Heterogeneous hydrochlorination of lipids mediated by fatty acids in an indoor environment.

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.

The reliability and validity of a novel wearable inertial sensor to measure the cervical proprioception.

BACKGROUND: Proprioceptive function assessment is crucial in clinical practice for patients with chronic non-specific neck pain (CNNP) as it is a major issue affecting their condition. PURPOSE: To verify the reliability and validity of baiobit sensor in measuring the neck proprioceptive function of CNNP patients. METHODS: Fifty-three CNNP patients were recruited (36 females, 17 males; age range 21-60 years) and were assessed for cervical joint position error by two blinded raters using the Baiobit sensor and laser pointer devices. The second measurement was conducted by the same rater 48 h later. Intra and inter-rater reliability of the Baiobit sensor was evaluated using the intra-class correlation coefficient (ICC), while the validity of the Baiobit sensor was established using the Spearman correlation coefficient. RESULTS: The Baiobit sensor demonstrated moderate to excellent intra-rater reliability in flexion, extension, left lateral flexion, right lateral flexion, and right rotation (ICCs=0.71∼0.85, 95 %CIs: 0.50∼0.91), left-rotation shows poor to good intra-rater reliability (ICC=0.56, 95 %CI: 0.25∼0.75). The Baiobit sensor also demonstrated moderate to excellent inter-rater reliability in flexion, extension, left lateral flexion, right lateral flexion, and right rotation (ICCs=0.80∼0.88, 95 %CIs: 0.65∼0.91), left-rotation shows poor to good intra-rater reliability (ICC=0.59, 95 %CI: 0.29∼0.76). Validity analysis showed that the Baiobit sensor had a range of low to high validity (r = 0.46∼0.88) for measuring cervical proprioception function, with lower validity observed in the left flexion direction. The Baiobit showed good absolute reliability with low SEM and MDC90 values (0.35°âˆ¼2.42°). CONCLUSION: The new device could be used as an alternative tool to evaluate neck proprioception.

Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout.

OBJECTIVE: Hyperuricemia can be stratified into four subtypes according to renal uric acid handling. The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts. METHODS: Hyperuricemia subtype was defined as renal uric acid overload (ROL), renal uric acid underexcretion (RUE), combined, or renal normal. Twenty single nucleotide polymorphisms (SNPs) previously identified as gout risk loci or associated with serum urate (SU) concentration in the East Asian population were genotyped. Weighted polygenic risk scores were calculated to assess the cumulative effect of genetic risks on the subtypes. RESULTS: Of the 4,873 participants, 8.8% had an ROL subtype, 60.9% RUE subtype, 23.1% combined subtype, and 7.2% normal subtype. The ROL subtype was independently associated with older age at onset, lower SU, tophi, and diabetes mellitus; RUE was associated with lower body mass index (BMI) and non-diabetes mellitus; the combined subtype was associated with younger age at onset, higher BMI, SU, estimated glomerular filtration rate (eGFR), and smoking; and the normal subtype was independently associated with older age at onset, lower SU, and eGFR. Thirteen SNPs were associated with gout with 6 shared loci and subtype-dependent risk loci patterns. High polygenic risk scores were associated with ROL subtype (odds ratio [OR] = 9.63, 95% confidence interval [95% CI] 4.53-15.12), RUE subtype (OR = 2.18, 95% CI 1.57-3.03), and combined subtype (OR = 6.32, 95% CI 4.22-9.48) compared with low polygenic risk scores. CONCLUSION: Hyperuricemia subtypes classified according to renal uric acid handling have subtype-specific clinical and genetic features, suggesting subtype-unique pathophysiologic mechanisms.

Associations of micronutrient dietary patterns with sarcopenia among US adults: a population-based study.

Background: Current epidemiological evidence points to an association between micronutrient (MN) intake and sarcopenia, but studies have focused on single MN, and no combined effects on MNs have been reported. The aim of this study was to investigate the relationship between different MN intake patterns and sarcopenia and skeletal muscle mass. Methods: We performed a population-based cross-sectional study, with a total of 5,256 U.S. adults aged 20-59 years, and we collected total daily MN intake and appendicular skeletal muscle mass measured by Dual-Energy X-ray Absorptiometry (DXA). Principal component analysis (PCA) was used to obtain nutrient patterns and principal component scores based on the intake of 14 MNs, and logistic regression analysis was used to assess the effects of single MN and MN intake patterns on sarcopenia and muscle mass. Results: We defined three MN intake patterns by PCA: (1) adherence to VitB-mineral, high intake of vitamin B and minerals; (2) adherence to VitAD-Ca-VB12, high intake of vitamin A, vitamin D, calcium and vitamin B12; and (3) adherence to Antioxidant Vit, high intake of antioxidant vitamins A, C, E, and K. These three nutrient patterns explained 73.26% of the variance of the population. A negative association was observed between most single MN intakes and sarcopenia, and after adjusting for confounders, adherence to the highest tertile of the three nutrient patterns was associated with a lower risk of sarcopenia and relatively higher skeletal muscle mass compared to the lowest adherence. In subgroup analysis, MN intake patterns were significantly correlated with sarcopenia in middle-aged females. Conclusion: Nutritional patterns based on MN intake were significantly related to sarcopenia, indicating that MNs interact with each other while exerting their individual functions, and that MN dietary patterns may provide promising strategies for preventing the loss of muscle mass, with further prospective studies warranted in the future.

The value of musculoskeletal ultrasound in predicting gout flares in index joints: A prospective cohort study of people with gout starting urate-lowering therapy.

OBJECTIVES: To evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months. METHODS: This single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (≥2) gout flares in the index joint over 12 months. RESULTS: Frequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26-21.41), 7.91 [(95%CI: 2.23-28.14), and 13.79 [(95%CI: 3.79-50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85-29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44-54.18), P < 0.001 at the MTP1, 7.05 (1.98-25.12), P < 0.001 at the ankle. CONCLUSION: Ultrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.

Natural Changbai mineral water reduces obesity risk through regulating metabolism and gut microbiome in a hyperuricemia male mouse model.

Access to clean and safe drinking water is essential. This study aimed to evaluate the effect of a kind of small molecular natural mineral water, C-cell mineral water on hyperuricemia male mice metabolism condition. A 13-week drinking water intervention study was conducted in Uox-knockout mice (KO). The hepatic metabolite profiling and related genes expression were detected by UPLC-TOF-MS and transcriptomic, and the gut microbiota of KO mice was determined by metagenomics sequencing. Results showed that the body weight of mice fed with C-cell water was remarkably lower than that of control mice on D 77 and D 91. Hepatic metabolite profiling revealed a shift in the pathway of glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, and biosynthesis of cofactors in KO mice fed with C-cell mineral water. Increased energy metabolism levels were related to increased hepatic expression of genes responsible for coenzyme metabolism and lipid metabolism. Gut microbiota was characterized by increasing activity of beneficial bacteria Blautia, and reducing activity of pathobiont bacteria Parasutterella. These genera have been reported to be associated with obesity. Small molecular mineral-rich natural water ingestion regulates metabolism and gut microbiota, protecting against obesity induced by hyperuricemia through mediating a microbiota-liver axis.

Bioactives and Biomaterial Construction for Modulating Osteoclast Activities.

Bone tissue constitutes 15-20% of human body weight and plays a crucial role in supporting the body, coordinating movement, regulating mineral homeostasis, and hematopoiesis. The maintenance of bone homeostasis relies on a delicate balance between osteoblasts and osteoclasts. Osteoclasts, as the exclusive "bone resorbers" in the human skeletal system, are of paramount significance yet often receive inadequate attention. When osteoclast activity becomes excessive, it frequently leads to various bone metabolic disorders, subsequently resulting in secondary bone injuries, such as fractures. This not only reduces life quality of patients, but also imposes a significant economic burden on society. In response to the pressing need for biomaterials in the treatment of osteoclast dysregulation, there is a surge of research and investigations aimed at osteoclast regulation. Promising progress is achieved in this domain. This review seeks to provide a comprehensive understanding of how to modulate osteoclast activities. It summarizes bioactive substances that influence osteoclasts and elucidates strategies for constructing related biomaterial systems. It offers practical insights and ideas for the development and application of biomaterials and tissue engineering, with the hope of guiding the clinical treatment of osteoclast-related bone diseases using biomaterials in the future.

COVID-19 Vaccination and Gout Flare Risk in Patients With Infrequent or Frequent Flares: A Prospective Cohort Study.

OBJECTIVE: To assess post-COVID-19 vaccination gout flare risk with differing baseline flare burden. METHODS: We prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year or ≥2 flares/year, respectively. COVID-19 vaccine-naive patients managed with urate-lowering therapy between February and June 2021 were included and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups. RESULTS: Of 530 participants, 308 (58.1%) had infrequent flares and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent and 106 frequent) receiving two-dose COVID-19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs 10.8%, P = 0.001, compared with 60.4% vs 65.5%, P = 0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs 12.0%, P = 0.017). Multivariable analyses showed that vaccination (odds ratio [OR] 2.82, 95% confidence interval [95% CI] 1.50-5.30, P = 0.001), flare in the preceding year (OR 1.95, 95% CI 1.03-3.71, P = 0.04), and body mass index (OR 1.09, 95% CI 1.01-1.19, P = 0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dl) was an independent risk factor in the frequent flare group (OR 1.23, 95% CI 1.05-1.45, P = 0.012). CONCLUSION: COVID-19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.

Superiority of Low-Dose Benzbromarone Add-On to Low-Dose Febuxostat Compared With Febuxostat Monotherapy in Gout With Combined-Type Hyperuricemia.

OBJECTIVE: There is an unmet need for simpler urate-lowering therapy (ULT) regimens that achieve the serum urate target and improve the overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add-on to low-dose febuxostat in gout specifically with combined renal urate underexcretion and overload. METHODS: A prospective randomized trial was conducted on patients with combined-type hyperuricemia and estimated glomerular filtration rate >60 mL/min/1.73 m2 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20 mg/day of febuxostat if not at target) or febuxostat monotherapy (initially 20 mg/day, escalating to 40 mg/day if not at target). The primary end point at 12 weeks was the proportion achieving a serum urate (SU) level <360 µmol/L. Other outcomes included altered liver and kidney function, new-onset urolithiasis, and gout flares. RESULTS: There were 250 participants randomized; 219 completed 12-week treatment. More patients in the febuxostat and benzbromarone combination group achieved the SU target compared to patients in the febuxostat monotherapy group (75.5% vs 47.7%; odds ratio 3.37 [95% confidence interval 1.90-5.98]). Safety profiles were comparable between the two groups. CONCLUSION: Simply adding on low-dose benzbromarone (25 mg/day) to low-dose (20 mg/day) febuxostat showed superior urate lowering compared to febuxostat monotherapy in gout with a combined-type hyperuricemia. For selected patients, expedited achievement of the SU target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard ULT regimens.

The PG-SGA outperforms the NRS 2002 for nutritional risk screening in cancer patients: a retrospective study from China.

Background and aims: As a chronic wasting disease, cancer can lead to metabolic and physiological changes in patients, resulting in severe malnutrition. Therefore, accurate assessment of nutritional status and adoption of scientifically sound nutritional interventions are of great importance for patients with cancer. This study aimed to assess the necessity of implementing the Nutrition Risk Screening 2002 (NRS 2002) tool in conjunction with the Patient-Generated Subjective Global Assessment (PG-SGA) in patients with cancer. Methods: This retrospective study collected the clinical data of cancer patients from November 2011 to December 2018 in the Department of Oncology, Cancer Center, First Hospital of Jilin University. The NRS 2002 and the PG-SGA were used as screening tools for malnutrition. Clinical characteristics and laboratory results were detected. Anthropometric indices including hand-grip strength (HGS), visceral fat area (VFA), calf circumstance (CC), and appendicular skeletal muscle mass index (ASMI) were also collected. The diagnostic results from the NRS 2002 were compared to the malnutrition diagnosis using the PG-SGA. Results: Of the 2,645 patients included in this retrospective study, the nutritional risk was found in 1763 (66.6%) patients based on the PG-SGA, and in 240 (9.1%) patients based on the NRS 2002, respectively. Among the 240 patients evaluated by the NRS 2002 for risk of malnutrition, 230 were also assessed by the PG-SGA as malnourished. There were no significant differences observed in the clinical characteristics and laboratory parameters between the two groups. Conclusion: The PG-SGA is effective and had a higher positive rate in screening malnutrition for patients with cancer. The NRS 2002 is not necessary for patients who are to be assessed with the PG-SGA.

Cross-cultural adaptation and validation of the Mental Health Quality of Life (MHQoL) questionnaire in a Chinese-speaking population with chronic musculoskeletal pain.

BACKGROUND: The Mental Health Quality of Life (MHQoL) questionnaire is concise and suitable for rapid assessment of CMP (chronic musculoskeletal pain) patients in primary care. However, there is a lack of Chinese versions of the MHQoL. OBJECTIVE: To cross-culturally translate the MHQoL into Chinese and to assess its psychometric properties in Chinese-speaking patients with CMP. METHODS: The MHQoL was translated into Chinese according to the International Guidelines for the Cross-Cultural Adaptation of Self-Report Measures. 171 CMP patients were recruited to receive the Chinese versions of the MHQoL, SF-36, and HADS tests, and the MHQoL was retested seven days later. RESULT: The Chinese version of MHQoL had good retest reliability (MHQoL-7D: ICC = 0.971; MHQoL-VAS: ICC = 0.988) and internal consistency (Cronbach's alpha = 0.829). It showed a moderate correlation with the SF-36 total score (r=-0.509); the MHQoL-VAS moderately correlated with the Hospital Anxiety Depression Scale (r=-0.548). The MHQoL-7D showed no correlations with the SF-36's PF (r=-0.083) and BP (r=-0.170), weak correlations with RP (r=-0.284), RE (r=-0.298), and SF (r=-0.380), and moderate-to-strong correlations with GH (r=-0.638), VT (r=-0.480), and MH (r=-0.632). CONCLUSION: The Chinese version of the MHQoL can be used in clinical practice and research in Chinese-speaking CMP patients.

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout.

BACKGROUND: While xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia. METHODS: A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12. RESULTS: Fewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target. CONCLUSIONS: People with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

Anomaly Detection of Wind Turbine Driveline Based on Sequence Decomposition Interactive Network.

Aimed at identifying the health state of wind turbines (WTs) accurately by using the comprehensive spatio and temporal information from the supervisory control and data acquisition (SCADA) data, a novel anomaly-detection method called decomposed sequence interactive network (DSI-Net) is proposed in this paper. Firstly, a DSI-Net model is trained using preprocessed data from a healthy state. Subsequences of trend and seasonality are obtained by DSI-Net, which can dig out underlying features both in spatio and temporal dimensions through the interactive learning process. Subsequently, the trained model processes the online data and calculates the residual between true values and predicted values. To identify anomalies of the WTs, the residual and root mean square error (RMSE) are calculated and processed by exponential weighted moving average (EWMA). The proposed method is validated to be more effective than the existing models according to the control experiments.

Prognostic value of the combined effect of nutritional status and body water component in patients with colorectal cancer.

The aim of this study was to explore the impact of Geriatric Nutritional Risk Index (GNRI) and body water component (BWC) on the survival of colorectal cancer (CRC) patients and whether the combined effect had a potential prognostic and predictive efficacy. We evaluated the accuracy of GNRI for malnutrition and estimated the predictive capacity of BWC for survival. Kaplan-Meier survival curves and cox regression analyses were used to examine the prognostic effects. A nutrition-water score (NWS) model was developed and evaluated the survival predictive power. GNRI and extracellular water-to-intracellular water ratio (ECW/ICW) were integrated, with the cut-off values of 103.5 and 63.7%. Lower GNRI and higher ECW/ICW were independent risk factors for poor prognosis in CRC patients. The combination of the two into the NWS model demonstrated a higher risk of death for patients with NWS ≥ 1 compared to those with NWS of 0. NWS showed a better predictive capability compared to GNRI and ECW/ICW, with the concordance index of 0.681. Our study demonstrates GNRI and ECW/ICW's prognostic utility in CRC, with their combination improving survival prediction to help guide patient-centered treatment.

Cadmium exposure dysregulates purine metabolism and homeostasis across the gut-liver axis in a mouse model.

Cadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.

Construction of Unique Spiro[dibenzo[a,f]azulene-6,2'-indenes] via Unprecedented Annulation of ortho-C-H Bond of Benzylidene Group.

The domino reaction of alkyl and aryl isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C resulted in unique functionalized spiro[dibenzo[a,f]azulene-6,2'-indenes] in good yields, in which the two 2-arylidene-1,3-indanediones acted as different building blocks to construct the polycyclic system. More importantly, the unprecedented anticipation of the ortho-position of benzylidene group to form a novel dibenzo[a,f]azulene ring through a formal [5 + 2] cycloaddition process was first observed. On the other hand, DABCO-promoted reaction of the isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C afforded functionalized spiro[cyclopenta[a]-indene-2,2'-indene] derivatives.

The Effect of Decrease in Serum Urate for the Risk of Gout Flares During Urate-Lowering Therapy Initiation Among Chinese Male Gout Patients: A Prospective Cohort Study.

Purpose: Higher baseline serum urate or higher initial urate-lowering medication dose increased risk of gout flares during urate-lowering therapy (ULT) initiation. The decrease in serum urate may play a crucial role in this process. Therefore, we aim to explore the relationship between decrease in serum urate and the risk of gout flares during ULT initiation. Patients and Methods: A 12-week prospective cohort study of Chinese male gout patients was conducted at Shandong Provincial Clinical Research Center for Immune Diseases and Gout in China. Patients were grouped by baseline serum urate (7-7.9 mg/dL, 8-8.9 mg/dL and ≥9 mg/dL). All patients received febuxostat 20 mg daily during weeks 0-4, then escalated to 40mg during weeks 4-12 if serum urate >6mg/dL. The main outcomes were the number of gout flares and the decrease in serum urate. Poisson regression was performed. Results: A total of 282 participants were enrolled, of whom 260 completed (84, 87 and 89 in each group) from March 2021 to December 2021. A 44.2% of all participants experienced at least one gout flare. In the multivariate Poisson regression 1, Δ serum urate 0-12 weeks (IRR 1.184, 95% CI, 1.062-1.320; P=0.002), the number of gout flares before treatment 1 year (1.017, 1.010-1.024; P<0.001) and tophus (1.580, 1.023-2.440; P=0.039) were independently associated with the number of gout flares. While in the multivariate Poisson regression 2, baseline serum urate (1.256, 1.050-1.503; P=0.013) and the number of gout flares before treatment 1 year (1.014, 1.007-1.022; P<0.001) were independently associated with the number of gout flares, Δ serum urate 0-12 weeks (1.055, 0.923-1.207; P=0.433) was no longer a risk factor. Conclusion: ULT-induced gout flares depend on the degree of decrease in serum urate, which is affected by baseline serum urate. Higher baseline serum urate and greater decrease in serum urate lead to higher risk of gout flares.

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.

BACKGROUND: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 µmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Comparison of the different monosodium urate crystals in the preparation process and pro-inflammation.

OBJECTIVES: The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. METHODS: MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1ß, TNF-α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. RESULTS: For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of IL-1ß, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1ß secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. CONCLUSIONS: All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.