Lower Uric Acid Research Articles

A dose-escalation study of HP501, a highly selective URAT1 inhibitor, in male Chinese patients with hyperuricemia

HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor used for treating hyperuricemia. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of HP501 in male Chinese patients. Patients with hyperuricemia were sequentially assigned to receive oral doses of HP501 (30, 50, 60, 90, and 120 mg) as a single dose on Day 1 and as once-daily doses from Days 4 to 13. Safety, pharmacokinetic, and pharmacodynamic data were collected. Multiple oral doses of HP501 were well-tolerated in all the cohorts. The most common adverse events (≥ 10% of patients) of any grade regardless of drug relationship were gout flare (14 patients, 25.93%), diarrhea (12 patients, 22.22%), elevated ALT (8 patients, 14.81%), hypertriglyceridemia (7 patients, 12.96%), dry mouth (7 patients, 12.96%) and oral ulcer (7 patients, 12.96%). All adverse events were mild or moderate. The Cmax and exposure (AUC) of HP501 was approximately dose-proportional between 30 and 120 mg. A dose-dependent serum uric acid (UA)-lowering effect was observed in the dose range of 30 to 60 mg and the serum UA lowering effect was similar between 90 and 120 mg on day 13, indicating that the maximal serum UA lowering effect of HP501 was achieved at 90 mg in the patients with hyperuricemia. In conclusion, the tolerability, pharmacokinetics, and pharmacodynamics supported 90 mg HP501 for subsequent clinical studies of this highly selective URAT1 inhibitor.Clinical Trial registration: No. CTR20212259 (http://www.chinadrugtrials.org.cn/) was registered in September 2021, and No. CTR20222257 was registered in September 2022.

THE CORRELATION BETWEEN PHYSICAL ACTIVITY AND STRESS AND THEIR IMPACT ON URIC ACID LEVELS IN OLDER INDIVIDUALS

The elderly population, who are more susceptible to infection and chronic illnesses, are particularly susceptible to gout. The Pakong Health Center Working Area has a high prevalence of gout among the elderly population. The study examines the relationship between physical activity and stress, with uric acid levels as the dependent variable. The study involved 60 patients with gout, with a sample size of 53. The DASS physical activity questionnaire was used to gather data. The results showed that 77% of participants engaged in moderate physical activity, while almost 40% fell into the moderate stress group. The majority of uric acid levels were elevated, with 36 out of 68% being elevated. The Spearman Rank analysis yielded a p-value of 0.005, indicating a correlation between physical activity and uric acid levels in the elderly. Additionally, a p-value of 0.000, indicating a link between stress levels and gout occurrence, suggests that older individuals should enhance their physical activity and manage their nutrition to lower uric acid levels. Additionally, seniors should reduce stress by improving their religious practices, expressing their concerns, and maintaining a positive mindset.

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

Effects of different levels of dried onion powder on nutrient digestibility, biochemical parameters, and nitrogen balance in Wistar albino rats with induced hyperuricemia.

Introduction: Onions (Allium cepa L.) are excellent sources of bioactive compounds and phytochemicals such as allicin, quercetin, fisetin, and other sulfurous compounds. Therefore, our study aimed to investigate the effects of dried onion powder on growth performance, nitrogen balance, and biochemical parameters in Wistar albino rats with induced hyperuricemia. Methods: A total of 24 rats were randomly divided into four groups, with six in each group: HU (positive control) and HOT1, HOT2, and HOT3 groups, which received a diet containing onion powder at concentrations of 11.13, 14.84, and 18.61g/100g, respectively. Hyperuricemia was induced in rats by administering a new formulation intraperitoneally (250mg/kg potassium oxonate) and orally (40mg/kg potassium bromate) daily for 14days. After confirmation of hyperuricemia induction, rats were fed with onion-treated diets with various concentrations of quercetin for 21days. Results: Significant decreases (p ≤ 0.05) in serum uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total cholesterol, and low-density lipoprotein were observed. An increasing trend (p ≤ 0.05) in the levels of hemoglobin (Hb), white blood cell (WBC), red blood cell (RBC), and platelet count was observed. An improvement in the levels of serum high-density lipoprotein, triglycerides, blood urea nitrogen, serum creatinine, serum total protein and neutrophils, lymphocytes, and monocytes was observed. A positive progress (p ≤ 0.05) was observed in growth performance and nutrient digestibility. Conclusion: In conclusion, a significantly lower uric acid level was observed in rats fed with HOT2 diet. Based on the ratio of the surface area (human/rat), the best recommended dose of onion for the incidence and prevention of hyperuricemia is 189.95g, corresponding to the dose of 204mg/day of quercetin in humans.

Eupatilin inhibits xanthine oxidase in vitro and attenuates hyperuricemia and renal injury in vivo

Uric acid (UA) is the final metabolite of purines in the liver that can cause hyperuricemia at high levels. The kidneys are the main excretory organs for UA. The excessive accumulation of UA in the kidneys causes the development of hyperuricemia that often leads to renal injury. Eupatilin (Eup) is a flavonoid natural product that possesses various pharmacological properties such as antioxidant, anti-cancer, and anti-inflammatory. We were interested in exploring the potential role of Eup in lowering UA and nephroprotective. We initially investigated the effects of Eup on xanthin oxidase (XOD) activity in vitro, followed by investigating its ability to lower UA levels, anti-inflammatory effects, nephroprotective effects, and the underlying mechanisms using hyperuricemia rats sustained at high UA level. The results showed that Eup had an inhibitory effect on XOD activity in vitro and significantly reduced serum UA, creatinine, BUN, IL-1β and IL-6 levels in hyperuricemic rats, ameliorating inflammation, renal oxidative stress and pathological injury. Furthermore, Eup inhibited ADA and XOD enzyme activities in the liver and serum and modulated GLUT9, URAT1 and ABCG2 protein expression in the kidneys and ileum. Our findings provide a scientific basis for suggesting Eup as an option for a potential treatment for hyperuricemia.

Which patients with coronary artery disease should include oral nitrates on their discharge medication list?

Background Which patients with coronary artery disease (CAD) should have oral nitrates on their discharge medication list after coronary angiography (CAG)? To assess the relationship between oral nitrates included in the discharge medication list and major adverse cardiovascular events (MACEs) among CAD patients, we designed this retrospective cohort study. Methods A total of 2979 CAD patients hospitalised in the Department of Cardiology, Affiliated Hospital of Jining Medical University from May 2013 to October 2015 were enrolled, grouped according to whether oral nitrates were included at discharge after CAG, and followed up for MACEs for a mean of 4.42 years after discharge. The primary endpoint was MACEs. Multivariate Cox proportional hazards models were used to analyses potential confounding factors. Stratified analysis was used to observe the relationship between oral nitrates and MACEs by different covariates. Results The median follow-up time was 4.61 years, and 296 (9.94%) patients experienced MACEs. Multivariate Cox proportional hazards model analysis showed no association between oral nitrates on the discharge medication list and the occurrence of MACEs among patients with CAD (p > 0.05) after adjusting for some covariates, such as SYNTAX score (hazard ratio (HR): 1.18, 95% confidence interval (CI): 0.90–1.55, p = 0.2420). Stratified analysis revealed a higher incidence of MACEs among hypertensive patients prescribed oral nitrates at discharge (HR: 1.67, 95% confidence CI: 1.13–2.46, p = 0.0046). However, prescribing nitrates at discharge for patients with low uric acid levels increased the incidence of MACEs, which showed a possible trend towards significance (HR: 1.44, 95% CI: 0.99–2.09, p = 0.0525) Conclusion There was no association between oral nitrates included in the discharge medication list and the development of MACEs among patients with CAD after adjusting for some covariates, such as SYNTAX score. Oral nitrates after discharge for CAD patients combined with hypertension increased the occurrence of MACEs. Oral nitrates after discharge for CAD patients combined with low uric acid levels may increase theoccurrence of MACEs, and close monitoring for any adverse events is recommended.

Amelioration of hyperuricemia by Lactobacillus acidophilus F02 with uric acid-lowering ability via modulation of NLRP3 inflammasome and gut microbiota homeostasis

Hyperuricemia is a metabolic disease caused by disturbances in purine metabolism and imbalances in the formation and excretion of uric acid. It is closely related to the gut microbiota, which is considered a therapeutic target. Some lactic acid bacteria with a uric acid lowering effect have the potential to ameliorate hyperuricemia in the host. However, the mechanism of action remains unclear. Here, we screened a strain of Lactobacillus acidophilus F02 that efficiently degrades uric acid precursors (inosine and guanosine) and further investigated its underlying mechanism on the alleviation of hyperuricemia in high fructose-adenine induced mice. Results showed that L. acidophilus F02 administration reduced serum uric acid levels in hyperuricemia mice by inhibiting xanthine oxidase and adenosine deaminase activity, while protecting hepatorenal injury and systemic inflammation by regulating the relative expression of NLRP3 inflammasome. Most importantly, it restored gut microbial homeostasis and the abundance of bacterial taxa (i.e., a balance in the relative abundance of Firmicutes and Actinobacteria and an increase in the abundance of Bacteroides, Ruminococcus and Lactobacillus). Furthermore, the ability of L. acidophilus F02 to lower uric acid and suppress NLRP3 inflammasome expression was confirmed in the HK-2 cell model, as well as the multiple immunomodulatory effects on RAW264.7 cells. Taken together, we speculate that fructose-adenine induced hyperuricemia triggers hepatorenal injury and gut microbiota dysbiosis, which is ameliorated by L. acidophilus F02. Collectively, the results suggest that lowering uric acid synthesis, increasing uric acid excretion and reducing NLRP3-related IL-1β levels are effective strategies to ameliorate hyperuricemia. Such information could inform future studies on the ecology of L. acidophilus and guide the use of this species for dietary applications in the food industry.

J-shaped association between serum uric acid levels and chronic kidney disease: a cross-sectional study using large health examination data

Abstract Introduction Hyperuricemia has been recognized as a risk for cardiovascular disease based on the results of many observational studies. On the other hand, a J-shaped association has been reported in which people with very low serum uric acid levels also have increased cardiovascular risk. Although renal dysfunction is closely associated with cardiovascular disease, there are no reports on whether serum uric acid levels and renal function show a J-shaped association. Hypouricemia, defined as a serum uric acid level of 2.0 mg/dL or less, is relatively common among Japanese, but the absence of symptoms and low prevalence (0.2% in men and 0.4% in women) have made epidemiological studies difficult. Therefore, we used the large-sized data from Japanese population that underwent health examinations and evaluated the association between serum uric acid levels and chronic kidney disease. Methods Data from 227,672 individuals (104,854 men and 122,818 women) who underwent health examinations between 2001 and 2018 were included. All analyses were performed separately for men and women because of sex differences in serum uric acid levels. Participants were classified according to serum uric acid (SUA) quartiles, with hypouricemia SUA below 2.0 mg/dL being classified as a separate category, resulting in five groups (men: ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL; women: ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL) to describe the characteristics. We defined chronic kidney disease (CKD) as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and examined the association between SUA category and CKD by univariable and multivariable logistic regression analysis, which included age, BMI, alcohol intake, presence of hypertension, dyslipidemia, and diabetes as covariates. Results The characteristics of the population were as follows. Men: age 56 ± 15 years, SUA 5.9 ± 1.3 mg/dL, eGFR 80 ± 17 mL/min/1.73 m2, CKD 9.4%; women: age 57 ± 15 years, SUA 4.5 ± 1.1 mg/dL, eGFR 81 ± 18 mL/min/1.73m2, CKD 9.4%. The results of univariable and multivariable analyses of the association between SUA categories and CKD by gender are shown in Table. Compared to the reference group (men, SUA 2.1-5.1 mg/dL; women, SUA 2.1-3.7 mg/dL), CKD risk was increased not only in the higher uric acid groups but also in the hypouricemia group with SUA 2.0 mg/dL or less. Conclusion For both men and women, serum uric acid levels and CKD prevalence showed a J-shaped association. Uric acid is itself an important antioxidant in vivo, and its absence may have induced a worsening of renal function due to increased oxidative stress.

Is Serum Uric Acid Level Associated with Disease Activity in Rheumatoid Arthritis Patients.

An association between serum uric acid (UA) and disease activity in rheumatoid arthritis (RA) patients has not been well studied. We describe RA patients with high and normal UA and study its association with RA activity. Adult RA patients from the Kuwait Registry for Rheumatic Diseases (KRRD) were studied from February 2012 through March 2022. Patients with documented UA levels were included. UA of >357 µmol/L (6mg/dL) was considered high. Statistical comparison and correlation were made using multivariate logistic regression. Overall, 1054 patients with documented UA. A total of 158 patients (15%) had high UA level with a mean of 409± 44.4µmol/L. The mean age for the high UA group and low UA group were 59.3 ± 10.7 years and 54.5 ± 12.4 years, respectively (p<0.001). 49.4% were female in high UA group, and 62.2% were female in low UA group, respectively (p<0.05). Logistic analysis showed an inverse relation between DAS28 and UA, as lower DAS28 score was associated with higher UA level (p=0.032) OR 1.39. There was a direct relation with HAQ, creatinine and UA. A higher HAQ is associated with a higher UA level (p=0.019) OR 0.78. High creatinine level is also associated with high UA level (p<0.001) OR 0.24. The use of antirheumatic drugs was similar among patients with high and normal UA. RA patients with a higher UA had a lower disease activity despite using similar antirheumatic drugs. The reasons behind this association need to be further studied.

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients’ responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer–Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 μmol/L vs. 332.7 ± 56 μmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974–0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 μmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer–Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit. Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children.What is Known:• Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events.What is New:• A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

High serum uric acid levels are protective against cognitive impairment in amyotrophic lateral sclerosis

BackgroundUric acid (UA) has emerged as a factor that can modify cognitive function both in the general population and in people with neurodegenerative disorders. Since very few data are available concerning amyotrophic lateral sclerosis (ALS), we explored the correlation of UA levels and cognitive impairment in a large cohort of ALS patients.MethodsWe enrolled ALS patients consecutively seen at the Turin ALS expert center in the 2007–2018 period who underwent both cognitive/behavioral and UA evaluation at diagnosis. Patients were classified in 5 categories: normal cognition (ALS-CN), isolated cognitive impairment (ALSci), isolated behavioural impairment (ALSbi), cognitive and behavioural impairment (ALScbi), frontotemporal dementia (ALS-FTD). For this study, ALSci, ALSbi and ALScbi were merged as ALS with intermediate cognitive impairment (ALS-INT).ResultsOut of the 841 ALS patients, 422 had ALS-CN, 271 ALS-INT and 148 ALS-FTD. The mean values of UA were significantly different among the cognitive subgroups of patients, with the lowest values in the ALS-FTD (ALS-CN, 288.5 ± 78.0 (μmol/L; ALS-INT, 289.7 ± 75.5 μmol/L; ALS-FTD, 271.8 ± 74.9 μmol/L; p = 0.046). The frequency of ALS-FTD was significantly higher in the 1st tertile of UA. Lower UA levels were independently associated with FTD (OR 1.32, 95% c.i. 1.01–1.43; p = 0.038) in binary logistic regression.ConclusionsWe found that in ALS lower UA serum levels are correlated with reduced frequency of co-morbid FTD. Patients with intermediate cognitive impairment showed UA levels similar to ALS-CN but higher than ALS-FTD, implying that higher UA levels can prevent or delay cognitive function deterioration.

Assessing the effects of microencapsulated Lactobacillus salivarius and cowpea seed supplementation on broiler chicken growth and health status.

This study aimed to assess the nutritional quality of cowpea seeds (cv. Doljana - CSD) and the impact of partially replacing soybean meal with CSD, along with the supplementation of microencapsulated Lactobacillus salivarius (LS), on the growth performance, selected carcass traits, biochemical plasma profile, tibia bone quality, and microbial populations in the ceca and excreta of broiler chickens aged 1 to 35 days. A total of 432 mixed-sex Ross 308 broiler chickens, aged one day, were randomly allocated to four groups, with 108 birds in each group, further divided into 6 pens containing 18 birds each. The experimental design featured a 2 × 2 factorial arrangement, with two cowpea seed levels (CSD0 and CSD15%) and the presence or absence (Yes/No) of microencapsulated LS probiotic (0 and 1 g/kg feed). The experimental diets did not significantly influenced (p > 0.05) production performances. However, the production efficiency factor was notably higher in the CSD0 (336.8%) and CSD15 (332.2%) groups with LS compared to CSD0 (322.4%) and CSD15 (320.6%) groups without LS supplementation. Regarding carcass traits, the CSD15 group with LS supplementation exhibited higher dressing (70.69%) and liver (2.47%) percentages compared to the other groups. Plasma profile analysis revealed significant reductions (p < 0.05) in total cholesterol (from 115 mg/dL to 105 mg/dL) and triglycerides (from 54.80 mg/dL to 46.80 mg/dL) in the CSD15 group with LS supplementation compared to the CSD0 group, with or without LS supplementation. Moreover, the CSD15 group with LS had significantly higher total protein, albumin, and calcium levels and significantly lower (p < 0.05) uric acid levels compared to the CSD0 group, irrespective of LS supplementation. Tibia bone traits and minerals showed no significant effects. However, the pH exhibited a linear decrease from 6.90 in the CSD0 group without LS to 6.69 in the CSD15 group with LS supplementation. In terms of cecal microbial populations, Coliforms decreased from 7.14 CFU/g in the CSD15 group without LS to 5.48 CFU/g in the CSD15 group with LS. Significant alterations were also observed in Clostridium spp., E. coli, Enterococcus spp., and Staphylococcus spp. in the ceca and excreta of the CSD15 group with LS supplementation compared to the CSD0 group, with or without LS supplementation. Beneficial bacteria, specifically Lactobacillus spp., significantly increased in the cecal content of CSD0 (9.06 CFU/g) and CSD15 (9.01 CFU/g) groups with LS compared to CSD0 (8.41 CFU/g) and CSD15 (8.11 CFU/g) groups without LS. In summary, this study suggests that cowpea seeds can be used as a partial replacement for soybean meal in broiler chicken diets, and microencapsulated Lactobacillus salivarius can be employed as a probiotic supplement.

Uric acid is a biomarker for heart failure, but not therapeutic target: result from a comprehensive meta-analysis.

This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53-2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25-1.66), cardiac death (RR: 1.56, 95% CI: 1.32-1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37-3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05-1.25). Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.

Uric Acid Levels, Number of Standard Modifiable Cardiovascular Risk Factors, and Prognosis in Patients With Coronary Artery Disease: A Large Cohort Study in Asia.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0-1 versus 2-3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow-up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high-UA-level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197-1.804]) and medium-UA-level group (adjusted HR, 1.478 [95% CI, 1.012-2.160]), compared with the low-UA-level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence-based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.

Low vitamin D and uric acid status in patients with benign paroxysmal positional vertigo.

Growing evidence reported that vitamin D and uric acid metabolism played roles in the occurrence of benign paroxysmal positional vertigo, an otoconia-related vestibular disorder. We aimed to investigate the serum 25-hydroxy vitamin D (25(OH)D) and uric acid in patients with benign paroxysmal positional vertigo and to determine the risk factor for benign paroxysmal positional vertigo. This case-control study comprised 182 patients with benign paroxysmal positional vertigo and 182 age- and gender-matched controls. All subjects' age, body mass index, systolic blood pressure, diastolic blood pressure, 25-hydroxyvitamin D (25(OH)D), uric acid and serum calcium measurements were analyzed. We found a female preponderance of benign paroxysmal positional vertigo patients, with a median of 60 (52-66) years old. The results showed low vitamin D status both in benign paroxysmal positional vertigo and controls, with no significant difference of 25(OH)D levels between benign paroxysmal positional vertigo patients and controls (P > 0.05). Compared with the control group, patients with benign paroxysmal positional vertigo had a higher prevalence of vitamin D deficiency and a lower prevalence of vitamin D sufficiency (P < 0.05). Uric acid was significantly lower in the benign paroxysmal positional vertigo groups (P < 0.05). Logistic regression analysis revealed that age and uric acid were considered higher risk predictors for benign paroxysmal positional vertigo. Our study observed low vitamin D status in patients with benign paroxysmal positional vertigo, with no significant differences of the 25(OH)D level in patients with benign paroxysmal positional vertigo and controls. Elderly, vitamin D deficiency and low uric acid levels may be risk factors for benign paroxysmal positional vertigo occurrence.

Effects of Natural Substances on Lowering Uric Acid

Uric acid (UA) metabolism, which includes uric acid production controlled by purine metabolism and uric acid excretion controlled by the gastrointestinal tract and kidneys, is the primary way to maintain the concentration of uric acid in the body. Abnormal functionalizing of the metabolism may cause hyperuricemia, gout, kidney injury, and other diseases. Over the last decade, numerous studies have been conducted on the effect of natural products, including active ingredients of medicinal plants, natural compounds, plant and fungal extracts, traditional herbal formulations, microbial products, alkaloids, etc., on the downward regulation of uric acid for treating uric acid related diseases. Based on the potential sources from 2018 to 2022, 16 studies were reviewed and considered relevant to the topic. This paper is a preliminary summary of the effects of active ingredients of plants, the extracts of plants, and traditional herbal formulations on regulating uric acid levels.

Association of hyperuricemia with ischemic stroke in adult population

Background: Stroke is the second most prevalent cause of dementia, the third biggest cause of mortality, and the top cause of disability globally. In addition to the conventionally recognized risk factors including smoking, diabetes, hypertension, ischemic heart disease, etc. Recent research on acute ischemic stroke has identified fresh risk variables, such as blood calcium, uric acid, homocysteine, and albumin levels. Hyperuricemia is frequently seen in patients with vascular risk factors and either directly or indirectly through the conventional risk factors.&#x0D; Study: Case control study of 200 patients, 100 patients with stroke and 100 unmatched controls were accessed for vascular risk factor and hyperuricemia and odds ratio was calculated.&#x0D; Results: Out of 100 patients in the case group, 25 (25%) and 75 (75%) had and did not have hyperuricemia. Whereas, out of 100 patients in the control group, 07 (7%) and 9 3 (93%) had and did not have hyperuricemia. The P-value was 0.001. Odds ratio was 4.42.&#x0D; Conclusion: Hyperuricemia is linked positively to occurrence of ischemic stroke as evidenced by the positive odds ratio, further studies need to be done whether uric acid lowering therapy is useful in preventing stroke or reducing mortality.

Serum uric acid levels and health outcomes in CKD: a prospective cohort study.

Hyperuricemia is prevalent in individuals with chronic kidney disease (CKD). Elevated serum uric acid (SUA) concentrations have been considered an independent risk factor for the onset of CKD. However, the relationship between SUA concentrations and long-term health outcomes among patients with CKD remains unclear. We performed a prospective cohort study with nationally representative sample to investigate the relationship between SUA concentrations and mortality risk including all-cause, cardiovascular disease (CVD) and cancer mortality, among patients with CKD. The weighted restricted cubic spline analyses combined with the multivariate-adjusted Cox proportional hazard models were used to test the nonlinearity of relationship. The 6642 patients participating in National Health and Nutrition Examination Survey 1999-2018 were enrolled. During 656885 person-months of follow-up time, 2619 all-cause deaths were recorded, including 1030 CVD deaths and 458 cancer deaths. Our study presented J-shaped non-linear relationships between SUA concentrations and all-cause and CVD mortality with inflection points at 311.65μmol/L and 392.34μmol/L, respectively. When SUA concentration was higher than those inflection points, every increase of 50μmol/L SUA was associated with 11.7% and 17.0% greater multivariable-adjusted hazard ratio of all-cause and CVD mortality, respectively. In addition, a negative linear correlation with cancer mortality was detected. These findings suggested that maintaining appropriate SUA concentrations may improve long-term health outcomes among CKD patients. The corresponding inflection points of J-shaped non-linear relationships were 311.65 and 392.34μmol/L for all-cause and CVD mortality. Further clinical trials are required to investigate uric acid-lowering targets.

The Chemical Composition of Soyhulls and Their Effect on Amino Acid and Nutrient Digestibility in Laying Hens during the Peak of Production.

This study investigates the chemical composition of soyhulls (SHs) as an alternative feed ingredient and their effect on nutrient and amino acid (AA) digestibility in laying hens during peak production. A total of 200 golden brown hens (28 weeks old) were subjected to random allocation across 5 dietary treatments: a corn-soybean meal (SBM) reference diet and 4 test diets with 25% SHs from different mills (SH1, SH2, SH3, and SH4). Each treatment was replicated four times with ten birds per replicate. Digesta samples were collected during three phases (28-32, 32-36, and 36-40 weeks of age) to measure apparent metabolizable energy (AME), the apparent ileal digestibility (AID) of nutrients, and the standard ileal digestibility (SID) of AAs. The SBM diet had 30.0% crude protein (CP) and 3.78% crude fiber (CF), while the SH diets had 21.0 to 21.5% CP and 11.6% CF. The findings revealed that the AME was lower (p < 0.05) with SH diets (2404 kcal/kg) compared to the SBM diet (2627 kcal/kg) in all three phases. The SH diets had a lower AID of dry matter (DM), crude protein (CP), ash, ether extract (EE), and crude fiber (CF) than the SBM diet by an average of 2.88, 2.25, 4.93, 4.99, and 3.36%, respectively. The AID of nitrogen-free extract (NFE) was higher in the SH diets than the SBM diet by 3.42% in all three phases (p < 0.05). The SH diets had lower uric acid excretion (about 66.93 mg/100 mL) than the SBM diet (about 76.43 mg/100 mL) on average in all three phases. The SH diets had a lower SID of arginine, histidine, isoleucine, lysine, cysteine, valine, and tyrosine than the SBM diet by 2 to 10%, while the SID of methionine was higher in the SH diets than the SBM diet by 2.2% on average in all three phases (p < 0.05). The SH from Sadiq Brother Feed (SH1) had the highest AME and AID of DM, ash, CP, EE, CF, and the SID of AA among the SH diets. These results indicate that SH can partially replace SBM in laying hen diets, but the source and quality of SH should be considered.