Differential Associations of Erythrocyte Membrane Saturated Fatty Acids with Glycemic and Lipid Metabolic Markers in a Chinese Population: A Cross-Sectional Study.

Mounting evidence indicates a complex link between circulating saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk factors, but research on erythrocyte membrane SFA associations with metabolic markers remains limited. Our study sought to investigate the correlations between erythrocyte membrane SFAs and key metabolic markers within glycemic and lipid metabolism in a Chinese population of 798 residents aged 41 to 71 from Guangzhou. Using gas chromatography-mass spectrometry, we assessed the erythrocyte membrane saturated fatty acid profile and performed multiple linear regression to evaluate the relationship between different SFA subtypes and metabolic markers. Our findings revealed that the odd-chain SFA group (C15:0 + C17:0) exhibited negative associations with fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and triglycerides (TG). Conversely, the very-long-chain SFA group (C20:0 + C22:0 + C23:0 + C24:0) exhibited positive associations with fasting insulins (FINS), HOMA-IR, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Furthermore, there was no evidence supporting an association between the even-chain group (C14:0 + C16:0 + C18:0) and metabolic markers. Our findings suggest that different subtypes of SFAs have diverse effects on glycemic and lipid metabolic markers, with odd-chain SFAs associated with a lower metabolic risk. However, the results concerning the correlations between even-chain SFAs and very-long-chain SFAs with markers of glycemic and lipid metabolism pathways are confusing, highlighting the necessity for further exploration and investigation.

Positive Airway Pressure and Metabolic Markers in Children With Obstructive Sleep Apnea.

BACKGROUND: Increasing evidence suggests an association between childhood obstructive sleep apnea (OSA) and metabolic syndrome, with more research available on the potential impacts of positive airway pressure (PAP) on metabolic markers in children. The purpose of this systematic review is to provide a systematic synthesis of the evidence on the effect of PAP use on metabolic markers in children with OSA. METHODS: A search strategy with terms for "OSA" and metabolic markers in pediatrics was run to systematically assess 5 databases until August 26, 2022. Two reviewers independently screened eligible articles, extracted data, and conducted quality appraisal. Meta-analysis was done using random-effects models. Body mass index (BMI), glycemic, lipid, cardiovascular, and other metabolic and inflammatory markers were reported. RESULTS: Sixteen studies (N = 1,213) were included, 15 observational studies and 1 randomized controlled trial (RCT); most reported outcomes in children with obesity. Meta-analysis of 4 studies found no changes in BMI at median average follow-up of 12 months after PAP initiation. A reduction in heart rate and blood pressure parameters was demonstrated in several studies in children with OSA with and without obesity at a median average follow-up of 4.9 months after PAP initiation. Research in echocardiographic outcomes is limited, including one RCT in children with Down syndrome and OSA showing no changes in heart rate variability parameters. Evidence of improvements in glycemic and/or lipid control, liver enzymes, and inflammatory markers with PAP therapy is even more limited and of limited clinical importance. Risk of bias was moderate to critical and outcome evidence very low. CONCLUSIONS: Although evidence on effects of PAP on metabolic markers in children with OSA is encouraging, available literature is limited. Longitudinal studies are still required to further assess the long-term influence of PAP on metabolic and inflammatory markers, particularly in children with obesity.

Untargeted metabolomics unveiled the role of butanoate metabolism in the development of Pseudomonas aeruginosa hypoxic biofilm.

Pseudomonas aeruginosa is a versatile opportunistic pathogen which causes a variety of acute and chronic human infections, some of which are associated with the biofilm phenotype of the pathogen. We hypothesize that defining the intracellular metabolome of biofilm cells, compared to that of planktonic cells, will elucidate the metabolic pathways and biomarkers indicative of biofilm inception. Disc-shaped stainless-steel coupons (12.7 mm diameter) were employed as a surface for static biofilm establishment. Each disc was immersed in a well, of a 24-well microtiter plate, containing a 1-mL Lysogeny broth (LB) suspension of P. aeruginosa ATCC 9027, a strain known for its biofilm prolificacy. This setup underwent oxygen-depleted incubation at 37°C for 24 hours to yield hypoxic biofilms and the co-existing static planktonic cells. In parallel, another planktonic phenotype of ATCC 9027 was produced in LB under shaking (200 rpm) incubation at 37°C for 24 hours. Planktonic and biofilm cells were harvested, and the intracellular metabolites were subjected to global untargeted metabolomic analysis using LC-MS technology, where small metabolites (below 1.5 kDa) were selected. Data analysis showed the presence of 324 metabolites that differed (p < 0.05) in abundance between planktonic and biofilm cells, whereas 70 metabolites did not vary between these phenotypes (p > 0.05). Correlation, principal components, and partial least square discriminant analyses proved that the biofilm metabolome is distinctly clustered away from that of the two planktonic phenotypes. Based on the functional enrichment analysis, arginine and proline metabolism were enriched in planktonic cells, but butanoate metabolism was enriched in biofilm cells. Key differential metabolites within the butanoate pathway included acetoacetate, 2,3-butandiol, diacetyl, and acetoin, which were highly upregulated in the biofilm compared to the planktonic cells. Exogenous supplementation of acetoin (2 mM), a critical metabolite in butanoate metabolism, augmented biofilm mass, increased the structural integrity and thickness of the biofilm, and maintained the intracellular redox potential by balancing NADH/NAD+ ratio. In conclusion, P. aeruginosa hypoxic biofilm has a specialized metabolic landscape, and butanoate pathway is a metabolic preference and possibly required for promoting planktonic cells to the biofilm state. The butanoate pathway metabolites, particularly acetoin, could serve as markers for biofilm development.

Zonulin and copeptin relation to some metabolic markers in school-aged obese children.

BACKGROUND: Using Zonulin and Copeptin as potential obesity markers in children, hasn't yet been focused. AIM: To evaluate the association between serum levels of both Zonulin and Copeptin with the obesity markers, and to assess their role as metabolic disturbance predictors in obese children. METHODS: A case-control study comprised 111 Egyptian children (45 males and 66 females); aged 6-10 years to avoid the effect of puberty (prepubertal). They were classified according to their body mass index (BMI) percentiles into: 72 obese (BMI ≥ 95th ), and 39 control ones (BMI > 15th - <85th ), based on the Egyptian Growth Charts for children and adolescents. Anthropometric parameters and blood pressure were measured, and body composition analysis, lipid profile, Zonulin, and Copeptin levels were assessed. RESULTS: The obese group showed a significantly higher value of Copeptin and a lower value of Zonulin than the control one Also, the obese group showed significant negative correlations between Zonulin and both anthropometric obesity markers and body composition, whereas Copeptin showed significant positive ones. Moreover, significant positive correlations were found between Copeptin and both body weight and fat distribution. Insignificant correlations were observed between both serum Zonulin and Copeptin levels and blood pressure and lipid profile. CONCLUSION: Zonulin and Copeptin cannot be used as metabolic disturbance predictors, among Egyptian children, as they were insignificantly correlated with lipid profile or blood pressure.

Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study.

BACKGROUND: Depression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms. METHODS: The Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis. RESULTS: Some metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms. LIMITATIONS: Although the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered. CONCLUSIONS: Our results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.

The triglycerides and glucose index is more strongly associated with metabolically healthy obesity phenotype than the lipid and obesity indices.

PURPOSE: The triglycerides and glucose (TyG) index is a reliable biomarker for estimating insulin resistance; however, evidence regarding the use of the TyG index in individuals with metabolically healthy obesity (MHO) is scarce. Thus, we examined the association between the TyG index and the MHO phenotype. METHODS: Apparently healthy men and women aged 18 years or more with obesity (body mass index [BMI] ≥ 30 kg/m2) were allocated into the following groups: MHO and metabolically unhealthy obesity (MUO). The MHO phenotype was defined by obesity and the absence of the following metabolic disorders: elevated triglyceride concentrations, elevated glucose levels, elevated blood pressure, and low HDL-C. The MUO was defined by individuals with obesity and at least one of the aforementioned cardiovascular risk factors. RESULTS: A total 827 individuals, 605 (73.1%) women and 222 (26.9%) men were enrolled and allocated into the MHO (n = 104) and MUO (n = 723) groups. The adjusted regression analysis by age, sex, BMI, and waist circumference showed that fasting glucose (OR = 0.90; 95% CI: 0.88-0.93), and triglycerides (OR = 0.97; 95% CI: 0.96-0.98), as well as the triglycerides/HDL-C (OR = 0.18; 95% CI: 0.13-0.26), lipid accumulation product (OR = 0.95; 95% CI: 0.93-0.96), visceral adipose index (OR = 0.38; 95% CI: 0.31-0.46), and TyG index (OR = 0.001; 95% CI: 0.000-0.004) are inversely associated with the MHO, while the HDL-C (OR = 1.10; 95% CI: 1.07-1.12) had a direct association. CONCLUSIONS: Our results show that the TyG index is more strongly associated with the MHO phenotype than the lipid and obesity indices.

Germplasm Resources and Metabolite Marker Screening of High-Flavonoid Tartary Buckwheat (Fagopyrum tataricum).

Tartary buckwheat is an annual minor cereal crop with a variety of secondary metabolites, endowing it with a high nutritional and medicinal value. Flavonoids constitute the primary compounds of Tartary buckwheat. Recently, metabolomics, as an adjunct breeding method, has been increasingly employed in crop research. This study explores the correlation between the total flavonoid content (TFC) and antioxidant capacity in 167 Tartary buckwheat varieties. Ten Tartary buckwheat varieties with significant differences in flavonoid content and antioxidant capacity were selected by cluster analysis. With the use of liquid chromatography-mass spectrometry, 58 flavonoid compounds were identified, namely, 42 flavonols, 10 flavanols, 3 flavanones, 1 isoflavone, 1 anthocyanidin, and 1 proanthocyanidin. Different samples were clearly separated by employing principal component analysis and partial least-squares discriminant analysis. Eight differential flavonoid compounds were further selected through volcano plots and variable importance in projection. Differential metabolites were highly correlated with TFC and antioxidant capacity. Finally, metabolic markers of kaempferol-3-O-hexoside, kaempferol-7-O-glucoside, and naringenin-O-hexoside were determined by the random forest model. The findings provide a basis for the selection and identification of Tartary buckwheat varieties with high flavonoid content and strong antioxidant activity.

Metabolic profile of blood serum in experimental arterial hypertension.

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.

Effect of Prebiotic Dietary Supplement Acacia senegal on Hormonal and Metabolic Markers in Polycystic Ovary Syndrome Patients: A Pilot Study.

Background The most prevalent endocrine condition affecting women of reproductive age is polycystic ovarian syndrome (PCOS), which is linked to a variety of metabolic abnormalities. Although the pathogenesis of PCOS is not fully understood, it is known that oxidative stress, altered gut microbiome, and increased gonadotrophin-releasing hormone play a significant role. Gum arabic (GA) is an edible, dried, gummy exudate from the Acacia senegal tree, well-known for its prebiotic and antioxidant effects. The main objective of the study was to assess the changes in hormonal and metabolic profiles in PCOS patients after the ingestion of gum arabic. Method This was a clinical trial conducted on fifteen patients suffering from PCOS, with a mean age of 27.8 years (20-39 years). All patients experienced irregular cycles. Hormonal and metabolic markers (follicular stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), fasting insulin, total cholesterol (TC), and glycosylated hemoglobin (HBA1c) were measured before and after the ingestion of gum arabic (30 g/day of GA dissolved in 250 ml water for eight weeks) on the second day of the menstrual cycle after granting ethical approval from the National Medicine and Poisons Board and from the participants of the study. Results The study demonstrated a significant decrease in the luteinizing hormone level, FSH/LH ratio, and cholesterol pre- and post-gum arabic ingestion (p-values 0.001, 0.013, and 0.007, respectively). Follicular stimulating hormone slightly reduced post-ingestion with no significant difference (p-value 0.414). No significant changes were seen in the testosterone, insulin, or HBA1c levels. Conclusion The study concluded that gum arabic ingestion for eight weeks decreases the luteinizing hormone and LH/FSH ratio and improves the metabolic profile by reducing the cholesterol level in PCOS patients.

Impact of home-based training and nutritional behavior on body composition and metabolic markers in cancer patients: data from the CRBP-TS study.

Introduction: Obesity and physical inactivity are known to affect cancer's development and prognosis. In this context, physical aerobic and resistance training as well as a Mediterranean nutrition have been proven to have many positive health effects. The aim of this study was therefore to investigate the effect of home-based training on body composition and certain metabolic laboratory parameters. Methods: Patients with breast, colorectal and prostate cancer who underwent curative surgery at stages T1N0M0-T3N3M0 were eligible for this trial and randomized to an intervention and control group. In the intervention group the patients carried out online-based strength-endurance home training during the 6-month study period. Body composition was assessed via bioelectrical impedance analysis (baseline, 3 months and 6 months). Metabolic blood parameters were also analyzed and nutrition behavior determined using the Mediterranean Diet Adherence Screener (MEDAS). Results: The intervention group's fat mass decreased while their lean body mass increased (time effect p = 0.001 and p = 0.001, respectively). We found no interaction effect in body weight (p = 0.19), fat mass [p = 0.06, 6-months estimates -0.9 (95% CI -1.8 to -0.1)] and lean body mass (p = 0.92). Blood samples also failed to show a statistically significant interaction effect between time × group for HbA1c% (p = 0.64), Insulin (p = 0.33), Adiponectin (p = 0.87), Leptin (p = 0.52) and Triglycerides (p = 0.43). Only Adiponectin revealed significance in the time effect (p < 0.001) and Leptin in the group effect (p = 0.03). Dietary behavior during the study period was similar in patients in the intervention and control groups (interaction p = 0.81; group p = 0.09 and time p = 0.03). Discussion: Individualized online-based home training in postoperative cancer patients revealed only minor changes, with no group differences in body composition or metabolic laboratory parameters, which were predominantly in the reference range at baseline. More studies investigating effects of online-based home training on body composition and nutrition behavior are needed. Trial registration: https://drks.de/search/en/trial/DRKS00020499, DRKS-ID: DRKS00020499.

Number of contiguous vertebral cross-links in the spine indicates bone formation: a cross-sectional study.

BACKGROUND: As an indicator to evaluate the risk of fracture in diffuse idiopathic skeletal hyperostosis, the maximum number of vertebral bodies' bone cross-linked with contiguous adjacent vertebrae (max VB) was developed. This study retrospectively investigates the relationship between max VB, bone mineral density (BMD), and bone metabolic markers (BMM). METHODS: In this cross-sectional study (from April 2010 to January 2022), males (n = 114) with various max VB from the thoracic vertebra to the sacrum, measured using computed tomography scans, were selected to assess femur BMD and BMM. The association of max VB with the total type I procollagen N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and bone turnover ratio (BTR = TRACP-5b/P1NP) as well as its relationship with femur BMD with P1NP and TRACP-5b, were investigated. Furthermore, the relationship between P1NP and TRACP-5b was investigated. RESULTS: P1NP increased in proportion to max VB and TRACP-5b increased in proportion to P1NP. Moreover, BTR was inversely proportional to max VB. Finally, femur BMD was inversely proportional to P1NP and TRACP-5b. CONCLUSION: As max VB increased with P1NP-a potential osteogenesis indicator-and BTR was inversely proportional to max VB with compensatory TRACP-5b increase, max VB can be considered as a possible predictor of bone fusion.

Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes.

Background: Conditions in utero influence intrauterine and postnatal infant growth and a few studies indicate that maternal inflammation and insulin resistance might affect birth and breastfeeding outcomes. Furthermore, hormones in human milk (HM) may influence infant appetite-regulation and thereby milk intake, but the associations are less understood. Objective: (1) To investigate associations between maternal inflammatory, lipid and metabolic markers and birth and breastfeeding outcomes, and (2) to assess predictors of maternal inflammatory, lipid and metabolic markers in pregnancy. Methods: Seventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality (MILQ) study were included in the present study. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0 to 8.5 months, where milk intake was assessed using 24-h test weighing. Maternal plasma inflammatory, lipid and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-α (TNFα), interferon-γ (IFNγ), Interleukin (IL)-6, IL-8, high-, low-, and very-low-density lipoprotein (HDL, LDL, VLDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, C-peptide, the homeostasis model assessment of insulin resistance (HOMA-IR) and glucose concentration at t = 120 min following an oral glucose tolerance test. Of these, TNFα, IFNγ, IL-6, IL-8, leptin, adiponectin and insulin were also measured in HM samples. Results: HDL in pregnancy was inversely associated with gestational age (GA) at birth and GA-adjusted birthweight z-score, whereas triglycerides and glucose (t = 120) were positively associated with GA-adjusted birthweight z-score. Higher hs-CRP, VLDL and triglycerides were associated with a higher placental weight. Furthermore, higher HDL, insulin, leptin and HOMA-IR were associated with longer duration of exclusive breastfeeding (EBF). Higher pre-pregnancy BMI was the main predictor of higher levels of hs-CRP, log-TNFα, leptin, insulin, C-peptide, and HOMA-IR. Conclusion: Maternal lipid and metabolic markers influenced birthweight z-score and placental weight as well as duration of EBF. Furthermore, pre-pregnancy BMI and maternal age predicted levels of several inflammatory and metabolic markers during pregnancy. Our findings indicate that maternal lipid and metabolic profiles in pregnancy may influence fetal growth and breastfeeding, possibly explained by overweight and/or higher placental weight. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT03254329.

Lower serum branched-chain amino acid catabolic intermediates are predictive signatures specific to patients with diabetic foot.

Diabetic foot (DF) is one of the serious chronic complications of diabetes. Accurate prediction of the risk of DF may take timely intervention measures to prevent its occurrence. The understanding of metabolomic changes in the progression of diabetes to DF may reveal new targets for interventions. We hypothesized that changes in metabolic pathways during DF would lead to changes in the metabolic profile, which could be predictive signature specific to it. In the present study, 43 participants with type 2 diabetes mellitus (T2DM), 32 T2DM participants with DF (T2DM-F), and 36 healthy subjects were enrolled and their serum samples were used for targeted and nonpolar metabolic analysis with liquid chromatography-tandem mass spectrometry. Differential metabolites related to T2DM-F were discovered in metabolomic analysis. Lasso machine learning regression model, random forest algorithm, causal mediation analysis, disease risk assessment, and clinical decision model were carried out. T2DM and T2DM-F groups could be distinguished with the healthy control group. The differential metabolites were all enriched in alpha-linolenic acid and linoleic acid metabolic pathways including arachidonic acid, docosapentaenoic-acid 22N-6, and docosahexaenoic-acid, which were significantly lower in the T2DM and T2DM-F groups compared with the healthy control group. The differential metabolites in T2DM-F vs T2DM groups were enriched to branched-chain amino acid (BCAA) catabolic pathways involving in methylmalonic acid, succinic acid, 3-methyl-2-oxovaleric acid, and ketoleucine, which were the BCAA catabolic intermediates and significantly lower in the T2DM-F compared with the T2DM group except for succinic acid. We reveal a new set of predictive signatures and associate the lower BCAA catabolic intermediates with the progression from T2DM to T2DM-F.

Precision Concussion Management: Approaches to Quantifying Head Injury Severity and Recovery.

Mitigating the substantial public health impact of concussion is a particularly difficult challenge. This is partly because concussion is a highly prevalent condition, and diagnosis is predominantly symptom-based. Much of contemporary concussion management relies on symptom interpretation and accurate reporting by patients. These types of reports may be influenced by a variety of factors for each individual, such as preexisting mental health conditions, headache disorders, and sleep conditions, among other factors. This can all be contributory to non-specific and potentially misleading clinical manifestations in the aftermath of a concussion. This review aimed to conduct an examination of the existing literature on emerging approaches for objectively evaluating potential concussion, as well as to highlight current gaps in understanding where further research is necessary. Objective assessments of visual and ocular motor concussion symptoms, specialized imaging techniques, and tissue-based concentrations of specific biomarkers have all shown promise for specifically characterizing diffuse brain injuries, and will be important to the future of concussion diagnosis and management. The consolidation of these approaches into a comprehensive examination progression will be the next horizon for increased precision in concussion diagnosis and treatment.

Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes.

BACKGROUND: Hepatocellular carcinoma (HCC) is difficult to diagnose with poor therapeutic effect, high recurrence rate and has a low survival rate. The survival of patients with HCC is closely related to the stage of diagnosis. At present, no specific serological indicator or method to predict HCC, early diagnosis of HCC remains a challenge, especially in China, where the situation is more severe. AIM: To identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators. METHODS: The clinical data of patients in the Affiliated Hospital of North Sichuan Medical College from 2016 to 2020 were collected, using a retrospective study method. The results of needle biopsy or surgical pathology were used as the grouping criteria for the experimental group and the control group in this study. Based on the time of admission, the cases were divided into training cohort (n = 1739) and validation cohort (n = 467). Using HCC as a dependent variable, the research indicators were incorporated into logistic univariate and multivariate analysis. An HCC risk prediction model, which was called NSMC-HCC model, was then established in training cohort and verified in validation cohort. RESULTS: Logistic univariate analysis showed that, gender, age, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II, gamma-glutamyl transferase, aspartate aminotransferase and hepatitis B surface antigen were risk factors for HCC, alanine aminotransferase, total bilirubin and total bile acid were protective factors for HCC. When the cut-off value of the NSMC-HCC model joint prediction was 0.22, the area under receiver operating characteristic curve (AUC) of NSMC-HCC model in HCC diagnosis was 0.960, with sensitivity 94.40% and specificity 95.35% in training cohort, and AUC was 0.966, with sensitivity 90.00% and specificity 94.20% in validation cohort. In early-stage HCC diagnosis, the AUC of NSMC-HCC model was 0.946, with sensitivity 85.93% and specificity 93.62% in training cohort, and AUC was 0.947, with sensitivity 89.10% and specificity 98.49% in validation cohort. CONCLUSION: The newly NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.

L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.

BACKGROUNDS: Chronic obstructive pulmonary disease (COPD) is a frequent and common disease in clinical respiratory medicine and its mechanism is unclear. The purpose of this study was to find the new biomarkers of COPD and elucidate its role in the pathogenesis of COPD. Analysis of metabolites in plasma of COPD patients were performed by ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (TOF-MS). The differential metabolites were analyzed and identified by multivariate analysis between COPD patients and healthy people. The role and mechanisms of the differential biomarkers in COPD were verified with COPD rats, arginosuccinate synthetase 1 (ASS-l) KO mice and bronchial epithelial cells (BECs). Meanwhile, whether the differential biomarkers can be the potential treatment targets for COPD was also investigated. 85 differentials metabolites were identified between COPD patients and healthy people by metabonomic. RESULTS: L-Arginine (LA) was the most obvious differential metabolite among the 85 metabolites. Compare with healthy people, the level of LA was markedly decreased in serum of COPD patients. It was found that LA had protective effects on COPD with in vivo and in vitro experiments. Silencing Ass-1, which regulates LA metabolism, and α-methy-DL-aspartic (NHLA), an Ass-1 inhibitor, canceled the protective effect of LA on COPD. The mechanism of LA in COPD was related to the inhibition of ROS/NLRP3/NF-κB signaling pathway. It was also found that exogenous LA significantly improved COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. L-Arginine (LA) as a key metabolic marker is identified in COPD patients and has a protective effect on COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. CONCLUSION: LA may be a novel target for the treatment of COPD and also a potential substitute for treating COPD.

The relationship between coronary artery calcification and bone metabolic markers in maintenance hemodialysis patients.

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.

Comparing Literature- and Subreddit-Derived Laboratory Values in Polycystic Ovary Syndrome (PCOS): Validation of Clinical Data Posted on PCOS Reddit Forums.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects 4% to 21% of people with ovaries. Inaccessibility or dissatisfaction with clinical treatment for PCOS has led to some individuals with the condition discussing their experiences in specialized web-based forums. OBJECTIVE: This study explores the feasibility of using such web-based forums for clinical research purposes by gathering and analyzing laboratory test results posted in an active PCOS forum, specifically the PCOS subreddit hosted on Reddit. METHODS: We gathered around 45,000 posts from the PCOS subreddit. A random subset of 5000 posts was manually read, and the presence of laboratory test results was labeled. These labeled posts were used to train a machine learning model to identify which of the remaining posts contained laboratory results. The laboratory results were extracted manually from the identified posts. These self-reported laboratory test results were compared with values in the published literature to assess whether the results were concordant with researcher-published values for PCOS cohorts. A total of 10 papers were chosen to represent published PCOS literature, with selection criteria including the Rotterdam diagnostic criteria for PCOS, a publication date within the last 20 years, and at least 50 participants with PCOS. RESULTS: Overall, the general trends observed in the laboratory test results from the PCOS web-based forum were consistent with clinically reported PCOS. A number of results, such as follicle stimulating hormone, fasting insulin, and anti-Mullerian hormone, were concordant with published values for patients with PCOS. The high consistency of these results among the literature and when compared to the subreddit suggests that follicle stimulating hormone, fasting insulin, and anti-Mullerian hormone are more consistent across PCOS phenotypes than other test results. Some results, such as testosterone, sex hormone-binding globulin, and homeostasis model assessment-estimated insulin resistance index, were between those of PCOS literature values and normal values, as defined by clinical testing limits. Interestingly, other results, including dehydroepiandrosterone sulfate, luteinizing hormone, and fasting glucose, appeared to be slightly more dysregulated than those reported in the literature. CONCLUSIONS: The differences between the forum-posted results and those published in the literature may be due to the selection process in clinical studies and the possibility that the forum disproportionally describes PCOS phenotypes that are less likely to be alleviated with medical intervention. However, the degree of concordance in most laboratory test values implied that the PCOS web-based forum participants were representative of research-identified PCOS cohorts. This validation of the PCOS subreddit grants the possibility for more research into the contents of the subreddit and the idea of undertaking similar research using the contents of other medical internet forums.

The impact of high intensity interval training in a diverse group of cancer survivors: CAPABLE, a pilot study.

Purpose: Given the well-documented benefits of regular exercise to cancer survivors, current American Cancer Society guidelines recommend that patients engage in a minimum of 150 min per week of moderate-to-vigorous physical activity with a minimum of two days of strength training. However, few survivors meet this goal, particularly among minorities. Methods: The CAPABLE study is a single-arm, pilot exercise intervention that introduced 48 cancer survivors to a high intensity interval and strength training program three days a week for 12 weeks. We evaluated the impact of this unique training method on bodyweight, % body fat, serum markers correlated with an adverse cardiometabolic profile and health-related quality of life (HRQoL). Measures were summarized at baseline and program exit. Paired t-tests were used to assess change in each of these measures over time. Results: We observed losses in weight, body mass index, and % body fat, and glycosylated hemoglobin (HbA1c) levels over 12-weeks. There were also clinically meaningful improvements in reported overall HRQoL (FACTG total change +9.5 (95% CI, 4.6, 14.4)) and in each one of the individual domains (physical, social, emotional, and functional well-being). Conclusions: We observed meaningful improvements in body composition, HbA1c and quality of life over 12 weeks among cancer survivors participating in a high-intensity interval training program. Future work will include a control arm for comparison and address barriers to participation and adherence which will be important in using this intervention and others like it to improve outcomes and reduce cancer health disparities.

Metabolic Markers Associated with Progression of Type 2 Diabetes Induced by High-Fat Diet and Single Low Dose Streptozotocin in Rats.

Science is still searching for readily available, cost-effective biomarkers to assess metabolic disorders occurring before the onset and during the development of type-2 diabetes (T2DM). The aim of the present study was to induce T2DM in rats through a high-fat diet, followed by a single administration of low dose streptozotocin (STZ), and make an assessment of the development of the disease. The rats were divided into two groups-experimental and control-and were monitored for a period of 10 days. Changes in anthropometric parameters, glucose, insulin, lipids, uric acid, advanced oxidation protein products (AOPP), as well as the histological changes in the liver and pancreas, were recorded. To assess insulin resistance, we used the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and beta cell function (HOMA-ß) and visceral obesity-adiposity index (AI). The data demonstrate that the increasing values of glucose, HOMA-IR, AI, total cholesterol, triacylglycerols, low- and very-low-density lipoproteins are important markers of the pre-diabetic state. The stable hyperglycemia and increased levels of TC, TG, VLDL, LDL, uric acid and AOPP in experimental rats strongly suggest the development of T2DM. HOMA-IR, HOMA-ß, AI, and uric acid are reliable criteria for T2DM in rats.