Is lactic acid a misunderstood trigger of gout attack for a century?

A gout attack could be viewed as a nucleation event. Many reports have shown that the typical molecular structure of crystallization inhibitors usually contains carboxyl and hydroxyl groups, which could interact with solute molecules through hydrogen bonding, thereby suppressing the nucleation and growth of crystals. Since 1923, l-lactic acid (LA), a molecule with structural features of inhibitors, has been speculated to be a trigger for acute gout because metabolized LA temporarily reduces uric acid excretion and leads to a slow increase in serum uric acid concentration. However, many cases of gout presumably triggered by elevated lactate in a very short period of 4 h are often inexplicable. Here, we present the unexpected result that LA has a significant "opposite effect" on the nucleation and growth of gouty pathological crystals, which is that as the concentration of the additive LA increases, the nucleation and growth of the crystals is suppressed and then facilitated. This approach may help our clarifying the long-standing "misunderstandings" and further understanding the association between metabolized LA and increased risk of gout attacks. Finally, a novel mechanism called "tailed-made occupancy (TMO)" was used to explain the nucleation and crystallization effects of LA on sodium urate monohydrate (MSUM).

Modulation of the dissolution with ASP from a supersaturated solution on a bionic platform for gout pathology crystals.

The core to the treatment of gout is the elimination of pathologic crystal, monosodium urate monohydrate (MSUM). The primary treatment available is to gradually dissolve the "culprit crystals" by lowering the blood uric acid concentration with medications, which often takes a long time and in severe cases must still be treated surgically. Herein, we developed a dynamic bionic platform based on a hydrogel composite membrane (HCM) to screen the direct facilitated solubilization of MSUM crystals by small organic molecules in bionic saturated, or even supersaturated, solutions. The customized and biologically safe (NAGA/PEGDA/NIPAM) HCM, which is consistent with the main amino acid composition of articular cartilage, well mimics the entire process of organic molecules leading to the dissolution of MSUM crystals in the joint system. With the verifications of this platform, it is shown that l-aspartic acid (ASP) significantly promotes the dissolution of MSUM crystals not only in saturated but also in supersaturated solutions. Furthermore, a novel mechanism called "crane effect" was used to explain this "dissolution effect" of ASP on MSUM, which stems from the ability of ASP to lock onto the surface of MSUM crystals through hydrogen bonding by virtue of its two carboxyl groups, and simultaneously its amino group lifts the uric acid molecules from the surface of MSUM crystals by virtue of interactions of hydrogen bonding. The results of bulk crystallization, scanning electron microscopy (SEM), powder X-diffraction (PXRD), and density-functional theory (DFT) studies are quantitatively consistent with this hypothetical "crane effect" mechanism. Hence, this HCM-based functional platform could provide entirely novel ideas and methods for drug design and screening for the treatment of pathological crystal diseases of gout.

Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Asthma with recurrent middle lobe syndrome in children: Clinical features and lung function patterns.

Background: Middle lobe syndrome (MLS) is a complication of childhood asthma. This study aimed to compare the clinical features and lung function between asthmatic children with recurrent MLS and transient right middle lobe (RML) and/or lingula atelectasis. Methods: This study retrospectively analyzed asthmatic children with RML and/or lingula atelectasis between 2010 and 2020 using data from the pediatric pulmonary department. According to the episodes of atelectasis, children were divided into recurrent (≥2 episodes) and non-recurrent (only 1 episode) MLS groups, to compare clinical features and lung function. Spirometry during acute asthma exacerbation and stable stages were recorded, and variations were calculated. Results: A total of 35 children with asthma and RML and/or lingula atelectasis were included, 15 of whom had recurrent MLS. The recurrent MLS group had a higher proportion of girls, infections, family allergy history, severe asthma, severe exacerbation, and higher levels of total IgE than the non-recurrent MLS group (P < 0.05). The recurrent MLS group had a significantly higher % predicted and z-scores for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), a greater proportion of high FEV1 and higher variations in FEV1 and FVC than that in the non-recurrent group (P < 0.05). After excluding children with mild to moderate asthma in the recurrent MLS group, the differences in clinical features disappeared, but the results regarding lung function remained similar, when compared to severe asthma patients without RML and/or lingula atelectasis. Conclusions: Childhood asthma with recurrent MLS has more frequent severe asthma and exacerbation but high lung function and variations.

Utility of umbilical cord blood 25-hydroxyvitamin D levels for predicting bronchopulmonary dysplasia in preterm infants with very low and extremely low birth weight.

Background and objective: There remains controversy regarding vitamin D deficiency and bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) and extremely low birth weight (ELBW) preterm infants. This study aimed to determine the prevalence of vitamin D deficiency assessed by umbilical cord blood 25-hydroxyvitamin D [25(OH)D] in preterm infants in northeast China and to evaluate the ability and optimal threshold of 25(OH)D for predicting BPD. Methods: The clinical data of VLBW and ELBW preterm infants with known cord-blood 25(OH)D levels were analyzed retrospectively. Infants were divided into groups based on their cord-blood 25(OH)D levels and BPD diagnosis. Logistic regression was performed to assess the risk factors for BPD and a nomogram was established. Receiver operating characteristic (ROC) curve analysis was used to evaluate the optimal threshold of cord-blood 25(OH)D concentration for predicting BPD. Results: A total of 267 preterm infants were included, of which 225 (84.3%) exhibited vitamin D deficiency and 134 (50.2%) were diagnosed with BPD. The incidence of BPD was lower in the group with a 25(OH)D level of >20 ng/ml than in the other groups (P = 0.024). Infants with BPD had lower cord-blood 25(OH)D levels than those without BPD (11.6 vs. 13.6 ng/ml, P = 0.016). The multivariate logistic regression model revealed that 25(OH)D levels (odds ratio [OR] = 0.933, 95% confidence interval [95% CI]: 0.891-0.977), gestational age (OR = 0.561, 95% CI: 0.425-0.740), respiratory distress syndrome (OR = 2.989, 95% CI: 1.455-6.142), and pneumonia (OR = 2.546, 95% CI: 1.398-4.639) were independent risk factors for BPD. A predictive nomogram containing these four risk factors was established, which had a C-index of 0.814. ROC curve analysis revealed that the optimal cutoff value of 25(OH)D for predicting BPD was 15.7 ng/ml (area under the curve = 0.585, 95% CI: 0.523-0.645, P = 0.016), with a sensitivity of 75.4% and a specificity of 42.9%. Conclusions: A cord-blood 25(OH)D level of <15.7 ng/ml was predictively valuable for the development of BPD. The nomogram established in this study can help pediatricians predict the risk of BPD more effectively and easily.