A prognostic nomogram integrating carcinoembryonic antigen levels for predicting overall survival in elderly patients with stage II-III colorectal cancer.

Background: With the aging of the population, colorectal surgeons will have to face more elderly colorectal cancer (CRC) patients in the future. We aim to analyze independent risk factors affecting overall survival in elderly (age ≥65 years) patients with stage II-III CRC and construct a nomogram to predict patient survival. Methods: A total of 3,016 elderly CRC patients with stage II-III were obtained from the SEER database. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen independent prognostic factors, and a survival prediction nomogram was constructed based on the results. The consistency index (C-index), decision curve analysis (DCA), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to compare the predictive ability between the nomogram and tumor-node-metastasis (TNM) stage system. All patients were classified into high-risk and low-risk groups based on risk scores calculated by nomogram. The Kaplan-Meier method was used to compare the survival differences between two groups. Results: The 3- and 5-year area under the curve (AUC) values of the prediction nomogram model were 76.6% and 74.8%, respectively. The AIC, BIC, and C-index values of the nomogram model were 6,032.502, 15,728.72, and 0.707, respectively, which were better than the TNM staging system. Kaplan-Meier survival analysis showed a significant survival difference between high-risk and low-risk groups (P<0.0001). Conclusions: We constructed a prediction nomogram for stage II-III elderly CRC patients by combining pre-treatment carcinoembryonic antigen (CEA) levels, which can accurately predict patient survival. This facilitates clinicians to accurately assess patient prognosis and identify high-risk patients to adopt more aggressive and effective treatment strategies.

Identification of a novel immune-related transcriptional regulatory network in sarcopenia.

BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or < - 1, p < 0.05), 4 DETFs (log2FC > 0.7 or < - 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or < - 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or < - 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia.

Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation.

MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/- mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. "MycKO" mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

BACKGROUND: The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM. METHODS: We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People's Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4. RESULTS: BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4. CONCLUSIONS: BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.

Iron metabolism mediates the relationship between Vitamin C and hepatic steatosis and fibrosis in NAFLD.

Vitamin C (Vit C) and iron metabolism are closely related to metabolic disorders. However, the relation between iron storage protein ferritin and Vit C has not been elucidated. We aimed to investigate the crosstalk between Vit C and ferritin and its implications on non-alcoholic fatty liver disease (NAFLD). Clinical information of 3,614 subjects was obtained from the NHANES Public Data 2017-2018. FibroScan data, which estimates liver steatosis and fibrosis and Vit C, were selected to assess factors influencing NAFLD in this cross-sectional study. Ferritin and Vit C among different categories of liver steatosis and fibrosis were assessed by CAP and E value. Logistic regression and RCS models were used to analyze the correlations. In vitro study in hepG2 were conducted to validate the regulations. Ferritin increased while Vit C decreased with more severe hepatic steatosis and hepatic fibrosis (all P < 0.001). Logistic regression models indicated that increased serum ferritin was a risk factor for NAFLD while increased Vit C was a protective factor for NAFLD and hepatic fibrosis after adjusting the continuous and categorical variables. Vitamin C was negatively associated with ferritin. Further mediation analysis identified that ferritin mediates the impact of Vit C on NAFLD (P < 0.05) and cirrhosis (P < 0.001). The experiments on cellular level suggested Vit C alleviated PA/OA induced steatosis and maintains iron homeostasis through inhibiting PA/OA induced upregulation of iron bound protein ferritin and labile iron pool (LIP) induction in hepG2 cells. In conclusion, Vit C was a protective factor, whereas ferritin was a risk factor for hepatic steatosis and fibrosis. Vitamin C alleviated NAFLD and maintained iron homeostasis via ferritin suppression and LIP induction.

Prognostic Effect of Thoracic Sarcopaenia on Short- and Long-Term Clinical Outcomes in Patients Who Underwent Cardiac Valve Surgery.

BACKGROUND: As the proportion of elderly patients increases, higher incidence of malnutrition is found among patients with valvular heart disease. Sarcopaenia is one of the main manifestations of malnutrition. Studies have shown the certain predictive effect of sarcopaenia on the clinical outcome in different cases. This study aims to clarify the impact of computed tomography (CT)-derived thoracic sarcopaenia on clinical outcomes of patients who underwent cardiac valve surgery. METHODS: The clinical data of 216 patients who underwent cardiac valve surgery from December 2015 to June 2020 were retrospectively collected. Skeletal muscle mass at 12th thoracic vertebra level was measured to diagnose thoracic sarcopaenia. Postoperative complications and follow-up data were collected. Medium follow-up was 3.2 years. RESULTS: The prevalence of thoracic sarcopaenia was 16.7% in this study. The incidence of total complications and in-hospital mortality were higher in thoracic sarcopaenia group (p=0.024 and p=0.014, respectively). Multivariate analysis revealed that thoracic sarcopaenia is a significant predictor for postoperative complications (OR 2.319; 95% CI 1.003-5.366; p=0.049). Decreased long-term survival was observed in patients with thoracic sarcopaenia. Thoracic sarcopaenia (HR 4.178; 95% CI 2.062-8.465; p<0.001) was determined to be an independent risk factor for late mortality. CONCLUSION: Thoracic sarcopaenia defined by chest CT was independently associated with higher incidence of postoperative complications and long-term mortality. Routine preoperative evaluation of thoracic sarcopaenia deserves further consideration to enhance the predictive performance for operation risk.

Relationship of Vitamin A and Thyroid Function in Individuals With Obesity and After Laparoscopic Sleeve Gastrectomy.

Vitamin A deficiency (VAD) occurs in obesity and may be associated with thyroid dysfunction. We aimed to investigate the association of VA with thyroid function in obesity and after laparoscopic sleeve gastrectomy (LSG). Nine hundred and seventy-six obese subjects were enrolled for this study and were divided into VAD, marginal vitamin A deficiency (MVAD), and vitamin A normal (NVA) groups. VAD was defined as VA ≤ 200 ng/ml, MVAD was defined as VA > 200 but <300 ng/ml, and NVA was defined as VA ≥ 300 ng/ml. Thyroid function was compared among groups and the relationship of VA and thyroid function was analyzed. Two hundred and forty-four of the 976 obese subjects underwent LSG, and the change in thyroid function and VA at 3, 6, and 12 months after surgery was measured. Results showed that 37% of all the subjects had subclinical hypothyroidism (SH), and the SH group had lower VA levels than the non-SH group (P = 0.008). Forty-nine percent of all the subjects had MVAD, 9% had VAD, while the MVAD or VAD group had lower FT4 than the NVA group (P = 0.005 and P = 0.001). The VAD group also had higher TSH than NVA group (P = 0.037). VA was significantly negatively associated with TSH (r = -0.151, P = 0.006) and positively associated with FT4 (r = 0.228, P < 0.001). TSH was significantly decreased at 3, 6, and 12 months (3M: from 4.43 ± 2.70 to 2.63 ± 1.46 mU/l, P < 0.001; 6M: from 4.43 ± 2.70 to 3.84 ± 2.34 mU/l, P = 0.041; 12M: from 4.43 ± 2.70 to 2.85 ± 1.68 mU/l, P = 0.024). After LSG surgery, VA levels were slightly increased, when compared to pre-surgery levels, at 3, 6, and 12 months (3M: from 262.57 ± 68.19 to 410.33 ± 76.55 ng/ml, P = 0.065; 6M: from 262.57 ± 68.19 to 281.36 ± 93.23 ng/ml, P = 0.343; 12M: from 262.57 ± 68.19 to 300.37 ± 86.03 ng/ml, P = 0.083). SH group also had lower TSH and higher VA than the non-SH group at 3 months post-surgery [TSH: -1.4(-2.3, -0.3) vs. -0.2(-0.8, -0.2) mU/l, P < 0.001; VA: 163.99 ± 32.58 vs. 121.69 ± 27.59 ng/ml, P = 0.044]. In conclusion VA, which is related to thyroid hormone production, protects against thyroid dysfunction in obese subjects. The improvement of thyroid function in subjects with SH after LSG may be related to the increased VA levels observed post-surgery. Clinical Trial Registration: ClinicalTrial.gov ID: NCT04548232.

Association Between Abdominal Adipose Tissue Distribution and Obstructive Sleep Apnea in Chinese Obese Patients.

Purpose: Factors related to the occurrence of obstructive sleep apnea syndrome (OSAS) in obesity have not been fully clarified. The aim of this study was to identify the association between OSAS and abdominal fat distribution in a cohort of Chinese obese patients. Methods: This cross-sectional study collected demographic data of 122 obese patients who were admitted into the in-patient unit of the Department of Endocrinology, Shanghai Tenth People's Hospital from July 2018 to January 2021. OSAS was diagnosed based on the results of overnight polysomnography, and the abdominal fat distribution was measured by bioelectrical impedance analysis (BIA). Univariate and multivariate logistic regression analyses were used to investigate the association between OSAS and the distribution of abdominal fat. Results: (1) The mean age (SD) of the obese patients included was 32.44 (11.81) years old, and the overall incidence rate of OSAS was 51.06%. Twenty-four (25.53%) patients had mild OSAS, 10 (10.64%) had moderate OSAS, and 14 (14.89%) had severe OSAS. The apnea hypopnea index (AHI) of men was significantly higher than that of women (5.50, interquartile range (IQR) 3.80-30.6 vs. 4.2, IQR 1.4-12 events/h, p = 0.014). Meanwhile, men had a significantly higher visceral fat area when compared with women (180.29 ± 51.64 vs. 143.88 ± 53.42 cm2, p = 0.002). (2) Patients with OSAS had a significantly higher waist circumference, fasting plasma glucose, 2 h postprandial plasma glucose, glycated hemoglobin, and visceral fat area than patients without OSAS (all p < 0.05). (3) AHI was significantly positively associated with BMI, neck circumference, waist circumference, and visceral fat area (r = 0.306, p = 0.003; r = 0.380, p < 0.001; r = 0.328, p = 0.002; r = 0.420, p < 0.001) but not with subcutaneous fat area (p = 0.094). Multivariate analysis demonstrated that abdominal fat area and fasting plasma glucose were independent risk factors for OSAS (odds ratio, 1.016; 95% confidence interval, 1.005-1,026, p = 0.005; odds ratio, 1.618; 95% confidence interval, 1.149-2.278, p = 0.006). Conclusions: In obese patients, the abdominal visceral adipose deposit but not the subcutaneous fat area was associated with OSAS and was an independent risk factor for OSAS. Therefore, improving the distribution of abdominal fat may contribute to alleviating the severity of OSAS in obesity.

Bone morphogenetic protein 4 alleviates nonalcoholic steatohepatitis by inhibiting hepatic ferroptosis.

Nonalcoholic steatohepatitis (NASH) is a state of simple steatosis that progresses to inflammation and liver injury accompanied by ferroptosis. Bone morphogenetic protein 4 (BMP4) plays an important role in adipogenesis and differentiation, as well as in hepatic steatosis and iron regulation. However, the direct impact of BMP4 on NASH remains unclear. In this study, our aim was to investigate the effect of BMP4 on NASH and its underlying mechanism. We first explored BMP4 expression in vivo in mice and patients and in vitro in HepG2 and LO2 cell lines, and then, determined whether ferroptosis occurs in NASH. Further overexpression or inhibition of BMP4 was induced to observe the effect of BMP4 on liver ferroptosis in NASH. BMP4 expression was upregulated in patients and mice with nonalcoholic fatty liver disease, and free fatty acid (FFA)-induced HepG2 and LO2 cell lines. We observed ferroptosis in high-fat diet and high-fructose diet-fed mice and FFA-induced HepG2 and LO2 cell lines. BMP4 overexpressing plasmid was constructed and the HepG2 and LO2 cells were transfected with lentivirus (oe-BMP4), or treated with exogenously added recombinant human BMP4 or BMP antagonist noggin. BMP4 suppressed the markers of hepatic steatosis, liver inflammation, and liver injury. Upregulated BMP4 expression in HepG2 and LO2 cells reduced reactive oxygen species and malondialdehyde content and relieved ferroptosis. Mechanistically, BMP4 overexpression in hepatocytes upregulated the mRNA and protein levels of glutathione peroxidase 4 (GPX4), a central regulator of ferroptosis, while exogenous inhibition of BMP4 by noggin decreased their levels. Immunoprecipitation assays demonstrated a physical interaction between BMP4 and GPX4 in HepG2 and LO2 cells, and confocal imaging confirmed colocalization of BMP4 and GPX4. Consistently, BMP4 overexpression plays an important role in NASH by increasing GPX4 expression, therefore decreasing hepatic ferroptosis. This study proposes BMP4 as a therapeutic target for preventing steatohepatitis.

Nrf2 contributes to the benefits of exercise interventions on age-related skeletal muscle disorder via regulating Drp1 stability and mitochondrial fission.

The progressive and generalized loss of skeletal muscle mass and function, also known as sarcopenia, underlies disability, increasing adverse outcomes and poor quality of life in older people. Exercise interventions are commonly recommended as the primary treatment for sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a vital role in regulating metabolism, mitochondrial function, and the ROS-dependent adaptations of skeletal muscle, as the response to exercise. To investigate the contribution of Nrf2 to the benefits of exercise interventions in older age, aged (∼22 month old) Nrf2 knockout (Nrf2-KO) mice and age-matched wild-type (WT) C57BL6/J mice were randomly divided into 2 groups (sedentary or exercise group). We found that exercise interventions improved skeletal muscle function and restored the sarcopenia-like phenotype in WT mice, accompanied with the increasing mRNA level of Nrf2. While these alternations were minimal in Nrf2-KO mice after exercise. Further studies indicated that Nrf2 could increase the stability of Drp1 through deubiquitinating and promote Drp1-dependent mitochondrial fission to attenuate mitochondrial disorder. We also observed the effects of sulforaphane (SFN), a Nrf2 activator, in restoring mitochondrial function in senescent C2C12 cells and improving sarcopenia in older WT mice, which were abolished by Nrf2 deficiency. These results indicated that some benefits of exercise intervention to skeletal muscle were Nrf2 mediated, and a future work should focus on Nrf2 signaling to identify a pharmacological treatment for sarcopenia.

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism.

Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes.

Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway. METHODS: Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared. RESULTS: Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g, P = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g, P = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g, P = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT). CONCLUSION: Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway.

Low 25-hydroxyvitamin D is associated with arterial stiffness in Chinese with Type 2 diabetes mellitus.

OBJECTIVES: Arterial stiffness (AS), one of the complications of diabetes, associated with many metabolic factors. This study aimed to investigate the association between 25-hydroxyvitamin D(25(OH)D) and AS in type 2 diabetes mellitus (T2DM). METHODS: We identified 1335 diabetic patients from the Department of Endocrinology, Shanghai Tenth People's Hospital. Finally, 603 T2DM patients were included in the study. They were divided into two groups: AS group (baPWV ≥ 15,500 cm/s) and the control group (baPWV < 1550 cm/s). RESULTS: (1) Heart rate (HR) and systolic pressure (SBP) were higher while body weight and body mass index (BMI) were smaller in AS group than the control group (all P < 0.05). (2) Compared to patients without AS, patients with AS showed lower 25(OH)D and higher rate of 25(OH)D deficiency (42 ± 16 vs. 45 ± 17 mol/l, 68% vs. 64%, all P < 0.05). (3) BaPWV was negatively associated with 25(OH)D (r = -0.12, P = 0.004), while positively associated with age, duration of diabetes, HR, SBP, and low-density lipoprotein cholesterol and negatively associated with body weight and BMI (all P < 0.05). (4) Multiple linear regression showed that 25(OH)D was the negatively influencing factor of baPWV (ß = -2.2, P = 0.01). Logistic regression showed that age and SBP were risk factor of AS (OR:1.07, 95% CI: 1.05-1.10, P < 0.001; OR:1.03, 95% CI: 1.02-1.04, P < 0.001) while 25(OH)D was protective factor of AS (OR:0.987, 95% CI: 0.976-0.998, P = 0.024). CONCLUSIONS: T2DM patients with AS had lower 25(OH)D and higher rate of 25(OH)D deficiency. There was a negative relationship between 25(OH)D and AS assessed by baPWV.

Feasibility of substituting handgrip strength for muscle mass as a constituent standard in the Global Leadership Initiative on Malnutrition for diagnosing malnutrition in patients with gastrointestinal cancers.

OBJECTIVES: The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer. METHODS: The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS. RESULTS: There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P < 0.001) in patients with gastric cancer and 0.872 (P < 0.001) in those with colorectal cancer. CONCLUSION: HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer.

Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Iron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated. OBJECTIVE: We aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity. METHODS: A total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery. RESULTS: (1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, p = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all p < 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (p = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all p < 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all p < 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all p < 0.05). CONCLUSIONS: Overall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.

Development and validation of a nomogram to predict the prognosis of patients with gastric cardia cancer.

Our goal was to develop a prognostic nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric cardia cancer (GCC). Patients diagnosed with GCC from 2004 to 2015 were screened from the surveillance, epidemiology, and end results (SEER) database. A nomogram was developed based on the variables associated with OS and CSS using multivariate Cox analysis regression models, which predicted 3- and 5-year OS and CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), calibration curve and decision curve analysis (DCA), and the nomogram was calibrated for 3- and 5-year OS and CSS. A total of 7,332 GCC patients were identified and randomized into a training cohort (5,231, 70%) and a validation cohort (2,200, 30%). Multivariate Cox regression analysis showed that marital status, race, SEER stage, grade, T stage, N stage, M stage, tumor size, and surgery were independent risk factors for OS and CSS in GCC patients. Based on the multivariate Cox regression results, we constructed prognostic nomograms of OS and CSS. In the training cohort, the C-index for the OS nomogram was 0.714 (95% CI = 0.705-0.723), and the C-index for the CSS nomogram was 0.759 (95% CI = 0.746-0.772). In the validation cohort, the C-index for the OS nomogram was 0.734 (95% CI = 0.721-0.747), while the C-index for the CSS nomogram was 0.780 (95% CI = 0.759-0.801). Our nomogram has better prediction than the nomogram based on TNM stage. In addition, in the training and external validation cohorts, the calibration curves of the nomogram showed good consistency between the predicted and actual 3- and 5-year OS and CSS rates. The nomogram can effectively predict OS and CSS in GCC patients, which may help clinicians personalize prognostic assessments and clinical decisions.

Glucose-Lipid Metabolism in Obesity with Elevated Prolactin Levels and Alteration of Prolactin Levels After Laparoscopic Sleeve Gastrectomy.

PURPOSE: We investigated the differences in metabolism between obesity with or without increased prolactin (PRL) and the change in PRL after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients were divided into two groups: obesity with normal PRL (NP, n = 123) and high PRL (HP, n = 108). Glucose-lipid metabolism and inflammation were measured. A total of 115 patients with obesity (NP, n = 64; HP, n = 51) underwent LSG were recruited, and PRL was measured at 12 months after LSG. RESULTS: (1) Blood glucose (BG), total cholesterol (TCH), LDL, triglyceride, and TNF-α were lower in the HP than in the NP group in the cross-sectional study (all P < 0.05). (2) PRL was negatively associated with neck circumference, waist-to-hip ratio, systolic blood pressure, heart rate, basal metabolism rate (BMR), ALP, TCH, and LDL in all subjects. PRL levels were positively associated with weight, HC, and BMR in males but were negatively associated with ALT, AST, ALP, BG 30 min, BG 60 min, FFA, and TCH in females (all P < 0.05). (3) Regression analysis showed that PRL negatively correlated with ALP and LDL-C in the whole baseline (ß = - 0.051, P = 0.002; ß = - 1.372, P = 0.033). PRL was a negative factor for ALP in females and a positive factor for BMR2 in males (ß = - 0.099, P = 0.041; ß = 0.005, P = 0.006). (4) PRL decreased in the HP group and increased in the NP group at 12 months post-operation (all P < 0.05). Increased PRL was associated with a change in TCH in the NP group (P < 0.05). CONCLUSION: Increased PRL resulted in improved glucose-lipid metabolism and chronic low-grade inflammation. LSG led to increased PRL in NP and decreased PRL in HP. Improved lipid was associated with increased PRL in NP after surgery. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OCS-12002381.