Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Determining the 1-hour post-load glucose which identifies diabetes in Africans: Insight from the Africans in America study.

Diagnosing diabetes by shortening the OGTT to 1-h and substituting 1-h post-load glucose (PG) ≥ 209 mg/dL for 2-h PG≥200 mg/dL has been proposed. One-hour PG≥209 mg/dL is from a meta-analysis without any African-descent populations. Our data suggest 1-h PG≥183 mg/dL maybe more optimal for Africans. As with waist circumference guidelines, population-specific thresholds may be appropriate.

Feasibility and efficacy of pemafibrate for prevention of maternal high-fat intake-induced glucose metabolic dysfunction in offspring.

Given the significance of the intrauterine lipid environment in glucose metabolic homeostasis in offspring, the present study was undertaken to investigate the feasibility and efficacy of pemafibrate, a triglyceride-lowering peroxisome proliferator-activated agent, for maternal high-fat diet (HFD) intake-induced glucose metabolic dysfunction in offspring. A mouse model of HFD-induced gestational obesity was employed, and pemafibrate was orally administered from day 10 of gestation until delivery. The influences of maternal pemafibrate treatment on biological processes and toxicity were evaluated in both newborns and 12-week-old offspring. The findings of a dose-dependent decrease of ß cell islet mass and of impairment of glucose tolerance and insulin sensitivity in offspring suggest that maternal pemafibrate intervention can prevent maternal HFD-intake-induced diabetes in offspring. Of particular interest in the prevention of future glucose metabolic dysfunction in offspring, low-dose maternal pemafibrate treatment (0.02 mg/kg/day) had sufficient efficacy and appeared to be safe in offspring. Therefore, pemafibrate may be a potential agent for the prevention of maternal high-fat exposure-induced diabetes in offspring. Abbreviations: CD, control diet; DEG, differentially expressed genes; GTT, glucose tolerance test; HFD, high-fat diet; ITT, insulin tolerance test; MC, 0.5w/v% methyl cellulose 400 solution; PPAR, triglyceride-lowering peroxisome proliferator-activated receptor; RNA-seq, RNA sequencing; TC, total cholesterol; TG, triglycerides.

The potential of glucose management indicator for the estimation of glucose disposal rate in people with type 1 diabetes.

BACKGROUND AND AIMS: Insulin resistance is a growing feature in type 1 diabetes (T1D). It can be quantified by calculating the estimated glucose disposal rate (eGDR) with the Epstein's formula, which includes laboratory-measured glycated hemoglobin (HbA1c). We aimed the current research to assess the agreement between the conventional eGDR formula and an alternative one (eGDR-GMI) incorporating the glucose management indicator (GMI) derived from continuous glucose monitoring (CGM). We also explored the relationship between eGDR-GMI, cardiovascular risk factors, and the prevalence of diabetes-related complications. METHODS AND RESULTS: We designed a cross-sectional study that included adults with T1D. eGDR-GMI and eGDR (mg/kg/min) were calculated using GMI or HbA1c, waist circumference, and hypertensive state. Clinical data were collected from electronic medical records. The analyses encompassed 158 participants with a mean age of 39 ± 13 years. The Bland-Altman analysis showed a good agreement between eGDR-GMI and eGDR. When we divided participants in eGDR-GMI tertiles we found a higher prevalence of diabetes-related complications and a less favorable metabolic profile in the lowest eGDR-GMI tertile. The relative risk of retinopathy, nephropathy, and neuropathy significantly increased by approximately 1 unit with each decrease in eGDR-GMI, regardless of age, sex, disease duration, lipids, and smoking habit. CONCLUSIONS: eGDR-GMI represents a valid and robust alternative to the eGDR to assess insulin resistance in T1D. Low eGDR-GMI is associated with diabetes complications and a less favorable metabolic profile. Incorporating the eGDR-GMI into clinical practice can enhance the characterization of T1D people and allow for a more personalized treatment approach.

Associations of fasting plasma glucose and glycosylated hemoglobin levels at less than 24 weeks of gestation with hypertensive disorders of pregnancy: the BOSHI study.

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

GDF15 regulated by HDAC2 exerts suppressive effects on oxygen-glucose deprivation/reoxygenation-induced neuronal cell pyroptosis via the NLRP3 inflammasome.

Background: Pyroptosis, inflammation-related programed cell death mediated by NLRP3 inflammasome, is involved in the pathogenesis of cerebral hypoxic-ischemic injury. Our study aims to explore the biological role of growth differentiation factor (GDF)15 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal pyroptosis. Methods: HT22 neurons were subjected to OGD/R to simulate cerebral hypoxic-ischemic injury. Cells were transfected with plasmids to overexpress GDF15, or lentiviral-based shRNAs constructs to silence GDF15. ELISA assay was used to detect GDF15, IL-1ß, IL-18, and neuron specific enolase (NSE) levels. Cell pyroptosis was measured by flow cytometery. Chromatin immunoprecipitation assay was used to detect interaction of H3K27ac with GDF15 promoter. GDF15, NLRP3, Caspase-1 p20 and GSDMD-N expressions were measured by Western blotting. Results: Patients with malignant middle cerebral artery infarction showed decreased GDF15, but increased IL-1ß, IL-18, and NSE levels in serum compared to healthy controls. OGD/R treatment caused significant increases in the levels of IL-1ß, IL-18 and NSE, percentages of pyroptotic cells, and expressions of NLRP3, Caspase-1 p20, and GSDMD in HT22 cells, which were markedly reversed by GDF15 overexpression. However, GDF15 knockdown resulted in neuronal injury similar to those observed in OGD/R treatment. The GDF15 knockdown-induced effects were counteracted by treatment with NLRP3 inhibitor. OGD/R decreased the enrichment of H3K27ac in the promoter of GDF15 to down-regulate GDF15, but was compromised by co-treatment with HDAC2 inhibitor. Conclusion: Our data demonstrates that GDF15 attenuates OGD/R-induced pyroptosis through NLRP3 inflammasome. HDAC2 is involved in mediating OGD-induced GDF15 down-regulation via H3K27ac modification. GDF15 overexpression and HDAC2 inhibition hold potential as useful therapeutic strategies for neuroprotection.

Insights into the phytochemical profiling, antidiabetic and antioxidant potentials of Lepionurus sylvestris Blume extract in fructose/streptozotocin-induced diabetic rats.

In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1ß, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1ß, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant.

Chronic kidney disease combined with metabolic syndrome is a non-negligible risk factor.

Metabolic syndrome (MetS) is a group of conditions characterized by hypertension (HTN), hyperglycaemia or insulin resistance (IR), hyperlipidaemia, and abdominal obesity. MetS is associated with a high incidence of cardiovascular events and mortality and is an independent risk factor for chronic kidney disease (CKD). MetS can cause CKD or accelerate the progression of kidney disease. Recent studies have found that MetS and kidney disease have a cause-and-effect relationship. Patients with CKD, those undergoing kidney transplantation, or kidney donors have a significantly higher risk of developing MetS than normal people. The present study reviewed the possible mechanisms of MetS in patients with CKD, including the disorders of glucose and fat metabolism after kidney injury, IR, HTN and the administration of glucocorticoid and calcineurin inhibitors. In addition, this study reviewed the effect of MetS in patients with CKD on important target organs such as the kidney, heart, brain and blood vessels, and the treatment and prevention of CKD combined with MetS. The study aims to provide strategies for the diagnosis, treatment and prevention of CKD in patients with MetS.

Association between triglyceride-glucose index and sarcopenia in patients with chronic inflammatory airway disease.

Objective: This research sought to explore the association between the triglyceride-glucose (TyG) index and the risk of sarcopenia in patients with chronic inflammatory airway disease (CIAD). Methods: Data were obtained from the National Health and Nutrition Examination Survey 2011-2018. Grouping was performed using TyG index tertiles and multiple logistic regression was employed to assess the correlation between TyG levels and the risk of sarcopenia. The Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the prognostic value of the TyG index for sarcopenia. Linear regression analysis was utilized to elucidate the direct relationship between TyG index and sarcopenia. Additionally, the curve between the TyG and sarcopenia indices was examined using a generalized additive model. Results: The study included 981 individuals diagnosed with CIAD. After adjusting for potential confounders, a significant positive correlation was observed between TyG and sarcopenia (OR = 1.70, 95 % CI: 1.20-2.39, P = 0.002). Trend analysis using the chi-square test revealed an increase in sarcopenia prevalence concomitant with higher TyG levels (P < 0.05). Furthermore, linear regression analysis revealed a notable inverse linear association between the TyG and sarcopenia indices (ß = -0.03; 95 % CI: -0.07-0.01; P = 0.020). The ROC curves corroborated the robust predictive capacity of TyG for sarcopenia among patients with CIAD, with an AUC of 0.685 (95 % CI: 0.636-0.735, P < 0.001). Conclusion: Our research indicates a positive association between TyG and sarcopenia in CIAD patients. The TyG index may serve as a reliable marker for predicting sarcopenia risk in CIAD patients.

Comprehensive analysis of bioactive compounds in Crocus sativus stamens extracts by HPLC-DAD: investigating antidiabetic activity via in vitro, in vivo, and molecular docking simulation.

Introduction: Medicinal herbs used in traditional diabetes treatment are a rich source of anti-diabetic compounds. Pancreatic α-amylase inhibitors offer an effective strategy to reduce postprandial hyperglycemic levels via control of starch degradation. In this context, our study for the first time investigates the effect of Crocus sativus stamens extracts on α-amylase inhibition. Material and methods: The hydromethanolic and hydroethanolic extracts were obtained by macerating the dried stamen powder with methanol/water or ethanol/water, respectively. The total phenolic content of the stamen extracts was assessed using the Folin-Ciocalteu reagent method, while the total flavonoid content was determined using the Aluminum Chloride method. Phytochemicals were further quantified and identified using HPLC-DAD. For evaluation of hypoglycemic activity, in vitro α-amylase enzyme inhibition was calculated. The results were confirmed in vivo using an oral starch tolerance test in both normal and diabetic rats. Results: Our findings demonstrated a higher level of polyphenols and flavonoids in the hydroethanolic extract. Important flavonoids found were kaempferol, rutin, and vanillic acid, while prominent carotenoids contained trans- and cis-crocins. The in vitro study showed that both hydromethanolic and hydroethanolic extracts had considerable inhibitory effects, with maximum inhibitions of approximately 83% and 89%, respectively. In vivo tests indicated that both extracts effectively lowered peak blood glucose and area under the curve in both normal and diabetic rats following oral starch treatment. The obtained results are also supported by a docking study. Conclusion: These findings imply that C. sativus stamens possess a distinctive capability to reduce postprandial blood glucose levels. This effect is likely mediated through the inhibition of α-amylase, presenting a novel dietary avenue for managing diabetes.

Association between the triglyceride glucose index and the risk of acute kidney injury in critically ill patients with hypertension: analysis of the MIMIC-IV database.

Background: The triglyceride glucose (TyG) index, a metric computed from the levels of fasting triglyceride (TG) and fasting plasma glucose (FPG), has emerged as a simple surrogate measure for insulin resistance (IR) in recent years. In multiple critical care scenarios, such as contrast-induced acute kidney injury (AKI) and cardiorenal syndrome, a high TyG index levels shows a notable correlation with AKI incidence. However, its predictive value for AKI in critically ill hypertensive patients remains uncertain. Methods: Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into quartiles based on the TyG index. The primary focus of the study was to investigate the risk of acute kidney injury (AKI), with in-hospital mortality as a secondary endpoint, assessed among all study subjects as well as specifically among AKI patients. The use of renal replacement therapy (RRT), indicative of AKI progression, was also considered a secondary endpoint reflecting renal outcomes. To explore the correlation between the TyG index and AKI risk in critically ill hypertensive patients, the study employed a restricted cubic splines model and Cox proportional hazards (CPH) models. Additionally, Kaplan-Meier survival analysis was utilized to assess differences in primary and secondary outcomes across groups categorized by their TyG index. Analyses were conducted to ensure the consistency of the predictive capability of TyG index across various subgroups. Results: Our study included 4,418 participants, with 57% being male patients. AKI occurred in 56.1% of cases. Through the CPH analysis, we identified a significant association between the TyG index and AKI occurrence in critically ill hypertensive patients. With the help of a restricted cubic splines model, we observed a direct relationship between an elevated TyG index and an increased AKI. Subgroup examinations consistently proved the predictive value of the TyG index across categories. Furthermore, Kaplan-Meier survival analysis revealed notable differences in RRT among AKI patients. Conclusion: The findings underscore the importance of the TyG index as a reliable predictor for the occurrence of AKI and adverse renal outcomes among hypertensive patients in critical ill states. Nevertheless, validating causality mandates extensive prospective investigations.

A comparative analysis of NADPH supply strategies in Saccharomyces cerevisiae: Production of d-xylitol from d-xylose as a case study.

Enhancing the supply of the redox cofactor NADPH in metabolically engineered cells is a critical target for optimizing the synthesis of many product classes, such as fatty acids or terpenoids. In S. cerevisiae, several successful approaches have been developed in different experimental contexts. However, their systematic comparison has not been reported. Here, we established the reduction of xylose to xylitol by an NADPH-dependent xylose reductase as a model reaction to compare the efficacy of different NADPH supply strategies in the course of a batch fermentation, in which glucose and ethanol are sequentially used as carbon sources and redox donors. We show that strains overexpressing the glucose-6-phosphate dehydrogenase Zwf1 perform best, producing up to 16.9 g L-1 xylitol from 20 g L-1 xylose in stirred tank bioreactors. The beneficial effect of increased Zwf1 activity is especially pronounced during the ethanol consumption phase. The same notion applies to the deletion of the aldehyde dehydrogenase ALD6 gene, albeit at a quantitatively lower level. Reduced expression of the phosphoglucose isomerase Pgi1 and heterologous expression of the NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase Gdp1 from Kluyveromyces lactis acted synergistically with ZWF1 overexpression in the presence of glucose, but had a detrimental effect after the diauxic shift. Expression of the mitochondrial NADH kinase Pos5 in the cytosol likewise improved the production of xylitol only on glucose, but not in combination with enhanced Zwf1 activity. To demonstrate the generalizability of our observations, we show that the most promising strategies - ZWF1 overexpression and deletion of ALD6 - also improve the production of l-galactonate from d-galacturonic acid. Therefore, we expect that these findings will provide valuable guidelines for engineering not only the production of xylitol but also of diverse other pathways that require NADPH.

Triglyceride-Glucose Index as a Predictor of Major Adverse Cardiovascular Events in Post-PCI Patients Diagnosed with In-Stent Restenosis.

Background: The triglyceride-glucose index (TyG) is a reliable indicator for predicting the prognosis of patients with coronary heart disease (CAD) after percutaneous coronary intervention (PCI). However, its influence on patients with in-stent restenosis (ISR) is unclear. This study was designed to evaluate the association between the TyG index and the occurrence of major adverse cardiovascular events (MACEs) after PCI in patients with ISR. Methods: This retrospective study included 1654 patients who underwent PCI between 2016 and 2022 at Nanjing First Hospital. Patients were stratified into three groups based on the quantile level of the TyG index. The TyG index was determined as Ln (triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Results: Individuals with the highest TyG index showed an increased risk of MACEs compared to those with the lowest level of the TyG index (HR 1.60; 95% CI 1.11-2.30; P = 0.01). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.51 (95% CI: 1.11-2.05; P = 0.01). For the male subgroup and the diabetes subgroup, this trend was even more pronounced (HR 1.269; 95% CI 1.055-1.527; P = 0.011; HR 1.385; 95% CI 1.125-1.706; P = 0.002). Additionally, the landmark analysis showed that patients with the highest level of TyG had an increased risk of MACEs 6 months after the PCI (P = 0.019). Conclusion: Elevated TyG index is associated with increased risk of adverse cardiovascular events in patients with ISR, and the extent of increase in the risk is more significant in male patients with diabetes.

The role and mechanism of action of miR-483-3p in mediating the effects of IGF-1 on human renal tubular epithelial cells induced by high glucose.

This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson's staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P < 0.05). Conversely, in the HG + inhibitor group, the protein expression of Collagen I and FN was notably reduced compared to the HG group (P < 0.05). The dual luciferase reporter assay confirmed that miR-483-3p could inhibit the luciferase activity of IGF-1's 3'-UTR region (P < 0.05). miR-483-3p exerts targeted regulation on IGF-1, promoting apoptosis and fibrosis in renal tubular epithelial cells induced by high glucose conditions.

Association between glucose levels and all-cause mortality in cancer survivors: findings from NHANES 1999-2018.

BACKGROUND: Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. METHODS: We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. RESULTS: In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. CONCLUSIONS: HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.

Characterization of a Syngeneic Orthotopic Model of Cholangiocarcinoma by [18F]FDG-PET/MRI.

Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice. The imaging groups included contrast-enhanced (CE) MR, CE-MR with static [18F]FDG-PET, and dynamic [18F]FDG-PET. Tumor volume and FDG uptake were measured weekly over four weeks. Early tumor formation was visible in CE-MR images, with a gradual increase in volume over time. Dynamic FDG-PET revealed an increase in the metabolic glucose rate (MRGlu) over time. Blood analysis showed pathological changes in liver-related parameters. Lung metastases were observed in nearly all animals after four weeks. The study concludes that PET-MR imaging effectively monitors tumor progression in the CCA mouse model, providing insights into CCA development and potential treatment strategies.

Radiomics-Guided Deep Learning Networks Classify Differential Diagnosis of Parkinsonism.

The differential diagnosis between atypical Parkinsonian syndromes may be challenging and critical. We aimed to proposed a radiomics-guided deep learning (DL) model to discover interpretable DL features and further verify the proposed model through the differential diagnosis of Parkinsonian syndromes. We recruited 1495 subjects for 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning, including 220 healthy controls and 1275 patients diagnosed with idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), or progressive supranuclear palsy (PSP). Baseline radiomics and two DL models were developed and tested for the Parkinsonian diagnosis. The DL latent features were extracted from the last layer and subsequently guided by radiomics. The radiomics-guided DL model outperformed the baseline radiomics approach, suggesting the effectiveness of the DL approach. DenseNet showed the best diagnosis ability (sensitivity: 95.7%, 90.1%, and 91.2% for IPD, MSA, and PSP, respectively) using retained DL features in the test dataset. The retained DL latent features were significantly associated with radiomics features and could be interpreted through biological explanations of handcrafted radiomics features. The radiomics-guided DL model offers interpretable high-level abstract information for differential diagnosis of Parkinsonian disorders and holds considerable promise for personalized disease monitoring.

Evaluation of Plasma Atherogenic Index, Triglyceride-Glucose Index and Other Lipid Ratios as Predictive Biomarkers of Coronary Artery Disease in Different Age Groups.

(1) Background: Dyslipidaemia and insulin resistance are major risk factors for coronary artery disease (CAD). This study investigated the relationship between plasma atherogenic index (PA-I), triglyceride-glucose index (TGI) and other lipid ratios with the presence and prediction of CAD among different age categories. (2) Methods: The study included 223 participants diagnosed with CAD and those with normal coronary arteries (normal group) by coronary computed tomography angiography (CCTA). Participants were categorised by age and sex: premature CAD (PCAD) for men under 55 and women under 65, and older groups as elderly. (3) Results: PA-I, Lipid Combined Index, Castelli Risk Indices, and TGI were significantly higher in the PCAD group compared to the control group (p < 0.05). ROC analysis showed that a PA-I cut-off of 0.41 had a sensitivity of 62% and a specificity of 58% for predicting PCAD, while a TGI cut-off of 8.74 had a sensitivity of 68% and a specificity of 62%. In the elderly, no significant differences in these indices were found between the CAD and normal groups. (4) Conclusions: Traditional lipid profiles and non-traditional lipid indices such as PA-I and TGI show significant differences in predicting CAD in younger populations but not in older groups. TGI and PA-I may be promising biomarkers for the prediction of PAD, although further validation is needed.

Role of the Stress Index in Predicting Mortality among Patients with Traumatic Femoral Fractures.

BACKGROUND: Traumatic femoral fractures, often resulting from high-energy impacts such as traffic accidents, necessitate immediate management to avoid severe complications. The Stress Index (SI), defined as the glucose-to-potassium ratio, serves as a predictor of mortality and adverse outcomes in various trauma contexts. This study aims to evaluate the prognostic value of the SI in patients with traumatic femoral fractures. METHODS: This retrospective cohort study included adult trauma patients aged 20 or above with traumatic femoral fractures from the Trauma Registry System at a level 1 trauma center in southern Taiwan between 1 January 2009 and 31 December 2022. At the emergency room, serum electrolyte levels were assessed using baseline laboratory testing. By dividing blood glucose (mg/dL) by potassium (mEq/L), the SI was calculated. The best cut-off value of the SI for predicting mortality was determined using the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). RESULTS: A total of 3717 patients made up the final group, of which 3653 survived and 64 died. In comparison to survivors, deceased patients had substantially higher blood glucose levels (199.3 vs. 159.0 mg/dL, p < 0.001) and SIs (53.1 vs. 41.6, p < 0.001). The optimal SI cut-off value for predicting mortality was 49.7, with a sensitivity of 53.1% and a specificity of 78.7% (AUC = 0.609). High SI was associated with increased mortality (4.2% vs. 1.0%, p < 0.001) and longer hospital stays (12.8 vs. 9.5 days, p < 0.001). The adjusted odds ratios of mortality, controlled by comorbidities, the Glasgow Coma Scale, and the Injury Severity Score, were significantly higher in patients with a higher SI (AOR 2.05, p = 0.016) than those with a lower SI. CONCLUSIONS: Elevated SI upon admission correlates with higher mortality and extended hospital stay in patients with traumatic femoral fractures. Although the SI has a moderate predictive value, it remains a useful early risk assessment tool, necessitating further prospective, multi-center studies for validation and standardization.

Sodium-Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome.

Metabolic syndrome (MetS) is a multifactorial condition that significantly increases the risk of cardiovascular disease and chronic kidney disease (CKD). Recent studies have emphasized the role of lipid dysregulation in activating cellular mechanisms that contribute to CKD progression in the context of MetS. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy in improving various components of MetS, including obesity, dyslipidemia, and insulin resistance. While SGLT2i have shown cardioprotective benefits, the underlying cellular mechanisms in MetS and CKD remain poorly studied. Therefore, this review aims to elucidate the cellular mechanisms by which SGLT2i modulate lipid metabolism and their impact on insulin resistance, mitochondrial dysfunction, oxidative stress, and CKD progression. We also explore the potential benefits of combining SGLT2i with other antidiabetic drugs. By examining the beneficial effects, molecular targets, and cytoprotective mechanisms of both natural and synthetic SGLT2i, this review provides a comprehensive understanding of their therapeutic potential in managing MetS-induced CKD. The information presented here highlights the significance of SGLT2i in addressing the complex interplay between metabolic dysregulation, lipid metabolism dysfunction, and renal impairment, offering clinicians and researchers a valuable resource for developing improved treatment strategies and personalized approaches for patients with MetS and CKD.