Inflammatory subphenotypes previously identified in ARDS are associated with mortality at intensive care unit discharge: a secondary analysis of a prospective observational study.

BACKGROUND: Intensive care unit (ICU)-survivors have an increased risk of mortality after discharge compared to the general population. On ICU admission subphenotypes based on the plasma biomarker levels of interleukin-8, protein C and bicarbonate have been identified in patients admitted with acute respiratory distress syndrome (ARDS) that are prognostic of outcome and predictive of treatment response. We hypothesized that if these inflammatory subphenotypes previously identified among ARDS patients are assigned at ICU discharge in a more general critically ill population, they are associated with short- and long-term outcome. METHODS: A secondary analysis of a prospective observational cohort study conducted in two Dutch ICUs between 2011 and 2014 was performed. All patients discharged alive from the ICU were at ICU discharge adjudicated to the previously identified inflammatory subphenotypes applying a validated parsimonious model using variables measured median 10.6 h [IQR, 8.0-31.4] prior to ICU discharge. Subphenotype distribution at ICU discharge, clinical characteristics and outcomes were analyzed. As a sensitivity analysis, a latent class analysis (LCA) was executed for subphenotype identification based on plasma protein biomarkers at ICU discharge reflective of coagulation activation, endothelial cell activation and inflammation. Concordance between the subphenotyping strategies was studied. RESULTS: Of the 8332 patients included in the original cohort, 1483 ICU-survivors had plasma biomarkers available and could be assigned to the inflammatory subphenotypes. At ICU discharge 6% (n = 86) was assigned to the hyperinflammatory and 94% (n = 1397) to the hypoinflammatory subphenotype. Patients assigned to the hyperinflammatory subphenotype were discharged with signs of more severe organ dysfunction (SOFA scores 7 [IQR 5-9] vs. 4 [IQR 2-6], p < 0.001). Mortality was higher in patients assigned to the hyperinflammatory subphenotype (30-day mortality 21% vs. 11%, p = 0.005; one-year mortality 48% vs. 28%, p < 0.001). LCA deemed 2 subphenotypes most suitable. ICU-survivors from class 1 had significantly higher mortality compared to class 2. Patients belonging to the hyperinflammatory subphenotype were mainly in class 1. CONCLUSIONS: Patients assigned to the hyperinflammatory subphenotype at ICU discharge showed significantly stronger anomalies in coagulation activation, endothelial cell activation and inflammation pathways implicated in the pathogenesis of critical disease and increased mortality until one-year follow up.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

Myokine Secretion following an Aerobic Exercise Intervention in Individuals with Type 2 Diabetes with or without Exercise Resistance.

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.

Inflammatory depression is associated with selective glomerular hypofiltration.

BACKGROUND: Systemic low-grade inflammation may be a pathophysiological mechanism in a subtype of depression. In this study we investigate a novel candidate mechanism of inflammatory depression - Selective Glomerular Hypofiltration Syndromes (SGHS) - which are characterized by a reduced estimated glomerular filtration rate (eGFR) based on cystatin C (cysC) relative to eGFR based on creatinine (crea). SGHS have been associated with increased blood levels of pro-inflammatory markers, but have never been investigated in a sample of depressed individuals. METHOD: The prevalence of SGHS was compared between 313 patients with difficult-to-treat depression and 73 controls. Since there is no single established eGFRcysC/eGFRcrea-ratio cut-off to define SGHS, several cut-offs were investigated in relation to a depression diagnosis, inflammation, and symptom severity. Plasma inflammatory markers tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6, IL-8, and IL-10 were available from 276 depressed patients. We examined mediation effects of IL-6 on the relationship between SGHS and depression. RESULTS: Depressed patients were more likely to have SGHS compared to controls defining SGHS as either eGFRcysC/eGFRcrea-ratio < 0.9 (33.2 % vs 20.5 %, p = 0.035) or < 0.8 (15.7 % vs 5.5 %, p = 0.023). Lower eGFRcysC/eGFRcrea-ratio was associated with higher levels of inflammatory markers in depressed patients. IL-6 partly mediated the relationship between SGHS and depression. CONCLUSION: This is the first study to demonstrate a link between SGHS and inflammatory depression. If replicated in independent and longitudinal cohorts, this may prove to be a relevant pathophysiological mechanism in some cases of depression that could be targeted in future intervention and prevention studies.

The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway.

BACKGROUND AND OBJECTIVES: Metformin, an oral hypoglycemic drug, has been suggested to possess antitumour activity in several types of cancers. Additionally, interleukin-8 (IL-8) has been reported to be involved in the development and metastasis of many cancers. However, the effect of metformin on IL-8 expression in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to investigate whether metformin could inhibit IL-8 expression to exert an inhibitory effect on HCC progression. MATERIALS AND METHODS: The IL-8 levels were measured in the plasma of 159 HCC patients (86 men, 73 women; average age 56 years) and in the culture supernatant of HCC cells (Hep3B and HuH7) using flow cytometry. In addition, the protein expression levels of IL-8 were also validated by the Human Protein Atlas (HPA) database. The prognostic value of IL-8 was evaluated using the Kaplan-Meier Plotter database. The association between IL-8 expression and immune checkpoints was estimated using the TIMER and The Cancer Genome Atlas (TCGA) databases. What's more, bioinformatics analysis, western blotting, and transwell assays were conducted to illustrate the molecular mechanism of metformin (≤1 mM) on IL-8 in HCC. RESULTS: IL-8 expression was found to be increased in the plasma of HCC patients, which is consistent with the expression of IL-8 in HCC cells and tissues. High expression of IL-8 was significantly related to poor prognosis. In addition, IL-8 was positively correlated with immune checkpoints in HCC. Notably, we found that low-dose metformin could inhibit the secretion of IL-8 by HCC cells and the migration of HCC cells. Mechanistically, low-dose metformin significantly suppresses HCC metastasis mainly through the AMPK/JNK/IL-8/MMP9 pathway. CONCLUSION: The results indicate that low-dose metformin can inhibit HCC metastasis by suppressing IL-8 expression. Targeting the AMPK/JNK/IL-8 axis may be a promising treatment strategy for patients with HCC metastasis.

Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Evaluation of interleukin-8 levels in the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

This study aimed to determine the level of interleukin (IL)-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, haematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84 ± 15.38 years, while that of the controls was 58.38 ± 16.64 years. Of the patients, 2/25 were classified as having 'proven', 13/25 as 'probable', and 10/25 as 'possible' invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cutoff value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/l; sensitivity was 72%; specificity was 64%; PPV was 50%; and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.

Although a significant cutoff value for serum interleukin (IL)-8 was found in the diagnosis of IPA, there was no statistical difference in serum IL-8 when subgroup analysis was performed with neutropenic control patients. Therefore, serum IL-8 is not a successful marker in diagnosing neutropenic patients with IPA.

Universal nanocomposite coating with antifouling and redox capabilities for electrochemical affinity biosensing in complex biological fluids.

Electrochemical affinity biosensors have the potential to facilitate the development of multiplexed point-of-care diagnostics in complex biological fluids. However, their commercial viability has been hindered by challenges such as electrode biofouling and the lack of inherent redox properties. To address this unmet need, we have developed a universal nanocomposite coating which is unique in its ability to not only allow oriented conjugation of the biorecognition element but also specific detection directly in complex biological fluids like serum and urine owing to its built-in antifouling and redox capabilities, thus improving suitability for point of care testing. This multifunctional coating comprises a 3D porous crosslinked bovine serum albumin matrix for oriented conjugation and antifouling properties with embedded graphene nanosheets modified with amino-ferrocene for enhanced conductivity and mediator-free biosensing. The coating showed minimal signal degradation despite prolonged exposure to 1% bovine serum albumin, artificial urine and untreated human serum for up to 30 days. To demonstrate its utility, we fabricated and tested proof-of-concept electrochemical immunosensors for bladder cancer protein biomarkers, specifically interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The practical feasibility was highlighted by the excellent sensitivity and specificity observed for IL-8 and VEGF with a limit of detection of 41 pg mL-1 and 67 pg mL-1, respectively. Consequently, this universal nanocomposite-based electrochemical biosensing platform can be extended to the point of care testing of a broad spectrum of biomarkers present in complex biological fluids, thus enabling reliable and early diagnostics.

Serum Levels of Interleukins in Endometriosis Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis. DATA SOURCES: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed. METHODS OF STUDY SELECTION: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis. Meta-analysis was performed on IL-1RA, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-37. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 651 studies, of which 77 underwent a full-text review. A total of 30 studies met inclusion criteria for the meta-analysis. IL-1Ra, IL-6, and IL-37 serum levels were 2.56 (95% CI 2.20-2.92, p <.001), 1.38 (95% CI 0.58-2.17, p <.001), and 1.77 (95% CI 1.33-2.20, p <.001) standard deviations higher in the patients with endometriosis compared with patients without endometriosis while IL-23 serum levels 0.40 (95% CI -0.73 to -0.07, p = .02) standard deviations lower, respectively. CONCLUSION: There is mounting evidence that ILs, especially IL-6, may be good candidates for unique noninvasive diagnostic tools and/or treatment pathways for endometriosis.

Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006).   Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

DiGeorge syndrome presenting with palmoplantar pustules: Comparative analysis of serum IL-22, NETs and IL-8 with usual palmoplantar pustulosis.

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, shows cellular immunodeficiency due to by thymic hypoplasia and hypocalcemia caused by hypoparathyroidism. It was reported that erythrodermic psoriasis occurred in a patient with 22q11 deletion syndrome. Here, we report the first case of DiGeorge syndrome presenting with a severe palmoplantar pustulosis (PPP)-like eruption with extra-palmoplantar lesions on the distal limbs. Given that PPP is a subtype of pustular psoriasis, the pustular eruption may be associated with DiGeorge syndrome. We measured serum levels of citrullinated histone H3 (CitH3), a representative marker of neutrophil extracellular traps, interleukin (IL)-8, and IL-22 and compared them with nine cases of typical PPP. In the PPP patients, the three markers were higher than in healthy subjects with significant correlations between CitH3 and IL-8/IL-22. In our patient, CitH3, IL-8, and IL-22 were also high, and IL-22 was remarkably elevated compared with the PPP patients. Our case suggests that a certain T cell abnormality associated with DiGeorge syndrome induces IL-22 overproduction, leading to the PPP-like eruption with extra- palmoplantar lesions.

Interleukin-8 is superior to CRP for the prediction of severe complications in a prospective cohort of patients undergoing major liver resection.

INTRODUCTION: Early detection of severe complications may reduce morbidity and mortality in patients undergoing hepatic resection. Therefore, we prospectively evaluated a panel of inflammatory blood markers for their value in predicting postoperative complications in patients undergoing liver surgery. METHODS: A total of 139 patients undergoing liver resections (45 wedge resections, 49 minor resections, and 45 major resections) were prospectively enrolled between August 2017 and December 2018. Leukocytes, CRP, neutrophil-lymphocyte ratio (NLR), thrombocyte-lymphocyte ratio (TLR), bilirubin, INR, and interleukin-6 and -8 (IL-6 and IL-8) were measured in blood drawn preoperatively and on postoperative days 1, 4, and 7. IL-6 and IL-8 were measured using standardized immunoassays approved for in vitro diagnostic use in Germany. ROC curve analysis was used to determine predictive values for the occurrence of severe postoperative complications (CDC ≥ 3). RESULTS: For wedge and minor resections, leukocyte counts at day 7 (AUC 0.80 and 0.82, respectively), IL-6 at day 7 (AUC 0.74 and 0.73, respectively), and CRP change (∆CRP) at day 7 (AUC 0.72 and 0.71, respectively) were significant predictors of severe postoperative complications. IL-8 failed in patients undergoing wedge resections, but was a significant predictor of severe complications after minor resections on day 7 (AUC 0.79), had the best predictive value in all patients on days 1, 4, and 7 (AUC 0.72, 0.72, and 0.80, respectively), and was the only marker with a significant predictive value in patients undergoing major liver resections (AUC on day 1: 0.70, day 4: 0.86, and day 7: 0.92). No other marker, especially not CRP, was predictive of severe complications after major liver surgery. CONCLUSION: IL-8 is superior to CRP in predicting severe complications in patients undergoing major hepatic resection and should be evaluated as a biomarker for patients undergoing major liver surgery. This is the first paper demonstrating a feasible implementation of IL-8 analysis in a clinical setting.

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes.

OBJECTIVES: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers. METHODS: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers. RESULTS: Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index. CONCLUSIONS: Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

[Analysis of current status and influencing factors of inflammatory factors among electrical workers in Hainan province].

Objective: To analyze the level and influence factors of inflammatory factors among electrical workers in Hainan Province. Methods: A total of 509 electrical workers were selected as the research subjects with random cluster sampling in September 2020. Basic information was collected by questionnaire, the serum IL-6, IL-8 and TNF-α levels of the subjects were detected by Luminex.Mann-Whitney U test and Kruskal-wallis H test were used for univariate analysis. Ordinal logistic regression analysis was used for potential influencing factors of the level of inflammatory factors. Results: The median concentrations of IL-6, IL-8 and TNF-α in serum were 2.78, 9.77 and 8.18 pg/ml. Compared with women, male was a risk factor for the increase of IL-6 levels (OR=1.80, 95%CI: 1.08~3.00, P=0.024) . Compared with 51-60 years old, 21-31 years old (OR=0.27, 95%CI: 0.18~0.42, P<0.001) , 31-41 years old (OR=0.27, 95%CI: 0.17~0.43, P<0.001) and 41-51 years old (OR=0.64, 95%CI: 0.41~0.99, P=0.043) were protective factors for the increase of IL-8 level. Compared with day shift workers, shift work was a risk factor for the increase of IL-8 level (OR=1.73, 95%CI: 1.21~2.48, P=0.003) . Compared with women, male was a risk factor for the increase of TNF-α levels (OR=2.87, 95%CI: 1.70~4.86, P<0.001) . Compared with workers who exposed to 7 or more occupational hazard factors, exposed to 1~3 (OR=0.53, 95%CI: 0.30~0.92, P=0.024) occupational hazard factors were protective factors for the increase of TNF-α levels. Conclusion: The level of inflammatory factors was related to sex, age, work system and occupational environment, which can provide basic data for follow-up research on occupational population.

PLR and IL-8 were Potential Markers in Differential Diagnosis and Disease Activity in Ulcerative Colitis Patients.

BACKGROUND: At present, the most direct method to evaluate mucosal healing in patients with ulcerative colitis (UC) is endoscopy, but it is costly and invasive. Therefore, it is necessary to find a biomarker with low cost, easy access, high sensitivity and specificity as an indicator of UC activity. This study aimed to examine the level of platelet to lymphocyte ratio (PLR) and interleukin-8 (IL-8) in UC patients and evaluate their roles in differential diagnosis and disease activity assessment. METHODS: A retrospective study involving 130 UC patients and 141 irritable bowel syndrome (IBS) patients was performed. The UC patients were divided into remission group and active group according to the Modified Mayo score. The receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cutoff value of PLR and IL-8 in differential diagnosis between UC patients and IBS patients. RESULTS: The levels of WBC, PLR, and IL-8 in UC patients were higher than those compared with IBS controls. The optimal cutoff to differentiate UC and IBS patients was 6.76 109/L, 114.70, and 19.42 pg/mL for WBC, PLR, and IL-8, respectively (sensitivity, 36.9% vs. 83.8% vs. 72.3%; specificity, 83.0% vs. 65.2% vs. 94.3%; AUC, 0.601 vs. 0.815 vs. 0.859). IL-8 had the highest AUC and specificity. Among 130 patients, 75 patients (57.6%) had mucosal inflammation. The cutoff value of IL-8 for predicting disease severity of UC patients was 22.21 pg/mL (AUC: 0.861). The sensitivity, specificity, and Youden index of IL-8 for predicting severe UC were 92.0%, 81.8%, and 0.702, respectively. CONCLUSIONS: PLR and IL-8 showed great performance in distinguishing UC from IBS patients. Moreover, elevated IL-8 level indicated mucosal inflammation, reflecting disease severity in UC patients.

Peripheral cytokine levels as novel predictors of survival in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear. Methods: A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1ß, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-ß) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed. Results: Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21-2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67-2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98-2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70-2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method. Conclusion: The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.

Elevated G-CSF, IL8, and HGF in patients with definite Meniere's disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation.

The etiology and mechanism causing Meniere's disease (MD) are not understood. The present study investigated the possible molecular mechanism of autoimmunity and autoinflammation associated with MD. Thirty-eight patients with definite MD and 39 normal volunteers were recruited, and 48 human cytokines/chemokines were quantified. In patients with MD pure tone audiograms, tympanograms and standard blood tests were performed. The mean hearing loss in the worse ear was 44.1 dB nHL. Compared to the referents, the concentrations of TNFα, IL1α, IL8, CTACK, MIP1α, MIP1ß, G-CSF, and HGF in the sera of patients with MD were significantly elevated, while those of TRAIL and PDGFBB were significantly decreased. The area under the receiver operating characteristic curve (AUC) showed that G-CSF, MIP1α, and IL8 were above 0.8 and could be used to diagnose MD (p < 0.01), and the AUCs of CTACK and HGF were above 0.7 and acceptable to discriminate the MD group from the control group (p < 0.01). The revised AUCs (1 - AUC) of TRAIL and PDGFBB were above 0.7 and could also be used in the diagnosis of MD (p < 0.01). The linear regression showed significant correlations between MIP1α and GCSF, between IL2Rα and GCSF, between IL8 and HGF, between MIP1α and IL8, and between SCF and CTACK; there was a marginal linear association between IP10 and MIP1α. Linear regression also showed that there were significant age-related correlations of CTACK and MIG expression in the MD group (p < 0.01, ANOVA) but not in the control group. We hypothesize that G-CSF, IL8, and HGF, which are involved in the development of neutrophil extracellular traps (NETs) and through various mechanisms influence the functions of macrophages, lymphocytes, and dendritic cells, among others, are key players in the development of EH and MD and could be useful in elucidating the pathophysiological mechanisms leading to MD. Biomarkers identified in the present study may suggest that both autoimmune and autoinflammatory mechanisms are involved in MD. In the future, it will be valuable to develop a cost-effective method to detect G-CSF, IL8, HGF, CTACK, MIP1α, TRAIL, and PDGFBB in the serum of patient that have diagnostic relevance.

[Long noncoding RNA LOC102640791 alleviates sepsis inflammation in mice by sponging miR-320-5p].

Objective To investigate the role and mechanism of long noncoding RNA (lncRNA) LOC102640791 in sepsis inflammatory response. Methods The mice model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). The cell model of sepsis was established by treating of RAW264.7 macrophages with LPS. Mice or cells were randomly divided into the control group and the LPS group. The levels of lncRNA and miRNA in serum were detected by microarrays. The levels of LOC102640791 and miR-320-3p were tested by the real time quantitative PCR. The levels of TNF-α, IL-6, IL-8, IL-4 and IL-10 in serum and cell culture supernatant of RAW264.7 were detected by the ELISA. Luciferase reporter gene technology was used to verify the relationship between LOC102640791 and miR-320-3p. Results Compared with the control group, the LPS group had lower expression of LOC102640791 and higher expression of miR-320-3p. Compared with the LPS group, the LPS group with high expression of LOC102640791 and the LPS group with low expression of miR-320-3p had higher expression of pro-inflammatory factors (TNF-α, IL-6 and IL-8) and lower expression of anti-inflammatory factors (IL-4 and IL-10). Wild type LOC102640791 can inhibit the luciferase activity of miR-320-3p. Conclusion LOC102640791 alleviates sepsis inflammatory response by sponging miR-320-5p.