Exploration of Stress and Inflammatory Biomarkers Among Non-Hispanic Black and Hispanic Cancer Survivors.

OBJECTIVES: To evaluate associations among social determinants of health (SDOH), stress, interleukin-6 (IL-6), and quality of life among non-Hispanic Black and Hispanic cancer survivors. SAMPLE & SETTING: Individuals who had completed cancer treatment and did not identify as White (N = 46) were recruited through community partnerships in western Massachusetts and a state cancer registry. METHODS & VARIABLES: This descriptive cross-sectional study used questionnaires and morning salivary samples to collect data between June 2022 and September 2023. RESULTS: Most participants were breast cancer survivors, were female, identified as African American or Black, and reported moderate levels of stress and low physical activity. Cortisol levels were higher among African American or Black participants, those with lower body mass index, and those with less consumption of fruit and vegetables. Higher symptom experience was associated with higher IL-6 levels. No associations were identified between IL-6 and cortisol or perceived stress and cortisol levels. IMPLICATIONS FOR NURSING: Incorporating SDOH in self-reported outcomes, including health behaviors and associated biologic indicators, can facilitate early identification and interventions to improve symptom experience and health outcomes of cancer survivors.

[Chinese expert consensus on off-label use of Tocilizumab in rheumatic diseases].

The interleukin-6 (IL-6) pathway plays a crucial role in various rheumatic diseases. Tocilizumab, a biologic targeting IL-6 receptor, has been widely used in clinical practice, though it's officially approved in China for only three indications. To address clinical challenges associated with the off-label use of tocilizumab in treating rheumatic diseases, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists engaged multidisciplinary experts and highlight 12 related clinical issues. We aggregated the drug specifications, the guidelines for clinical management of rheumatic diseases and the evidence from clinical research. Recommendations were formed through voting with the consensus conference method incorporating the Oxford evidence-based medicine criteria to evaluate the strength of evidence and recommendations. We have formulated 10 recommendations for off-label use of tocilizumab related to giant cell arteritis, polymyalgia rheumatica, Takayasu arteritis, systemic sclerosis, adult-onset Still's disease, rheumatoid arthritis, and juvenile idiopathic arthritis. This consensus aims to provide references for the rational use of tocilizumab in clinical practice and enhance pharmacovigilance monitoring.

[Resveratrol attenuates neuroinflammation and alleviates emotional dysfunction in mice with sepsis-associated encephalopathy through promoting chaperone-mediated autophagy (CMA)].

Objective To elucidate the role of chaperone-mediated autophagy (CMA) in alleviating emotional dysfunction in mice with sepsis-associated encephalopathy (SAE). Methods The SAE mouse model was established by cecal ligation and perforation (CLP). The severity of sepsis was assessed using the sepsis severity score (MSS). Emotional function in SAE mice was assessed by the open-field test and elevated plus-maze. The expression levels of cognitive heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2A (LAMP2A) and high mobility group box 1 protein B1 (HMGB1) were detected using Western blotting. Co-localization of LAMP2A in the hippocampal neurons was observed by immunofluorescence. The release of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using ELISA. Following 12 hours post-CLP, mice were orally administered resveratrol at a dose of 30 mg/kg once daily until day 14. Results The mortality rate of CLP mice was 45.83% 24 days post CLP, and all surviving mice exhibited emotional disturbances. 24 hours after CLP, a significant decrease in HSC70 and LAMP2A expression in hippocampal neurons was observed, indicating impaired CMA activity. Meanwhile, HMGB1 and inflammatory cytokines (IL-6 and TNF-α) levels increased. After resveratrol treatment, an increase of HSC70 and LAMP2A expression, and a decrease of HMGB1 expression and inflammatory cytokine release were observed, suggesting enhanced CMA activity and reduced neuroinflammation. Behavioral tests showed that emotional dysfunction was improved in SAE mice after resveratrol treatment. Conclusion CMA activity of hippocampal neurons in SAE mice is significantly reduced, leading to emotional dysfunction. Resveratrol can alleviate neuroinflammation and emotional dysfunction in SAE mice by promoting CMA and inhibiting the expression of HMGB1 and the release of inflammatory factors.

Correlation of amniotic fluid inflammatory markers with preterm birth: a meta-analysis.

BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.

Effects of IL-6, JAK, TNF inhibitors, and CTLA4-Ig on knee symptoms in patients with rheumatoid arthritis.

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.

Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model.

PURPOSE: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. METHODS: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. RESULTS: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). CONCLUSIONS: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.

Ethanol extract from Astilbe chinensis inflorescence suppresses inflammation in macrophages and growth of oral pathogenic bacteria.

Chronic oral inflammation and biofilm-mediated infections drive diseases such as dental caries and periodontitis. This study investigated the anti-inflammatory and antibacterial potential of an ethanol extract from Astilbe chinensis inflorescence (GA-13-6) as a prominent candidate for natural complex substances (NCS) with therapeutic potential. In LPS-stimulated RAW 264.7 macrophages, GA-13-6 significantly suppressed proinflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor (TNF), and nitric oxide (NO), surpassing purified astilbin, a known bioactive compound found in A. chinensis. Furthermore, GA-13-6 downregulated the expression of cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), indicating an inhibitory effect on the inflammatory cascade. Remarkably, GA-13-6 exhibited selective antibacterial activity against Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis, key players in dental caries and periodontitis, respectively. These findings suggest that complex GA-13-6 holds the potential for the treatment or prevention of periodontal and dental diseases, as well as various other inflammation-related conditions, while averting the induction of antibiotic resistance.

In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights.

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis.

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.

Brazilin cream from Caesalpinia sappan inhibit periodontal disease: in vivo study.

Background: Gingivitis is an inflammation of the gums that is the initial cause of the development of periodontal disease by the activity of Nuclear Factor-kappa B (NF-κB), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), p38, and Tumor Necrosis Factor-α (TNF-α). Unaddressed chronic inflammation can lead to persistent disturbances in other parts of the body. Brazilin is a naturally occurring plant chemical that may have antibacterial and anti-inflammatory effects. Treatment based on the natural plant compound, brazilin, is developed in the form of a topical cream for easy application. Objective: The aim is to develop the natural compound brazilin in the form of a topical cream as an anti-inflammatory agent to reduce NF-κB expression through Imunohistochemistry (IHC) methods, and the expression of pro-inflammatory genes IL-1ß, IL-6, p38, and TNF-α. Methods: Male Sprague-Dawley rats were induced with gingivitis using P. gingivalis bacteria. The observed groups included rats treated with a single application of brazilin cream and rats treated with two applications of brazilin cream. The treatment was administered for 15 days. On days 3, 6, 9, 12, and 15, anatomical wound observations and wound histology using hematoxylin-eosin and Masson's Trichrome staining were performed. NF-κB protein expression was analyzed using the IHC method. Gingival inflammation gene expression of NF-κB, IL-1ß, IL-6, p38, and TNF-α was measured using q-RTPCR. Results: Single and double applications of brazilin cream increased angiogenesis and decreased NF-κB protein expression, in addition to the IL-1ß, IL-6, p38, and TNF-α gene expressions. Conclusion: In a rat gingivitis model, Brazilin cream may function as an anti-inflammatory agent in the gingival tissue.

Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3ß, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19.

INTRODUCTION: Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. METHODS: Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. RESULTS: A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3ß, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. CONCLUSION: We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

[Protective effect and mechanism of methylene blue on myocardial injury in rats with sepsis].

OBJECTIVE: To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway. METHODS: A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting. RESULTS: Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 vs. 248.90±12.76 at 6 hours of modeling, 80.13±7.94, 190.40±9.56 vs. 288.90±6.01 at 12 hours of modeling; all P < 0.05]. Western blotting showed that compared with the sham operation group, the protein expressions of iNOS, LC3, and p62 in the sepsis model group were significantly higher at 6 hours and 12 hours after modeling; compared with the sepsis model group, the protein expressions of iNOS, LC3, and p62 in the MB treatment group and MB prevention group were significantly lower at 6 hours and 12 hours after modeling (iNOS/GAPDH: 0.38±0.04, 0.60±0.04 vs. 0.77±0.04 at 6 hours of modeling; 0.38±0.02, 0.66±0.04 vs. 0.79±0.05 at 12 hours of modeling; LC3/GAPDH: 0.13±0.07, 0.42±0.07 vs. 1.05±0.16 at 6 hours of modeling; 0.08±0.02, 0.25±0.03 vs. 0.48±0.09 at 12 hours of modeling; p62/GAPDH: 0.17±0.05, 0.44±0.10 vs. 1.19±0.07 at 6 hours of modeling; 0.07±0.00, 0.28±0.08 vs. 0.69±0.02 at 12 hours of modeling; all P < 0.05). CONCLUSIONS: MB can reduce myocardial oxidative stress by inhibiting iNOS expression and mitochondrial autophagy in septic rats, thereby alleviating myocardial damage in sepsis, and has protective effect on myocardial damage in sepsis.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

The potential presence of infection may be indicated through non-invasive prediction of procalcitonin and C-reactive protein levels within the initial three days after cervical cerclage: a retrospective case-control study.

PURPOSE: To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. METHODS: The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians' judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. RESULTS: Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P < 0.01, P < 0.05). The CRP levels on day 1 were significantly higher in the infected group compared to the uninfected group in two statistical ways (P < 0.05). On day 3, the mean CRP value was significantly elevated in the infected group compared to the uninfected group (P < 0.05). Analyses of IL-6, WBC, NEU, and NEU_P did not yield clinically significant results. The area under the ROC curves for CRP, PCT, and CRP-PCT on day 1 and day 3 were all below 0.7. In the preventive CC group, the AUC values of CRP and CRP-PCT obtained on d1 were found to be higher than 0.7, indicating moderate diagnostic accuracy. CONCLUSION: For women after CC surgery, especially of preventive aim, increased serum CRP and PCT levels from post-CC day 1 to day 3 may signal a potential postoperative infection, warranting close monitoring.

Cigarette smoke promotes IL-6-dependent lung cancer migration and osteolytic bone metastasis.

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.

Integrating network pharmacology and experimental models to investigate the efficacy and mechanism of Tiansha mixture on xerosis.

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM's effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application.

Utility of the WHO dengue guidelines in pediatric immunological studies.

Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

[Effects of "brain-gut coherence" method of acupuncture on motor function and intestinal microflora in the patients with cerebral ischemic stroke].

OBJECTIVE: To observe the clinical effect of "brain-gut coherence" method of acupuncture on cerebral ischemic stroke (CIS) and explore its action mechanism. METHODS: A total of 82 patients with CIS were randomly divided into an observation group (41 cases, 3 cases dropped out, 2 cases discontinued) and a control group (41 cases, 4 cases dropped out, 2 cases excluded). The conventional basic treatment was administered in the two groups. Additionally, in the observation group, "brain-gut coherence" method of acupuncture was delivered. The stimulating points included the parietal and temporal anterior oblique line on the affected side, Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, the routine acupuncture was operated at Baihui (GV 20), Yintang (GV 24+), bilateral Fengchi (GB 20) and Zusanli (ST 36), and Hegu (LI 4), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5), Futu (ST 32), Sanyinjiao (SP 6) and Taichong (LR 3) on the affected side. Acupuncture stimulation lasted 30 min each time, once daily, and for 5 days a week. The intervention for 4 weeks was required. The scores of Fugl-Meyer assessment scale (FMA), Berg balance scale (BBS) and the modified Barthel index (MBI), as well as the score of gastrointestinal symptoms were compared before and after treatment in the two groups. The neutrophil count (NUE) and the content of the serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected before and after treatment in the two groups. Using 16S rRNA gene sequencing, the structure and relative abundance of intestinal microflora was detected before and after treatment; and with the enzyme linked immunosorbent assay (ELISA) adopted, the levels of intestinal fatty acid-binding protein (iFABP), D-lactate (D-LA), lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), tumor necrosis factor-α(TNF-α), interleukin (IL)-1ß and IL-6 in the serum were detected before and after treatment in the two groups. RESULTS: After treatment, the scores of FMA, BBS and MBI were increased (P<0.05), and the scores of gastrointestinal symptoms were decreased (P<0.05) compared with those before treatment in the two groups. Compared with the control group, the scores of FMA, BBS and MBI were higher (P<0.05) and the score of gastrointestinal symptoms was lower (P<0.05) in the observation group after treatment. NEU and the content of serum NT-proBNP were reduced in the two groups (P<0.05), and the content of serum NT-proBNP in the observation group was lower than that of the control group (P<0.05) after treatment. Chao1, Ace, Sobs and Shannon indexes were increased after treatment compared with those before treatment in the two groups (P<0.05); and these indexes in the observation group were higher when compared with the control group (P<0.05). After treatment, the relative abundance of Bacteroidaceae, Enterobacteriaceae, Oscillospiraceae, Streptococcaceae and Sutterellaceae was reduced in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was lower in the observation group when compared with the control group (P<0.05). After treatment, the relative abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and Coriobacteriaceae was increased in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was elevated in the observation group when compared with the control group (P<0.05). After treatment, the levels of iFABP, D-LA, LPS, LBP, TNF-α, IL-1ß and IL-6 were reduced when compared with those before treatment in the two groups (P<0.05), and these levels of the observation group were lower than those of the control group (P<0.05). CONCLUSION: "Brain-gut coherence" method of acupuncture can improve the motor function and gastrointestinal function of the patients with cerebral ischemic stroke, which may be related to modulating the structure of intestinal microflora, alleviating inflammatory reactions and accelerating the intestinal barrier repair.

The relation between interleukin-6 and interleukin-8 serum levels and the severity of acquired aplastic anemia in adult patients: A single center study.

Aplastic anemia is a lethal bone marrow disease with a heterogeneous etiological background. Interleukin-6 (IL-6) and IL-8 were shown to affect the proliferation and differentiation of primitive hematopoietic cells. They may serve as potential markers for the assessment of severity/prognosis of aplastic anemia. The study aimed to evaluate the levels of IL-6 and IL-8-in patients with aplastic anemia and their relation to disease severity. This study included a total of 35 cases of aplastic anemia, and 27 normal subjects as controls. Levels of IL-6 and IL-8 were quantitatively measured by ELISA. The median serum IL-6 and IL-8 levels in aplastic anemia cases were 125.2 ng/l and 320 ng/l, respectively. These levels were significantly increased in the aplastic anemia patients than in the controls, as the median serum IL-6 was 29.7 ng/l and the median serum IL-8 97ng/l in the controls (p < 0.001). A significant correlation was observed between levels of both IL-6 and IL-8 and the severity of the disease (p <0.001). In conclusion, IL-6 and IL-8 serum levels are higher in patients with aplastic anemia and have a correlation to the severity of the disease.

Assessment value of interleukin-6, procalcitonin, and C-reactive protein early kinetics for initial antibiotic efficacy in patients with febrile neutropenia: A prospective study.

BACKGROUND: This study aims to investigate the early kinetics of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) on initial antibiotic efficacy in hematological disorder patients with febrile neutropenia (FN). METHODS: A total of 40 patients with 43 episodes of FN were enrolled and divided into initial antibiotic effective group (IAE group, n = 24) and initial antibiotic ineffective group (IAI group, n = 19). The levels of IL-6, PCT, and CRP before antibacterial treatment (T0), and 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) post-antibacterial treatment were determined, respectively. Furthermore, the receiver operating characteristic curve (ROC) analysis was performed to evaluate the clinical value of indicators. RESULTS: In IAE group, the IL-6 levels gradually decreased from T0 to T4, and the CRP levels significantly decreased at 48 to 72 h, whereas both IL-6 and CRP remained at high levels in the IAI group. The PCT levels in both groups increased at the early stage of anti-infection (T1-T2) and reached to peak at T1-T2 in effective group. ROC curve analysis identified IL-6 as a predictive biomarker for initial antibiotic efficacy at 12, 48, and 72 h after treatment, with the AUC of 0.698, 0.744, and 0.821, respectively. In addition, CRP demonstrated predictive ability of initial antibiotics against infection at 24, 48, and 72 h after therapy, with the AUC of 0.724, 0.741, and 0.797, respectively. ROC curve analysis of percentage changes demonstrated that IL-6 percentage change showed predictive ability of antibiotic efficacy at the early stage, and both the IL-6 and CRP percentage changes showed the predictive ability of antibiotic efficacy 48 or 72 h after antibiotics therapy. CONCLUSION: This study confirmed IL-6 and CRP levels, and the percentage change in IL-6 as the biomarkers for initial antibiotic efficacy prediction in hematological disorder patients with FN.