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Background: The pathogenic causes of primary gout include urate overproduction and/or renal or extra-renal urate underexcretion. The aim of this study was to evaluate the association of gout subtypes with the response to low-purine diet (LPD). Methods: This is a single-center prospective clinical study. Gout patients visiting from 2019 to 2022, from Shandong Gout Clinic Center at the Affiliated Hospital of Qingdao University, China, assigned to three groups according to clinical subtypes, were enrolled and all treated with 2-week low-purine diet. General characteristics, serum uric acid (sUA) and other clinical biochemical variables before and after the diet were evaluated. Results: A total of 626 gout patients (age 41.20 ± 13.41 years, male 98.0%) were included. Of these, 69 (11.0%) were overproduction type, 428 (68.37%) were underexcretion type, and 129 (20.61%) were combined type. Overall, there was a substantial decrease in sUA after a 2-week LPD (p < 0.001). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum triglycerides (TG), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower than those at baseline (p < 0.05). On the other hand, there were significant differences in the reduction of sUA among different types, the rank order being overproduction type (− 88.81 ± 63.01 μmol/L) > combined type (− 65.22 ± 44.13 μmol/L) > underexcretion type (− 57.32 ± 61.19 μmol/L). After adjusting for age, BMI and baseline sUA and eGFR, there were still significant differences in the decline of serum uric acid among different types. Higher baseline sUA (95%CI − 0.285, − 0.191; p < 0.001) and BUN (95%CI − 6.751, − 0.602; p < 0.001) were correlated with greater decrease of sUA. Conclusions: Our findings support the protective role of low-purine diet on sUA levels in gout patients, especially overproduction type. Furthermore, LPD could exert a beneficial effect on gout patients' blood pressure, BMI, blood lipid, BUN and Scr levels. Trial registration Registered with ChiCTR, No. ChiCTR1900022981 at 06/05/2019. [ABSTRACT FROM AUTHOR]

Background The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported. Methods A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017-2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey. Results The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA [greater than or equal to] 7 mg/dL or [greater than or equal to] 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones. Conclusions The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges., Author(s): Jie Lu [sup.1] [sup.2] [sup.3] , Wenyan Sun [sup.1] [sup.2] [sup.3] , Lingling Cui [sup.1] [sup.2] [sup.3] , Xinde Li [sup.1] [sup.2] [sup.3] , Yuwei He [sup.1] [sup.2] [sup.3] [...]

SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.

The human cationic antimicrobial protein LL-37 is a multifunctional host defense peptide with a wide range of immunomodulatory activities. Previous work has shown that LL-37 exerts both pro- and anti-inflammatory effects. The role of mitochondria in the skin inflammatory effects of LL-37 has not been well studied. Therefore, our aim was to investigate the immunomodulatory effect of LL-37 in HaCaT cells and to delineate the underlying mechanisms related to mitochondrial function. Immunohistochemistry results from tissue microarrays showed strong cytoplasmic LL-37 staining in inflammatory cells in chronic dermatic inflammation. Using exogenous LL-37 stimulation and LL-37 knockdown and overexpression, LL-37 was demonstrated to dramatically reduce the mRNA levels and protein secretion of inflammatory cytokines including IL-6, IL-8, IL-1α and tumor necrosis factor-α (TNF-α), which are induced by lipopolysaccharides (LPS). The anti-inflammatory effects of LL-37 are dependent upon its ability to increase mitochondrial biogenesis and to maintain mitochondrial homeostasis. Furthermore, we observed that LL-37 enhances the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and mammalian target of rapamycin (mTOR). The mTOR inhibitor rapamycin can neutralize the protective effects of LL-37 on mitochondria. In conclusion, these results suggest that high LL-37 expression levels correlate with chronic skin inflammation; mitochondrial dysfunction occurs in HaCaT cells during inflammation; and LL-37 attenuates inflammatory impairment by stimulating mitochondrial biogenesis and protecting mitochondrial function, which are dependent upon mTOR signaling. These findings provide new insights into targeting mitochondria with LL-37 to prevent skin inflammatory reactions.

Aims and Objectives: (i) To estimate the national incidence of unplanned removal of peripherally inserted central catheters (PICCs) in China. (ii) To explore the associated risk factors to provide evidence for the prevention. Design: A multi‐centre prospective cohort study. Methods: A representative sample of 3222 Chinese adult patients with successful PICC insertion was recruited for the PICC Safety Management Research (PATH) using a two‐stage cluster sampling method from December 2020 to June 2022. Sixty hospitals from seven Chinese provinces representing all geographical regions were selected. Demographic information and PICC characteristics were collected using a standard online case report form. Risk factors for the unplanned removal of PICCs were assessed using a cause‐specific hazard model and verified using a sub‐distribution hazard model. STROBE guidelines were followed in reporting this study. Results: Three thousand one hundred and sixty‐six patients were included in the final analysis with a mean age of 59 years and a total of 344,247 catheter days. The incidence of unplanned removal was 10.04%. Female, with thrombosis history, PICC insertion due to infusion failure, valved catheter and double‐lumen catheter were risk factors, whereas longer insertion and exposure length were protective factors in the cause‐specific hazard model. Higher BMI became an independent risk factor in the sub‐distribution hazard model. Conclusions: Unplanned removal of PICCs is a serious clinical challenge in China. Our findings call for prevention strategies targeting the identified risk factors. Relevance to Clinical Practice: Our study characterised the epidemiology of unplanned removal of PICCs among Chinese adult inpatients, highlighting the need for prevention among this population and providing a basis for the formulation of relevant prevention strategies. Patient or Public Contribution: Patients contributed through sharing their information required for the case report form. Healthcare professionals who provide direct care to the patient at each medical centre contributed by completing the online case report form. [ABSTRACT FROM AUTHOR]