The aim of this study was to explore the uric acid-lowering effect and renal protective effect of Eucommia ulmoides leaf extract (EULE). The results of xanthine oxidase inhibition assay showed EULE exhibited a high inhibition rate similar to that of allopurinol, with an IC50 value of 1.53 mg/mL. A chronic kidney disease (CKD) model was established in adenine-induced rats to investigate the therapeutic effect of EULE on CKD. The results demonstrated EULE could reduce blood pressure and improve renal index. Additionally, EULE could regulate serum and urine indicators of renal function injury, and restore renal tissue morphology. Mechanistically, EULE was found to downregulate levels of malondialdehyde (MDA), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), while upregulating total antioxidant capacity (T-AOC), thereby alleviating inflammatory response in rats, leading to a reduction in renal damage. the Our findings provide potential applications of EULE as a natural product for the improvement of renal injury.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

Xanthine oxidase (XO) is a typical target for hyperuricemia and gout, for which there are only three commercial xanthine oxidase inhibitors (XOIs): febuxostat, topiroxostat and allopurinol. However, these inhibitors have problems such as low bioactivity and several side effects. Therefore, the development of novel XOIs with high bioactivity for the treatment of hyperuricemia and gout is urgently needed. In this work we constructed a XO immobilized cellulose membrane colorimetric biosensor (XNCM) by the TEMPO oxidation, amide bond coupling and nitro blue tetrazolium chloride (NBT) loading method. As expected, the XNCM was able to detect xanthine, with high selectivity and sensitivity by colorimetric method with a distinctive color change from yellow to purple, which can be easily observed by the naked-eye in just 8 min without any complex instrumentation. In addition, the XNCM sensor performed screening of 21 different compounds and have been successfully pre-screened out XOIs with biological activity. Most importantly, the XNCM was able to quantitatively detect the IC50 values of two commercial inhibitors (febuxostat and allopurinol). All the results confirmed that the XNCM is a simple and effective tool which can be used for the accelerated screening of XOIs and has the potential to uncover additional XOIs.

BACKGROUND: In recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated.
OBJECTIVE: This study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism.
METHODS: The buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting.
RESULTS: The buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.

OBJECTIVE: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D).
METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort.
RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 μmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 μmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 μmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship.
CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 μmol/L could potentially enhance this reduced mortality.

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout.
METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1β), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups.
RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 μmol/L ± 17.23 μmol/L vs. S198.32 μmol/L ± 18.34 μmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025).
CONCLUSIONS: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.

Epigallocatechin gallate (EGCG), a prominent bioactive compound found in tea, offers numerous health benefits. Previous studies have highlighted its potential in mitigating hyperuricemia. In this study, hyperuricemic mice induced by potassium oxonate (PO) were treated with EGCG or the anti-hyperuricemia medication allopurinol (AP) to investigate the mechanisms underlying their anti-hyperuricemic effects. The results demonstrated that both EGCG and AP significantly reduced serum uric acid (UA) levels. Further analysis revealed that EGCG promoted the expression of UA secretion transporter genes (Oat1 and Oct1) while inhibiting the expression of UA reabsorption transporter genes (Urat1 and Glut9) in the kidney. By 16S rDNA sequencing, EGCG, but not AP, was found to alter the composition of the gut microbiota. Notably, EGCG induced significant changes in the relative abundance of specific bacteria such as Lactobacillus, Faecalibaculum, and Bifidobacterium, which displayed high correlations with serum UA levels and UA-related gene expression. Metabolomic analysis suggested that EGCG-induced modifications in bacterial metabolites might contribute to the alleviation of hyperuricemia. Transcriptomic analysis of the intestinal epithelium identifies 191 differentially expressed genes (DEGs) in EGCG-treated mice, including 8 purine-related genes. This study elucidates the anti-hyperuricemic mechanisms of EGCG, particularly its influence on the gut microbiota and gene expression in the intestinal epithelium.

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting.
METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3.
RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well.
CONCLUSIONS: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong.
METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020.
RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%).
CONCLUSIONS: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

OBJECTIVE: Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood. This knowledge gap necessitates a comprehensive analysis and evidence update to guide drug selection for physicians and patients.
METHODS: We conducted a systematic analysis by extracting relevant clinical studies from four medical literature databases. Forest plots, funnel plots, sensitivity analysis, Egger\'s test, and subgroup analysis were utilized to compare relevant indicators.
RESULTS: The advantages and disadvantages of the two drugs were evaluated based on various indicators such as serum uric acid (SUA), triglyceride (TG), urinary uric acid (UUA), white blood cell count (WBC), total cholesterol (TC), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine (SC). Benzbromarone demonstrated better efficacy in rapidly reducing SUA levels and inhibiting inflammation for hyperuricemia and gout patients. Febuxostat was slightly less effective in lowering SUA, but there was no significant difference in its impact on liver and kidney function after long-term use.
CONCLUSIONS: This study highlights the superiority of benzbromarone in rapidly reducing SUA and inhibiting inflammation. Febuxostat shows comparable effects on liver and kidney function after long-term use. These findings provide valuable insights for clinicians and patients in drug selection. Key Points • Benzbromarone stands out as a highly effective treatment for hyperuricemia and gout, offering rapid reduction of serum uric acid levels and potent anti-inflammatory effects. • When it comes to long-term use, febuxostat demonstrates comparable effects on liver and kidney function. This provides reassurance for patients who require extended treatment duration. • Moreover, our study goes beyond previous research by presenting a more comprehensive and detailed analysis.