The neutrophil-to-lymphocyte ratio (NLR) is recognized as a biomarker for systemic inflammation and immune activation. However, its connection with the mortality risk in individuals with rheumatoid arthritis (RA) is not well understood. This study aimed to investigate the association between NLR and all-cause and cardiovascular mortality risk in U.S. adults with RA.Data were gathered from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 1999 to March 2020. We included adults aged ≥20 years. The NLR was computed by dividing the neutrophil count by the lymphocyte count from complete blood counts. The maximally selected rank statistics method helped identify the optimal NLR cutoff value associated with significant survival outcomes. Multivariable logistic regression models were performed to investigate the relationship between the NLR and the all-cause and cardiovascular mortality of RA. Restricted cubic spline (RCS) analyses were utilized to detect whether there were linear or non-linear relationships between NLR and mortality.In this study, 2002 adults with RA were included, with 339 having a higher NLR (≥3.28) and 1663 having a lower NLR (<3.28). During a median follow-up of 84 months, 79 RA individuals died. Participants with higher NLR had a 2-fold increased risk of all-cause (HR = 2.02, 95% CI: 1.53-2.66) and cardiovascular mortality (HR = 2.48, 95% CI: 1.34-4.57) versus lower NLR, after adjusting for demographics, socioeconomic status, and lifestyle factors. Kaplan-Meier analysis revealed that the survival rate for the higher NLR group was significantly lower than the lower NLR group, in terms of both all-cause and cardiovascular mortality (both P<0.0001). The RCS curve demonstrated a positive linear association between the NLR and all-cause and cardiovascular mortality.A higher NLR was independently predictive of elevated long-term mortality risk in U.S. adults with RA. The NLR may serve as an inexpensive, widely available prognostic marker in RA.

The neutrophil-lymphocyte ratio predicts all-cause and cardiovascular mortality among U.S. adults with rheumatoid arthritis: results from NHANES 1999-2020

Background Traditional Chinese herbal medicine draws more attention to explore an effective therapeutic strategy for Alzheimer's disease (AD). Shenqi Yizhi granule (SQYG), a Chinese herbal recipe, has been applied to ameliorate cognitive impairment in mild-to-moderate AD patients. However, the overall molecular mechanism of SQYG in treating AD has not been clarified. Objective This study aimed to investigate the molecular mechanism of SQYG on AD using an integration strategy of network pharmacology and molecular docking. Methods The active compounds of SQYG and common targets between SQYG and AD were screened from databases. The herb-compound network, compound-target network, and protein-protein interaction network were constructed. The enrichment analysis of common targets and molecular docking were performed. Results 816 compounds and 307 common targets between SQYG and AD were screened. KEGG analysis revealed that common targets were mainly enriched in lipid metabolism, metal ion metabolism, IL-17 signaling pathway, GABA receptor signaling, and neuroactive ligand-receptor interaction. Molecular docking analysis showed high binding affinity between ginsenoside Rg1 and Aβ1–42, tanshinone IIA and BACE1, baicalin, and AchE. Conclusions The therapeutic mechanisms of SQYG on AD were associated with regulating lipid metabolism, metal ion metabolism, IL-17 signaling pathway, and GABA receptor signaling. Ginsenoside Rg1, tanshinone IIA, baicalin, astragaloside IV, and folic acid may play an important role in AD treatment.

Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer's Disease

Importance of hematological markers in familial Mediterranean fever in terms of disease severity and amyloidosis

Introduction As a systemic autoimmune disorder, the prognosis of rheumatoid arthritis (RA) is intricately linked to inflammation. This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a comprehensive indicator of inflammation combined with nutritional status, and all-cause and cardiovascular mortality among patients diagnosed with RA. Methods The 2,305 RA patients from NHANES (2001–2018) included in the analysis were categorized into three groups according to ALI tertiles. Weighted Kaplan–Meier and multivariate COX regression analyses evaluated the relationship between ALI and mortality. The time-dependent characteristic curve (ROC) was used to assess the prediction accuracy of ALI. Results During a median follow-up of 7.92 years, 591 participants died from all causes, including 197 from cardiovascular diseases. Increased ALI was associated with a decreased probability of death. The full COX model revealed lower all-cause mortality hazard risks in the T2 (HR: 0.67, 95%CI: 0.54–0.83) and T3 (HR: 0.47 95%CI: 0.33–0.67, p for tend &amp;lt;0.001) groups compared to T1, and the risk of cardiovascular mortality was also lower in the groups of T2 (HR: 0.47, 95%CI: 0.31–0.70) and T3 (HR: 0.34, 95%CI: 0.19–0.62, p for trend &amp;lt;0.001). Furthermore, the ROC analysis underscored the strong predictive capability of ALI (AUC for 1-year all-cause and cardiovascular mortality were 0.73 and 0.79, respectively). Conclusion This cohort study demonstrated the higher accuracy of ALI in predicting mortality in RA patients, highlighting the important clinical value of ALI in risk assessment and prognosis evaluation. 

pdf/association-of-advanced-lung-cancer-inflammation-index-with-2pbyc85szp.pdf

Association of advanced lung cancer inflammation index with all-cause and cardiovascular mortality in US patients with rheumatoid arthritis

Many markers are used for clinical diagnosis in rheumatic diseases; rheumatoid factor (RF) is the most frequently used marker. However, RF is not specific to rheumatoid arthritis (RA). RF positivity is widely observed in patients with advanced age, infectious, autoimmune, and lymphoproliferative diseases. In this context, the objective of this study is to investigate the demographic characteristics, frequency of antinuclear antibody (ANA) and anti-cyclic citrullinated peptide (anti-CCP) positivity, hemogram parameters and distribution of the diagnoses in RF-positive patients followed at the rheumatology clinic.The population of this retrospective study consisted of patients above 18 years of age who were referred to have RF positivity by nephelometric method at Kahramanmaraş Necip Fazıl City Hospital Rheumatology Clinic between January 2020 and June 2022.The mean age of the 230 patients with a positive RF test result, 155 (76%) male and 55 (24%) female, was 52.7 ± 15.5 years. There were 81 (35.2%), 54 (23.5%), 73 (31.7%) and 22 (9.6%) patients with RF levels between 20 and 50 IU/mL, 50 and 100 IU/mL, 100 and 500 IU/mL, and above 500 IU/mL, respectively. There was no significant difference detected between the groups that were created based on the RF titers regarding demographic characteristics (P > 0.05). The rate of being diagnosed with any rheumatic disease was significantly lower in the group with RF levels between 20 and 50 IU/mL compared to other groups (P = 0.001). The distribution of rheumatic and non-rheumatic disease diagnoses according to RF levels did not reveal any significant difference between the groups (P = 0.369 and P = 0.147, respectively). RA was the most common (62.2%) rheumatic disease diagnosis among the patients included in the study. The leukocyte count was significantly higher in the group with RF levels above 500 IU/mL compared to the group with RF levels between 20 and 50 IU/mL (P = 0.024). There was no significant difference between the groups in other laboratory results, that is, hemogram, sedimentation, C-reactive protein, platelet, and lymphocyte/monocyte ratio (P > 0.05).The study findings indicate that RF positivity can be seen in the context of different rheumatological diseases; hence RF levels alone may not predict rheumatological disease. There was also no significant relationship between RF levels and ANA and anti-CCP positivity. The most common diagnosis in patients presenting with elevated RF levels was RA. Nevertheless, it should be noted that RF can be found asymptomatically in the general population. 

The assessment of rheumatoid factor levels and hemogram parameters as predictors for rheumatologic disease

Background: To investigate the diagnostic performance of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in the diagnosis of rheumatoid arthritis (RA) in subjects with undifferentiated inflammatory arthritis (UIA). Methods: This retrospective cohort study investigated 201 female patients with UIA (≥1 swollen joint) and 280 age-matched, healthy female controls. “Clinical RA” was defined based on the clinical judgment of a rheumatologist and “disease-modifying anti-rheumatic drugs (DMARDs) RA” was defined as a case of initiating DMARDs treatment within 6 months after the first visit. “Classified RA” was defined as fulfilling the 2010 classification criteria for RA. Receiver operating characteristics were used to determine the optimal cut-off value. Results: UIA patients had a significantly higher NLR, PLR, and MLR than the controls. Among the 201 UIA patients, 65 (32.3%), 63 (31.3%), and 61 (30.3%) subjects were classified as clinical RA, DMARDs RA, and classified RA, respectively. At a cut-off of 0.24, MLR showed moderate accuracy for the diagnosis of DMARDs RA (sensitivity, 65.1%; specificity, 62.3%; area under the curve [AUC], 0.701; p < 0.001). However, the diagnostic accuracies of NLR and PLR were low. Conclusions: MLR may be used as a complementary diagnostic indicator for RA diagnosis in patients with UIA.

/pdf/diagnostic-value-of-neutrophil-to-lymphocyte-platelet-to-27hfw6fg.pdf

Diagnostic Value of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Monocyte-to-Lymphocyte Ratios for the Assessment of Rheumatoid Arthritis in Patients with Undifferentiated Inflammatory Arthritis

This study was to investigate the effects of Biyeom-go (BYG, an herbal formula) on immune biomarkers present in the nasal mucosa of patients with allergic rhinitis under exposure to particulate matter 2.5 (PM2.5), and on changes in goblet cells and immune biomarkers in mice under exposure to Korea diesel particulate matter (KDP20). Thirty patients showing characteristic allergic rhinitis symptoms were enrolled in Jeonju-si, Korea, and treated with BYG thrice a day for four weeks. Changes in the expression of immune biomarkers (interleukin 4 (IL-4), IL-5, IL-8, IL-13, IL-33, and thymic stromal lymphopoietin (TSLP) mRNA), total nasal symptom scores (TNSS), mini-rhinitis-specific quality of life questionnaire (RQLQ) results, and visual analog scale scores were evaluated after 4 weeks of treatment. Additionally, the difference in PM2.5 concentrations in the air in Jeonju-si, Korea (November, 2019 ∼ March, 2020), was analyzed to determine the change in TNSS. KDP20 (100 μg/mL) was exposed to C57BL/6 mice for 10 days; 0.05% Nasonex (a positive control, mometasone furoate), or BYG was administrated for 5 days twice a day. The expression of inflammatory factors was detected via qRT-PCR using nasopharynx tissue samples of mice. BYG treatment was found to be associated with significant improvement in total nasal symptoms, especially itching and sneezing (p < 0.0001), and mini-RQLQ after 4 weeks. IL-8 (p < 0.01), IL-33 (p < 0.01), and TSLP (p < 0.001) expression levels decreased after BYG treatment. In mice, administration of BYG reduced the number of goblet cells increased through KDP20 treatment. KDP20-induced immune biomarkers (IL-33, TSLP, tumor necrosis factor alpha, and IL-8) were also significantly downregulated in the nasopharynx tissue after BYG treatment. Therefore, BYG may show therapeutic effects against allergic rhinitis in humans, and it was confirmed that the expression of PM-induced inflammatory factors in mice was decreased via BYG treatment.

Particulate Matter Exposure and the Changes in Immune Biomarkers: Effects of Biyeom-Go on the Nasal Mucosa of Patients with Allergic Rhinitis and a Particulate Matter-Treated Mouse Model

Objective: To compare the effects of atorvastatin monotherapy and the combination of atorvastatin with curcetin (a mixture of the bioflavonoids curcumin and quercetin) on lipid profile and inflammatory biomarkers in patients with unstable angina after COVID-19 (“Long COVID”).Material. An open simple comparative randomized study was conducted in 186 patients with unstable angina, including 77 (Group I) in whom angina destabilization occurred as a result of COVID-19 during 4-8 weeks prior to inclusion in the study, and 109 patients (Group II) in whom destabilization was not associated with infection.Results: In group I, the level of hsC-reactive protein [5,4 (2,06-7,4) g/l and IL-6 8,6 (5,4-10,3) pg/ml] was higher (P < 0,05) than in group II patients [3,8 (1,2-4,0) g/l and 6,9 (2,2-10,2) pg/ml], respectively. In subgroup I of patients after COVID-19, atorvastatin monotherapy (n = 43) did not have a significant effect after two months of treatment, while in subgroup II the combined use of atorvastatin with curcetin (n = 34) for 2 months reduced the level of hsCRP by 49,0% (P < 0,05) and Il-6 by 40,0% (P < 0,05).Conclusion. In patients with unstable angina after COVID-19, combination treatment with atorvastatin and curcetin reduced concentrations of inflammatory biomarkers compared with atorvastatin monotherapy.

Effects of the combined use of atorvastatin and curcetin on inflammatory biomarkers in patients with unstable angina after COVID-19 (“Long COVID”)

INTRODUCTION
We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database.


METHODS
Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis.


RESULTS
This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041).


CONCLUSION
Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

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Papers

Diagnostic Value of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Monocyte-to-Lymphocyte Ratios for the Assessment of Rheumatoid Arthritis in Patients with Undifferentiated Inflammatory Arthritis

Particulate Matter Exposure and the Changes in Immune Biomarkers: Effects of Biyeom-Go on the Nasal Mucosa of Patients with Allergic Rhinitis and a Particulate Matter-Treated Mouse Model

Effects of the combined use of atorvastatin and curcetin on inflammatory biomarkers in patients with unstable angina after COVID-19 (“Long COVID”)

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.