The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Association between circadian physical activity trajectories and incident type 2 diabetes in the UK Biobank.

Physical activity (PA) is linked to a decreased risk of type 2 diabetes mellitus (T2DM). However, the influence of circadian PA trajectories remains uncertain. This study aims to explore the optimal circadian PA trajectory pattern for reducing the risk of T2DM. Methods: A total of 502,400 participants were recruited from the UK Biobank between 2006 and 2010, and 102,323 participants provided valid accelerometer-captured acceleration data. After excluding individuals with prior T2DM, 99,532 participants were included in the final analysis. We initially investigated the association between PA intensity at 24 hourly time points and T2DM. Subsequently, PA trajectories were identified using K-means cluster analysis. Cox proportional hazard models were employed to estimate hazard ratios (HR). Four distinct PA trajectories were identified: consistently low, single peak, double peak, and intense trajectories. Compared to consistently low, single peak, double peak and intense PA trajectory reduced the risk of T2DM progressively. Sensitivity analyses, further excluding individuals with glycated hemoglobin (HbA1c) ≥ 6.5% or random glucose ≥ 11.1 mmol/L and adjusted for daily average acceleration, yielded consistent results. This confirms that the ideal circadian PA trajectory serves as a protective factor, independently of PA intensity. Subgroup analyses indicated that these effects were more pronounced in men and individuals with eGFR < 60 mL/(min*1.73 m2). In conclusion, ideal circadian PA trajectory patterns (especially intense and then double peak) reduced risk of T2DM.

Association between the trajectory of ideal cardiovascular health metrics and incident chronic kidney disease among 27,635 older adults in northern China-a prospective cohort study.

BACKGROUND: There is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD). OBJECTIVE: This study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD. METHODS: In total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models. RESULTS: Six distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH. CONCLUSION: The higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.

Ideal 24-h physical activity trajectory reduces all-cause, cause-specific mortality and cardiovascular outcomes through aging deceleration and inflammation regulation: A UK biobank study.

BACKGROUND: Physical activity (PA) is associated with mortality and cardiovascular disease (CVD). However, the effect of circadian PA trajectories remains ambiguous. This study aimed to explore ideal circadian PA patterns to reduce mortality and CVD, and potential mediators. METHODS: 502,400 participants from UK Biobank were recruited between 2006 and 2010. Among them, 102,323 participants got valid continuously capturing acceleration data over 7 days by wrist-worn accelerometer. K-means cluster analysis was used to identify PA trajectories. The associations of PA with all-cause, cause-specific mortality and CVD were assessed by cox regression. A sensitivity test was also conducted, starting from the time of acceleration collection and excluding participants with corresponding disease prior to it. Furthermore, the mediation of aging and inflammation were explored. RESULTS: During a median follow-up of 12.9 years, 3482 deaths were recorded (704 were due to CVD). Five distinct PA trajectories were identified: Persistently Low, Moderate and Stable, Single Increase, Double Increase, and Vigorous patterns. Ideal PA trajectory patterns offered progressively protective benefits against all-cause, CVD caused mortality and CVD, especially in Double Increase and Vigorous patterns. Other cause-specific mortality and renal failure incidence showed similar trend. The sensitivity result was consistent. The mediating effects of phenotypic age and inflammation markers were statistically significant. CONCLUSION: Ideal PA trajectories offered protective benefits against all-cause, cause-specific mortality and CVD. The protection was associated with both intensity and circadian distribution. Double Increase and Vigorous activity patterns decreased these risks more significantly. Crucially, this protection was mediated by aging deceleration and inflammation regulation.

Single-Cell Sequencing Reveals the Expression of Immune-Related Genes in Macrophages of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is characterized by macrophage infiltration, which requires further investigation. This study aims to identify immune-related genes (IRGs) in macrophage and explore their potential as therapeutic targets. This study analyzed isolated glomerular cells from three diabetic mice and three control mice. A total of 59 glomeruli from normal kidney samples and 66 from DKD samples were acquired from four kidney transcriptomic profiling datasets. Bioinformatics analysis was conducted using both single-cell RNA (scRNA) and bulk RNA sequencing data to investigate inflammatory responses in DKD. Additionally, the "AUCell" function was used to investigate statistically different gene sets. The significance of each interaction pair was determined by assigning a probability using "CellChat." The study also analyzed the biological diagnostic importance of immune hub genes for DKD and validated the expression of these immune genes in mice models. The top 2000 highly variable genes (HVGs) were identified after data normalization. Subsequently, a total of eight clusters were identified. It is worth mentioning that macrophages showed the highest percentage increase among all cell types in the DKD group. Furthermore, the present study observed significant differences in gene sets related to inflammatory responses and complement pathways. The study also identified several receptor-ligand pairs and co-stimulatory interactions between endothelial cells and macrophages. Notably, SYK, ITGB2, FCER1G, and VAV1 were identified as immunological markers of DKD with promising predictive ability. This study identified distinct cell clusters and four marker genes. SYK, ITGB2, FCER1G, and VAV1 may be important roles. Consequently, the present study extends our understanding regarding IRGs in DKD and provides a foundation for future investigations into the underlying mechanisms.

Association between circadian physical activity patterns and cancer incidence through regulation of inflammation: A UK biobank study.

BACKGROUND: Physical activity (PA) has been linked with cancer incidence. However, the effects and mechanisms underpinning circadian PA trajectories on cancer remain elusive. This study aimed to explore the optimal PA patterns in reducing cancer incidence and the associated potential mediators. METHODS: Between 2006 and 2010, 502,400 participants were recruited from the UK Biobank. Out of these, 102,323 participants wore accelerometers, which allowed for collecting acceleration data continuously over 7 days. After excluding participants with previous cancer history, 96,687 participants were included in K-means cluster analysis to identify PA trajectories. The association between PA and cancer incidence was assessed using Cox regression analysis. Additionally, we investigated the mediating role of inflammation. RESULTS: A total of 5995 cancer cases were recorded during a median follow-up of 7.1 years. Four distinct PA trajectories (persistent low, single peak, double peak, and vigorous) were identified. The ideal PA patterns reduced the risk of 7 out of 17 site-specific cancers, with the lowest hazard ratios and 95% confidence intervals of cancer for bladder (0.59, 0.40-0.86), breast (0.73, 0.60-0.89), kidney (0.45, 0.26-0.78), lung (0.59, 0.41-0.84), myeloma (0.49, 0.27-0.88), and oral & pharynx (0.51, 0.26-0.98) in the vigorous pattern and for colorectal (0.71, 0.54-0.93) in the double peak pattern. Moreover, the mediating effects of inflammation were significant. CONCLUSION: Optimal PA trajectories reduced cancer incidence, especially in double peak and vigorous patterns. The protective effect was associated with both intensity and circadian rhythm. Crucially, this protection was mediated by inflammation regulation.

Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial.

BACKGROUND: Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic patients. This study evaluated the effect of canagliflozin on intrarenal lipid content and oxygenation in newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 64 newly diagnosed T2DM patients with normal renal function were randomly divided into canagliflozin (n = 33) and glimepiride control (n = 31) groups. All patients underwent functional magnetic resonance imaging (fMRI) scanning to assay patients' intrarenal lipid content and oxygenation level before and after 24 weeks of treatment. Furthermore, the relationship between body mass index and intrarenal lipid content in T2DM patients was analyzed and the correlation between changes in intrarenal lipid content and improvements in renal hypoxia was further assessed. RESULTS: The canagliflozin group had a greater decrease in body weight and blood uric acid level than the glimepiride group (all P < 0.05). The intrarenal lipid content could be significantly reduced after canagliflozin treatment for 24 weeks. The R2* values, a parameter for quantifying the oxygen content in tissues and is inversely related to the oxygen content, of the renal cortex and medulla in the canagliflozin group decreased from the baseline by 6.40% (P < 0.01) and 12.09% (P = 0.000007), respectively. In addition, the degree of reduction of fat fraction (ΔFF) in the kidneys of the canagliflozin group was correlated with the degree of improvement of oxygenation level (ΔR2*) in the renal cortex (r = 0.422, P = 0.014). CONCLUSIONS: The early renal protective effect of SGLT2i in newly diagnosed T2DM patients may be partly attributed to the amelioration of renal hypoxia via the alleviation of ectopic lipid deposition in the kidneys. TRIAL REGISTRATION: Chu Hsien-I Memorial Hospital of Tianjin Medical University (ChiCTR2000037951).

O-GlcNAcylation regulates HIF-1α and induces mesothelial-mesenchymal transition and fibrosis of human peritoneal mesothelial cells.

O-GlcNAcylation is a post-translational modification of proteins that regulates various biological processes. However, its involvement in peritoneal dialysis fibrosis remains unclear. This study aimed to investigate the impact of O-GlcNAcylation on human peritoneal mesothelial cells (HPMCs) cultured in control and high-glucose medium. To manipulate cellular conditions, we employed knockdown techniques targeting HIF-1α and OGT, along with the administration of pharmacological agents (PUGNAc, OSMI-1, MG-132, FG-4592, and HIF-1α inhibitor). Our findings revealed that elevated glucose levels increased global O-GlcNAcylation and the abundance of HIF-1α, α-SMA, fibronectin, and COL1A2. Conversely, the expression of E-Cadherin was decreased. Significantly, a positive correlation was observed between O-GlcNAcylation, HIF-1α, mesothelial-to-mesenchymal transition (MMT), and fibrosis in HPMCs. Notably, O-GlcNAcylation was found to regulate HIF-1α, thereby promoting MMT and fibrosis under high glucose conditions. Furthermore, we discovered that high glucose levels induced O-GlcNAcylation of HIF-1α, preventing its ubiquitination and proteasomal degradation. In summary, our study demonstrates the critical role of O-GlcNAcylation-mediated regulation of HIF-1α in MMT and fibrosis during peritoneal dialysis.

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial.

Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns. Funding: Southern Medical University and Nanfang Hospital.

Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS: The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Canagliflozin alleviates high glucose-induced peritoneal fibrosis via HIF-1α inhibition.

The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin in vitro by simulating hypoxia with CoCl2 in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl2 hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-ß/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-ß/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-ß/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-ß/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-ß/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.

The development of neurocritical care in China from the perspective of evaluation and treatment of critical neurological diseases.

Objective: To understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China. Design: A cross-sectional questionnaire study. The study was completed in three main steps: filling in the questionnaire, sorting out the survey data, and analyzing the survey data. Results: Of 206 NCUs, 165 (80%) provided relatively complete information. It was estimated that 96,201 patients with severe neurological diseases were diagnosed and treated throughout the year, with an average fatality rate of 4.1%. The most prevalent severe neurological disease was cerebrovascular disease (55.2%). The most prevalent comorbidity was hypertension (56.7%). The most prevalent complication was hypoproteinemia (24.2%). The most common nosocomial infection was hospital-acquired pneumonia (10.6%). The GCS, APACHE II, EEG, and TCD were the most commonly used (62.4-95.2%). The implementation rate of the five nursing evaluation techniques reached 55.8-90.9%. Routinely raising the head of the bed by 30°, endotracheal intubation and central venous catheterization were the mostprevalent treatment strategies (97.6, 94.5, and 90.3%, respectively). Traditional tracheotomy, invasive mechanical ventilation and nasogastric tube feeding (75.8, 95.8, and 95.8%, respectively) were more common than percutaneous tracheotomy, non-invasive mechanical ventilation and nasogastric tube insertion (57.6, 57.6, and 66.7%, respectively). Body surface hypothermia brain protection technology was more commonly used than intravascular hypothermia technology (67.3 > 6.1%). The rates of minimally invasive hematoma removal and ventricular puncture were only 40.0 and 45.5%, respectively. Conclusion: In addition to traditional recognized basic life assessment and support technology, it is necessary to the use of promote specialized technology for neurological diseases, according to the characteristics of critical neurological diseases.

Clinical characteristics and risk factors of cardiac surgery associated-acute kidney injury progressed to chronic kidney disease in adults: A retrospective, observational cohort study.

Introduction: To retrospectively investigate the clinical characteristics and risk factors of cardiac surgery associated-acute kidney injury (CS-AKI) progressed to chronic kidney disease (CKD) in adults and to evaluate the performance of clinical risk factor model for predicting CS-AKI to CKD. Methods: In this retrospective, observational cohort study, we included patients who were hospitalized for CS-AKI without a prior CKD [estimated glomerular filtration rate (eGFR) < 60 ml · min-1·1.73 m-2] at Central China Fuwai Hospital from January 2018 to December 2020. Survived patients were followed up for 90 days, the endpoint was CS-AKI to CKD, and then divided them into two groups (with or without CS-AKI to CKD). The baseline data including demographics, comorbidities, renal function, and other laboratory parameters were compared between two groups. The logistic regression model was used to analyze the risk factors for CS-AKI to CKD. Finally, receiver operator characteristic (ROC) curve was drawn to evaluate the performance of the clinical risk factor model for predicting CS-AKI to CKD. Results: We included 564 patients with CS-AKI (414 males, 150 females; age: 57.55 ± 11.86 years); 108 (19.1%) patients progressed to new-onset CKD 90 days after CS-AKI. Patients with CS-AKI to CKD had a higher proportion of females, hypertension, diabetes, congestive heart failure, coronary heart disease, low baseline eGFR and hemoglobin level, higher serum creatinine level at discharge (P < 0.05) than those without CS-AKI to CKD. Multivariate logistic regression analysis revealed that female sex(OR = 3.478, 95% CI: 1.844-6.559, P = 0.000), hypertension (OR = 1.835, 95% CI: 1.046-3.220, P = 0.034), coronary heart disease (OR = 1.779, 95% CI: 1.015-3.118, P = 0.044), congestive heart failure (OR = 1.908, 95% CI: 1.124-3.239, P = 0.017), preoperative low baseline eGFR (OR = 0.956, 95% CI: 0.938-0.975, P = 0.000), and higher serum creatinine level at discharge (OR = 1.109, 95% CI: 1.014-1.024, P = 0.000) were independent risk factors for CS-AKI to CKD. The clinical risk prediction model including female sex, hypertension, coronary heart disease, congestive heart failure, preoperative low baseline eGFR, and higher serum creatinine level at discharge produced a moderate performance for predicting CS-AKI to CKD (area under ROC curve = 0.859, 95% CI: 0.823-0.896). Conclusion: Patients with CS-AKI are at high risk for new-onset CKD. Female sex, comorbidities, and eGFR can help identify patients with a high risk for CS-AKI to CKD.

The influence of shorter red blood cell lifespan on the rate of HbA1c target achieved in type 2 diabetes patients with a HbA1c detection value lower than 7.

BACKGROUND: Variations in the red blood cell (RBC) lifespan can affect glycosylated hemoglobin (HbA1c) test values, but there is still a lack of evidence regarding how and to what degree the RBC lifespan influences HbA1c in the type 2 diabetes mellitus (T2DM) population owing to the restriction of traditional RBC lifespan-detection means. This study aimed to investigate the influence of RBC lifespan variation on HbA1c values in T2DM patients with a HbA1c detection value lower than 7%. METHODS: Patients with HbA1c <7% were divided into two groups: RBC lifespan <90 days and RBC lifespan ≥90 days. We collected blood glucose levels at seven time points for three consecutive months, assessed the HbA1c and glycosylated albumin levels, and calculated the hemoglobin glycation index (HGI) for each patient. RESULTS: There were no statistical differences in the HbA1c value between two groups, but the estimated glycosylated hemoglobin (eHbA1c) was significantly higher in patients with an RBC lifespan <90 days. The proportion of the eHbA1c ≥7% in the group with an RBC lifespan <90 days was significantly higher than the other group (33.87% vs. 12.50%, p < .01). Pearson analysis showed a significant negative correlation between RBC lifespan and the HGI in patients with T2DM (r = -0.348, p < .01). CONCLUSION: A reduced RBC lifespan in T2DM patients caused a noticeable underestimate of the blood glucose levels as presented by HbA1c detection value.

Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy.

Idiopathic membranous nephropathy is the main cause of chronic kidney disease (CKD). Studies have shown sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly delay renal outcomes in patients with CKD, but the exact mechanism remains unknown. In this study, we investigated the mechanism by which the SGLT2 inhibitor canagliflozin attenuates podocyte injury by reversing the imbalance in Helper T cell 1 (Th1)/Helper T cell 2 (Th2) in peripheral blood of rats with membranous nephropathy (MN). MN rats were gavaged with canagliflozin (10 mg/kg/d) and losartan (10 mg/kg/d), respectively, for eight weeks. Compared with the MN group, the urinary ratio of total protein and the creatinine levels of the canagliflozin group decreased significantly. Canagliflozin improved the glomerulus pathological damage, increased the expression levels of podocyte marker proteins. The protective effect of canagliflozin on kidneys was more obvious than that of losartan. Treatment with canagliflozin increased the proportion of Th1 cells by 2.3 times, decreased the proportion of Th2 cells by 68.5%, and significantly restrained the synthesis of immunoglobulin G1 in B-cells and glomerulus subepithelial immune complex deposition. Co-culture of B-cells derived from MN rats with podocytes triggered the activation of phosphorylation of mTOR and ULK1 of podocytes, inhibited podocyte autophagy and resulted in podocyte injury. B-cells derived from canagliflozin treatment rats reversed these effects above. In conclusion, canagliflozin exerts a protective effect on kidneys by reversing the imbalance in Th1/Th2 cells in MN rats and restoring the autophagy of podocytes inhibited by the abnormal immunoglobulin G secretion from B-cells.

Triglyceride-glucose index is significantly associated with the risk of hyperuricemia in patients with diabetic kidney disease.

Triglyceride-glucose (TyG) index has been proposed to be a simple, economical, and reliable marker of insulin resistance. We aimed to investigate whether TyG is an independent predictor of hyperuricemia in diabetic kidney disease (DKD) populations by conducting a cross-sectional and longitudinal study. A total of 6,471 patients were enrolled in cross-sectional analysis, and 3,634 patients without hyperuricemia at the baseline were included in longitudinal analysis and were followed up for a median of 23.0 months. Hyperuricemia was categorized as a serum uric acid level ≥ 420 umol/L (7 mg/dL). In this study, 19.58% of participants had hyperuricemia. In the cross-sectional analysis, multivariate logistics regression analysis showed that the ORs (95% CI) for hyperuricemia in the second, third, and fourth TyG quartiles were 1.40 (95% CI 0.73-2.65), 1.69 (95% CI 0.90-3.18), and 4.53 (95% CI 2.39-8.57), respectively, compared with the first quartile. Longitudinally, the Kaplan-Meier survival analysis showed that higher TyG levels predicted higher incidence of hyperuricemia. Multivariate Cox regression model revealed that the hazard ratios for hyperuricemia in the upper quartiles of the TyG index were 1.69 (95% CI 0.97-2.93), 2.23 (95% CI 1.33-3.75), and 2.50 (95% CI 1.46-4.27), respectively, compared with the first quartile. Moreover, the subgroup analyses revealed that the relationship between TyG levels and hyperuricemia was robust in DKD patients. Our findings indicate a significant independent correlation between the TyG index and the risk of hyperuricemia in DKD patients.

Estrogen receptor 1 inhibits the progression of hepatocellular carcinoma via positively regulating lncRNA maternally expressed gene 3 under high glucose conditions.

Background: Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) is crucial in the association of diabetes mellitus (DM) and hepatocellular carcinoma (HCC), and estrogen receptor 1 (ESR1) plays an essential role in various cancers. However, the underlying regulatory effect of ESR1/lncRNA MEG3 on HCC with DM remains unclear. This study explored the regulatory effect of ESR1/lncRNA MEG3 on HCC cell progression. Methods: Bioinformatics analysis was used to predict the promoter sequence of lncRNA MEG3 using UCSC (http://genome.ucsc.edu/), followed by luciferase reporter and RNA immunoprecipitation (RIP) assays to verify the specific combination between ESR1 and lncRNA MEG3 promoter. After cotransfection with ESR1, ESR1 siRNA or lncRNA MEG3 RNA, CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and colony formation assays were used to evaluate the cell proliferation capacity. Cell apoptosis was assessed using flow cytometry analysis. Next, wound healing and Transwell assays were conducted to examine cell invasiveness and migration. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were performed to quantify the expression of ESR1 or lncRNA MEG3. Results: ESR1 might be the transcription factor (TF) of lncRNA MEG3, and ESR1 bound with lncRNA MEG3 promoter. Overexpression of ESR1 repressed the proliferation, migration and invasion of HepG2 cells, and promoted apoptosis of HepG2 cells under high glucose conditions. Silencing ESR1 decreased lncRNA MEG3 expression in HepG2 cells but enhanced proliferation, migration and invasion. Meanwhile, a rescue assay demonstrated that silencing lncRNA MEG3 reversed the inhibitory effect of ESR1 on HepG2 cell progression. Conclusions: ESR1 inhibits HCC cell progression through positively regulating lncRNA MEG3, and the results provide a promising strategy for HCC management.

Red Blood Cell Lifespan < 74 Days Can Clinically Reduce Hb1Ac Levels in Type 2 Diabetes

Variations in the red blood cell (RBC) lifespan can affect glycosylated hemoglobin (HbA1c) test values, but there is still a lack of evidence regarding how and to what degree the RBC lifespan influences HbA1c in the type 2 diabetes mellitus (T2DM) population owing to the restriction of traditional RBC lifespan detection means. In this study, we monitored 464 T2DM patients and 231 healthy control finger blood glucose levels at seven time points for three consecutive months. The HbA1c levels were assessed at the end of the third month as well as the RBC lifespan was measured through the CO breath test. T2DM patients were stratified into four quartile groups according to their RBC lifespans. There was no statistical significance in HbA1c among these four groups. However, the average blood glucose in the Q1 group was significantly higher than those in the other groups. Additionally, the contribution of RBC lifespan to HbA1c test value in the Q1 group was 14.07%, which was significantly higher than those in the other groups. Finally, we used multiple linear regression models to construct a mathematical formula to correct the HbA1c test value in the Q1 group, which would benefit the management of T2DM.

Joint exposure to outdoor ambient air pollutants and incident chronic kidney disease: A prospective cohort study with 90,032 older adults.

Objectives: There is paucity of studies to investigate the association between combined and long-term exposure to air pollution and the risk of incident chronic kidney disease (CKD) in older adults. Methods: A prospective cohort of 90,032 older adults who did not have CKD at baseline were followed up from January 1, 2017, to December 31, 2019. Various pollutant data, including particulate matter with diameters ≤ 2.5 mm (PM2.5), ≤ 10 mm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), Ozone (O3), and carbon monoxide (CO), from all monitoring stations in Binhai New Area, Tianjin were considered in calculating the mean exposure concentration of each pollutant over 2 years. By summing each pollutant concentration weighted by the regression coefficients, we developed an air pollution score that assesses the combined exposure of these air pollutants. Due to the strong correlation between air pollutants, Principal Component Analysis (PCA) score was also developed. The association between air pollutants and incident CKD in the elderly was analyzed. Results: A total of 90,032 subjects participated in this study with a median follow-up of 545 days. Among them, 22,336 (24.8%) developed CKD. The HR (95% CI) for air pollution score and incidence of CKD was 1.062 (1.060-1.063) and p <0.001 after adjusting for all confounders. The adjusted HRs for the quartile subgroups of combined air pollution score were: Q2: 1.064 (1.013-1.117); Q3: 1.141 (1.088-1.198); and Q4: 3.623 (3.482-3.770), respectively (p for trend <0.001). The adjusted HRs for the quartile subgroups of air quality index (AQI) were: Q2: 1.035 (0.985-1.086); Q3: 1.145 (1.091-1.201); and Q4: 3.603 (3.463-3.748), respectively (p for trend <0.001). When the risk score was over 86.9, it significantly rose in a steep curve. The subgroup analysis showed that male, younger or exercise were more likely to develop CKD. Conclusion: Combined air pollution score, AQI, and PCA score were associated with an increased risk of CKD in an exposure-response relationship. Our current results might also provide evidence for developing environmental protection policies.