The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker.

BACKGROUND: The role of the macrophage migration inhibitory factor (MIF) has recently attracted considerable attention in cancer research; nonetheless, the insights provided by current investigations remain constrained. Our main objective was to investigate its role and the latent mechanisms within the pan-cancer realm. METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool. RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions. CONCLUSION: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.

Glycemic variability evaluated by HbA1c rather than fasting plasma glucose is associated with adverse cardiovascular events.

Background: Although studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs). Results: In total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13-1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01). Conclusion: In adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy.

Association between prehospital time and in-hospital outcomes in out-of-hospital cardiac arrests according to resuscitation outcomes consortium epidemiologic registry.

INTRODUCTION: For out-of-hospital cardiac arrests (OHCAs), time is of the essence. While the relationship between EMS response time (ERT) and OHCA outcomes is well studied, a more comprehensive assessment of the effects of other intervention time is needed, which is essential to guide clinical practice. OBJECTIVES: Evaluating how a longer total pre-hospital time (TPT), ERT, advance life support response time (ART) and EMS cardiopulmonary resuscitation time (ECT) increase the mortality rates, unfavorable neurological outcomes, and severe complications at discharge of OHCAs. METHODS: 31,926 OHCAs from the USA and Canada were identified in Resuscitation Outcomes Consortium Epidemiologic Registry. Twelve adjusted models were used to analyze the relationship between the prehospital time (TPT, ERT, ART and ECT) and three outcomes (in hospital mortality, unfavorable neurological outcomes, and severe complications for surviving OHCAs). RESULTS: Every 10-min increase in TPT was associated with a 0.14-fold increase in the risk of death (adjusted odds ratio [OR] = 1.14, 95 % confidence interval [CI] = 1.10-1.17) and a 0.13-fold increase of adverse neurological outcomes (OR = 1.13, CI =1.08-1.18). The risk of patient mortality markedly increased with every 5 min increase in ERT (OR = 1.36, CI = 1.26-1.47), ART (OR =1.10, CI = 1.06-1.15), and ECT (OR = 1.46, CI = 1.37-1.56). Adverse neurological outcome was associated with ERT and ECT, and severe complications with ERT and ART. CONCLUSION: Prolonged prehospital time, particularly ERT and ECT, are closely associated with in-hospital mortality, unfavorable neurological functions, and severe complications at discharge in OHCAs.

Racial and ethnic disparities in bystander resuscitation for out-of-hospital cardiac arrests.

INTRODUCTION: Bystander-provided cardiopulmonary resuscitation (CRP) influences the survival rates of out-of-hospital cardiac arrests (OHCAs). Disparities on bystander resuscitation measures between Black, Hispanic, Asians and Non-Hispanic White OHCAs is unclear. Examining racial and ethnic differences in bystander resuscitations is essential to better target interventions. METHODS: 15,542 witnessed OHCAs were identified between April 1, 2011, and June 30, 2015 using the Resuscitation Outcomes Consortium Epidemiologic Registry 3, a multi-center, controlled trial about OHCAs in the United States and Canada. Multivariable logistic regression model was used to analyze the differences in bystander resuscitation (bystander CRP [B-CPR], CPR plus ventilation, automated external defibrillators/defibrillator application [B-AED/D], or delivery of shocks) and clinical outcomes (death at the scene or en route, return of spontaneous circulation upon first arrival at the emergency department [ROSC-ED], survival until ED discharge [S-ED], survival until hospital discharge [S-HOS], and favorable neurological outcome at discharge) between Black, Hispanic, or Asian victims and Non-Hispanic White victims. RESULTS: Compared to OHCA victims in Non-Hispanic Whites, Black, Hispanic, and Asians were less likely to receive B-CPR (adjusted OR: 0.79; 95 % CI: 0.63-0.99), and B-AED/D (adjusted OR: 0.80; 95 % CI: 0.65-0.98) in public locations. And, Black, Hispanic, and Asian OHCAs were less likely to receive bystander resuscitation in street/highway locations and public buildings, and less likely to have better clinical outcomes, including ROSC-ED, S-ED and S-HOS. CONCLUSION: Black, Hispanic and Asian victims with witnessed OHCAs are less likely to receive bystander resuscitation and more likely to get worse outcomes than Non-Hispanic White victims.

Higher plasma aldosterone concentrations in patients with aortic diseases and hypertension: a retrospective observational study.

BACKGROUND: Aortic diseases remain a highly perilous macrovascular condition. The relationship between circulating aldosterone and aortic diseases is rarely explored, thus we investigated the difference in plasma aldosterone concentration (PAC) between patients with and without aortic disease in hypertensive people. METHODS: We analyzed 926 patients with hypertension, ranging in age from 18 to 89 years, who had their PAC measured from the hospital's electronic database. The case group and control group were defined based on inclusion and exclusion criteria. The analysis included general information, clinical data, biochemical data, and medical imaging examination results as covariates. To further evaluate the difference in PAC between primary hypertension patients with aortic disease and those without, we used multivariate logistic regression analysis and also employed propensity score matching to minimize the influence of confounding factors. RESULTS: In total, 394 participants were included in the analysis, with 66 individuals diagnosed with aortic diseases and 328 in the control group. The participants were predominantly male (64.5%) and over the age of 50 (68.5%), with an average PAC of 19.95 ng/dL. After controlling for confounding factors, the results showed hypertension patients with aortic disease were more likely to have high PAC levels than those without aortic disease (OR = 1.138, 95% CI [1.062 to 1.238]). Subgroup analysis revealed consistent relationship between PAC and primary hypertensive patients with aortic disease across the different stratification variables. Additionally, hypertensive patients with aortic disease still have a risk of higher PAC levels than those without aortic disease, even after propensity score matching. CONCLUSIONS: The results of this study suggest that primary hypertensive patients with aortic diseases have elevated levels of PAC, but the causal relationship between PAC and aortic disease requires further study.

A Digital Mask-Voiceprint System for Postpandemic Surveillance and Tracing Based on the STRONG Strategy.

Lockdowns and border closures due to COVID-19 imposed mental, social, and financial hardships in many societies. Living with the virus and resuming normal life are increasingly being advocated due to decreasing virus severity and widespread vaccine coverage. However, current trends indicate a continued absence of effective contingency plans to stop the next more virulent variant of the pandemic. The COVID-19-related mask waste crisis has also caused serious environmental problems and virus spreads. It is timely and important to consider how to precisely implement surveillance for the dynamic clearance of COVID-19 and how to efficiently manage discarded masks to minimize disease transmission and environmental hazards. In this viewpoint, we sought to address this issue by proposing an appropriate strategy for intelligent surveillance of infected cases and centralized management of mask waste. Such an intelligent strategy against COVID-19, consisting of wearable mask sample collectors (masklect) and voiceprints and based on the STRONG (Spatiotemporal Reporting Over Network and GPS) strategy, could enable the resumption of social activities and economic recovery and ensure a safe public health environment sustainably.

Molecular Subtypes and Machine Learning-Based Predictive Models for Intracranial Aneurysm Rupture.

BACKGROUND: The determination of biological mechanisms and biomarkers related to intracranial aneurysm (IA) rupture is of utmost significance for the development of effective preventive and therapeutic strategies in the clinical field. METHODS: GSE122897 and GSE13353 datasets were downloaded from Gene Expression Omnibus. Data extracted from GSE122897 were used for analyzing differential gene expression, and consensus clustering was performed to identify stable molecular subtypes. Clinical characteristics were compared between subgroups, and fast gene set enrichment analysis and weighted gene coexpression network analysis were performed. Hub genes were identified via least absolute shrinkage and selection operator analysis. Predictive models were constructed based on hub genes using the Light Gradient Boosting Machine, eXtreme Gradient Boosting, and logistic regression algorithm. Immune cell infiltration in IA samples was analyzed using Microenvironment Cell Population counter, CIBERSORT, and xCell algorithm. The correlation between hub genes and immune cells was analyzed. The predictive model and immune cell infiltration were validated using data from the GSE13353 dataset. RESULTS: A total of 43 IA samples were classified into 2 subgroups based on gene expression profiles. Subgroup I had a higher risk of rupture, while 70% of subgroup II remained unruptured. In subgroup I, specific genes were associated with inflammation and immunity, and weighted gene coexpression network analysis revealed that the black module genes were linked to IA rupture. We identified 4 hub genes (spermine synthase, macrophage receptor with collagenous structure, zymogen granule protein 16B, and LIM and calponin-homology domains 1), which constructed predictive models with good diagnostic performance in differentiating between ruptured and unruptured IA samples. Monocytic lineage was found to be a significant factor in IA rupture, and the 4 hub genes were linked to monocytic lineage (P < 0.05). CONCLUSIONS: We reveal a new molecular subtype that can reflect the actual pathological state of IA rupture, and our predictive models constructed by machine learning algorithms can efficiently predict IA rupture.

Sex-specific differences in the association between steps per day and all-cause mortality among a cohort of adult patients from the United States with congestive heart failure.

BACKGROUND: There is a lack of understanding of how daily step counts differentially affect the risk of all-cause mortality in adult with congestive heart failure (CHF) by sex in the United States (US). OBJECTIVES: To explore the relationship between daily step counts and all-cause mortality in patients with CHF by sex. METHODS: This is a cohort analysis from the National Health and Nutrition Examination Survey from 2005 to 2006. Multiple Cox hazard regression was performed to explore the association of step counts and all-cause mortality in patients with CHF by sex. RESULTS: In this study, 363 unweighted samples were enrolled from NHANES 2005-2006, representing about 8.4 million of the US population. Further, 46.28% were women, and the average age was 46 years. Patients with CHF in the more than 5581 steps/day group (HR, 0.31 [95% CI, 0.16-0.58]) had a significantly reduced risk of all-cause mortality compared with the patients in the less 5581 steps/day group after accounting for all covariates. In men, after accounting for all the covariates, there was a significant difference in more than 5581 steps/day group (HR, 0.33 [95% CI, 0.14-0.76]) on all-cause mortality in men with CHF compared with men in the less than 5581 steps/day group. CONCLUSIONS: Step count is associated with all-cause mortality in patients with CHF. Taking 5581 daily steps was associated with a decreased risk of all-cause mortality in patients with CHF.

Hemolysis associated with Russula subnigricans ingestion in a patient with glucose-6-phosphate dehydrogenase deficiency.

INTRODUCTION: Russula subnigricans is now one of the leading lethal mushroom species in China, with a mortality rate of more than 50%. The typical clinical manifestation of Russula subnigricans poisoning is rhabdomyolysis, and we are unaware of previous reports of Russula subnigricans-associated hemolysis. CASE SERIES: Herein we report a cluster of five patients with confirmed Russula subnigricans poisoning. Four of the patients who ingested sun-dried Russula subnigricans never developed rhabdomyolysis. However, in one patient, acute hemolysis developed on the second day following ingestion and was associated with a fall in hemoglobin concentration and a rise in unconjugated bilirubin concentration. Further investigation revealed that the patient had glucose-6-phosphate dehydrogenase deficiency. CONCLUSION: This case cluster suggests that the toxin of Russula subnigricans could cause hemolysis in a susceptible patient and warrants further study.

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection.

Background: Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD. Methods: The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson's correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types. Results: The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells (γδ T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD. Conclusions: Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.

Relationship Between Regional Adiposity Distribution and Incident Heart Failure in General Populations without Cardiovascular Disease.

BACKGROUND: Obesity is associated with a high risk of heart failure. However, the contribution of regional fat distribution evaluated using bioimpedance analysis toward heart failure risk in the general population without cardiovascular disease has rarely been studied. METHODS: This study included 483,316 participants without heart failure and cardiovascular disease from the UK Biobank study. The regional fat mass was determined by bioimpedance analysis and calculated by dividing the square of height in meters (kg/m2). This study evaluated the association of regional fat mass (arm fat index [AFI], trunk fat index [TFI], and leg fat index [LFI]) with the risk of incident heart failure and whether regional fat mass adds a further prognostic value for heart failure besides body mass index (BMI) in a large prospective cohort study. RESULTS: During the median 12.1 years, 3134 incident heart failure cases occurred. After adjustment for BMI and other confounding factors, each 1-standard deviation increase in LFI was associated with a 21% lower heart failure risk even after adjusting for BMI and other confounding factors (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.73-0.85). However, we did not observe heart failure-associated risks with AFI and TFI (HR 1.04; 95% CI, 0.99-1.09; HR 0.97, 95% CI, 0.91-1.04, respectively). Subgroup analysis demonstrated that the protective role of LFI was more prominent in the elderly and female participants (P < .01). CONCLUSION: Regional fat measurement other than BMI can improve heart failure risk stratification; leg fat plays a protective role, yet arm and trunk fat do not, in the general population without cardiovascular disease.

The association between bedtime at night and hypertension in adults.

OBJECTIVE: This research was conducted to explore the association between bedtime at night and the prevalence of hypertension in adults. METHODS: We conducted a cross-sectional study of 14,536 participants with data from the NHANES database. Bedtime was determined from the question in the sleep questionnaire: 'What time do you usually fall asleep on weekdays or workdays?.' Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, or diastolic blood pressure (DBP) ≥ 90 mmHg, or having been told by a doctor to have high blood pressure, or taking antihypertensive medication. We conducted a weighted multiple logistic regression analysis to explore the relationship between bedtime at night and the prevalence of hypertension in adults. RESULTS: The association between bedtime and hypertension showed a significantly U-shaped relationship. People who went to bed at 23:00 had the lowest risk of developing hypertension (OR, 0.68 [95%CI, 0.58, 0.81]). This U-shaped association still existed in different genders. In males (n = 7159), the adjusted OR was still lowest at 23:00. However, the adjusted OR was lowest at 0:00 in females(n = 7377). The interaction effect between bedtime and gender was significant (P = 0.0187). CONCLUSION: With the delay in bedtime, the association between bedtime and hypertension showed a significantly U-shaped relationship. Falling asleep at 23:00 has the lowest risk of developing hypertension.

Changes in body mass index and waist circumference and heart failure in type 2 diabetes mellitus.

Background: To determine the association of unintentional changes in body mass index (BMI) and waist circumference (WC) with the risk of heart failure (HF) among adults with type 2 diabetes mellitus (T2DM). Methods: This was a randomized controlled trial (the Action to Control Cardiovascular Risk in Diabetes [ACCORD] study), with a double 2×2 factorial design conducted at 77 clinical centers across the United States and Canada. In total, the study comprised 10,251 patients with T2DM and cardiovascular disease (CVD) or at a high risk of CVD. The outcome of interest in the present analysis was incident HF, defined as the first hospitalization event for HF or death due to HF. Hospitalization for HF was based on documented clinical and radiological evidence. Death due to HF was based on clinical, radiological, or postmortem evidence of HF, with an absence of an acute ischemic event according to clinical or postmortem evidence. Results: Participants with class III obesity had the smallest BMI and WC changes, followed by those with normal weight, overweight, class I obesity, and class II obesity. Increasing BMI (hazard ratio [HR] per standard deviation increase, 1.24; 95% confidence interval [CI], 1.07-1.45) and WC (1.27; 1.10-1.47) were significantly associated with a higher risk of HF. The relationship between BMI and WC changes and HF formed a J-shaped curve, while stable BMI and WC were associated with lower risks of HF. Compared with participants in the first tertiles of BMI and WC change, those in the third tertiles had HRs of 1.41 (95% CI, 1.07-1.45) and 1.48 (1.12-1.95), respectively. Conclusion: In conclusion, our findings suggest a noteworthy association between BMI and WC changes among adults with T2DM in HF. We observed a distinctive J-shaped curve in this relationship, indicating that participants with both low and high BMI and WC changes were more susceptible to developing HF. Trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Obesity is associated with greater cognitive function in patients with type 2 diabetes mellitus.

Background: The impact of obesity on cognitive function in patients with type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to evaluate whether obesity, assessed by body mass index (BMI) was associated with cognitive function among T2DM patients and whether the effect of obesity on cognitive function was through brain structure. Methods: This was a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study. The cognitive test battery included the Digit Symbol Substitution Test (DSST), Mini-Mental State Exam (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and STROOP test, which were administered at baseline, and at 20, 40, and 80 months. A subgroup (n = 614) of the ACCORD-MIND study underwent MRI scanning at baseline and at 40 and 80 months. The total brain volume (TBV), abnormal white matter volume (AWM), abnormal gray matter volume (AGM), and abnormal basal ganglia volume (ABG) were estimated. The outcomes of this study were cognitive function and brain structure. Results: In the adjusted analyses, BMI was positively associated with the MMSE (ß:0.08, 95%CI,0.01-0.16, per standard deviation [SD] increase) and RAVLT scores (ß:0.09, 95%CI,0.01-0.18). It was also associated with a greater TBV (ß:7.48, 95%CI,0.29-14.67). BMI was not associated with the DSST or STROOP scores, and AWM, AGM, ABG. Mediation analysis found that the effect of BMI on MMSE/RAVLT was mediated through TBV. Conclusion: Obesity may be associated with greater cognitive function and the effect of BMI on cognitive function may be mediated by TBV among patients with T2DM. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier NCT00000620.

Admission Lysophosphatidic Acid Is Related to Impaired Kidney Function in Acute Aortic Dissection: 2-Year Retrospective Follow-Up Study.

Background: Delayed treatment of acute aortic dissection (AAD)-related acute kidney injury (AKI) significantly increases the burden of chronic kidney disease (CKD) and mortality. Lysophosphatidic acid (LPA) is a shared mediator of kidney disease and AAD. Here, we evaluated the relationship between LPA and kidney injury in AAD patients. Methods: We measured the plasma concentration of LPA in a cohort of 80 patients with AAD. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Logistic regression were used to evaluate the effect and interaction of LPA on AKI. Additive generalized model and penalized spline method were used to describe the non-linear association. Multivariable analyses with the Cox proportional-hazards model were used for subgroup analysis and interaction in LPA and subsequent CKD. Results: The participant's average age was 54.27 ± 11.00 years, 68.75% of them were males, and the incidence of AKI was 43.75%. Patients with AKI had higher levels of LPA on admission, and the more significant the increase, the higher the risk of AKI. There was a non-linear positive correlation between admission LPA and AKI, and the premeditated inflection point was 346.33 (µg/dL) through two-piecewise linear regression and recursive algorithm. Subgroup analysis identified a stronger association between admission LPA and AKI in the elder, female and medically treated patients. The incidence of CKD was 22.67% in the 2-year follow-up. Patients with subsequent CKD had higher LPA levels on admission in the follow-up cohort, and a similar interaction trend was also observed through Cox proportional-hazards model. Conclusion: Admission LPA levels show a non-linear positive correlation with AKI and increase the risk of subsequent CKD, which is more pronounced in elderly, female, and medically treated patients.

A Prediction Model of the Incidence of Nonalcoholic Fatty Liver Disease With Visceral Fatty Obesity: A General Population-Based Study.

Objective: This study aimed to distinguish the risk variables of nonalcoholic fatty liver disease (NAFLD) and to construct a prediction model of NAFLD in visceral fat obesity in Japanese adults. Methods: This study is a historical cohort study that included 1,516 individuals with visceral obesity. All individuals were randomly divided into training group and validation group at 70% (n = 1,061) and 30% (n = 455), respectively. The LASSO method and multivariate regression analysis were performed for selecting risk factors in the training group. Then, overlapping features were selected to screen the effective and suitable risk variables for NAFLD with visceral fatty obesity, and a nomogram incorporating the selected risk factors in the training group was constructed. Then, we used the C-index, calibration plot, decision curve analysis, and cumulative hazard analysis to test the discrimination, calibration, and clinical meaning of the nomogram. At last, internal validation was used in the validation group. Results: We contract a nomogram and validated it using easily available and cost-effective parameters to predict the incidence of NAFLD in participants with visceral fatty obesity, including ALT, HbA1c, body weight, FPG, and TG. In training cohort, the area under the ROC was 0.863, with 95% CI: 0.84-0.885. In validation cohort, C-index was 0.887, with 95%CI: 0.857-0.888. The decision curve analysis showed that the model's prediction is more effective. Decision curve analysis of the training cohort and validation cohort showed that the predictive model was more effective in predicting the risk of NAFLD in Japanese patients with visceral fatty obesity. To help researchers and clinicians better use the nomogram, our online version can be accessed at https://xy2yyjzyxk.shinyapps.io/NAFLD/. Conclusions: Most patients with visceral fatty obesity have a risk of NALFD, but some will not develop into it. The presented nomogram can accurately identify these patients at high risk.

Obesity Increases In-Hospital Mortality of Acute Type A Aortic Dissection Patients Undergoing Open Surgical Repair: A Retrospective Study in the Chinese Population.

Objective: The prevalence of obesity is increasing worldwide, and the role of the obesity paradox in cardiovascular surgery remains controversial. In this study, we redefined obesity according to the Chinese criteria and examined the relationship between obesity and in-hospital mortality in patients with acute type A aortic dissection (AAD) undergoing open surgical repair. Materials and Methods: A total of 289 patients with AAD (between 2014 and 2016) were divided into the non-obese group and obese group for correlation analysis, general information, demographic factors, blood biochemistry, surgical details, and complications, which were used as covariates. Survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression were used to evaluate the effect and interaction of obesity on surgical mortality. Results: All the 289 patients had a mean age of 48.64 (IQR 44.00-55.00) and 74.39% were men. Of the 289 patients, 228 were non-obese (78.89%) and 61 were obese (21.11%). Patients with obesity were younger and more prone to unstable blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], preoperative hypoxemia and delirium, prolonged operative time, and surgical wound deep infection (p < 0.05). In the fully adjusted model, we observed an increased risk of in-hospital mortality in patients with obesity after fine-tuning other covariates including age and sex (HR = 2.65; 95% CI = 1.03 to 6.80; p = 0.042). The interaction suggested that obesity was more likely to cause death in elderly patients (age ≥ 60), although it was more common in younger patients (test for interaction, p = 0.012). Conclusion: Obesity, interacting with age, increases the risk of in-hospital mortality in patients with AAD undergoing open surgical repair. Although more verification is needed, we believe these findings provide further evidence for the treatment of AAD.

A retrospective observational study of serum uric acid and in-hospital mortality in acute type A aortic dissection.

There is currently insufficient evidence of correlation between on-admission serum uric acid and in-hospital mortality of patients with acute type A aortic dissection. Thus, this study analysed the relation between serum uric acid and in-hospital deaths in patients with acute type A aortic dissection. A total of 1048 patients with acute type A aortic dissection participated in this study between January 2010 and December 2018. The independent variable was on-admission serum uric acid, whilst the dependent variable was in-hospital deaths. The covariates of the study included patient age, gender, body mass index, smoking status, hypertension, diabetes, Marfan syndrome, bicuspid aortic valve, chronic renal insufficiency, stroke, atherosclerosis, time to presentation, systolic blood pressure, diastolic blood pressure, aortic diameter, aortic regurgitation, abdominal vessel involvement, arch vessel involvement, ejection fraction value, laboratory parameters, symptom, coronary malperfusion, mesenteric malperfusion, cerebral malperfusion, hypotension/shock, cardiac tamponade and operation status. The mean age of the sample was 50.17 ± 11.47 years, with approximately 24.24% of the participants being female. After analysis, it was found that the admission serum uric acid of patients with acute type A aortic dissection was positively correlated with in-hospital death (OR = 1.04, 95% CI 1.02-1.06). Subsequently, a non-linear relationship was determined between admission serum uric acid (point 260 µmol/L) and in-hospital mortality for patients with acute type A aortic dissection. The effect sizes and confidence intervals of the right (serum uric acid > 260 µmol/L) and left (serum uric acid ≤ 260 µmol/L) aspects of the inflection point were 1.04 (1.02-1.05) and 1.00 (0.99-1.02), respectively. Furthermore, subgroup analysis indicated a stable relationship between serum uric acid and in-hospital mortality, whilst an insignificant difference was found for the interactions between different subgroups. Overall, a non-linear correlation was determined between admission serum uric acid and in-hospital mortality of patients with acute type A aortic dissection. When serum uric acid > 260 µmol/L, it showed a positive correlation with in-hospital mortality.

Genetic or siRNA inhibition of MBD2 attenuates the UUO- and I/R-induced renal fibrosis via downregulation of EGR1.

DNA methylation plays a pivotal role in the progression of renal fibrosis. Methyl-CpG-binding domain protein 2 (MBD2), a protein reader of methylation, is involved in the development of acute kidney injury (AKI) caused by vancomycin. However, the role and mechanism of action of MBD2 in renal remain unclear. In this study, MBD2 mediated extracellular matrix (ECM) production induced by TGF-ß1 in Boston University mouse proximal tubule (BUMPT) cells，and upregulated the expression EGR1 to promote ECM production in murine embryonic NIH 3T3 fibroblasts. ChIP analysis demonstrated that MBD2 physically interacted with the promoter region of the CpG islands of EGR1 genes and then activated their expression by inducing hypomethylation of the promoter region. In vivo, PT-MBD2-KO attenuated unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis via downregulation of EGR1, which was demonstrated by the downregulation of fibronectin (FN), collagen I and IV, α-SMA, and EGR1. Injection of MBD2-siRNA attenuated the UUO- and I/R-induced renal fibrosis. Those molecular changes were verified by biopsies from patients with obstructive nephropathy (OB). These data collectively demonstrated that inhibition of MBD2 reduces renal fibrosis via downregulating EGR1, which could be a target for treatment of fibrotic kidney disease.

Methyl-CpG-binding domain protein 2 contributes to renal fibrosis through promoting polarized M1 macrophages.

Recent studies reported that Methyl-CpG-binding domain protein 2 (MBD2) promoted M2 macrophages accumulation to increase bleomycin-induced pulmonary fibrosis. However, the role and mechanism of action of MBD2 in macrophages differentiation and renal fibrosis remain largely unknown. In the current study, MBD2 not only promoted the differentiation of resting M0 macrophages to polarized M2 macrophages, but also induced them to polarized M1 macrophages and the transition of M2 to M1 macrophages. ChIP analysis demonstrated that MBD2 physically interacted with the promoter region of the CpG islands of G0S2 genes, and then activated their expression by inducing hypomethylation of the promoter region. Interestingly, the data demonstrated that the role of G0S2 in macrophages differentiation is consistent with MBD2. Furthermore, Co-culture of activated M1 macrophages and murine embryonic NIH 3T3 fibroblasts indicated that MBD2 mediated the M1-induction of ECM production by embryonic NIH 3T3 fibroblasts via promotion of G0S2. In addition, we also found that inhibition of MBD2 suppressed LPS induced the expression of p53 as well as activation and expression of stat3 in RAW264.7 macrophages. In vivo, MBD2 LysMcre attenuated unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R)-induced renal fibrosis via downregulation of G0S2, which was demonstrated by the downregulation of fibronectin (FN), collagen I and IV, α-SMA, G0S2. These data collectively demonstrated that MBD2 in macrophages contributed to UUO and I/R-induced renal fibrosis through the upregulation of G0S2, which could be a target for treatment for chronic kidney disease.