Jia Zhou

Background: Gout is an inflammatory arthritis characterized by hyperuricemia in humans. Male patients with gout or hyperuricemia have a wide range of reproductive health challenges. However, research on the sexual and reproductive health of male patients with gout or hyperuricemia remains limited. Objective: This systematic review and meta-analysis investigated the impact of gout and/or hyperuricemia and its associated factors on male sexual and reproductive health. Methods: The PubMed, Cochrane, Embase, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant articles from January 2000 to October 2025. Two reviewers extracted the data and completed quality assessment using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist. Meta-analysis was conducted using Review Manager 5.4 and Stata 18.0. The protocol was registered on PROSPERO (CRD 420261302205). The outcomes such as sexual function, reproductive hormones, and fertility were evaluated. Results: In the literature search, 1,527 articles were retrieved. Among these, 11 studies met the inclusion criteria. This meta-analysis included 104,277 patients with gout or hyperuricemia and 342,621 control subjects. The meta-analysis results showed that the risk of erectile dysfunction was higher in patients with gout (RR = 1.37; 95% CI = 1.14 to 1.65, P < 0.001). Compared with the control group, patients with gout or hyperuricemia showed lower levels of testosterone and estradiol (testosterone: MD = −1.00, 95% CI = −1.39 to −0.62, P < 0.001; estradiol: MD = −4.67, 95% CI = −9.31 to −0.02, P = 0.05). A single study showed that semen volume and total sperm counts were lower among infertile men in the hyperuricemia group. Conclusion: Male patients with gout or hyperuricemia are more prone to erectile dysfunction and lower levels of reproductive hormones. Patients with gout showed significantly lower testosterone levels in the subgroup analyses. These findings emphasize the clinical need for increased awareness of male reproductive health problems in men with gout and implementation of effective intervention measures. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261302205.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease and increasing evidence suggests that disturbances in the composition and function of gut microbiota are potentially implicated in the progression of RA. Further revealing the microbiota and related metabolic disorders in the preclinical stage of RA (pre-RA) is of great significance for exploration of disease mechanisms. Methods: DBA/1 mice were injected with type II collagen on days 0 and 21 to establish collagen-induced arthritis (CIA) mouse model. Footpad thickness, serum autoantibodies, and joint histopathology were used to assess the progression of RA. A combination of 16S rRNA sequencing, untargeted metabolomics and targeted short-chain fatty acids (SCFAs) analysis were employed to comprehensively investigate the alterations of gut microbiota and fecal metabolites in CIA during the pre-RA stage. Results: 20 days after the initial collagen immunization, CIA mice showed immune responses without joint symptoms, alongside gut microbiota disruption. Alterations were observed in 20 microbial taxa, including Oscillospira, Bifidobacterium, Ruminococcus, Allobaculum, Alistipes, Lactobacillus, and Candidatus_Arthromitus, etc. Untargeted and targeted metabolomics identified 33 altered fecal metabolites, mainly including sugars and their derivatives, amino acids, long-chain fatty acids and SCFAs, etc. Correlation analysis showed significant correlations between specific gut microbial abundances and fecal metabolite levels. Especially, SCFAs were strongly associated with Bifidobacterium, Alistipes, Ruminococcus, Anaerotruncus, and Allobaculum. Conclusion: These findings suggest that collagen immunization leads to disruption of gut microbiome and induces changes of fecal metabolites in mice, which may play a key role in early development of RA in CIA mice.

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography–mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA.

Ankylosing spondylitis (AS) is a type of chronic rheumatic immune disease, and the crucial point of AS treatment is identifying the correct stage of the disease. However, there is a lack of effective diagnostic methods for AS staging. The primary objective of this study was to perform an untargeted metabolomic approach in AS patients in an effort to reveal metabolic differences between patients in remission and acute stages. Serum samples from 40 controls and 57 AS patients were analyzed via gas chromatography–mass spectrometry (GC–MS). Twenty-four kinds of differential metabolites were identified between the healthy controls and AS patients, mainly involving valine/leucine/isoleucine biosynthesis and degradation, phenylalanine/tyrosine/tryptophan biosynthesis, glutathione metabolism, etc. Furthermore, the levels of fatty acids (linoleate, dodecanoate, hexadecanoate, and octadecanoate), amino acids (serine and pyroglutamate), 2-hydroxybutanoate, glucose, etc., were lower in patients in the acute stage than those in the remission stage, which may be associated with the aggravated inflammatory response and elevated oxidative stress in the acute stage. Multiple stage-specific metabolites were significantly correlated with inflammatory indicators (CRP and ESR). In addition, the combination of serum 2-hydroxybutanoate and hexadecanoate plays a significant role in the diagnosis of AS stages. These metabolomics-based findings provide new perspectives for AS staging, treatment, and pathogenesis studies.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a remarkable predominance in female, suggesting that steroid hormones may be involved in the pathogenesis. However, steroid signature of SLE patients has not been fully explored.Methods: A metabolic profiling analysis based on gas chromatography/mass spectrometry (GC/MS) with high sensitivity and reproducibility was employed to comprehensively reveal SLE-specific steroid alterations.Results: More than 70 kinds of steroids in urine were detected by gas chromatography/mass spectrometry (GC/MS) to reveal SLE-specific steroid alterations. Principle component analysis demonstrated that the steroid profile was obviously distinguished between patients with SLE and controls. A lower level of total androgens was observed in patients, and nine androgens [dehydroepiandrosterone (DHEA), testosterone, Etio, androsterone, βαβ-Diol, Epi-An, Epi-DHT, 16α-OH-DHEA, and A-Diol] underwent significant decrease. Moreover, patients with SLE exhibited a slightly higher level of total estrogens than controls, and three estrogens (17-Epi-E3, 17α-E2, and E3) were remarkably increased. Furthermore, we identified the elevation of two sterols (Lan and Chol), and the reduction of one corticoid (11-DeoxyF) and two progestins (5α-DHP and 11β-OH-Prog) in patients.Discussion: In this study, metabolic signature of urinary steroids associated with SLE was comprehensively defined by GC/MS for the first time, and steroid metabolism disorders were found in patients with SLE, especially the conversion of androgens to estrogens. Our findings will provide new insights for a deeper understanding of the mechanism of steroid hormones in the pathogenesis of SLE and will help to unravel the reason of sexual disparity in SLE.

Objective: This study aims to evaluate pharmacological and behavioral interventions for the treatment of fatigue in Parkinson's disease (PD) patients. Methods: We systematically searched PubMed, PsycINFO, Web of Science, EMBASE, CNKI, Wan fang, and VIP up to July 31, 2022. We used Revman 5.3 software for the meta-analysis. The outcomes included Fatigue Severity Scale (FSS) and Parkinson's Fatigue Scale (PFS). The mean difference (MD) and 95% confidence intervals (CI) were collected or calculated. Results: Thirteen randomized controlled trials (RCTs) with a total of 1758 patients were included. The meta-analysis showed that current clinical treatments reduced FSS (MD: −1.60, 95% CI: −3.14 to −0.05) and PFS (MD: −0.61, 95% CI: −1.17 to −0.05) in patients with PD. Subgroup meta-analysis showed that: (1) neither pharmacological interventions nor behavioral interventions reduced FSS in PD patients; (2) dopaminergic drugs dose-dependently significantly reduced the PFS in patients with PD; (3) behavioral interventions have an almost significant effect (MD: −6.69, 95% CI: −13.71 to 0.33, P = 0.06, I² = 74%) on alleviating PFS in PD patients; (4) vestibular rehabilitation training significantly reduced the PFS in patients with PD. Conclusions: Current clinical treatments alleviate fatigue in PD patients. Dopaminergic drugs may act a stronger effect than amphetamines. Behavioral interventions, especially vestibular rehabilitation training, may be a promising way for the treatment of fatigue in patients with PD though further evidence is still needed.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and the dysregulation of lipid metabolism has been found to play an important role in the pathogenesis of RA and is related to the severity and prognosis of patients. Tripterygium wilfordii glycosides (TWG) is extracted from the roots of Tripterygium wilfordii Hook F. with anti-inflammatory and immunosuppressive effects, and numerous clinical trials have supported its efficacy in the treatment of RA. Some evidence suggested that TWG can modulate the formation of lipid mediators in various innate immune cells; however whether it can improve RA-related lipid disorders has not been systematically studied. In the study, type Ⅱ collagen-induced arthritis (CIA) model was used to investigate the efficacy of TWG in the treatment of RA and its effect on lipid metabolism. Paw volume, arthritis score, pathological changes of ankle joint, serum autoantibodies and inflammatory cytokines were detected to assess the therapeutic effect on arthritis in CIA rats. Then, shotgun lipidomics based on multi-dimensional mass spectrometry platform was performed to explore the alterations in serum lipidome caused by TWG. The study showed that TWG could effectively ameliorate arthritis in CIA rats, such as reducing paw volume and arthritis score, alleviating the pathological damages of joint, and preventing the production of anti-CII autoantibodies and IL-1β cytokine. Significant increase in ceramide and decrease in lysophosphatidylcholine were observed in CIA rats, and were highly correlated with arthritis score and IL-1β level. After TWG treatment, these lipid abnormalities can be corrected to a great extent. These data demonstrate that TWG exerts a beneficial therapeutic effect on aberrant lipid metabolism which may provide new insights for further exploring the role and mechanism of TWG in the treatment of RA.

Exploring the dynamic changes of metabolites and metabolic pathways during the development of the disease can help to further understand the etiology and pathogenesis of systemic lupus erythematosus (SLE). In this study, serum metabolomics based on gas chromatography/mass spectrometry (GC/MS) was employed to investigate the metabolic alterations at different stages of SLE using lupus-prone mice (MRL/lpr) of 9, 11, and 13 weeks of age. Multivariate statistical analysis was performed to view the alterations of metabolic profiles between MRL/lpr mice and age-matched C57BL/6 mice, and t-test and fold change criteria were used to identify differential metabolites at each stage. 11 changed metabolites were found in MRL/lpr mice at 9 weeks of age, which were mainly involved in the tricarboxylic acid (TCA) cycle, glycolysis, and butanoate metabolism; with the increase of week age, the TCA cycle was still disturbed, and the biosynthesis of fatty acids was significantly upregulated since 11 weeks of age; in addition, urea, urate, and indole-3-lactate were increased at 13 weeks of age. We found a time course of metabolic alterations in MRL/lpr mice, which may be related to the progression of SLE. These findings could provide a reference for studying the mechanism of SLE and judging the pathological stage and severity of the disease. The MS data have been deposited in Mendeley (https://www.mendeley.com/).

Objectives. Gout is a common type of inflammatory arthritis. The aim of this study was to detect urinary metabolic changes in gout patients which may contribute to understanding the pathological mechanism of gout and discovering potential metabolite markers. Methods. Urine samples from 35 gout patients and 29 healthy volunteers were analyzed by gas chromatography–mass spectrometry (GC–MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between two groups, and the variable importance for projection (VIP) values and Student’s t-test results were combined to define the significant metabolic changes caused by gout. Further, binary logistic regression analysis was performed to establish a model to distinguish gout patients from healthy people, and receiver operating characteristic (ROC) curve was made to evaluate the potential for diagnosis of gout. Result. A total of 30 characteristic metabolites were significantly different between gout patients and controls, mainly including amino acids, carbohydrates, organic acids, and their derivatives, associated with perturbations in purine nucleotide synthesis, amino acid metabolism, purine metabolism, lipid metabolism, carbohydrate metabolism, and tricarboxylic acid cycle. Binary logistic regression and ROC curve analysis showed the combination of urate and isoxanthopterin can effectively discriminate the gout patients from controls with the area under the curve (AUC) of 0.879. Conclusion. Thus, the urinary metabolomics study is an efficient tool for a better understanding of the metabolic changes of gout, which may support the clinical diagnosis and pathological mechanism study of gout.