Association between oxidative balance score and serum uric acid and hyperuricemia: a population-based study from the NHANES (2011–2018)

BackgroundOxidative Balance Score (OBS) is a novel indicator of the overall antioxidant/oxidant balance, providing a comprehensive reflection of the body’s overall oxidative stress status, with higher OBS suggesting more substantial antioxidant exposures. We aimed to investigate the possible relationship between OBS with serum uric acid (SUA) and hyperuricemia.MethodsData utilized in this study were sourced from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Participants under 18 years old, those with ≤16 complete data out of 20 OBS components, incomplete serum uric acid data, and missing covariates were excluded from the analysis. OBS was computed by evaluating 16 nutrients and 4 lifestyle factors, encompassing 5 pro-oxidants and 15 antioxidants, guided by a priori knowledge of their relationship with oxidative stress.ResultsA total of 1,5096 individuals were included in our analysis with 49.7% being male, and an average age of 49.05 ± 17.56 years. The mean OBS was 19.76 ± 7.17. Hyperuricemia was present in 19.28% of participants. Due to the right-skewed distribution of the OBS, a natural log transformation was applied to address this issue, and Quartiles of lnOBS 1, 2, 3, and 4 were 1.10–2.56 (N=3526), 2.64–2.94 (N=3748), 3.00–3.22 (N=4026), and 3.26–3.61 (N=3796), respectively. Multivariable logistic regression showed that higher lnOBS quantiles were correlated with lower serum uric acid levels. Compared with the lowest lnOBS quantile, participants in the highest lnOBS quantile had a significant serum uric acid decrease of 16.94 μmol/L for each unit increase in lnOBS (β=-16.94, 95% CI: -20.44, -13.45). Similar negative associations were observed in the second-highest (β=-8.07, 95% CI: -11.45, -4.69) and third-highest (β=-11.69, 95% CI: -15.05, -8.34) lnOBS quantiles. The adjusted odds ratios (ORs) for hyperuricemia in Quartiles 1, 2, 3, and 4 were 1.00, 0.84 (95% CI: 0.75, 0.95), 0.78 (95% CI: 0.69, 0.88), and 0.62 (95% CI: 0.55, 0.71), respectively. Compared to Quartile 1, participants in Quartile 4 had a 38% lower prevalence of hyperuricemia. Subgroup analysis and interaction test showed that there was a significant dependence of sex between OBS and serum uric acid (p for interaction <0.05), but not hyperuricemia (p for interaction >0.05). Subgroup analysis stratified by age, BMI, hypertension, diabetes, and hyperlipidemia showed there is no significant dependence on these negative correlations (all p for interaction >0.05).ConclusionsThe serum uric acid levels and prevalence of hyperuricemia in US adults exhibited a negative association with OBS. By exploring this connection, our research aims to gain a better understanding of how oxidative balance affects the prevalence of hyperuricemia. This could provide valuable insights for developing preventive strategies and interventions for hyperuricemia. Additional large-scale prospective studies are required to explore the role of OBS in hyperuricemia further

Shared decision making in sarcopenia treatment

The implementation of shared decision making (SDM) in management of sarcopenia is still in its nascent stage, especially compared to other areas of medical research. Accumulating evidence has highlighted the importance of SDM in older adults care. The current study overviews general SDM practices and explores the potential advantages and dilemmas of incorporating these concepts into sarcopenia management. We present common patient decision aids available for sarcopenia management and propose future research directions. SDM can be effectively integrated into daily practice with the aid of structured techniques, such as the “seek, help, assess, reach, evaluate” approach, “making good decisions in collaboration” questions, “benefits, risks, alternatives, doing nothing” tool, or “multifocal approach to sharing in shared decision making.” Such techniques fully consider patient values and preferences, thereby enhancing adherence to and satisfaction with the intervention measures. Additionally, we review the barriers to and potential solutions to SDM implementation. Further studies are required to investigate measurement and outcomes, coordination and cooperation, and digital technology, such as remote SDM. The study concludes that sarcopenia management must go beyond the single dimension of “Paternalism” choice. Integrating SDM into clinical practice offers promising opportunities to improve patient care, with patient-centered care and partnership of care approaches positively impacting treatment outcomes

Guideline adherence of β-blocker initiating dose and its consequence in hospitalized patients with heart failure with reduced ejection fraction

Background: We aim to investigate the guideline adherence of β-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes.Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed.Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization.Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization

CCNB2, TOP2A, and ASPM Reflect the Prognosis of Hepatocellular Carcinoma, as Determined by Weighted Gene Coexpression Network Analysis

Background. Hepatocellular carcinoma (HCC) is characterized by increased mortality and poor prognosis. We aimed to identify potential prognostic markers by weighted gene coexpression network analysis (WGCNA), to assist clinical outcome prediction and improve treatment decisions for HCC patients. Methods. Prognosis-related gene modules were first established by WGCNA. Venn diagrams obtained intersection genes of module genes and differentially expressed genes. The Kaplan-Meier overall survival curves and disease-free survival curves of intersection genes were further analyzed on the Gene Expression Profiling Interactive Analysis website. Chi-square tests were performed to explore the associations between prognostic gene expressions and clinicopathological features. Results. CCNB2, TOP2A, and ASPM were identified as both prognosis-related genes and differentially expressed genes. TOP2A (HR: 1.7, P=0.003) and ASPM (HR: 1.8, P<0.001) exhibited a significant difference between the high- and low-expression groups in the overall survival analysis, while CCNB2 (HR: 1.4, P=0.052) was not statistically significant. CCNB2 (HR: 1.5, P=0.006), TOP2A (HR: 1.7, P<0.001), and ASPM (HR: 1.6, P=0.003) were all statistically significant in the disease-free survival analysis. All three genes were significantly associated with race and fetoprotein values (P<0.05). CCNB2 expression was associated with tumor stage (P=0.01), and ASPM expression was associated with new tumor events (P=0.03). Conclusion. Overexpression of CCNB2, TOP2A, and ASPM are associated with poor prognosis, and these genes could serve as potential prognostic markers and therapeutic targets for HCC

Hypocalciuric Hypercalcemia due to Impaired Renal Tubular Calcium Excretion in a Type 2 Diabetic Patient

The case we presented here was a 73-year-old gentleman, who was admitted to endocrinology department due to recurrent fatigue for 1 year. He had medical histories of type 2 diabetes for 18 years and developed CKD 4 years ago. He also suffered from dilated cardiomyopathy, and coronary heart disease, moderate sleep apnea syndrome, primary hypothyroidism, and gout. His treatment regimen was complicated which included Caltrate D and compound α-keto acid (1200 mg calcium/d). Laboratory examination revealed that his serum calcium level elevated, 24-hour urine calcium output decreased, PTH level was suppressed, and 25-hydroxyvitamin D was in normal low range. No other specific abnormalities were found in serum bone turnover markers, ultrasonography, computed tomography, and bone scintigraphy. The diagnosis was suggested to be hypocalciuric hypercalcemia but was different from familial or acquired hypocalciuric hypercalcemia which were featured by elevated PTH level. The patient was asked to restrict calcium intake and to take diuretics; then his serum calcium level gradually lowered. In brief, patients with CKD could present with hypocalciuric hypercalcemia due to impaired renal calcium excretion. In this case, calcium restriction should be applied for treatment

A novel uromodulin mutation in autosomal dominant tubulointerstitial kidney disease: a pedigree-based study and literature review

Autosomal dominant tubulointerstitial kidney disease caused by mutations in uromodulin gene (ADTKD-UMOD) is a spectrum of hereditary renal disorders, characterized by early-onset hyperuricemia, gout and progressive nephropathy. This study presented a novel UMOD mutation in an ADTKD pedigree and reviewed studies in Chinese population. The index patient is a 16-year-old girl with hypertension, hyperuricemia and normal serum creatinine level. Four affected and six unaffected members were available for genetic screen. The mutation analysis was performed by next-generation sequencing and direct sequencing. A literature research was conducted to review Chinese ADTKD-UMOD cases. MEDLINE and Chinese Biomedicine Databases were searched with ‘uromodulin’, ‘juvenile gout’ and their related terms. Genetic sequencing revealed a de novo mutation within exon 3 (Cys223Gly), which was co-segregating with phenotype in this pedigree. In the review, four studies and our study involving a total of 67 ADTKD patients from 11 families were identified. Of these patients, 27 were confirmed to carry UMOD mutations. Mutations occurred in exon 3 were commonly observed, while mutations within exon 4, 5 and 9 occurred less frequently in Chinese ADTKD-UMOD cases. Among these cases, median age of symptom onset was 26.5 years, median age of end-stage renal diseases (ESRD) or death by ESRD was 41.9 years without renal replacement treatment. Phenotype caused by mutations in D8C domain seemed to be severe than those in GPI domain. Compared with patients of other race, Chinese ADTKD-UMOD patients advanced more aggressively to ESRD

Interpretation of Consensus on Diagnosis and Management of Cushing&apos;s Disease: a Guideline Update of the International Pituitary Society——Diagnosis

Cushing disease, the most common cause of endogenous Cushing&apos;s syndrome characterized by hypercortisolemia, is a clinical syndrome caused by adrenocorticotropic hormone (ACTH) ——secreting pituitary adenomas. The excessive secretion of ACTH in Cushing&apos;s disease stimulates bilateral adrenal hyperplasia and causes hypercortisolemia, which can lead to a series of severe clinical syndromes such as electrolyte imbalance, glucose and lipid metabolism disorders, involving multiple organs and systems in the body. The clinical symptoms of Cushing&apos;s disease are complex and diverse, and its diagnosis and treatment are extremely challenging. In December 2021, the International Pituitary Society released the Consensus on Diagnosis and Management of Cushing&apos;s Disease: a Guideline Update, which focuses on the complications and comorbidities of Cushing&apos;s disease, such as hypercoagulability, cardiovascular disease, metabolic bone disease, growth hormone deficiency and infection, etc.; discusses the application of the latest evidence in clinical practice, with a particular focus on new treatment and screening options, diagnostic algorithms, and best practices for preventing disease recurrence. Based on the latest evidence-based medical evidence, this article focuses on the interpretation of Cushing&apos;s disease——related laboratory examinations, imaging examinations, diagnosis and treatment management procedures, and recurrence monitoring discussed in the Consensus on Diagnosis and Management of Cushing&apos;s Disease: a Guideline Update, in order to improve the general practitioners and specialists&apos;understanding of this syndrome and improve the prognosis of patients with Cushing&apos;s disease

Post‐translational regulation of muscle growth, muscle aging and sarcopenia

Abstract Skeletal muscle makes up 30–40% of the total body mass. It is of great significance in maintaining digestion, inhaling and exhaling, sustaining body posture, exercising, protecting joints and many other aspects. Moreover, muscle is also an important metabolic organ that helps to maintain the balance of sugar and fat. Defective skeletal muscle function not only limits the daily activities of the elderly but also increases the risk of disability, hospitalization and death, placing a huge burden on society and the healthcare system. Sarcopenia is a progressive decline in muscle mass, muscle strength and muscle function with age caused by environmental and genetic factors, such as the abnormal regulation of protein post‐translational modifications (PTMs). To date, many studies have shown that numerous PTMs, such as phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, glycation, methylation, S‐nitrosylation, carbonylation and S‐glutathionylation, are involved in the regulation of muscle health and diseases. This article systematically summarizes the post‐translational regulation of muscle growth and muscle atrophy and helps to understand the pathophysiology of muscle aging and develop effective strategies for diagnosing, preventing and treating sarcopenia

Circulating Betatrophin in Patients with Type 2 Diabetes: A Meta-Analysis

Objective. To investigate the association between circulating betatrophin level and type 2 diabetes mellitus (T2DM) in human. Methods. A comprehensive literature search was performed in PubMed and Embase databases to identify eligible studies assessing the circulating levels of betatrophin in both T2DM patients and nondiabetic adults. Results. A total of nine eligible studies with twelve comparisons were included for the final meta-analysis. Circulating betatrophin levels in T2DM patients were higher than those in the nondiabetic controls (random-effect SMD 0.53; 95% CI 0.13 to 0.94; P=0.010). In the subgroup of nonobese population but not the obese population, the overall betatrophin level in T2DM patients was much higher than that in the nondiabetic controls (nonobese: random-effect SMD, 0.82; 95% CI 0.42 to 1.21; P<0.001; obese: random-effect SMD, −0.39; 95% CI, −0.95 to 0.18; P=0.18). Metaregression indicated that body mass index of T2DM patients was associated with mean difference of betatrophin level between T2DM and nondiabetic adults (slope, −578.8; t=-2.7; P=0.02). Conclusion. Based on the findings of our meta-analysis, circulating betatrophin level of T2DM patients is higher than that of nondiabetic adults in the nonobese population, but not in the obese population

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Abstract Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases