Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants.

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.

Dose-Response Relationship Between Alcohol Consumption and Gout Risk: Do Subtypes of Alcoholic Beverages Make a Difference?

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.

Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia.

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.

Selenium deficiency induces irritable bowel syndrome: Analysis of UK Biobank data and experimental studies in mice.

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 (0.2 ppm) or low (0.02 ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16 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.

Assessing the relationship between gut microbiota and irritable bowel syndrome: a two-sample Mendelian randomization analysis.

BACKGROUND: Growing evidence has suggested that gut microbiota is closely related to the risk of irritable bowel syndrome (IBS), but whether there is a causal effect remains unknown. We adopted a Mendelian randomization (MR) approach to evaluate the potential causal relationships between gut microbiota and the risk of IBS. METHODS: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics of IBS were drawn from a GWAS including 53,400 cases and 433,201 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Finally, reverse MR analysis was performed to evaluate the possibility of reverse causation. RESULTS: We identified suggestive associations between three bacterial traits and the risk of IBS (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.02, 1.15; p = 0.011 for phylum Actinobacteria; OR: 0.95; 95% CI: 0.91, 1.00; p = 0.030 for genus Eisenbergiella and OR: 1.10; 95% CI: 1.03, 1.18; p = 0.005 for genus Flavonifractor). The results of sensitivity analyses for these bacterial traits were consistent. We did not find statistically significant associations between IBS and these three bacterial traits in the reverse MR analysis. CONCLUSIONS: Our systematic analyses provide evidence to support a potential causal relationship between several gut microbiota taxa and the risk of IBS. More studies are required to show how the gut microbiota affects the development of IBS.

Norcantharidin ameliorates the development of murine lupus via inhibiting the generation of IL-17 producing cells.

Systemic lupus erythematosus (SLE) is a devastating autoimmune disorder associated with severe organ damage. The abnormality of T cell apoptosis is considered as an important pathogenetic mechanism of SLE. Norcantharidin (NCTD), a derivative of Cantharidin, is an efficacious anti-cancer drug by inhibiting cell proliferation and inducing cell apoptosis. Besides, NCTD has also been proved to protect the function of kidneys, while damaged renal function is the most important predictor of morbidity and mortality in SLE. All these suggest the potential effects of NCTD in SLE treatment. In this study we investigated whether NCTD exerted therapeutic effects in a mouse SLE model. Lupus prone female MRL/lpr mice were treated with NCTD (1, 2 mg·kg-1·d-1, ip) for 8 weeks. We showed that NCTD administration significantly decreased mortality rate, diminished the expression of anti-dsDNA IgG antibody, a diagnostic marker for SLE, as well as restored renal structure and function in MRL/lpr mice. Moreover, NCTD administration dose-dependently inhibited lymphoproliferation and T cell accumulation in the spleens of MRL/lpr mice. We further revealed that NCTD specifically inhibited DN T cell proliferation and Th17 cell differentiation both via blocking activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. On the other hand, NCTD did not affect T cell apoptosis in MRL/lpr mice. Taken together, our data suggest that NCTD may be as a promising therapeutic drug through targeting T cells for the treatment of SLE.

Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice.

Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations of Alistipes, Prevotella, and Ruminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation of Akkermansia and Parabacteroides caused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression of Hspa1a and Hspa1b in the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite.

Genetically Predicted Serum Iron Status Is Associated with Altered Risk of Systemic Lupus Erythematosus among European Populations.

BACKGROUND: Observational epidemiological studies have reported an inconsistent relation between iron status and risk of systemic lupus erythematosus (SLE). Moreover, it remains uncertain whether the observed association is causal or due to confounding or reverse causality. OBJECTIVES: We aimed to investigate the association between serum iron status and risk of SLE using a 2-sample Mendelian randomization (MR) approach. METHODS: Genetic instruments for iron status including serum iron, log-transformed ferritin, transferrin saturation, and transferrin were identified from a large-scale genome-wide association study (GWAS) performed by the Genetics of Iron Status Consortium among 48,972 individuals of European ancestry (55% female). Three independent single nucleotide polymorphisms (rs1800562, rs1799945, and rs855791) concordantly related with 4 iron status biomarkers were selected as instrumental variables. Summary statistics of SLE were obtained from a publicly available GWAS of 4036 patients with SLE and 6959 controls of European descent. The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with MR-Egger regression and simple- and weighted-median methods. Leave-one-out analysis was further performed to test the robustness of our findings. ORs with 95% CIs were calculated. RESULTS: Genetically predicted iron status was associated with altered risk of SLE, with ORs of 0.79 (95% CI: 0.66, 0.94), 0.54 (95% CI: 0.34, 0.85), 0.82 (95% CI: 0.71, 0.94), and 1.36 (95% CI: 1.06, 1.76) per 1-SD increase in iron, log-transformed ferritin, transferrin saturation, and transferrin using the IVW method, respectively. MR-Egger regression did not indicate potential pleiotropic bias. Sensitivity analyses produced similar findings, suggesting the robustness of the association. CONCLUSIONS: Our study suggested that high iron status may be associated with a reduced risk of SLE among European populations. Further studies are warranted to elucidate the mechanism underlying the protective role of iron against susceptibility to SLE.

Association of telomere length with risk of rheumatoid arthritis: a meta-analysis and Mendelian randomization.

OBJECTIVE: To evaluate the telomere length (TL) in patients with RA relative to that in controls and to test whether TL is causally associated with risk of RA. METHODS: Systematic review and meta-analysis of relevant literature was conducted to evaluate the association between TL and RA. Standardized mean differences with 95% CIs of TL in RA patients relative to controls were pooled using fixed or random-effects models. TL-related single-nucleotide polymorphisms were selected from a genome-wide association study of 37 684 individuals, and summary statistics of RA were obtained from a genome-wide association study meta-analysis including 14 361 RA patients and 43 923 controls. Mendelian randomization was performed using the inverse-variance weighted, weighted-median and likelihood-based methods. Sensitivity analyses were performed to test the robustness of the association. RESULTS: In the meta-analysis of 911 RA patients and 2498 controls, we found that patients with RA had a significantly shorter TL compared with controls (standardized mean differences = -0.50; 95% CI -0.88, -0.11; P = 0.012). In the Mendelian randomization analysis, we found that genetically predicted longer TL was associated with a reduced risk of RA [odds ratio = 0.68; 95% CI 0.54, 0.86; P = 0.002 using the inverse-variance weighted method]. Sensitivity analyses using alternative Mendelian randomization approaches yielded similar findings, suggesting the robustness of the causal association. CONCLUSION: Our study provides evidence for a negative causal association of TL with risk of RA. Further studies are warranted to elucidate the underlying mechanism for the role of telomeres in the development of RA.

Dynamic metabolic and transcriptional profiling of Rhodococcus sp. strain YYL during the degradation of tetrahydrofuran.

Although tetrahydrofuran-degrading Rhodococcus sp. strain YYL possesses tetrahydrofuran (THF) degradation genes similar to those of other tetrahydrofuran-degrading bacteria, a much higher degradation efficiency has been observed in strain YYL. In this study, nuclear magnetic resonance (NMR)-based metabolomics analyses were performed to explore the metabolic profiling response of strain YYL to exposure to THF. Exposure to THF slightly influenced the metabolome of strain YYL when yeast extract was present in the medium. The metabolic profile of strain YYL over time was also investigated using THF as the sole carbon source to identify the metabolites associated with high-efficiency THF degradation. Lactate, alanine, glutarate, glutamate, glutamine, succinate, lysine, trehalose, trimethylamine-N-oxide (TMAO), NAD(+), and CTP were significantly altered over time in strain YYL grown in 20 mM THF. Real-time quantitative PCR (RT-qPCR) revealed changes in the transcriptional expression levels of 15 genes involved in THF degradation, suggesting that strain YYL could accumulate several disturbances in osmoregulation (trehalose, glutamate, glutamine, etc.), with reduced glycolysis levels, an accelerated tricarboxylic acid cycle, and enhanced protein synthesis. The findings obtained through (1)H NMR metabolomics analyses and the transcriptional expression of the corresponding genes are complementary for exploring the dynamic metabolic profile in organisms.

Association between combined exposure to ambient air pollutants, genetic risk, and incident gout risk: A prospective cohort study in the UK Biobank.

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.

Associations of modifiable factors with risk of irritable bowel syndrome.

Background: Modifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS. Methods: Summary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations. Results: Seven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, p = 1.03 × 10-4), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, p = 3.49 × 10-6), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, p = 4.02 × 10-4), chronotype (OR = 0.92, 95% CI = 0.88-0.96, p = 4.42 × 10-4), insomnia (OR = 1.19, 95% CI = 1.15-1.24, p = 7.59 × 10-19), education (OR = 0.80, 95% CI = 0.74-0.88, p = 5.34 × 10-7), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, p = 7.96 × 10-4). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype. Conclusion: This MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors.

Sleep pattern, genetic risk, and the risk of incident rheumatoid arthritis: A cohort study.

OBJECTIVE: To investigate the associations of sleep behaviors with the risk of rheumatoid arthritis, and whether the associations differ among individuals with low, intermediate, or high genetic risk. METHODS: We included participants who were free of rheumatoid arthritis at baseline based the UK Biobank. We evaluated the associations of five sleep behaviors with the risk of rheumatoid arthritis using Cox proportional hazard regression models. We then generated a sleep risk score which combined five sleep behaviors and assessed its association with the risk of rheumatoid arthritis. We finally generated a genetic risk score and examined the joint effects of sleep patterns and genetic susceptibility on the risk of rheumatoid arthritis. RESULTS: Of the 375,133 participants at baseline, 4913 incident rheumatoid arthritis cases were identified over a median follow-up of 11.73years. We found that insomnia and daytime sleepiness were associated with a 33% and a 38% increased risk of rheumatoid arthritis. A U-shaped association was observed between sleep duration and the risk of rheumatoid arthritis, with a 29% higher risk for those with short sleep and a 30% higher risk for those with long sleep. Participants with unfavorable sleep patterns had a 63% increased risk of rheumatoid arthritis compared with those with favorable sleep patterns. Participants with unfavorable sleep patterns and high genetic risk showed the highest risk of rheumatoid arthritis although no statistically significant multiplicative or additive interaction was found. CONCLUSIONS: Our study suggested that insomnia, daytime sleepiness, and short or long sleep duration, as well as sleep risk score were associated with an increased risk of rheumatoid arthritis.

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.

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.

TCMSSD: A comprehensive database focused on syndrome standardization.

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.

Gut microbiota mediated the therapeutic efficiency of Simiao decoction in the treatment of gout arthritis mice.

BACKGROUND: Gut microbiota plays a significant role in the development and treatment of gouty arthritis. Simiao decoction has been shown to alleviate gouty arthritis by inhibiting inflammation, regulating NLRP3 inflammasome, and altering gut microbiota. However, there is no evidence to prove whether gut microbiota directly mediates the therapeutic efficiency of Simiao decoction in treating gout arthritis. METHODS: In this study, fecal microbiota transplantation (FMT) was used to transfer the gut microbiota of gout arthritis mice treated with Simiao decoction or allopurinol to blank gout arthritis mice, in order to investigate whether FMT had therapeutic effects on gout arthritis. RESULTS: Both Simiao decoction and allopurinol effectively reduced the levels of serum uric acid, liver XOD activity, foot thickness, serum IL-1ß, and G-CSF in gout arthritis mice. However, Simiao decoction also had additional benefits, including raising the pain threshold, reducing serum TNF-α and IL-6, alleviating gut inflammation, and repairing intestinal pathology, which were not observed with allopurinol treatment. Moreover, Simiao decoction had a greater impact on gut microbiota than allopurinol, as it was able to restore the abundance of phylum Proteobacteria and genus Helicobacter. After transplantation into gout arthritis mice, gut microbiota altered by Simiao decoction exhibited similar therapeutic effects to those of Simiao decoction, but gut microbiota altered by allopurinol showed no therapeutic effect. CONCLUSIONS: These findings demonstrates that Simiao decoction can alleviate gout arthritis symptoms by regulating gut microbiota.

Fibromyalgia and risk of all-cause, specific mortality: A meta-analysis of observational studies.

OBJECTIVES: To evaluate the risk of all-cause, specific mortality among patients with fibromyalgia, which is a controversial topic. METHODS: We conducted a thorough search for cohort studies across the PubMed, Cochrane Library, and Embase databases, from their inception to 1 March 2023, using medical subject headings and relevant keywords. All data were meticulously analyzed using Stata statistical software version 16.0. The protocol was registered on PROSPERO (CRD42023402337). RESULTS: After analyzing seven cohort studies involving 152 933 individuals published between 2001 and 2020, we found no clear evidence linking fibromyalgia or widespread pain to all-cause mortality risk (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.81-1.53; I2 = 82.6%, p = .505). However, our subgroup analysis revealed that the risk of suicide was significantly higher in fibromyalgia patients compared with non-fibromyalgia patients (OR 5.39, 95% CI 2.16-13.43; I2 = 69.9%, p < .05). CONCLUSIONS: Our research did not discover any proof indicating a link between fibromyalgia or widespread pain and all-cause mortality. However, it is worth noting that there may be a potential correlation between individuals with fibromyalgia or widespread pain and a higher likelihood of suicide. As we had a limited number of participants in our study, further research is necessary to thoroughly investigate the relationship between these factors.

Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated. AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action. MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions. RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD. CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.

Efficacy and safety of tofacitinib combined with methotrexate in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of tofacitinib in combination with methotrexate (MTX) versus MTX monotherapy in patients with active rheumatoid arthritis (RA). Methods: Trials were identified from four electronic databases: PubMed, Web of science, Cochrane Library and EMBASE from inception to April 2022. Two independent reviewers evaluated each database to scan the title, abstract and keywords of each record retrieved. Full articles were further assessed when the information suggested that the study was a randomized clinical trial (RCT) comparing tofacitinib combined with MTX vs. MTX monotherapy in patients with active RA. Data were extracted from the literature, and the methodological quality of the included literature were evaluated and screened by two reviewers independently. The results were analyzed using RevMan5.3 software. The full text of the studies and extracted data were reviewed independently according to PRISMA guidelines. The outcome indicators were ACR 20, ACR 50, ACR 70, Disease activity score 28 (DAS28), erythrocyte sedimentation Rate (ESR) and adverse events (AEs). Results: Of 1152 studies yielded by the search, 4 were retained, totaling 1782 patients (1345 treated with tofacitinib combined with MTX vs 437 received MTX. In the trial of insufficient response to MTX treatment, tofacitinib combined with MTX had significant advantages compared with MTX monotherapy. Numerically higher ACR20, ACR50 and ACR70 response rates were observed in the tofacitinib combined with MTX groups versus MTX monotherapy. ACR20 (odds ratio (OR), 3.62; 95% CI, 2.84-4.61; P < 0.001), ACR50 (OR, 5.17; 95% CI, 3.62-7.38; P < 0.001), and ACR70 (OR, 8.44; 95% CI, 4.34-16.41; P < 0.001), DAS28 (ESR) < 2.6 (OR, 4.71, 95% CI, 2.06-10.77; P < 0.001). The probability of adverse events of tofacitinib combined with MTX was lower than that of MTX monotherapy (OR, 1.42; 95% CI, 1.08-1.88; P = 0.01). The number of cases discontinued due to lack of efficacy or adverse events was similar in both groups (OR, 0.93; 95% CI, 0.52-1.68). The probability of abnormal liver enzymes in the treatment of tofacitinib combined with MTX was significantly lower than that of MTX monotherapy (OR, 1.86; 95% CI, 1.35-2.56). However, there was no significant difference between the two groups in severe adverse reactions, neutropenia, anemia and cardiovascular disease. Conclusions: In terms of ACR20/50/70 and DAS28 (ESR), tofacitinib combined with MTX demonstrated superiority to MTX monotherapy in the treatment of patients with refractory RA. Considering the hepatoprotective and observably therapeutic efficacy, tofacitinib combined with MTX could be effective in treating refractory RA. However, in terms of hepatoprotective, it requires further large-scale and high-quality clinical trials to confirm.

Involvement of Fusobacterium nucleatum in malignancies except for colorectal cancer: A literature review.

Fusobacterium nucleatum (F. nucleatum) is originally an oral opportunistic pathogen and accumulating evidence links the presence of F. nucleatum with the pathogenicity, development, and prognosis of colorectal cancer (CRC). However, only limited preliminary data is available dealing with the role of F. nucleatum in other malignancies except for CRC. The present review aims to update and systematize the latest information about the mechanisms of F. nucleatum-mediating carcinogenesis, together with the detection rates, clinicopathological, and molecular features in F. nucleatum-associated malignancies. Comparing with adjacent non-tumorous tissue, previous studies have shown an overabundance of intratumoural F. nucleatum. Although the prognostic role of F. nucleatum is still controversial, a higher prevalence of F. nucleatum was usually associated with a more advanced tumor stage and a worse overall survival. Preliminary evidence have shown that epithelial-to-mesenchymal transition (EMT) and relevant inflammation and immune response aroused by F. nucleatum may be the probable link between F. nucleatum infection and the initiation of oral/head and neck cancer. Further studies are needed to elucidate the etiologic role of the specific microbiota and the connection between the extent of periodontitis and carcinogenesis in different tumor types. The mechanisms of how the antibiotics exerts the critical role in the carcinogenesis and antitumor effects in malignancies other than CRC need to be further explored.