Non-thyroidal disease syndrome in patients with systemic lupus erythematosus: relation to disease inflammatory activity.

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.

The Systemic Immune-Inflammation Index Predicts In-Hospital Mortality in Patients Who Underwent On-Pump Cardiac Surgery. / O Índice de Imuno Inflamação Sistêmica Prevê Mortalidade Hospitalar em Pacientes Submetidos à Cirurgia Cardíaca com Circulação Extracorpórea.

BACKGROUND: Systemic immune-inflammation index (SII), a new inflammatory index calculated using platelet, neutrophil, and lymphocyte counts, has been demonstrated to be an independent risk factor for the identification of high-risk coronary artery disease in patients undergoing percutaneous coronary intervention and cardiovascular surgery with cardiopulmonary bypass (CPB). The relationship between SII and CPB-related mortality rates remains unclear. OBJECTIVE: This research was designed to investigate the use of SII to predict in-hospital mortality in patients undergoing cardiac surgery with CPB. METHODS: Four hundred eighty patients who underwent a cardiac procedure involving CPB over 3 years, were obtained from the hospital's database. The demographic data, comorbidities, hematological and biochemical profiles, and operative data of the groups were compared. Multiple logistic regression analyses were done to determine independent predictors of mortality. Prognostic factors were assessed by multivariate analysis, and the predictive values of SII, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) for mortality were compared. A p-value <0.05 was considered significant. RESULTS: Of 480 patients, 78 developed in-hospital mortality after cardiac surgery. SII was an independent predictor of in-hospital mortality (Odds ratio: 1.003, 95% confidence interval: 1.001-1.005, p<0.001). The cut-off value of the SII was >811.93 with 65% sensitivity and 65% specificity (area under the curve: 0.690). The predictive values of SII, PLR, and NLR were close to each other. CONCLUSION: High preoperative SII scores can be used for early determination of appropriate treatments, which may improve surgical outcomes of cardiac surgery in the future.

FUNDAMENTO: O índice de imuno-inflamação sistêmica (SII), um novo índice inflamatório calculado usando contagens de plaquetas, neutrófilos e linfócitos, demonstrou ser um fator de risco independente para a identificação de doença arterial coronariana de alto risco em pacientes submetidos a intervenção coronária percutânea e cardiovascular e cirurgia com circulação extracorpórea (CEC). A relação entre as taxas de mortalidade relacionadas ao SII e à CEC permanece obscura. OBJETIVO: Esta pesquisa foi desenhada para investigar o uso do SII para prever mortalidade hospitalar em pacientes submetidos à cirurgia cardíaca com CEC. MÉTODOS: Quatrocentos e oitenta pacientes submetidos a procedimento cardíaco envolvendo CEC durante 3 anos foram coletados do banco de dados do hospital. Foram comparados os dados demográficos, comorbidades, perfis hematológicos e bioquímico e dados operatórios dos grupos. Análises múltiplas de regressão logística foram feitas para determinar preditores independentes de mortalidade. Os fatores prognósticos foram avaliados por análise multivariada e os valores preditivos de SII, relação neutrófilo-linfócito (NLR) e razão plaqueta-linfócito (PLR) para mortalidade foram comparados. Um valor de p <0,05 foi considerado significativo. RESULTADOS: Dos 480 pacientes, 78 desenvolveram mortalidade hospitalar após cirurgia cardíaca. O SII foi um preditor independente de mortalidade hospitalar (odds ratio: 1,003, intervalo de confiança de 95%: 1,001-1,005, p<0,001). O valor de corte do SII foi >811,93 com sensibilidade de 65% e especificidade de 65% (área sob a curva: 0,690). Os valores preditivos de SII, PLR e NLR foram próximos entre si. CONCLUSÃO: Altos escores pré-operatórios do SII podem ser usados para determinação precoce de tratamentos apropriados, o que pode melhorar os resultados cirúrgicos de cirurgia cardíaca no futuro.

TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.

Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here, we demonstrate that TNF-like ligand 1A (TL1A) is an epithelial alarmin, constitutively expressed in alveolar epithelium at steady state in both mice and humans, which cooperates with IL-33 for early induction of IL-9high ILC2s during the initiation of allergic airway inflammation. Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low "ILC9" phenotype and produce prodigious amounts of IL-9. A combination of large-scale proteomic analyses, lung intravital microscopy, and adoptive transfer of ILC9 cells revealed that high IL-9 expression distinguishes a multicytokine-producing state-of-activated ILC2s with an increased capacity to initiate IL-5-dependent allergic airway inflammation. Similar to IL-33 and TSLP, TL1A is expressed in airway basal cells in healthy and asthmatic human lungs. Together, these results indicate that TL1A is an epithelium-derived cytokine and an important cofactor of IL-33 in the airways.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

Predictive Value of NLR and PLR in Driver-Gene-Negative Advanced Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: A Single Institutional Cohort Study.

OBJECTIVE: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the efficacy and prognosis of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors in driver-gene-negative advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective analysis of 107 advanced NSCLC patients without gene mutations who received PD-1/PD-L1 inhibitors in our hospital from January 2020 to June 2022 was performed. NLR and PLR were collected before PD-1/PD-L1 inhibitors, the optimal cut-off values of NLR and PLR were determined according to the receiver operating characteristic (ROC) curve, and the effects of NLR and PLR on the efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC patients were analyzed. RESULTS: A total of 107 patients were included in this study. Receiver operating characteristic analysis showed that the optimal cut-off values of NLR and PLR were 3.825, 179, respectively. Kaplan-Meier curve showed that low baseline levels NLR and PLR were associated with an improvement in both progression-free survival (PFS) (P < .001, < .001, respectively) and overall survival (OS) (P = .009, .006, respectively). In first-line treatment and non-first-line treatment, low baseline levels NLR and PLR were associated with an improvement in PFS. In multivariate analysis, low baseline NLR and PLR showed a strong association with both better PFS (P = .011, .027, respectively) and longer OS (P = .042, .039, respectively). CONCLUSION: Low baseline NLR and PLR levels are significantly associated with better response in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors, which may be indicators to predict the efficacy of immunotherapy in advanced NSCLC with driver-gene-negative.

Platelet-lymphocyte ratio as a predictor of lymph node metastasis in small bowel cancer.

The purpose of this research was to investigate the potential predictive value of preoperative systemic inflammatory indexes in identifying lymph node metastasis among patients diagnosed with small bowel cancer. A retrospective analysis of clinical data was conducted on small bowel cancer patients who underwent surgical treatment at the gastrointestinal surgery department of our hospital between January 2010 and June 2021. Patients were divided into groups based on the presence or absence of lymph node metastasis as confirmed by postoperative pathological results. The study compared the differences in preoperative inflammatory indexes and clinical data between the two groups using single factor analysis and multifactorial Logistic regression analysis. Furthermore, a nomogram model for predicting lymph node metastasis in colorectal cancer was constructed using R software and internally validated. The study sample consisted of 140 small bowel cancer patients,postoperative pathology confirmed lymph node metastasis in 72 cases. Univariate analysis results indicated associations between preoperative inflammatory indexes and clinical data with lymph node metastasis in small bowel cancer. Multifactorial logistic regression analysis revealed that gender, PLR, number of lymph node dissection, and lymphovascular invasion independently influenced lymph node metastasis in small bowel cancer patients. The developed nomogram model demonstrated a C-index of 0.855 (95% CI 0.792-0.917), with a calibrated prediction curve closely resembling the ideal curve. An elevated PLR is an independent risk factor for LNM in patients with small bowel cancer.

Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model.

Background: Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. Methods: We developed an "immunotumoroid" cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses. Results: Six of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (<5%) in the primary tumor sample. The five remaining models contained immune cells (CD4+ and CD8+ T cells, and macrophages), non-immune cells (fibroblasts), and tumor cells. Chemotherapy and ICI drugs were tested in immunotumoroids from 5 cases and compared to clinical outcomes where data was available. Four/five models showed cell killing in response to chemotherapy and two/five showed sensitivity to ICI. In three cases, the immunotumoroid model accurately predicted the patient's clinical response or non-response to ICIs or chemotherapy. Conclusion: Our immunotumoroid model replicated the multicellular nature of the tumor microenvironment sufficiently for preclinical ICI screening. This model could enable valuable insights into the complex interactions between cancer cells, the immune system, and the microenvironment. This is a feasibility study on a small number of cases, and additional studies with larger case numbers are required including correlation with clinical response.

Association of the neutrophil-to-lymphocyte ratio with the occurrence of venous thromboembolism and arterial thrombosis.

OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.

Shorter telomere length increases the risk of lymphocyte immunodeficiency: A Mendelian randomization study.

BACKGROUND: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear. METHODS: The two-sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome-Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results. RESULTS: The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014-1.472, p = .035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, p < .001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive-mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. CONCLUSION: In summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation.

SIGNIFICANCE OF NEUTROPHIL-LYMPHOCYTE RATIO AND PLATELET-LYMPHOCYTE RATIO AS PROGNOSTIC MARKERS OF DISEASE SEVERITY IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Managing systemic lupus erythematosus (SLE) is challenging because of its diverse symptoms, relapses, and issues related to immunosuppressive therapy. Hence, the management of autoimmune disorder has become a hot topic in this era. Thus, the study aims to predict disease severity in SLE cases by assessing the value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. In this study, we included a total of 80 patients, of which 40 were controls and 40 were experimental group. We gathered the demographic data and each patient provided informed consent. Furthermore, the clinical examinations were done, and results were noted. The study compared 40 SLE patients with 40 controls. SLE patients had lower complement levels, higher rates of LN and encephalopathy, and elevated Hs-CRP and ESR. They also showed lower WBC, neutrophil, lymphocyte, and platelet counts, along with higher NLR and PLR. Higher SLEDAI scores correlated with elevated Hs-CRP and ESR, and lower C3. Neutrophils positively correlated with NLR, while lymphocytes negatively correlated with SLEDAI scores, NLR, and PLR. Platelets did not significantly correlate with these markers. SLE patients showed higher rates of LNand encephalopathy, elevated inflammatory markers, and altered blood cell counts. Lower SLEDAI scores correlated with less inflammation and higher C3 levels, potentially indicating disease severity. Neutrophils were closely linked to disease activity, while lymphocytes showed a strong negative correlation. Platelet count was not a significant marker. Understanding these aspects could improve diagnosis and management.

Gut microbiota as a key regulator of intestinal mucosal immunity.

Gut microbiota is a complex microbial community with the ability of maintaining intestinal health. Intestinal homeostasis largely depends on the mucosal immune system to defense external pathogens and promote tissue repair. In recent years, growing evidence revealed the importance of gut microbiota in shaping intestinal mucosal immunity. Therefore, according to the existing findings, this review first provided an overview of intestinal mucosal immune system before summarizing the regulatory roles of gut microbiota in intestinal innate and adaptive immunity. Specifically, this review delved into the gut microbial interactions with the cells such as intestinal epithelial cells (IECs), macrophages, dendritic cells (DCs), neutrophils, and innate lymphoid cells (ILCs) in innate immunity, and T and B lymphocytes in adaptive immunity. Furthermore, this review discussed the main effects of gut microbiota dysbiosis in intestinal diseases and offered future research prospects. The review highlighted the key regulatory roles of gut microbiota in intestinal mucosal immunity via various host-microbe interactions, providing valuable references for the development of microbial therapy in intestinal diseases.

The prognostic role of pre-treatment neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.

PURPOSE: In this study, we retrospectively investigated the prognostic role of pre-treatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in esophageal squamous cell carcinoma patients (ESCC) treated with concurrent chemo-radiotherapy (CCRT). METHODS: We retrospectively analyzed the records of 338 patients with pathologically diagnosed esophageal squamous cell carcinoma that underwent concurrent chemo-radiotherapy from January 2013 to December 2017. Univariate and multivariate analyses were used to identify prognostic factors for progression free survival (PFS) and overall survival (OS). RESULTS: The result showed that the thresholds for NLR and PLR were 2.47 and 136.0 by receiver operating characteristic curve. High NLR and PLR were both associated with tumor length (P < 0.05). High NLR and PLR were significantly associated with poor PFS and OS. Multivariate analyses identified NLR, PLR and TNM stage were independent risk factors for PFS and OS. CONCLUSIONS: We show that the pre-treatment NLR and PLR may serve as prognostic indicators for esophageal squamous cell carcinoma treated with concurrent chemo-radiotherapy.

Blood cell count-derived inflammation indices as predictors of the osteoporotic risk of postmenopausal women.

OBJECTIVE: We investigated the associations between osteoporosis (OP) and systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in postmenopausal women. PATIENTS AND METHODS: This retrospective study included 966 postmenopausal women. Logistic regression and receiver operating characteristic curve (ROC) analyses were applied to explore the relationships between SII, NLR, MLR, and PLR with the bone mineral density (BMD) and risk of OP. RESULTS: Logistic regression analyses showed that SII, PLR, NLR, and MLR had independent negative associations with the OP risk. The ROC curve analysis showed that SII, NLR, and MLR predicted a low BMD, with NLR having the highest predictive value (area under the curve = 0.624). SII > 504.09, PLR > 131.87, NLR > 2.02, and MLR > 0.12 correlated with a particularly high OP risk. CONCLUSIONS: High levels of SII, PLR, NLR, and MLR were associated with a high OP risk. In particular, NLR > 2.02 strongly predicted the risk of OP, thereby representing a valuable and convenient inflammatory marker of the OP risk.

Prognostic significance of inflammation scores in malignant mesothelioma.

OBJECTIVE: The relationship between inflammatory markers and survival in many cancers has been investigated previously. Inflammatory markers may also offer the possibility of predicting surveillance in patients with malignant mesothelioma. Our study seeks to enhance comprehension of how variables such as the nutritional status and inflammation indices of malignant mesothelioma patients impact the disease's progression and prognosis. PATIENTS AND METHODS: This study included patients who were treated at the Erciyes University Medical Oncology Clinic between 2010 and 2022 and diagnosed with malignant mesothelioma. This is a retrospective single-center cohort study. Receiver Operating Characteristic (ROC) analysis was applied to determine the inflammation markers' optimal cut-off values with high sensitivity and specificity. Patients were categorized based on these values. The differences in overall survival (OS) and progression-free survival (PFS) between categorized groups were assessed using Log-rank curves and Kaplan-Meier tests. Multivariate analysis was performed using Cox regression analysis on statistically significant data. The relationship between inflammation markers and malignant mesothelioma survival was evaluated. RESULTS: There are 115 patients in this study. Pre-treatment high neutrophil to lymphocyte ratio (NLR) (HR: 1.34, 95% CI: 1.12-2.83, p=0.04), high pan-immune inflammation value (PIIV) (HR: 2.01, 95% CI: 1.32-4.79, p=0.03), and high systemic inflammation response index (SIRI) (HR: 1.34, 95% CI: 1.2-2.78, p=0.04) were associated with poor OS. Conversely, high advanced lung cancer inflammation index (ALI) (HR: 0.73, 95% CI: 0.53-0.84, p=0.03) and high hemoglobin-albumin-lymphocyte and platelet (HALP) (HR: 0.67, 95% CI: 0.23-0.78, p=0.02) were associated with favorable survival. CONCLUSIONS: Our study investigated the prognostic value of various inflammation markers in malignant mesothelioma patients and suggests that composite formulas like NLR, PIIV, SIRI, ALI, and HALP that incorporate CBC cells and nutritional parameters like albumin, height, and weight could more consistently and accurately predict malignant mesothelioma prognosis.

[Clinical features and lymphocyte subtypes in patients with IgG4-related diseases].

Objective: To deepen understanding of IgG4-related diseases (RDs), we analyzed the associated lymphocyte subtypes, and explored the pathogenesis and potential immunotherapeutic targets. Methods: Eighty-six patients with IgG4-RDs were enrolled, and their clinical characteristics, peripheral lymphocyte subtypes, and disease course were analyzed. Results: The mean age of the participants was 36-87(62±11) years; 51 were male (59.3%) and 35 were women (40.7%); and 34.9% had a history of allergy. Follow-up lasted 4.8 (0.4, 14.1) months. The most common symptoms were abdominal pain, and submandibular gland and lacrimal gland swelling (each 20.9%). Sixty-five (75.6%) participants had multiple organ involvement, and the most frequently affected organs were the pancreas (52.3%), submandibular gland (51.2%), and lacrimal gland (34.9%). A high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and low complement C3 and C4 concentrations were present in 18.8% (16/85), 30.0% (24/80), 72.9% (62/85), 58.3% (28/48), 89.5% (77/86), 61.2% (52/85), and 50.0% (42/84), respectively, of the participants. In addition, 64.7% (55/85) were positive for autoantibodies, and the most frequent was anti-nuclear antibody (63.5%). The proportion of CD4+T lymphocytes increased in 25.7% (9/35) of the participants, which was accompanied by an increase in the ratio of CD4+/CD8+T lymphocytes (22.9%, 8/35). Importantly, most participants (90.0%, 18/20) had a high proportion of regulatory T (Treg) cells. High interleukin (IL)-2, IL-6, and IL-10 concentrations were present in 50.0% (11/22), 33.3% (10/30), and 16.7% (5/30), respectively, of the participants. Substantial lymphoplasmacytic infiltration, fibrosis, IgG4-positive plasma cell infiltration, and lymphoid follicle hyperplasia or ectopic formation were present in 79.2% (42/53), 67.9%(36/53), 35.8%(19/53) and 30.2% (16/53), respectively, of the participants. Fifty-three participants with detailed pathologic data were also further evaluated, of whom 24.5% (13/53), 3.8% (2/53), and 67.9% (36/53) had definite, probable, and possible diagnoses; and 3.8% (2/53) could not be diagnosed. Compared with baseline, the percentage of eosinophils and the IgE, IgG, and IgG4 concentrations decreased significantly; and the complement C3 and C4 concentrations had increased significantly after 6 months of treatment (all P<0.05). The IgG4 concentration after 6 months of treatment negatively correlated with that of C4, and positively correlated with the baseline concentration of IgE and the IgG4/IgG ratio. Conclusion: IgG4-RDs are a group of diseases characterized by male predisposition; multiple organ involvement; a high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and a low C3 concentration. Peripheral CD4+T cells and Treg cells are also more abundant. The diseases can be controlled with glucocorticoids and immunosuppressive drugs in the majority of instances. The IgG4 concentration after 6 months of treatment negatively correlates with the baseline complement C4 concentration and positively correlates with the IgE concentration and IgG4/IgG ratio, which suggests that IgG4/IgG, IgE, and complement should be closely monitored to evaluate disease activity and the efficacy of treatment in such patients.

Dysregulation of Wnt/ß-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells.

RORγt+ group 3 innate lymphoid cells (ILC3s) are essential for intestinal homeostasis. Dysregulation of ILC3s has been found in the gut of patients with inflammatory bowel disease and colorectal cancer, yet the specific mechanisms still require more investigation. Here we observe increased ß-catenin in intestinal ILC3s from inflammatory bowel disease and colon cancer patients compared with healthy donors. In contrast to promoting RORγt expression in T cells, activation of Wnt/ß-catenin signaling in ILC3s suppresses RORγt expression, inhibits its proliferation and function, and leads to a deficiency of ILC3s and subsequent intestinal inflammation in mice. Activated ß-catenin and its interacting transcription factor, TCF-1, cannot directly suppress RORγt expression, but rather alters global chromatin accessibility and inhibits JunB expression, which is essential for RORγt expression in ILC3s. Together, our findings suggest that dysregulated Wnt/ß-catenin signaling impairs intestinal ILC3s through TCF-1/JunB/RORγt regulation, further disrupting intestinal homeostasis, and promoting inflammation and cancer.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. METHODS: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. RESULTS: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. CONCLUSION: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

[Correlation Analysis between Neutrophil-to-lymphocyte Ratio 
and the Risk of Malnutrition in Stage IV Primary Lung Cancer].

BACKGROUND: Malnutrition is commonly associated with poor prognosis in patients with malignant tumors. The neutrophil-to-lymphocyte ratio (NLR) is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases; however, its association with malnutrition in lung cancer patients is unclear. The aim of this study is to clarify the association between NLR and nutritional status in stage IV primary lung cancer and to further determine the optimal NLR cut-off that best predicts the risk of malnutrition. METHODS: A retrospective analysis of 209 patients admitted to the Department of Medical Oncology, Tianjin Medical University General Hospital with a primary diagnosis of stage IV lung cancer from May 2019 to February 2021 was performed, and the nutritional risk screening 2002 (NRS 2002) was used to examine their nutritional status. Patient demographic information, pathology, Karnofsky performance status (KPS) score, body mass index (BMI), comorbidities and clinical biochemical indicators were also included. The correlation between NLR and NRS 2002 was investigated. Receiver operating characteristic (ROC) curve was used to determine the best NLR cut-off predi cting malnutrition risk. Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS: The rate of patients with stage IV primary lung cancer at nutritional risk was 36.36% (76/209). A significant positive correlation was observed between NLR values and NRS 2002 risk score (r=0.765, P<0.001). The ROC curve analysis indicated that an NLR of 3.94 was the optimal cut-off for predicting malnutrition risk (area under the curve=0.747, 95%CI: 0.678-0.815, P<0.001), which showed a sensitivity of 55%, a specificity of 86%, a positive predictive value of 68%, and a negative predictive value of 77%. Patients in the NLR>3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group (69.49% vs 23.33%, P<0.001). Furthermore, NLR was identified as a risk factor for malnutrition in stage IV primary lung cancer patients. CONCLUSIONS: NLR is associated with the risk of malnutrition in stage IV primary lung cancer, and NLR can be used as one of the indicators for screening nutritional risk in patients with stage IV primary lung cancer.