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BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.
Subject(s)
Cause of Death , Gout , Hyperuricemia , Nutrition Surveys , Vitamin D , Humans , Gout/blood , Gout/mortality , Gout/complications , Hyperuricemia/blood , Hyperuricemia/mortality , Hyperuricemia/complications , Vitamin D/analogs & derivatives , Vitamin D/blood , Male , Female , Middle Aged , Nutrition Surveys/statistics & numerical data , Adult , Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Neoplasms/mortality , Neoplasms/blood , Neoplasms/complications , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/mortality , Proportional Hazards ModelsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Qinghao-Biejia herb pair (QB) is the core herb pair of "Jieduquyuziyin prescription" and is one of the commonly used herb pairs for the clinical treatment of systemic lupus erythematosus (SLE). Previous studies have shown that QB reduces the expression of inflammatory cytokines like IL-6 and TNF-α in the serum and kidney of MRL/lpr mice. Additionally, it inhibits the expression of TLR4 and MyD88 in the kidney and aorta and reduces the deposition of renal complement C3 and aortic plaque after treatment. These findings suggest that QB has a preventive and therapeutic effect on lupus rats. AIM OF THE STUDY: This study sought to investigate the mechanisms underlying the anti-SLE combined with atherosclerosis activity of the Qinghao-Biejia herb pair. MATERIALS AND METHODS: Drug targets for QB were identified using the HERB database, while targets associated with SLE and atherosclerosis were retrieved from the GeneCards database. The intersection of these drug and disease targets was then analyzed using a protein-protein interaction (PPI) network with GO and KEGG pathway enrichment analysis. In vivo, apolipoprotein E-deficient (ApoE-/-) mice were induced to develop SLE-AS by intraperitoneal injection of pristane and continued feeding of a high-fat diet. The changes in relevant indexes were observed after 12 weeks of gavage treatment with hydroxychloroquine, QB, Q (Qinghao alone), and B (Biejia alone). Bone marrow-derived macrophages from ApoE-/- mice and Raw 264.7 macrophages were used to explore the mechanisms of QB treatment. RESULTS: The levels of inflammatory cytokines in serum and pathological liver changes in mice were improved to varying degrees in the treatment groups. Additionally, there was a reduction in aortic atheromatous plaque formation and some improvement in cholesterol efflux. Furthermore, QB suppressed the expression of inflammatory cytokines in M1 macrophages, suggesting a role in regulating macrophage polarization. CONCLUSION: QB demonstrates clear efficacy for treating SLE-AS, and its therapeutic mechanism may involve the regulation of macrophage phenotypes by promoting cholesterol efflux.
Subject(s)
ATP Binding Cassette Transporter 1 , Atherosclerosis , Cholesterol , Drugs, Chinese Herbal , Lupus Erythematosus, Systemic , Macrophages , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Atherosclerosis/drug therapy , Mice , Lupus Erythematosus, Systemic/drug therapy , Macrophages/drug effects , Macrophages/metabolism , ATP Binding Cassette Transporter 1/metabolism , Cholesterol/blood , Cholesterol/metabolism , RAW 264.7 Cells , Mice, Inbred C57BL , Female , Mice, Inbred MRL lpr , Mice, Knockout, ApoEABSTRACT
Dietary strategies rich in fiber have been demonstrated to offer benefits to individuals afflicted with rheumatoid arthritis (RA). However, the specific mechanisms through which a high-fiber diet (HFD) mitigates RA's autoimmunity remain elusive. Herein, we investigate the influence of pectin- and inulin-rich HFD on collagen-induced arthritis (CIA). We establish that HFD significantly alleviates arthritis in CIA mice by regulating the Th17/Treg balance. The rectification of aberrant T cell differentiation by the HFD is linked to the modulation of gut microbiota, augmenting the abundance of butyrate in feces. Concurrently, adding butyrate to the drinking water mirrors the HFD's impact on ameliorating CIA, encompassing arthritis mitigation, regulating intestinal barrier integrity, and restoring the Th17/Treg equilibrium. Butyrate reshapes the metabolic profile of CD4+ T cells in an AMPK-dependent manner. Our research underscores the importance of dietary interventions in rectifying gut microbiota for RA management and offers an explanation of how diet-derived microbial metabolites influence RA's immune-inflammatory-reaction.
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Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective cohort analysis and animal experiments to investigate Se deficiency as a potential risk factor for IBS. Using data from the UK Biobank, a longitudinal analysis was conducted to explore the associations between dietary Se intake and the risk of incident IBS. In animal study, C57BL/6 mice were fed diets with normal (0.2â¯ppm) or low (0.02â¯ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16â¯S rRNA sequencing, untargeted colonic fecal metabolomics analysis, and colon transcriptome profiling to uncover the regulatory mechanisms underlying Se deficiency-induced IBS. The analysis of UK Biobank data revealed a significant correlation between low dietary Se levels and an increased incidence of IBS. In the experimental study, a low Se diet induced IBS symptoms, evidenced by elevated abdominal withdrawal reflex scores, colon inflammation, and severe pathological damage to the colon. Additionally, the low Se diet caused disturbances in gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter, and a decrease in Bifidobacterium and Akkermansia. Combined colonic fecal metabolomics and colon transcriptome analysis indicated that Se deficiency might trigger IBS through disruptions in pathways related to "bile excretion", "steroid hormone biosynthesis", "arachidonic acid metabolism", and "drug metabolism-cytochrome P450". These findings underscore the significant adverse effects of Se deficiency on IBS and suggest that Se supplementation should be considered for IBS patients.
Subject(s)
Gastrointestinal Microbiome , Irritable Bowel Syndrome , Mice, Inbred C57BL , Selenium , Animals , Selenium/deficiency , Gastrointestinal Microbiome/drug effects , Mice , United Kingdom , Feces/chemistry , Male , Humans , Biological Specimen Banks , Female , Colon/drug effects , Colon/pathology , Diet , Middle Aged , Prospective Studies , UK BiobankABSTRACT
OBJECTIVE: Although previous studies have explored the association of drinking with gout risk, we sought to explore the dose-response relationship and the evidence between subtypes of alcoholic beverages and gout risk. METHODS: The weekly alcoholic beverage consumption of patients in the UK Biobank was collected and calculated. The Cox regression model was applied to assess the effects of drinking alcohol in general and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% CIs. Additionally, the restricted cubic splines were used to estimate the dose-response relationship between alcohol consumption and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics. RESULTS: During a mean follow-up period of 11.7 years, a total of 5728 new incident gout cases were diagnosed among 331,865 participants. We found that light alcohol consumption was linked to a slight decrease in gout incidence among female individuals (HR 0.78, 95% CI 0.65-0.94, P = 0.01), whereas there was no significant association in male individuals. Moreover, the dose-response relationship showed that drinking light red wine and fortified wine could reduce the gout risk, whereas beer or cider, champagne or white wine, and spirits increased the gout risk at any dose. CONCLUSION: Our study suggested a J-shaped dose-response relationship between drinking and gout risk in female individuals, but not in male individuals. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout incidence risk, although further validation is warranted.
Subject(s)
Alcohol Drinking , Alcoholic Beverages , Gout , Humans , Gout/epidemiology , Gout/etiology , Male , Female , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Middle Aged , Alcoholic Beverages/adverse effects , Incidence , Adult , Aged , United Kingdom/epidemiology , Risk Factors , Dose-Response Relationship, Drug , Proportional Hazards ModelsABSTRACT
BACKGROUND: Despite substantial research revealing that patients with rheumatoid arthritis (RA) have excessive morbidity and mortality of cardiovascular disease (CVD), the mechanism underlying this association has not been fully known. This study aims to systematically investigate the phenotypic and genetic correlation between RA and CVD. METHODS: Based on UK Biobank, we conducted two cohort studies to evaluate the phenotypic relationships between RA and CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), and stroke. Next, we used linkage disequilibrium score regression, Local Analysis of [co]Variant Association, and bivariate causal mixture model (MiXeR) methods to examine the genetic correlation and polygenic overlap between RA and CVD, using genome-wide association summary statistics. Furthermore, we explored specific shared genetic loci by conjunctional false discovery rate analysis and association analysis based on subsets. RESULTS: Compared with the general population, RA patients showed a higher incidence of CVD (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.15-1.28). We observed positive genetic correlations of RA with AF and stroke, and a mixture of negative and positive local genetic correlations underlying the global genetic correlation for CAD and HF, with 13 ~ 33% of shared genetic variants for these trait pairs. We further identified 23 pleiotropic loci associated with RA and at least one CVD, including one novel locus (rs7098414, TSPAN14, 10q23.1). Genes mapped to these shared loci were enriched in immune and inflammatory-related pathways, and modifiable risk factors, such as high diastolic blood pressure. CONCLUSIONS: This study revealed the shared genetic architecture of RA and CVD, which may facilitate drug target identification and improved clinical management.
Subject(s)
Arthritis, Rheumatoid , Cardiovascular Diseases , Coronary Artery Disease , Heart Failure , Stroke , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Genome-Wide Association Study/methods , Genetic Predisposition to Disease/genetics , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/epidemiology , Coronary Artery Disease/genetics , Stroke/epidemiology , Stroke/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: Limited research has been conducted on the association between long-term exposure to air pollutants and the incidence of gout. OBJECTIVES: This study aims to assess the individual and combined effects of prolonged exposure to five air pollutants (NO2, NOx, PM10, PMcoarse and PM2.52) on the incidence of gout among 458,884 initially gout-free participants enrolled in the UK Biobank. METHODS: Employing a land use regression model, we utilized an estimation method to ascertain the annual concentrations of the five air pollutants. Subsequently, we devised a weighted air pollution score to facilitate a comprehensive evaluation of exposure. The Cox proportional hazards model was utilized to investigate the association between ambient air pollution and gout risk. Interaction and stratification analyses were conducted to evaluate age, sex, BMI, and genetic predisposition as potential effect modifiers in the air pollution-gout relationship. Furthermore, mediation analyses were conducted to explore the potential involvement of biomarkers in mediating the association between air pollution and gout. RESULTS: Over a median follow-up time of 12.0 years, 7,927 cases of gout were diagnosed. Significant associations were observed between the risk of gout and a per IQR increase in NO2 (HR3: 1.05, 95 % CI4: 1.02-1.08, p = 0.003), NOx (HR: 1.04, 95 % CI: 1.01-1.06, p = 0.003), and PM2.5 (HR: 1.03, 95 % CI: 1.00-1.06, p = 0.030). Per IQR increase in the air pollution score was associated with an elevated risk of gout (p = 0.005). Stratified analysis revealed a significant correlation between the air pollution score and gout risk in participants ≥60 years (HR: 1.05, 95 % CI: 1.02-1.09, p = 0.005), but not in those <60 years (p = 0.793), indicating a significant interaction effect with age (p-interaction=0.009). Mediation analyses identified five serum biomarkers (SUA:15.87 %, VITD: 5.04 %, LDLD: 3.34 %, GGT: 1.90 %, AST: 1.56 %5) with potential mediation effects on this association. CONCLUSIONS: Long-term exposure to air pollutants, particularly among the elderly population, is associated with an increased risk of gout. The underlying mechanisms of these associations may involve the participation of five serum biomarkers.
Subject(s)
Air Pollutants , Air Pollution , Gout , Adult , Aged , Female , Humans , Male , Middle Aged , Air Pollutants/adverse effects , Air Pollution/adverse effects , Environmental Exposure/adverse effects , Genetic Predisposition to Disease , Gout/epidemiology , Gout/genetics , Incidence , Particulate Matter/adverse effects , Prospective Studies , Risk Factors , UK Biobank , United Kingdom/epidemiologyABSTRACT
Object: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant activity of the immune system. Plasmacytoid dendritic cells (pDCs) which the main producer of activated type I interferon, are related to SLE disease activity. To investigate the mechanism of Langchuangding (LCD) improving SLE based on TLR7-IRF7-IFNα pathway. Methods: SLE patients were randomly divided into Chinese medicine combined with western medicine (CWM) group and western medicine (WM) group, to observe the effect of LCD. The percent of pDCs in peripheral blood of SLE patients were detected by flow cytometry, and the influence of LCD on gene expression in SLE patients were detected by gene microarray. Mouse bone marrow cells were differentiated into dendritic like cells (DLC), then divided into Blank, immune complex (IC), LCD and dexamethasone (DXM) group. Employed RT-qPCR to detect MyD88, and IRF7 mRNA, and western blotting to determinate TLR7, MyD88, and p-IRF7 proteins. The IFNα in SLE patients were detected by enzyme-linked immunosorbent assay (ELISA). Employ dual luciferase to observe the interferon stimulated response element (ISRE) gene. Results: pDCs in WM group was higher than that of CWM group. The plasma IFNα in CWM group was significantly lower than that in WM group. The gene microarray showed that the gene expression of IFNα related signaling pathway in peripheral blood mononuclear cell (PBMC) and genes related to activation and proliferation of immune cells were down-regulated after LCD treatment. The DLCs MyD88, and IRF7 mRNA were down-regulated, TLR7, MyD88, and p-IRF7 proteins were significantly reduced, and the supernatant IFNα was significantly decreased in LCD group. LCD were mildly inhibited activation of ISRE in 293T cells. Conclusions: In certain degree, LCD is beneficial to SLE patients. LCD therapy SLE may be through TLR7 signaling pathway, and IRF7 may be a promising therapeutic target for the treatment of SLE.
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OBJECTIVE: This meta-analysis aims to explore the potential link between vaccines and systemic lupus erythematosus (SLE). METHODS: We systematically searched PubMed, Cochrane Library, and Embase for observational studies from inception to September 3, 2023, using medical subject headings (MeSH) and keywords. Study quality was assessed using the NOS scale. Statistical analyses were conducted using STATA software (version 14.0). Publication bias was evaluated using funnel plots and Egger's regression. RESULTS: The meta-analysis incorporated 17 studies, encompassing 45,067,349 individuals with follow-up periods ranging from 0.5 to 2 years. The pooled analysis revealed no significant association between vaccinations and an increased risk of SLE [OR = 1.14, 95% CI (0.86-1.52), I2 = 78.1%, P = 0.348]. Subgroup analyses indicated that HBV vaccination was significantly associated with an elevated risk of SLE [OR =2.11, 95% CI (1.11-4.00), I2 = 63.3%, P = 0.02], HPV vaccination was slightly associated with an increased risk of SLE [OR = 1.43, 95% CI (0.88-2.31), I2 = 72.4%, P = 0.148], influenza vaccination showed no association with an increased risk of SLE [OR = 0.96, 95% CI (0.82-1.12), I2 = 0.0%, P = 0.559], and COVID-19 vaccine was marginally associated with a decreased risk of SLE [OR = 0.44, 95% CI (0.18-1.21), I2 = 91.3%, P = 0.118]. CONCLUSIONS: This study suggests that vaccinations are not linked to an increased risk of SLE. Our meta-analysis results provide valuable insights, alleviating concerns about SLE risk post-vaccination and supporting further vaccine development efforts.
Subject(s)
Lupus Erythematosus, Systemic , Vaccination , Humans , COVID-19 Vaccines , Lupus Erythematosus, Systemic/epidemiology , Vaccination/adverse effects , Influenza Vaccines , Observational Studies as TopicABSTRACT
Objective: Obesity has become a global health issue and a risk factor for hyperuricemia. However, the associations between obesity and hyperuricemia are sometimes confounding. In the present study, we performed mendelian randomization (MR) analysis to study their relationship and investigate the underlying mechanism by network pharmacology. Method: Body mass index (BMI) and uric acid related to single nucleotide polymorphism were selected as instrumental variables for MR analysis. Three robust analytical methods are used for bidirectional MR analysis such as inverse-variance weighting, weighted median and MR-Egger regression. Then, we further performed sensitivity analysis to evaluate the horizontal pleiotropy, heterogeneities, and stability. The targets related to obesity and hyperuricemia were collected, screened and further conducted for Kyoto Encyclopedia of Genes and Genomes pathway enrichment to explore the mechanism of obesity and hyperuricemia using network pharmacology. Results: The positive causality was indicated between BMI and hyperuricemia based on inverse variance-weighted analysis [odds ratio:1.23, 95% confidence interval: 1.11 to 1.30 for each standard deviation increase in BMI (4.6 kg/m2)]. Conversely, hyperuricemia did not influence BMI. 235 intersected targets from obesity and hyperuricemia were collected. Insulin resistance were the top 1 key target. The mechanism between obesity and hyperuricemia are associated with important pathways including adipocytokine signaling pathway, insulin resistance and cholesterol metabolism et al. Conclusions: Our MR analysis supported the causal association between obesity and hyperuricemia based on availablegenome-wide association analysis summary statistics. Obesity leads to hyperuricemia via insulin resistance, which is a key link in the huge network pathways using network pharmacology.
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BACKGROUD: Quantitative and standardized research on syndrome differentiation has always been at the forefront of modernizing Traditional Chinese Medicine (TCM) theory. However, the majority of existing databases primarily concentrate on the network pharmacology of herbal prescriptions, and there are limited databases specifically dedicated to TCM syndrome differentiation. PURPOSE: In response to this gap, we have developed the Traditional Chinese Medical Syndrome Standardization Database (TCMSSD, http://tcmssd.ratcm.cn). METHODS: TCMSSD is a comprehensive database that gathers data from various sources, including TCM literature such as TCM Syndrome Studies (Zhong Yi Zheng Hou Xue) and TCM Internal Medicine (Zhong Yi Nei Ke Xue) and various public databases such as TCMID and ETCM. In our study, we employ a deep learning approach to construct the knowledge graph and utilize the BM25 algorithm for syndrome prediction. RESULTS: The TCMSSD integrates the essence of TCM with the modern medical system, providing a comprehensive collection of information related to TCM. It includes 624 syndromes, 133,518 prescriptions, 8,073 diseases (including 1,843 TCM-specific diseases), 8,259 Chinese herbal medicines, 43,413 ingredients, 17,602 targets, and 8,182 drugs. By analyzing input data and comparing it with the patterns and characteristics recorded in the database, the syndrome prediction tool generates predictions based on established correlations and patterns. CONCLUSION: The TCMSSD fills the gap in existing databases by providing a comprehensive resource for quantitative and standardized research on TCM syndrome differentiation and laid the foundation for research on the biological basis of syndromes.
Subject(s)
Databases, Factual , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Medicine, Chinese Traditional/standards , Medicine, Chinese Traditional/methods , Drugs, Chinese Herbal/standards , Humans , Algorithms , SyndromeABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17. In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.
Subject(s)
Lupus Nephritis , Mice, Inbred MRL lpr , NF-kappa B , Oxidative Stress , PPAR gamma , Rutin , T-Lymphocytes , Rutin/pharmacology , Rutin/therapeutic use , Animals , PPAR gamma/metabolism , Oxidative Stress/drug effects , Lupus Nephritis/drug therapy , Lupus Nephritis/metabolism , Lupus Nephritis/pathology , Mice , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , NF-kappa B/metabolism , Female , STAT3 Transcription Factor/metabolism , Cytokines/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Antioxidants/pharmacologyABSTRACT
Background: Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases. Methods: Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad. Results: A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS' analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent. Conclusion: Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.
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OBJECTIVES: The aim of this study is to identify available reporting guidelines for traditional Chinese medicine (TCM), delineate their fundamental characteristics, assess the scientific rigor of their development process, and evaluate their dissemination. STUDY DESIGN AND SETTING: A search was conducted in Medline (via PubMed), China National Knowledge Infrastructure (CNKI), SinoMed, WANFANG DATA, and the EQUATOR Network to identify TCM reporting guidelines. A preprepared Excel database was used to extract information on the basic characteristics, development process, and dissemination information. The development process quality of TCM reporting guidelines was assessed by evaluating their compliance with the Guidance for Developers of Health Research Reporting Guidelines (GDHRRG). The extent of dissemination of these guidelines was analyzed by examining the number of citations received. RESULTS: A total of 26 reporting guidelines for TCM were obtained from 20 academic journals, with 61.5% of them published in English journals. Among the guidelines, 14 (53.8%) were registered in the EQUATOR Network. On average, the compliance rate of GDHRRG guidelines was reported to be 63.3% ranging from 22.2% to 94.4%. Three steps showed poor compliance, namely guideline endorsement (23.1%), translated guidelines (19.2%), and developing a publication strategy (19.2%). Furthermore, the compliance rate of GDHRRG guidelines published in English journals was higher than that in Chinese journals. In terms of the dissemination, 15.4% of the guidelines had been cited over 100 times, while 73.1% had been cited less than 50 times. CONCLUSION: The development of TCM reporting guidelines still has limitations in terms of regarding scientific rigor and follow-up dissemination. Therefore, it is important to ensure adherence to the scientific process in the development of TCM reporting guidelines and to strengthen their promotion, dissemination, and implementation.
Subject(s)
Medicine, Chinese Traditional , Research Report , Humans , Cross-Sectional Studies , China , PubMedABSTRACT
BACKGROUND: Systemic immune-inflammation index (SII) is a new indicator of inflammation, and chronic kidney disease (CKD) has a connection to inflammation. However, the relationship between SII and CKD is still unsure. The aim of this study was whether there is an association between SII and CKD in the adult US population. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018, and multivariate logistic regression was used to explore the independent linear association between SII and CKD. Smoothing curves and threshold effect analyses were utilized to describe the nonlinear association between SII and CKD. RESULTS: The analysis comprised 40,660 adults in total. After adjusting for a number of factors, we found a positive association between SII and CKD [1.06 (1.04, 1.07)]. In subgroup analysis and interaction tests, this positive correlation showed differences in the age, hypertension, and diabetes strata (p for interaction<0.05), but remained constant in the sex, BMI, abdominal obesity, smoking, and alcohol consumption strata. Smoothing curve fitting revealed a non-linear positive correlation between SII and CKD. Threshold analysis revealed a saturation effect of SII at the inflection point of 2100 (1,000 cells/µl). When SII < 2100 (1,000 cells/µl), SII was an independent risk element for CKD. CONCLUSIONS: In the adult US population, our study found a positive association between SII and CKD (inflection point: 2100). The SII can be considered a positive indicator to identify CKD promptly and guide therapy.
Subject(s)
Renal Insufficiency, Chronic , Research , Adult , Humans , Nutrition Surveys , Alcohol Drinking , Inflammation , Renal Insufficiency, Chronic/epidemiologyABSTRACT
OBJECTIVE: To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA). METHODS: A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA. RESULTS: During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect. CONCLUSION: These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.
Subject(s)
Arthritis, Rheumatoid , Hyperglycemia , Metabolic Syndrome , Humans , Metabolic Syndrome/epidemiology , Metabolic Syndrome/complications , Prospective Studies , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/complications , Hyperglycemia/complications , Waist Circumference , Risk FactorsABSTRACT
Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.
Subject(s)
Lupus Erythematosus, Systemic , Humans , Mice , Animals , Ubiquitination , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/genetics , Protein Processing, Post-Translational , T-Lymphocytes , HomeostasisABSTRACT
Neurological manifestations of coronavirus disease 2019 (COVID-19) are less noticeable than the respiratory symptoms, but they may be associated with disability and mortality in COVID-19. Even though Omicron caused less severe disease than Delta, the incidence of neurological manifestations is similar. More than 30% of patients experienced "brain fog", delirium, stroke, and cognitive impairment, and over half of these patients presented abnormal neuroimaging outcomes. In this review, we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection. We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion. In addition, we discuss direct damage and other pathological conditions caused by SARS-CoV-2, such as an aberrant interferon response, cytokine storm, lymphopenia, and hypercoagulation, to provide treatment ideas. This review may offer new insights into preventing or treating brain damage in COVID-19.
Subject(s)
COVID-19 , Stroke , Humans , COVID-19/complications , COVID-19/metabolism , SARS-CoV-2 , Stroke/metabolism , Brain/diagnostic imaging , Brain/metabolismABSTRACT
Existing reporting checklists lack the necessary level of detail and comprehensiveness to be used in guidelines on Chinese patent medicines (CPM). This study aims to develop a reporting guidance for CPM guidelines based on the Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement. We extracted information from CPM guidelines, existing reporting standards for traditional Chinese medicine (TCM), and the RIGHT statement and its extensions to form the initial pool of reporting items for CPM guidelines. Seventeen experts from diverse disciplines participated in two rounds of Delphi process to refine and clarify the items. Finally, 18 authoritative consultants in the field of TCM and reporting guidelines reviewed and approved the RIGHT for CPM checklist. We added 16 new items and modified two items of the original RIGHT statement to form the RIGHT for CPM checklist, which contains 51 items grouped into seven sections and 23 topics. The new and revised items are distributed across four sections (Basic information, Background, Evidence, and Recommendations) and seven topics: title/subtitle (one new and one revised item), Registration information (one new item), Brief description of the health problem (four new items), Guideline development groups (one revised item), Health care questions (two new items), Recommendations (two new items), and Rationale/explanation for recommendations (six new items). The RIGHT for CPM checklist is committed to providing users with guidance for detailed, comprehensive and transparent reporting, and help practitioners better understand and implement CPM guidelines.
Subject(s)
Checklist , Medicine, Chinese TraditionalABSTRACT
OBJECTIVE: This study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. METHODS: MRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. RESULTS: TaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. CONCLUSION: This study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.