 vs. 263.87±195.75mU/L,p=0.008)and BMI(40.6±5.1 vs. 36.7±4.1kg/m2,p=0.024) compared to the OB group at baseline. The both groups did a obvious decrease in HOMA-IR after LSG; In AN group, there was a significant decrease in Lumbar vBMD(-4.4%,p=0.011), pelvic aBMD (-6.48%,p In conclusion, Insulin resistance was improved, and bone turnover was activated one year after LSG in both groups, but the bone loss was more likely to occur in the obese patients with acanthosis nigricans. Disclosure Y. Zhang: None. Z. Zhang: None. C. Zhu: None. S. Sun: None. Y. Yin: None. R. Cui: None. H. Sheng: None. S. Qu: None.