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.

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.

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.

Effects of oral non-protein calorie supplements on nutritional status among maintenance hemodialysis patients with protein-energy wasting: a multi-center randomized controlled trial.

Protein-energy wasting (PEW) is prevalent in maintenance hemodialysis (MHD) patients, and is one of the major risk factors for poor outcomes and death. This study aimed to investigate the effects of non-protein calorie supplements on the nutritional status of MHD patients with PEW. MHD patients with PEW were enrolled in this multi-center, open-label, randomized controlled trial. Then, they were randomly assigned to the intervention group to receive the non-protein calorie supplements containing 280 kcal of energy every day for 6 months or the control group to complete all aspects of the study without receiving supplements. Patients in both groups received dietary counselling from dietitians. Data on nutritional assessments, anthropometric measurements, blood analysis and dietary recall were collected at the baseline and at six months from both groups. Statistical analyses were performed using analysis of covariance (ANCOVA) adjusted for sex and baseline values. Ninety-two MHD patients completed the study. A significant increase in the subjective global assessment (SGA) score was found in the intervention group compared with the control group (4.88 ± 1.41 vs. 4.40 ± 1.16, p = 0.044). The ratio of PEW patients (diagnosed with SGA ≤5) in the intervention group (61.2%) was also significantly lower than that in the control group (83.7%) (p < 0.001). Moreover, significant improvements in body mass index (20.81 ± 2.46 kg m-2vs. 19.51 ± 2.60 kg m-2, p < 0.001), nutrition risk screening 2002 (2.45 ± 1.40 vs. 3.12 ± 1.37, p = 0.038), mid-upper arm circumference (23.30 ± 2.78 cm vs. 21.75 ± 2.87 cm, p = 0.001), and mid-arm muscle circumference (20.51 ± 2.32 cm vs. 19.06 ± 2.92 cm, p = 0.005) were observed in the intervention group compared with the control group. Patients in the intervention group took in more dietary energy than the control group (26.96 ± 4.75 kcal per kg body weight per day vs. 24.33 ± 2.68 kcal per kg body weight per day, p < 0.001). In conclusion, non-protein calorie supplements may improve the nutritional status of MHD patients with PEW.

High Blood Cu/Zn Ratio is Associated with Nutritional Risk in Patients Undergoing Maintenance Hemodialysis.

Patients undergoing maintenance hemodialysis (MHD) are at risk of an imbalance of copper and zinc homeostasis. We hypothesized that there is an association between the blood copper-zinc (Cu/Zn) ratio and nutritional status in these patients. For this cross-sectional study, blood samples were collected from patients undergoing MHD at Guangzhou Red Cross Hospital in September 2019. Zinc and copper levels were measured using inductively coupled plasma mass spectrometry. The seven-point subjective global assessment (SGA), nutritional risk screening 2002 (NRS2002), and geriatric nutritional risk index (GNRI) were used to evaluate the overall nutritional status. We enrolled 144 MHD patients (men:women = 78:66), with an average age of 64.33 ± 13.39 years and a median dialysis vintage of 33.50 (16.25-57.50) months. Patients with a higher blood Cu/Zn ratio had lower levels of hemoglobin, blood zinc, serum prealbumin, albumin, and creatinine as well as low SGA and GNRI scores, but higher modified Charlson comorbidity index score, serum C-reactive protein level, interleukin-6 level, blood copper level, and NRS2002 score (all p < 0.05). After adjustment for confounding factors in multivariable models, a high blood Cu/Zn ratio was independently associated with nutritional risk defined by all nutritional parameters (SGA, NRS2002, and GNRI). Prospective studies with larger sample sizes are warranted to confirm these results.

Nutritional assessment and risk factors associated to malnutrition in patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors. METHODS: A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status. RESULTS: PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition. CONCLUSION: Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients.

Nutritional status and survival of 8247 cancer patients with or without diabetes mellitus-results from a prospective cohort study.

BACKGROUND: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. METHODS: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer-specific survival (CSS) and overall survival (OS). RESULTS: The incidence of diabetes was 7.6% in the whole population. In comparison with the non-DM group, the DM group had greater body weight, but a similar fat-free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG-SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4-year CSS, 62% vs 73%) and OS (4-year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer-specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070-1.536) and overall (HR = 1.206, 95% CI 1.040-1.399) mortality. CONCLUSIONS: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.

Auxiliary genetic analysis in a Chinese adolescent NPH family by single nucleotide polymorphism screening.

Hereditary nephropathy is a progressive fatal renal disease caused by genetic changes. In this study, genetic screening was used to reveal mutations in a family in Southern China, in which there are two patients with confirmed hereditary nephropathy, who are alive at the time of publication. Imaging tests, including color Doppler ultrasonography and magnetic resonance imaging (MRI), as well as pathological examinations, including hematoxylin­eosin staining, electron microscopy and immunohistochemistry were performed. Target sequencing of nephrosis 2 (NPHS2), wilms tumor 1 (WT1), phospholipase C ε 1 (PLCE1), actinin α 4 (ACTN4), angiotensin I converting enzyme (ACE), uromodulin (UMOD) and nephrocystin 1 (NPHP1) was also carried out. This study indicated that heterozygous genetic variants of NPHS2, WT1, ACTN4, PLCE1 and UMOD found in the patients were gene polymorphisms. A renal biopsy showed sclerosing glomerulonephritis, dilated tubules and lymphocyte/monocyte infiltration in the interstitium of the index patients. Genetic analysis showed vertical transmission of the disease­causing mutations, including a homozygous deletion in NPHP1 and a nonsense mutation in ACE found via PCR­based single nucleotide polymorphism screening. Further network analysis identified direct and indirect co­location genes between NPHP1 and ACE. To conclude, familial adolescent nephronophthisis was diagnosed in two index patients in this study. It is recommended that comprehensive gene mutation screening is used in the diagnosis of complex hereditary diseases.

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°.

Low protein diet inhibits uric acid synthesis and attenuates renal damage in streptozotocin-induced diabetic rats.

AIM: Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN). Meanwhile, low protein diet (LPD) retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ-) induced diabetic rats. METHODS: STZ-induced and control rats were both fed with LPD (5%) and normal protein diet (18%), respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. RESULTS: Diabetic rats developed into constantly high levels of serum UA (SUA), creatinine (SCr) and 24 h amounts of urinary albumin excretion (UAE), creatinine (UCr), urea nitrogen (UUN), and uric acid (UUA). LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. CONCLUSION: LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

A multicentre assessment of malnutrition, nutritional risk, and application of nutritional support among hospitalized patients in Guangzhou hospitals.

BACKGROUND: To assess nutritional status, the prevalence of nutritional risk, and nutritional support in hospitalized patients in Guangzhou, to determine gender or age associated differences in the prevalence of nutritional risk. METHODS: A total of 2550 patients admitted during April to December 2008 from six departments (Gastroenterology, Pulmonology, Neurology, Nephrology, General Surgery and Thoracic Surgery) of four teaching hospitals were screened using the Nutritional Risk Screening 2002 tool. RESULTS: Overall prevalence of undernutrition and nutritional risk was 17.8% and 41.5%, respectively. The department of Pulmonology had the highest prevalence of undernutrition (28.2%) and nutritional risk (55.9%). The prevalence of nutritional risk was significantly higher in patients >=70 years of age than patients <70 years (64.2% vs 32.6%, p<0.001). No gender difference in the prevalence of nutritional risk was observed in general. In total, 47.6% of "at risk" and 19.4% of "not at risk" patients received nutritional support. Parenteral nutrition accounted for 88.8% of the nutritional support. CONCLUSIONS: The present study documented the prevalence of nutritional risk defined by NRS2002 and inappropriate assignment of nutritional interventions in Guangzhou hospitals.