Triglyceride-glucose index as a potential predictor for in-hospital mortality in critically ill patients with intracerebral hemorrhage: a multicenter, case-control study.

BACKGROUND: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH). METHODS: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Various statistical methods, including restricted cubic spline (RCS) regression, multivariable logistic regression, subgroup analysis, and sensitivity analysis, were employed to examine the relationship between the TyG index and the primary outcomes of ICH. RESULTS: A total of 791 patients from MIMIC-IV and 1,113 ones from eICU-CRD were analyzed. In MIMIC-IV, the in-hospital and ICU mortality rates were 14% and 10%, respectively, while in eICU-CRD, they were 16% and 8%. Results of the RCS regression revealed a consistent linear relationship between the TyG index and the risk of in-hospital and ICU mortality across the entire study population of both databases. Logistic regression analysis revealed a significant positive association between the TyG index and the likelihood of in-hospital and ICU death among ICH patients in both databases. Subgroup and sensitivity analysis further revealed an interaction between patients' age and the TyG index in relation to in-hospital and ICU mortality among ICH patients. Notably, for patients over 60 years old, the association between the TyG index and the risk of in-hospital and ICU mortality was more pronounced compared to the overall study population in both MIMIC-IV and eICU-CRD databases, suggesting a synergistic effect between old age (over 60 years) and the TyG index on the in-hospital and ICU mortality of patients with ICH. CONCLUSIONS: This study established a positive correlation between the TyG index and the risk of in-hospital and ICU mortality in patients over 60 years who diagnosed with ICH, suggesting that the TyG index holds promise as an indicator for risk stratification in this patient population.

Prognostic significance of the stress hyperglycemia ratio and admission blood glucose in diabetic and nondiabetic patients with spontaneous intracerebral hemorrhage.

BACKGROUND: The role of stress hyperglycemia ratio (SHR) on the prognosis of spontaneous intracerebral hemorrhage (ICH) in patients with different diabetic status has not been elucidated. This study aimed to evaluate the prognostic value of SHR and admission blood glucose (ABG) for the short- and long-term mortality in diabetic and nondiabetic populations with ICH. METHOD: Participants with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV). The primary outcome was all-cause 30-day and 1-year mortality. The association of SHR and ABG with the primary outcomes in diabetic and nondiabetic cohorts were assessed by Cox proportional hazard regression. RESULTS: Overall, 1029 patients with a median age of 71.09 (IQR: 60.05-81.97) were included. Among them, 548 (53%) individuals were male, and 95 (19%) as well as 323 (31%) ones experienced the 30-day and 1-year mortality, respectively. After adjusting for confounding variables, individuals in quintile 5 of SHR had significantly higher risk of the 30-day and 1-year mortality than those in quintile 1 in the whole cohort (30-day mortality: HR 3.33, 95%CI 2.01-5.51; 1-year mortality: HR 2.09, 95% CI 1.46-3.00) and in nondiabetic patients (30-day mortality: HR 4.55, 95%CI 2.33-8.88; 1-year mortality: HR 3.06, 95%CI 1.93-4.86), but no significant difference was observed in diabetic patients. Similar results were observed for ABG as a categorical variable. As continuous variable, SHR was independently correlated with the 30-day and 1-year mortality in both of the diabetic and nondiabetic cohorts (30-day mortality: HR 2.63, 95%CI 1.50-4.60. 1-year mortality: HR 2.12, 95%CI 1.33-3.39), but this correlation was only observed in nondiabetic cohort for ABG (HR 1.00, 95%CI 0.99-1.01 for both of the 30-day and 1-year mortality). Moreover, compared with ABG, SHR can better improve the C-statistics of the original models regarding the 30-day and 1-year outcomes, especially in patients with diabetes (p < 0.001 in all models). CONCLUSION: SHR might be a more useful and reliable marker than ABG for prognostic prediction and risk stratification in critically ill patients with ICH, especially in those with diabetes.

Serum uric acid to high-density lipoprotein cholesterol ratio is a promising marker for identifying metabolic syndrome in nondiabetic Chinese men.

OBJECTIVES: To explore the relationship between serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) ratio (UHR) and metabolic syndrome (MetS) in nondiabetic individuals. METHODS: A total of 15,760 nondiabetic participants were screened from the China National Diabetes and Metabolic Disorders Study. Pearson correlation was used to determine the correlation between the components of MetS and UHR, HDL-C, and UA. Receiver operating characteristic curves were used to evaluate the ability of UHR, HDL-C, and UA to identify MetS in the nondiabetic population. RESULTS: A total of 6,386 men and 9,374 women were enrolled in this study. There were 1,480 (23.2%) men and 1,828 (19.5%) women with MetS. UHR significantly correlated with the components of MetS in men and women, especially with waist circumference  and triglyceride. In men, although HDL-C showed a higher specificity index, UHR presented higher sensitivity index and area under the curve (AUC) than HDL-C (P = 0.0001) and UA (P < 0.0001), with AUC (95% CI) of 0.762 (0.752-0.773). Higher AUCs of UHR relative to HDL-C and UA were also observed in the age groups <40 and 40-59 years. There was no significant difference in AUC between UHR and HDL-C in the age group ≥60 years (P = 0.370). However, similar results were not observed in women. CONCLUSION: UHR significantly correlated with the components of MetS and could serve as a novel and reliable marker for identifying the population at a high risk of MetS in nondiabetic men, especially in younger adults.

DACH1 inhibits the proliferation and migration of papillary thyroid carcinoma.

DACH1 is an important component of the retinal determinate gene network (RDGN), which regulates the expression of target genes by directly binding or interacting with other factors. DACH1 shows inhibitory effects in most tumors, but its role in papillary thyroid carcinoma is unclear and warrants further investigation. We assessed the expression of DACH1 in different tissues and correlation with immune infiltration by The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMMER2.0 databases). The effects of DACH1 on the proliferation and migration of TPC-1 and Bcpap cells were assessed by cell viability assay, colony formation assay, wound healing assay, transwell migration assay, and flow cytometry. Finally, the effects of DACH1 on CXCL8, CXCL10, and CXCL12 expression in Nthy-ori-3-1, TPC-1 and Bcpap cells were assessed by enzyme-linked immunosorbent assay kit and real-time polymerase chain reaction, respectively. The results showed that DACH1 was differentially expressed in different tumors and tissues. Basal expression of DACH1 was lower in thyroid and papillary thyroid carcinoma than in other normal tissues and corresponding tumors, and positively correlated with CD8+ T cell infiltration. In Nthy-ori-3-1, TPC-1 and Bcpap cells, overexpression of DACH1 inhibited cell migration and proliferation, and the opposite results was obtained by knocking down DACH1 using small interfering RNA. We also demonstrated that DACH1 regulated chemokines CXCL8, CXCL10, and CXCL12, thereby modulating tumor immunity.

Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity. Aims: This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity. Results: Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), P=0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI. Conclusion: This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.

Using noninvasive anthropometric indices to develop and validate a predictive model for metabolic syndrome in Chinese adults: a nationwide study.

PURPOSE: Metabolic syndrome (Mets) is a pathological condition that includes many abnormal metabolic components and requires a simple detection method for rapid use in a large population. The aim of the study was to develop a diagnostic model for Mets in a Chinese population with noninvasive anthropometric and demographic predictors. PATIENTS AND METHODS: Least absolute shrinkage and selection operator (LASSO) regression was used to screen predictors. A large sample from the China National Diabetes and Metabolic Disorders Survey (CNDMDS) was used to develop the model with logistic regression, and internal, internal-external and external validation were conducted to evaluate the model performance. A score calculator was developed to display the final model. RESULTS: We evaluated the discrimination and calibration of the model by receiver operator characteristic (ROC) curves and calibration curve analysis. The area under the ROC curves (AUCs) and the Brier score of the original model were 0.88 and 0.122, respectively. The mean AUCs and the mean Brier score of 10-fold cross validation were 0.879 and 0.122, respectively. The mean AUCs and the mean Brier score of internal-external validation were 0.878 and 0.121, respectively. The AUCs and Brier score of external validation were 0.862 and 0.133, respectively. CONCLUSIONS: The model developed in this study has good discrimination and calibration performance. Its stability was proved by internal validation, external validation and internal-external validation. Then, this model has been displayed by a calculator which can exhibit the specific predictive probability for easy use in Chinese population.

Serum glycated albumin as good biomarker for predicting type 2 diabetes: A retrospective cohort study of China National Diabetes and Metabolic Disorders Survey.

AIMS: Glycated albumin (GA) is a biomarker for short-term (2-3 weeks) glycaemic control. However, the predictive utility of GA for diabetes and prediabetes is largely uncharacterised. We aimed to investigate the relationships of baseline serum GA levels with incident diabetes and prediabetes. METHODS: This was a longitudinal cohort study involving 516 subjects without diabetes or prediabetes at baseline. Blood glucose levels were observed during follow-up. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using COX proportional hazard models. Receiver operating characteristic curves and areas under the curves (AUCs) were used to evaluate the discriminating abilities of glycaemic biomarkers and prediction models. RESULTS: During a 9-year follow-up, 51 individuals (9.88%) developed diabetes and 92 (17.83%) prediabetes. Unadjusted HRs (95% CI) for both diabetes and prediabetes increased proportionally with increasing GA levels in a dose-response manner. Multivariable-adjusted HRs (95% CI) for diabetes were significantly elevated from 1.0 (reference) to 5.58 (1.86-16.74). However, the trend was no longer significant for prediabetes after multivariable adjustment. AUCs for GA, fasting blood glucose (FBG) and 2-h postprandial blood glucose (2h-PBG) for predicting diabetes were 0.698, 0.655 and 0.725, respectively. The AUCs for GA had no significant differences compared with those for FBG (p = 0.376) and 2h-PBG (p = 0.552). Replacing FBG or 2h-PBG or both with GA in diabetes prediction models made no significant changes to the AUCs of the models. CONCLUSIONS: GA is of good prognostic utility in predicting diabetes. However, GA may not be a useful biomarker for predicting prediabetes.

Development of a nomogram to predict 30-day mortality of patients with sepsis-associated encephalopathy: a retrospective cohort study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is related to increased short-term mortality in patients with sepsis. We aim to establish a user-friendly nomogram for individual prediction of 30-day risk of mortality in patients with SAE. METHODS: Data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database. SAE was defined by Glasgow Coma Score (GCS) < 15 or delirium at the presence of sepsis. Prediction model with a nomogram was constructed in the training set by logistic regression analysis and then undergone internal validation and sensitivity analysis. RESULTS: SAE accounted for about 50% in patients with sepsis and was independently associated with the 30-day mortality of sepsis. Variables eligible for the nomogram included patient's age and clinical parameters on the first day of ICU admission including the GCS score, lactate, bilirubin, red blood cell distribution width (RDW), mean value of respiratory rate and temperature, and the use of vasopressor. Compared with Sequential Organ Failure Assessment (SOFA) and Logistic Organ Dysfunction System (LODS), the nomogram exhibited better discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.763 (95%CI 0.736-0.791, p < 0.001) and 0.753 (95%CI 0.713-0.794, p < 0.001) in the training and validation sets, respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of 30-day mortality in both sets. Regarding to clinical usefulness, the DCA of the nomogram exhibited greater net benefit than SOFA and LODS in both of the training and validation sets. Besides, the nomogram exhibited acceptable discrimination, calibration, and clinical usefulness in sensitivity analysis. CONCLUSIONS: SAE is related to increased 30-day mortality of patients with sepsis. The nomogram presents excellent performance in predicting 30-day risk of mortality in SAE patients, which can be used to evaluate the prognosis of patients with SAE and may be more beneficial once specific treatments towards SAE are developed.

Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy.

BACKGROUND: Both protective and therapeutic functions of insulin-like growth factor-1 (IGF-1) in brain injury have been reported, but its effects on cognitive sequelae after septic encephalopathy (SE) remain unclear. MATERIALS AND METHODS: This study was divided into three parts, and a septic model was built by cecal ligation and puncture (CLP). First, survival analysis was performed, and IGF-1's effects on long-term cognition and depressive emotion were assessed. Second, the characteristics of IGF-1 function in cognition were evaluated. Finally, cytochrome C, caspase-9, tumor necrosis factor receptor (TNFR), and caspase-8 levels as well as cell apoptosis in the hippocampus were evaluated. RESULTS: IGF-1 did not reduce mortality or alleviate depressive symptoms in septic rats, but improved the memory of noxious stimulation and spatial learning and memory. These effects were observed only when IGF-1 was administered within 0-6 hours after CLP. Moreover, cytochrome C and caspase-9 expression levels were increased at 6 hours after CLP in the hippocampus, while TNFR and caspase-8 amounts were not increased until 12 hours after CLP. Cell apoptosis increased at 12 hours after CLP, but was inhibited by IGF-1. CONCLUSION: Cognitive impairment in rats recovering from SE is associated with cell apoptosis in the hippocampus. Supplementation of IGF-1 reduces cell apoptosis by preventing the over-expression of cytochrome C and TNFR, and results in improved cognitive function. However, improvement only occurs when IGF-1 is administered at the early stage (within 6 hours) of sepsis. As cytochrome C activation occurs earlier than that of TNFR in this study, cytochrome C may be the main factor inducing apoptosis in early SE.

Pulsed electromagnetic fields regulate osteocyte apoptosis, RANKL/OPG expression, and its control of osteoclastogenesis depending on the presence of primary cilia.

Growing evidence has shown that pulsed electromagnetic fields (PEMF) can modulate bone metabolism in vivo and regulate the activities of osteoblasts and osteoclasts in vitro. Osteocytes, accounting for 95% of bone cells, act as the major mechanosensors in bone for transducing external mechanical signals and producing cytokines to regulate osteoblastic and osteoclastic activities. Targeting osteocytic signaling pathways is becoming an emerging therapeutic strategy for bone diseases. We herein systematically investigated the changes of osteocyte behaviors, functions, and its regulation on osteoclastogenesis in response to PEMF. The osteocyte-like MLO-Y4 cells were exposed to 15 Hz PEMF stimulation with different intensities (0, 5, and 30 Gauss [G]) for 2 hr. We found that the cell apoptosis and cytoskeleton organization of osteocytes were regulated by PEMF with an intensity-dependent manner. Moreover, PEMF exposure with 5 G significantly inhibited apoptosis-related gene expression and also suppressed the gene and protein expression of the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in MLO-Y4 cells. The formation, maturation, and osteoclastic bone-resorption capability of in vitro osteoclasts were significantly suppressed after treated with the conditioned medium from PEMF-exposed (5 G) osteocytes. Our results also revealed that the inhibition of osteoclastic formation, maturation, and bone-resorption capability induced by the conditioned medium from 5 G PEMF-exposed osteocytes was significantly attenuated after abrogating primary cilia in osteocytes using the polaris siRNA transfection. Together, our findings highlight that PEMF with 5 G can inhibit cellular apoptosis, modulate cytoskeletal distribution, and decrease RANKL/OPG expression in osteocytes, and also inhibit osteocyte-mediated osteoclastogenesis, which requires the existence of primary cilia in osteocytes. This study enriches our basic knowledge for further understanding the biological behaviors of osteocytes and is also helpful for providing a more comprehensive mechanistic understanding of the effect of electromagnetic stimulation on bone and relevant skeletal diseases (e.g., bone fracture and osteoporosis).

Hepatoma-derived growth factor functions as an unfavorable prognostic marker of human gliomas.

Hepatoma-derived growth factor (HDGF) regulates various cellular processes involved in the onset and development of tumors. To evaluate the role of HDGF in human gliomas, western blotting analysis, immunohistochemistry staining and reverse transcription-quantitative polymerase chain reaction were performed to detect HDGF protein and mRNA expression levels in glioma and intractable epileptic brain tissue. Various clinicopathological characteristics, including age, gender, World health Organization grade, HDGF expression level, Karnofsky performance Status (KPS) and Ki-67 index were obtained from medical records. The correlation between HDGF expression and these clinicopathological characteristics was statistically evaluated. Following this, multivariate liner regression was used to evaluate their effect on patient survival time. HDGF expression, at the protein and mRNA levels, was observed to be more upregulated in glioma tissues compared with intractable epileptic brain tissue without tumor. Furthermore, the level of HDGF expression was positively associated with the grade of malignancy [grades II~IV, Ki-67 index ≥20% or KPS <80 (P<0.05)] and poor prognosis in glioma patients. Notably, the univariate survival analysis identified a negative correlation between HDGF-expression and survival time (P<0.01) and multivariate liner regression demonstrated that HDGF expression is an independent prognostic factor for gliomas (P=0.01). Overall, HDGF upregulation may be a crucial step in the development and invasion of glioma. Further survival analysis highlighted its prognostic value for this malignancy, implying its potential as a promising therapeutic target for gliomas.

Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.