Associations between pinch strength, cardiovascular events and all-cause mortality in patients undergoing maintenance hemodialysis.

BACKGROUND AND AIMS: Patients undergoing maintenance hemodialysis (MHD) experience increased mortality and cardiovascular disease (CVD) risks; however, the potential connection between pinch strength (PS) and the prognosis of these patients remains unknown. Consequently, this study aimed to comprehensively assess the influence of PS and handgrip strength (HGS) on both survival and cardiovascular events (CVE) in patients undergoing MHD. METHODS: Data were gathered from patients undergoing MHD at the Hemodialysis Center of Guangzhou Red Cross Hospital in March 2021. We performed a retrospective follow-up spanning 24 months, with death serving as the primary endpoint for observation and CVE as the secondary endpoint. Multifactorial Cox regression analysis, Kaplan-Meier survival curves, trend tests, and restricted cubic spline were applied to explore the association. RESULTS: During a 24-month follow-up, data were collected from 140 patients undergoing MHD with an average age of 66.71 ± 12.61 years. Among them, 52 (37.14%) experienced mortality, whereas 36 (40.00%) had CVE without baseline CVD. Kaplan-Meier survival curves demonstrated better survival rates and reduced CVE risk for patients in the second, third, and fourth quartiles compared with those in the first quartile for PS. Adjusted analyses in different models revealed higher PS levels were independently associated with all-cause mortality (major model, model 4, HR, 0.78; 95% CI, 0.64-0.95) but not with CVE risk (unadjusted HR, 0.90; 95% CI, 0.77-1.05). Compared with lower quartile PS levels, higher PS levels significantly reduced all-cause mortality (HR, 0.31; 95% CI, 0.10-1.02), and this trend remained consistent (P for trend = 0.021). Finally, the restricted cubic spline method using different models showed a linear relationship between PS and all-cause mortality (P > 0.05), when PS exceeded 4.99 kg, the all-cause mortality of MHD patients significantly decreased. CONCLUSIONS: PS was independently associated with all-cause mortality but not with CVE in patients undergoing MHD.

Single-pool model urea clearance index is associated with sarcopenia and nutritional status in patients undergoing maintenance hemodialysis: a cross-sectional study.

BACKGROUND: The single-pool model urea clearance index (single-pool Kt/Vurea; spKt/V) is the most commonly used method for dialysis adequacy assessment. However, only a few studies have examined the relationship between spKt/V values and parameters related to sarcopenia and nutritional status. This study aimed to evaluate whether the spKt/V is an indicator of sarcopenia and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: A total of 142 patients were included in this single-center, cross-sectional study. Venous blood samples were collected shortly before the hemodialysis session. The adequacy of dialysis in patients receiving MHD was assessed using spKt/V. Sarcopenia was identified according to the Asian Working Group for Sarcopenia (2019) definition. Receiver operating characteristic curve and area under the curve were used to evaluate the predictive value of spKt/V in sarcopenia. Univariate and multivariate binary logistic regression analyses were used to determine the association between spKt/V and sarcopenia and nutritional status. RESULTS: The mean spKt/V level was 1.3 ± 0.2, the prevalence of sarcopenia was 15.5% in patients on MHD. The best cutoff value of spKt/V in sarcopenia was 1.45 for both sexes, 1.33 and 1.45 for men and women, respectively (P < 0.05). The multivariate binary logistic regression shown that the spKt/V was independently positively associated with sarcopenia (OR = 122.88, 95% CI = 0.64-0.87, P = 0.002). Grouping spKt/V by the best cutoff value, when spKt/V ≥ 1.45, the OR of sarcopenia was 11.75 (95% CI = 3.16-43.67, P < 0.001). Subgroup analyses showed that when spKt/V ≥ 1.33 in men and spKt/V ≥ 1.45 in woman, the OR of sarcopenia was 9.73 (95% CI = 2.25-42.11, P = 0.002) and 14.52 (95% CI = 1.06-199.67, P = 0.045), respectively. CONCLUSIONS: The present study showed that spKt/V was an important influencing factor of sarcopenia and malnutrition in Asian patients on MHD.

Replacing of sedentary behavior with physical activity and the risk of mortality in people with prediabetes and diabetes: a prospective cohort study.

BACKGROUND: Sedentary behavior is prevalent among people with diabetes and is associated with unfavorable cardiometabolic health. However, there is limited evidence regarding the impact of replacing sedentary time (ST) with physical activity on mortality in people with prediabetes and diabetes. We prospectively examined the association between accelerometer-measured ST and mortality among people with prediabetes and diabetes after adjusting for demographic characteristics, lifestyle factors, and moderate- to vigorous-intensity PA (MVPA). We further determined the effect of replacing ST with equal time of different types of physical activities on all-cause mortality. METHODS: We included 1242 adults with prediabetes and 1037 with diabetes from the National Health and Nutrition Examination Survey. Restricted cubic splines were fitted to determine the dose-response association between ST and overall mortality. Isotemporal substitution modeling was used to explore the hazard ratio (HR) effects of ST replacement. RESULTS: During a median follow-up of 14.1 years, 424 adults with prediabetes and 493 with diabetes died. Compared with the lowest tertile of ST, the multivariable-adjusted HRs for all-cause mortality in the highest tertile were 1.76 (95% confidence interval [CI] 1.19, 2.60) for participants with prediabetes and 1.76 (1.17, 2.65) for those with diabetes. Additionally, a linear association between ST and all-cause mortality was observed in adults with prediabetes and diabetes, with HRs for each 60 min/day increment in ST of 1.19 (1.10, 1.30) and 1.25 (1.12, 1.40), respectively. Isotemporal substitution results indicated that individuals with prediabetes whose ST was replaced by 30 min of light-intensity physical activity (LPA) and MVPA had 9% and 40% lower all-cause mortality, respectively. In people with diabetes, replacing sedentary behavior with an equivalent time of LPA and MVPA was also associated with mortality risk reduction (HR 0.89; 95% CI 0.84, 0.95 for LPA; HR 0.73; 95% CI 0.49, 1.11 for MVPA). CONCLUSIONS: Higher ST was associated in a dose-response manner with an increased risk of premature mortality among adults with prediabetes and diabetes. Statistically replacing ST with LPA was potentially beneficial for health in this high-risk population.

Association between sedentary behavior and depression in US adults with chronic kidney disease: NHANES 2007-2018.

BACKGROUND: Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease. METHODS: This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007-2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship. RESULTS: The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P < 0.001). In the fully adjusted model, we found that compared with participants who had shorter durations of sedentary behavior, participants who had the highest durations of sedentary behavior had 1.69 times (odd ratio 1.69, 95% confidence interval: 1.27, 2.24) greater risk of being clinically depressed. After adjusting for confounding factors, subgroup analyses showed that the association between sedentary behavior and depression still existed in all stratifications. CONCLUSION: We found an association between longer duration of sedentary behavior and more severe depression in US adults with chronic kidney disease; however, prospective studies with larger sample sizes are still needed to confirm the effects of sedentary behavior on depression in the chronic kidney disease population.

Lower serum insulin-like growth factor-1 levels are independently associated with anemia in patients undergoing maintenance hemodialysis.

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.

Correlation between intestinal flora disruption and protein-energy wasting in patients with end-stage renal disease.

BACKGROUND: Different dialysis treatments may affect the composition and structure of the intestinal flora of dialysis-treated chronic kidney disease (CKD) patients. This study aimed to analyze the correlations between the different flora and the nutritional indexes and further explore the potential metabolic pathways in patients with CKD in end-stage renal disease (ESRD). METHODS: Altogether, 102 patients with ESRD were recruited and categorized into the hemodialysis (HD) group (N = 49) and the peritoneal dialysis (PD) group (N = 53). Their biochemical indexes, anthropometric indicators, and inflammatory markers were determined. The total genomic DNA was extracted for 16S ribosomal DNA sequencing. Furthermore, bioinformatics analysis was employed for functional analysis. RESULTS: Anthropometric indicators, including handgrip strength, mid-upper arm circumference, mid-upper arm muscle circumference, and body mass index, in the HD and PD groups showed a positive correlation with butyric acid-producing bacteria (Rosella and Phascolarctobacterium) and a negative correlation with conditional pathogens (Escherichia spp.). Meanwhile, the inflammatory markers, including high-sensitivity C-reactive protein and interleukin-6, were significantly higher in the PD-protein-energy wasting (PEW) group than in the PD-non-protein-energy wasting (NPEW) group; although they showed an increasing trend in the HD-PEW group, no significant difference was noted. Rosella was considerably scarce in the HD-PEW group than in the HD-NPEW group, whereas Escherichia was substantially more abundant in the PD-PEW group than in the PD-NPEW group. Compared with the HD group, the essential amino acid synthesis pathway, amino acid metabolism-related enzyme pathways, and aminoacyl-transfer RNA biosynthesis pathways were weakened in the PD group. Most carbohydrate metabolic pathways were weakened, although the tricarboxylic acid cycle was slightly enhanced. Concurrently, the fatty acid metabolism was enhanced, whereas fatty acid synthesis was weakened; the metabolic pathways of B vitamins were also weakened. These potential metabolic pathways of the various compounds released by intestinal flora showed a significant correlation with blood biochemical indexes, anthropometric indicators, and inflammatory markers. CONCLUSION: In patients with ESRD, different dialysis treatments affected the abundance of butyric acid-producing bacteria (Rosella and Phascolarctobacterium) and conditional pathogens (Escherichia spp.). Butyric acid-producing bacteria showed a positive correlation with PEW and showed a negative correlation with Escherichia. Improving the intestinal diversity and increasing the amount of butyric acid-producing bacteria, such as Blautella, Faecococcus, and Phascolarctobacterium, are potential therapeutic approaches to enhance protein-energy consumption in patients with ESRD.

Unfavorable dietary quality and overweight or obesity in kidney transplant recipients as judged by the Chinese diet balance index 2016 (DBI-16).

BACKGROUND AND OBJECTIVES: Little is known the effects of dietary quality (DQ) on kidney transplantation (KTR). We explored the associations between DQ assessed by the Chinese Diet Balance Index 2016 (DBI-16) and overweight or obesity in KTR. METHODS AND STUDY DESIGN: KTR aged 18-65 years from Guangdong Second Provincial General Hospital were participated in this cross-sectional study. Anthropometric measurements such as body weight, height, body mass index (BMI) and biochemical parameters were measured by standard methods. Dietary intake was assessed by 3-day, 24-hour food records and DQ by DBI-16. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% Cl) for leading to overweight in KTR by the components of DBI-16 and DQ scores. RESULTS: 97 KTR were enrolled and divided into overweight group (BMI ≥24 kg/m2, n=35) and non-overweight group (BMI <24 kg/m2, n=62) in the study. Compared with non-overweight individuals, overweight individuals took excessive grains, cooking oils, salts and didn't meet the recommended levels of vegetable and fruit intake (p<0.05) assessed by DBI-16. The lower bound score (LBS) was positively associated with overweight (29.7±5.42) in KTR (LBS: OR: 1.099, 95% CI: 1.019-1.185, p=0.014), and the higher bound score (HBS) score was negatively related with overweight (16.0±4.85) in KTR (HBS: OR: 0.903, 95% CI: 0.822-0.992, p=0.034). Combination of LBS and HBS predicted the occurrence of overweight in KTR (AUC: 0.705, p<0.001). CONCLUSIONS: Unfavorable DQ, including overall excessive consumption, excessive intake of grains, cooking oils, salts and insufficient intake of vegetable and fruit, was significantly associated with the occurrence of overweight or obesity in KTR.

Associations Between Blood Trace Element Levels and Nutritional Status in Maintenance Hemodialysis.

OBJECTIVE(S): We aimed to investigate the associations between blood trace element levels and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: This cross-sectional study included patients undergoing MHD who were treated at our center in September 2019. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and the levels of manganese, lead, selenium, zinc, and copper were measured by inductively coupled plasma mass spectrometry. The Simplified Nutritional Appetite Questionnaire scale was used to assess patient appetite. Skinfold thickness, bicep circumference, upper arm muscle circumference, 7-point Subjective Global Assessment, Nutritional Risk Screening 2002 (NRS 2002), and Geriatric Nutritional Risk Index (GNRI) were used to assess patient nutritional status. Univariate and multivariate logistic regression analyses were performed to study the relationship between trace elements and nutritional indicators. RESULTS: In total, 118 patients (64 males and 54 females) were included, with a median dialysis vintage of 34.0 months (16.0-54.5 months) and an average age of 63.20 ± 14.26 years. Malnourished patients, as defined by the GNRI, Subjective Global Assessment, and NRS 2002, accounted for 28.0%, 49.2%, and 26.3% of enrolled patients, respectively. The multivariate binary logistic regression showed that higher blood copper levels were independently associated with nutritional risk defined as GNRI ≤91.2 (odds ratio [OR] = 1.003, 95% confidence interval [CI] = 1.000-1.006; P = .020), whereas lower blood zinc levels (OR = 0.634, 95% CI = 0.439-0.916; P = .015), blood zinc < 4.220 mg/L (OR = 3.723, 95% CI = 1.274-10.879; P = .016), lower blood selenium levels (OR = 0.959, 95% CI = 0.929-0.990; P = .010), and blood selenium < 85 µg/L (OR = 5.568, 95% CI = 1.039-29.840; P = .045) were independently associated with a nutritional risk defined as NRS 2002 ≥ 3. CONCLUSION(S): Higher levels of blood copper and lower levels of blood zinc and selenium were independently associated with higher nutritional risk in MHD patients.

Bioelectrical Impedance Analysis-Derived Phase Angle Predicts Protein-Energy Wasting in Maintenance Hemodialysis Patients.

OBJECTIVE(S): To explore the validity of using bioelectrical impedance analysis (BIA)-derived 50 kHz phase angle (PhA) in predicting protein-energy wasting (PEW) in Chinese maintenance hemodialysis (MHD) patients. DESIGN AND METHODS: The design was a cross-sectional study. A total of 173 of MHD patients and 173 healthy adults were enrolled in the study. The prevalence of PEW in patients was performed by the International Society of Renal Nutrition and Metabolism criteria. The PhA, body cell mass, fat mass, body fat percentage, fat-free mass, and extracellular water/total body water were measured by InBody S10 body composition analyzer. The biochemical indices and anthropometric measurements were assessed using the way published elsewhere. The PhA, other values of BIA and its relationship with age, visceral protein, anthropometric measurements of the MHD patients were compared with the healthy group. The independent variables for predicting PEW and its cutoff values were explored using logistic regression model and receiver operating characteristic curve analysis, respectively. RESULTS: The MHD patients' PhA value was significantly lower than the healthy group (4.89°± 1.19 vs. 6.32°± 2.23, P < .01). A total of 34.1% MHD patients with PEW had significantly lower PhA values compared with well-nourished patients (P < .05). The PhA decreased more significantly with age in MHD (r = -0.35, P < .001), compared with controls (r = -0.26, P < .001). The PhA values were positively associated with nutritional indices related to serum albumin, prealbumin, fat-free mass, and mid-arm muscle circumference. PhA values were not associated significantly with fat mass and body fat percentage (P > .05). Multivariate logistic regression analysis showed that PhA and body mass index were independent predictors of PEW, but the PhA was the stronger predictor (odds ratio = 4.48, P < .05). Receiver operating characteristic curve analysis suggested that the optimal PhA cutoff value to predict PEW was 4.6°. CONCLUSIONS: BIA-derived PhA appears to be a useful bioelectrical marker for predicting PEW in Chinese hemodialysis patients with a cutoff value of 4.6°.

The non-linear associations between blood manganese level and sarcopenia in patients undergoing maintenance hemodialysis: A multicenter cross-sectional study.

BACKGROUND AND AIMS: Manganese (Mn), a vital element in energy metabolism, is predominantly stored in skeletal muscles and plays a crucial role in muscle function and strength. Patients on maintenance hemodialysis (MHD) often experience muscle wasting due to metabolic disruption and inflammation. This study aimed to explore the relationship between blood Mn levels and sarcopenia in a patient population. METHODS: In this multicenter cross-sectional study, conducted from March 2021 to March 2022, 386 patients on MHD from three medical centers were included. Blood Mn levels were measured using inductively coupled plasma mass spectrometry, and body composition was assessed post-dialysis using bioelectrical impedance analysis. Grip strength was measured using a digital dynamometer. The patients were categorized into groups with and without sarcopenia. Using a generalized additive model to fit a smooth curve, we employed a generalized linear model to identify the optimal inflection point and explore the threshold effect after discovering a segmented relationship. Subsequently, a binary logistic regression analysis was conducted to investigate the relationship between blood manganese levels and the risk of sarcopenia, with adjustments made for potential confounding factors. RESULTS: A negative correlation was observed between blood Mn levels and sarcopenia-related parameters (Appendicular Skeletal Muscle Mass Index and grip strength) in Spearman's correlation analysis (both P < 0.05). After adjusting for confounding factors, a nonlinear association was identified. When blood Mn was ≤ 10.6 µg/L, the increase in sarcopenia was not statistically significant (P > 0.05). Conversely, when blood Mn exceeded 10.6 µg/L, each 1 µg/L increase raised the risk of sarcopenia by 0.1 times. Considering confounders, multivariate binary logistic regression confirmed an independent association between elevated blood Mn levels and sarcopenia. CONCLUSION: This study revealed an independent association between elevated blood Mn levels (> 10.6 µg/L) and sarcopenia in patients undergoing MHD. These findings emphasize the importance of understanding the Mn metabolism in the context of muscle health in this patient population. Further research is warranted to explore the underlying mechanisms and potential interventions for mitigating sarcopenia in patients with elevated blood Mn levels undergoing MHD.

Regression equation for predicting dietary phosphorus intake based on estimated dietary protein intake: A multicenter cross-sectional study in China.

BACKGROUND: Protein and phosphorus intake, which affect chronic kidney disease (CKD), is assessed using cumbersome food diaries. Therefore, more straightforward and accurate methods of assessing protein and phosphorus intake are needed. We decided to investigate the nutrition status and dietary protein and phosphorus intake of patients with stages 3, 4, 5, or 5D CKD. METHODS: This cross-sectional survey included outpatients with CKD at seven class A tertiary hospitals in Beijing, Shanghai, Sichuan, Shandong, Liaoning, and Guangdong in China. Protein and phosphorus intake levels were calculated using 3-day food records. Protein levels and calcium and phosphorus serum concentrations were measured; urinary urea nitrogen was determined using a 24-h urine test. Protein and phosphorus intakes were calculated using the Maroni and Boaz formulas, respectively. The calculated values were compared with the recorded dietary intakes. An equation that regressed phosphorus intake on protein intake was constructed. RESULTS: The average recorded energy and protein intake was 1637.5 ± 595.74 kcal/day and 56.97 ± 25.25 g/day, respectively. Overall, 68.8% of patients had a good nutrition status (grade A on the Subjective Global Assessment). The correlation coefficient between protein intake and calculated intake was 0.145 (P = 0.376) and that between phosphorus intake and calculated intake was 0.713 (P < 0.001). CONCLUSION: Protein and phosphorus intakes correlated linearly. Chinese patients with stage 3-5 CKD had low daily energy intake but high protein intake. Malnutrition was present in 31.2% of patients with CKD. The phosphorus intake could be estimated from the protein intake.

Roles of IL-33 in the Pathogenesis of Cardiac Disorders.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is believed to play important roles in different diseases by binding to its specific receptor suppression of tumorigenicity 2 (ST2). In the heart, IL-33 is expressed in different cells including cardiomyocytes, fibroblasts, endothelium, and epithelium. Although many studies have been devoted to investigating the effects of IL-33 on heart diseases, its roles in myocardial injuries remain obscure, and thus further studies are mandatory to unravel the underlying molecular mechanisms. We highlighted the current knowledge of the molecular and cellular characteristics of IL-33 and then summarized its major roles in different myocardial injuries, mainly focusing on infection, heart transplantation, coronary atherosclerosis, myocardial infarction, and diabetic cardiomyopathy. This narrative review will summarize current understanding and insights regarding the implications of IL-33 in cardiac diseases and its diagnostic and therapeutic potential for cardiac disease management.

Higher Levels of Blood Selenium are Associated with Higher Levels of Serum Lipid Profile in US Adults with CKD: Results from NHANES 2013-2018.

The association between selenium (Se) and lipid profile has been controversial in different populations, and the aim of the study was to investigate the relationship between Se and lipid profile in patients with chronic kidney disease (CKD). A total of 861 US adult patients with CKD (male: female = 404:457) from the National Health and Nutrition Examination Survey database were enrolled in this cross-sectional study. We used smoothing spline plots and multivariate binary logistic regression analyses to elucidate the relationships between blood Se and lipid profile. Multivariate adjusted smoothing spline plots showed that higher levels of blood Se were associated with higher levels of serum remnant cholesterol (RC), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Threshold and saturation effects were also observed between serum RC, TC, TG, LDL-C, and blood Se. In multivariate binary logistic regression analyses, the fully adjusted model showed that as blood Se increases by every 1 µg/L, the OR of high RC, high TG and high LDL-C in patients was 1.012 (95% CI: 1.001, 1.023 P = 0.046), 1.011 (95% CI: 1.001, 1.021 P = 0.043) and 1.009 (95% CI: 1.003, 1.016 P = 0.012), respectively. Furthermore, stratified analyses showed that the associations between blood Se and high RC/high TG were significantly stronger in patients aged < 65 years. Higher levels of blood Se were associated with increased serum lipid profile levels and increased risk of high RC, high TC, high LDL-C, and low HDL-C dyslipidemia in adult patients with CKD in the US. However, the real associations between blood Se and lipid profiles in this population should be verified in future prospective and randomized trials.

Ferritinophagy in the etiopathogenic mechanism of related diseases.

Iron is an essential trace element that is involved in a variety of physiological processes. Ferritinophagy is selective autophagy mediated by nuclear receptor coactivator 4 (NCOA4), which regulates iron homeostasis in the body. Upon iron depletion or starvation, ferritinophagy is activated, releasing large amounts of Fe2+ and increasing reactive oxygen species (ROS), leading to ferroptosis. This plays a significant role in the etiopathogenesis of many diseases, such as metabolic diseases, neurodegenerative diseases, infectious diseases, tumors, cardiomyopathy, and ischemia-reperfusion ischemia-reperfusion injury. Here, we first review the regulation and functions of ferritinophagy and then describe its involvement in different diseases, with hopes of providing new understanding and insights into iron metabolism and iron disorder-related diseases and the therapeutic opportunity for targeting ferritinophagy.

Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study.

BACKGROUND: This study investigated the association between insulin-like growth factor-1 and nutritional status indicators in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients undergoing MHD for > 3 months were included in this single-center cross-sectional study in March 2021. Clinical, demographic, and body mass data and blood samples were collected before the hemodialysis sessions. Serum insulin-like growth factor-1 (IGF-1) levels were measured using a radioimmunoassay, and serum IGF-1 standard deviation score (SDS) was calculated for MHD patients according to age and sex. The nutritional status of patients was assessed using serum albumin, serum prealbumin, handgrip strength, pinching strength, upper arm muscle circumference, lean body mass, phase angle, seven-point subjective global assessment (SGA) score, and geriatric nutritional risk index (GNRI). The patients were divided into groups according to tertiles of serum IGF-1 SDS levels. Spearman correlation analyses and univariate and multivariate binary logistic regression analyses were used to determine the association between serum IGF-1 SDS and nutritional status parameters. RESULTS: A total of 155 MHD patients (male: female = 90:65) were enrolled in the study, with a median dialysis vintage of 28.0 (11.0, 55.0) months, and an average age of 66 (65.5 ± 13.0) years. The median of IGF-1 SDS was - 0.1 (- 0.6 to 0.6). Compared to patients with higher IGF-1 SDSs, patients with lower IGF-1 SDSs had lower levels of serum ceruloplasmin (341.0 [287.5, 416.0] vs 395.0 [327.0, 451.0] vs 409.0 [349.5, 507.5], p = 0.002), serum albumin (34.7 ± 3.0 vs 37.0 ± 3.1 vs 37.8 ± 2.6, p < 0.001), serum prealbumin (270.3 [233.7, 327.8] vs 326.0 [279.3, 355.6] vs 363.0 [324.2, 398.2], p < 0.001), handgrip strength (13.8 [10.0, 20.7] vs 17.7 [10.7, 22.5] vs 23.3 [16.6, 27.8], p < 0.001), pinch strength (4.6 [3.9, 6.0] vs 4.9 (3.9, 6.9) vs 6.5 [4.7, 8.7], p = 0.002), phase angle (3.3 [3.0, 3.8] vs 3.9 [3.4, 4.7] vs 4.3 [3.6, 5.2, p < 0.001), modified Creatinine Index (83.1 ± 19.7 vs 93.1 ± 23.4 vs 113.9 ± 24.3, p < 0.001), intracellular water (14.5 ± 4.4 vs 16.1 ± 4.9 vs 16.9 ± 4.4, p = 0.031), higher extracellular water (26.9 ± 5.8 vs 25.7 ± 5.5 vs 25.1 ± 3.1, p = 0.042), and higher malnutrition risk as defined by GNRI (49.0% vs 15.7% vs 11.5%, p < 0.001) and SGA (53.9% vs 23.5% vs 7.7%, p < 0.001). CONCLUSIONS: Lower IGF-1 SDSs are independently associated with higher malnutrition risk in patients with MHD.

Effect of flavonoids on skeletal muscle mass, strength and physical performance in middle-aged and older adults with or without Sarcopenia: A meta-analysis of randomized controlled trials.

The role of flavonoids in regulating the synthesis and function of skeletal muscles is increasingly recognized. However, randomized controlled trials have yielded inconsistent results on the influence of flavonoids on human muscular parameters. Therefore, we performed a meta-analysis to evaluate the possible effects of flavonoids on sarcopenia-related parameters in middle-aged and elderly people. Eligible literature and randomized controlled trials reports have been extensively searched from PubMed, Cochrane Library, Web of Science, and EMBASE databases until April 2022. A total of 20 articles involving 796 participants were available for the meta-analysis. There were significant benefits for participants in appendicular muscle mass gain (SMD = 0.29; 95% CI: 0.07, 0.52; P = 0.01) and 6-min walk distance (SMD = 0.37; 95% CI: 0.01, 0.73; P = 0.05). A subgroup analysis indicated that flavonoid significantly improves appendicular muscle mass (SMD = 0.50; 95% CI: 0.21, 0.80; P < 0.01) and Timed-Up and Go test (SMD = -0.47; 95% CI: -0.85, -0.09; P = 0.02) in Sarcopenia population. Our results provide insight into the effects of flavonoids on skeletal muscle mass and gait speed for those without exercise. However, there was no significant improvement in the subjects' muscle strength. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=334383, identifier: CRD42022334383.

AGEs-induced MMP-9 activation mediated by Notch1 signaling is involved in impaired wound healing in diabetic rats.

AIMS: To elucidate the relationship between advanced glycation end products (AGEs), Notch1 signaling, nuclear factor-kappa B (NF-κB), and matrix metalloproteinase-9 (MMP-9) in diabetic wound healing in vitro and in vivo. METHODS: We incubated primary keratinocytes with AGEs alone or AGEs along with γ-secretase inhibitor DAPT, and established diabetic rat wound model by intraperitoneal streptozotocin treatment. The Notch1 signaling components and MMP-9 expression were detected by qPCR, western blotting and gelatin zymography. RESULTS: The exposure of primary keratinocytes to AGEs led to a significant increase in Notch intracellular domain (NICD), Delta-like 4 (Dll4), and Hes1; however, Notch1 expression was inhibited by the RAGE siRNA. Furthermore, MMP-9 activation was up-regulated, secondary to AGEs treatment. In contrast, increased MMP-9 expression by AGEs-stimulation was eliminated after treatment with DAPT. NF-κB activation participated in the Notch1-modulated MMP-9 expression. Notably, in the diabetic animal model, inhibition of the Notch signaling pathway with DAPT attenuated NICD and MMP-9 overexpression, improved collagen accumulation, and ultimately accelerated diabetic wound healing. CONCLUSIONS: These findings identified that activation of the Notch1/NF-κB/MMP-9 pathway, in part, mediates the repressive effects of AGEs on diabetic wound healing and that targeting this pathway may be a potential strategy to improve impaired diabetic wound healing.

Diabetes remission after a lifestyle-medicine intervention on type 2 diabetes in lean and obese Chinese subjects: a prospective study.

BACKGROUND: Whether diabetes remission still happened among non-obese type 2 diabetes (T2DM) patients with a body mass index (BMI) <25 kg/m2 following lifestyle-medicine interventions was quite necessary to be reported because many diabetes happened with normal or low BMI in China. METHODS: The criteria for subject inclusion: <20 years after T2DM diagnosis, ≥6 months treatment with oral anti-diabetic drugs, without serious complications, and no history of insulin use. They were divided into two groups: the obesity group (BMI ≥25 kg/m2) and the lean group (BMI <25 kg/m2). All subjects received the following lifestyle-medicine interventions: stopping oral anti-diabetic therapy, initiating a low-carbohydrate (contributing by 35-40% to calorie intake) diet for the first month (gradual transition to a normal diet for the next 5 months), participating in resistance and aerobic exercise, and receiving strengthen management. Diabetes remission was defined as glycosylated hemoglobin (A1C) level <6.5% (<48 mmol/mol) after 6 months of not taking any anti-diabetic medications during the lifestyle-medicine intervention. Finally, 125 individuals completed the lifestyle-medicine intervention in the prospective study. The efficacy and safety of lifestyle-medicine intervention were assessed and compared between lean and obese Chinese subjects with T2DM. RESULTS: We found that 64.52% of the T2DM subjects in the obese group and 60.64% of T2DM subjects in the lean group achieved diabetes remission [i.e., an A1C level <6.5% (48 mmol/mol)] without any anti-diabetic medications after the 6-month lifestyle-medicine intervention. Our multiple linear regression analysis showed that decreases in the fasting plasma glucose (FPG) level had the most powerful effect on decreases in the A1C level after the intervention (R2=0.3072). CONCLUSIONS: Lifestyle-medicine interventions may have increased effectiveness in controlling mild T2DM as compared with the oral antidiabetic-based treatment; unexpectedly, there seems no further improvement in lean relative to obese patients. Three in five subjects could achieve diabetes remission though the lifestyle-medicine intervention regardless of whether their BMI was below or above 25 kg/m2.

Association Between the Blood Copper-Zinc (Cu/Zn) Ratio and Anemia in Patients Undergoing Maintenance Hemodialysis.

Copper (Cu) and zinc (Zn) imbalances are common in dialysis patients. This study aimed to investigate the relationship between the blood Cu/Zn ratio and anemia in patients undergoing maintenance hemodialysis (MHD) treatment. This cross-sectional study included patients undergoing MHD at our center in September 2019. Clinical and demographic data and blood samples were collected before the hemodialysis sessions, and the blood levels of Zn and Cu were measured by inductively coupled plasma mass spectrometry. Multivariable linear and binary logistic regression analyses were performed to study the relationship between blood Cu/Zn ratio and anemia. A total of 144 MHD patients were enrolled in this study. The patients had a mean age of 64.33 ± 13.39 years, a median dialysis vintage of 33.50 (16.25-57.50) months, with 66 being females (45.8%). The median blood Cu/Zn ratio was 15.55 (interquartile range: 12.47-20.31). Anemia was present in 99 patients (68.8%). Groups with higher hemoglobin levels had decreased blood Cu/Zn ratios (p < 0.05). After adjustments for confounding factors, higher blood Cu/Zn ratios were independently associated with lower hemoglobin levels and anemia in MHD patients based on multivariate linear and multivariate binary logistic regression, respectively, in different models. Our study found that the blood Cu/Zn ratio is independently associated with anemia in MHD patients, but prospective multicenter studies with larger sample sizes are still needed to determine the appropriate cutoff values for blood zinc, blood copper, and blood Cu/Zn levels in this patient population.