Protective effect of pentraxin 3 on pathological retinal angiogenesis in an in vitro model of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is the most common retinal microvascular disease caused by diabetes. Previous studies indicated that Pentraxin 3 (PTX3), an acute phase reactant, was closely related to the development of DR. But the exact effect of PTX3 in diabetic retinopathy needs more investigations. METHODS: Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) analysis and western blot (WB) were used to detect the expression of PTX3 in vitro. The Ki67 immunofluorescent staining, scratch-wound migration assay, and tube formation experiments were performed to detect the effect of PTX3 knockdown and overexpression on the fibroblast growth factor (FGF)-induced proliferation, migration and tube-forming ability of human retinal microvascular endothelial cells (HRMECs). The phosphorylation levels of extracellular regulated protein kinases (ERK) and fibroblast growth factor receptor (FGFR) in HRMECs were detected by WB. RESULTS: In vitro, the mRNA and protein expressions of PTX3 in the high-concentration glucose condition group were upregulated compared with the normal group (p < 0.05). The proliferation, migration and tube-forming abilities of HRMECs exposed to high-concentration glucose were enhanced (p < 0.01, p < 0.01, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.01, p < 0.05 respectively) compared with the normal condition group. Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 siRNA condition group were further strengthened (p < 0.001, p < 0.0001, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.001, p < 0.01 respectively). Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 overexpression condition group were compromised (p < 0.001, p < 0.05, p < 0.01 respectively), and the phosphorylation of FGFR and ERK1/2 were inhibited (p < 0.001, p < 0.0001 respectively). Neither the scramble siRNA condition group nor the blank plasmid condition group showed significant difference on the proliferation, migration and tube-forming abilities of HRMECs compared with the high glucose condition group (p > 0.05). CONCLUSIONS: The upregulated expression of PTX3 may play a protective role on pathological angiogenesis in DR. PTX3 may serve as a new target for the treatment of DR.

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome.

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People's Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

Evaluation of Serum Interleukin-38 Levels in Different Radiographic Grades of Idiopathic Knee Osteoarthritis.

The aim of this study was to assess interleukin-1ß (IL-1ß), IL-1Ra, IL-36, and IL-38 levels together with hs-CRP levels in patients with different radiographic grades of knee osteoarthritis (OA) in comparison to healthy individuals. Consecutive patients aged over 50 years who were admitted to our Orthopaedics and Traumatology department between November 2018 and March 2019 and diagnosed as knee OA according to the American College of Rheumatology criteria were included in this prospective case-control study. Patients with knee OA were staged according to radiographic Kellgren-Lawrence (K-L) classification and 20 patients were assigned to each group. An age and gender matched control group consisted healthy volunteers with no clinical and radiographic sign of arthritis were conducted as the control group. Venous blood samples were collected and assessed for hs-CRP, IL-1ß, IL-1Ra, IL-36, and IL-38 levels using the double-antibody sandwich ELISA method. The hs-CRP, IL-1ß, IL-36 and IL-38 levels did not significantly differ among controls and independent radiographic stage groups except IL-1Ra levels which was significantly higher in K-L grade 4 knee OA groups compared to healthy controls (P = 0.045). When we compared all patients with knee OA and healthy controls, we detected that IL-1 and IL-1Ra were significantly lower and IL-38 levels were significantly higher in healthy control group compared to patients with knee OA (P = <0.001, <0.001, and 0.019, respectively). According to results obtained from our study, IL-1ß, IL-1Ra, and IL-38 levels significantly differed between healthy individuals and patients with knee OA. However, we did not observe a significant difference and correlation between radiographic grade of knee OA and interleukin levels.

Case Report: Medullary Thyroid Cancer Workup Initiated by Unexpectedly High Procalcitonin Level-Endocrine Training Saves Life in the COVID-19 Unit.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic. The majority of medullary thyroid cancers present as a thyroid nodule. At the time of diagnosis, cervical lymph nodes and distant metastases are frequently detected. Case Report: Here, we present a case of a 46-year-old man with coronavirus disease (COVID) pneumonia, who had persistently high serum procalcitonin levels despite normal C-reactive protein levels. The attending infectologist happened to be a colleague who spent some time, as part of her internal medicine rotation, in the Endocrine Ward and recalled that medullary thyroid cancer might be the cause. This led to the timely workup and treatment of the medullary cancer.

Serum magnesium in patients with severe acute respiratory syndrome coronavirus 2 from Wuhan, China.

The aim of the study was to evaluate the significance of hypomagnesemia in patients with coronavirus disease 2019 (COVID-19) and clarify its possible pathogenesis. A retrospective cohort study was conducted by reviewing 83 patients hospitalized in Guanggu district, Wuhan Third Hospital, China. Clinical histories, laboratory findings and outcome data were collected. Eighteen patients had hypomagnesemia during hospitalization. Fourteen patients were in the critical group and six died. In the critical group, serum magnesium (0.72 ± 0.15 mmol/L) was much lower than that in the moderate and severe groups. At the same time, we also found that several indicators are correlated with the level of magnesium. The level of magnesium was positively associated with the lymphocyte count (r = 0.203, P = 0.004) and platelet count (r = 0.217, P = 0.002) but negatively related to the levels of CRP (r = -0.277, P = 0.000), LDH (r = -0.185, P = 0.011) and α-hydroxybutyrate dehydrogenase (r = -0.198, P = 0.008) in the critical group. Hypomagnesemia might increase symptoms and may be associated with mortality in COVID-19 by affecting enzyme activity and activating the inflammatory response. Thus, magnesium might play a key role in the pathogenesis of COVID-19.

Potential biomarkers of major depression diagnosis and chronicity.

BACKGROUND: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. METHODS: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. RESULTS: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. CONCLUSION: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.

The Effect of Statins on C-Reactive Protein in Stroke Patients: A Systematic Review of Clinical Trials.

BACKGROUND: Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive protein (CRP) or highly sensitive CRP (hs-CRP), a liver-derived marker of systemic inflammation, among stroke patients. METHODS: An online search was performed in Scopus, PubMed/MEDLINE, ISI Web of Science, and Google Scholar up to November 2020 to recognize clinical trials investigating the effects of statins on the CRP level in stroke patients. RESULTS: Overall, nine studies (11 treatment arms) with 1659 participants met the inclusion criteria. Six out of 9 studies (8 out of 11 arms) were categorized as studies with a high-quality methodological approach using the Cochrane Collaboration's tool. Data from 5 treatment arms indicated a significant decrease in CRP concentration, and in one treatment arm, CRP concentration did not suggest any considerable alteration following statin therapy. Moreover, two treatment arms showed a significant reduction in hs-CRP concentration and three treatment arms revealed no significant alteration in hs-CRP concentration following statin therapy. Generally, results were heterogeneous and independent of the type of statin, statin dose, treatment duration, and changes in plasma low-density lipoprotein cholesterol concentration. CONCLUSION: The results suggest that statin therapy could reduce and, therefore, could be considered in these patients as potential anti-inflammatory agents.

Assessment of Cardiovascular Risk in Women with Periodontal Diseases According to C-reactive Protein Levels.

Cardiovascular diseases (CVD) are highly prevalent non-communicable diseases worldwide. Periodontitis may act as a non-traditional cardiovascular risk (CVR) factor, linked by a low-grade systemic inflammation mediated by C-reactive protein (CRP). Patients with periodontitis reported higher serum CRP levels; however, a CRP systemic and periodontal correlation in gingival crevicular fluid (GCF) and its CVR impact have been barely studied. We aimed to assess the association between periodontal diseases and CVR in a group of adult women, based on serum high-sensitivity CRP (hs-CRP) levels; and secondly, to determine the association between serum and GCF CRP levels. Gingival crevicular fluid and blood samples were obtained from women with periodontitis, gingivitis, and healthy controls. Serum and GCF CRP were determined by turbidimetric method and Luminex technology, respectively. Data were analyzed and adjusted by CVR factors. All women presented moderate CVR, without an evident association between serum hs-CRP levels and periodontal diseases. While serum hs-CRP concentrations did not significantly differ between groups, patients with gingivitis and periodontitis showed higher CRP levels in GCF, which positively correlated to CRP detection in serum.

Levels of C-Reactive Protein and Sodium May Differentiate a Perforated Appendix from a Nonperforated Appendix in Children.

BACKGROUND: Acute appendicitis (AA) might be amenable to conservative antibiotic treatment, whereas a perforated appendix (PA) necessitates surgery. We investigated the value of clinical-laboratory markers in distinguishing AA from a PA. METHODS: Retrospectively obtained preoperative parameters for 306 consecutive patients (<18 years) with histologically confirmed appendicitis (AA (n = 237) vs. PA (n = 69)), treated at our institution between January 2014 and December 2017. RESULTS: A PA was associated with male preponderance, younger age, decreased sodium level and increased white blood cell count, Tzanakis score, C-reactive protein (CRP) level, and CRP-to-lymphocyte ratio (CLR). Upon discrimination analysis, CLR and CRP displayed the highest accuracy in differentiating a PA from AA. Regression analysis identified levels of CRP, sodium, and the Tzanakis score as independent predictors for a PA. CONCLUSION: Levels of CLR, CRP, sodium, and Tzanakis score might support decision-making regarding treatment options for pediatric appendicitis.

Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation.

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor playing an important role in immune response and inflammation. Lipopolysaccharide (LPS) stimulation can significantly induce PTX3 expression and secretion in adipocytes. Appropriate regulation of PTX3 secretion is critical for inflammatory homeostasis. Using chemical inhibitors of conventional and unconventional protein secretion, we explored the mechanisms that control LPS-stimulated PTX3 secretion in 3T3-L1 adipocytes. Inhibiting the conventional protein secretion blocked LPS-stimulated PTX3 secretion, resulting in cellular PTX3 accumulation in adipocytes. We also detected PTX3 in exosomes from LPS-treated adipocytes; inhibiting exosome trafficking attenuated PTX3 secretion. However, only 4.3% of secreted PTX3 was detected in exosomes compared to 95.7% in the non-exosomal fractions. The fractionation of isolated exosomes by the iodixanol density gradient centrifugation confirmed that a small portion of secreted PTX3 overlapped with exosomal markers in small extracellular-vesicle fractions. We conclude that PTX3 is secreted mainly through conventional protein secretion, and a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes.

Vagal Nerve Stimulation-Modulation of the Anti-Inflammatory Response and Clinical Outcome in Psoriatic Arthritis or Ankylosing Spondylitis.

OBJECTIVES: The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. METHODS: Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. RESULTS: In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. CONCLUSION: This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Forensic Biochemical Markers to Evaluate the Agonal Period: A Literature Review.

Currently, forensic research is multidisciplinary with new methods and parameters useful to define the cause and time of death as well as survival/agony times. The identification of biochemical markers able to estimate agonal period has been studied by many forensic researchers. It is known that the estimation of agonal time in different types of death is not always easy, hence our interest in literature's data. The studies analyzed in this review confirm the important role of thanatobiochemistry for the estimation of survival times. Regardless of the death cause, the survival/agony time between the primary event and death influences markers concentrations in biological samples (e.g., blood, urine, cerebrospinal fluid). Different biomarkers can be used for qualitative evaluations in deaths with short and long agony (e.g., C-reactive protein, ferritin, GFAP, etc.). Instead, the quantitative interpretation showed limits due to the lack of reference cut-offs. Thanatobiochemistry is a useful tool to confirm what emerged from autopsies findings (macroscopic and histological analysis), but further studies are desirable to confirm the evidence emerging from our review of the literature.

Pseudomonas aeruginosa DnaK Stimulates the Production of Pentraxin 3 via TLR4-Dependent NF-κB and ERK Signaling Pathways.

Microbe-derived factors trigger innate immune responses through the production of inflammatory mediators, including pentraxin 3 (PTX3). PTX3 is a soluble pattern recognition molecule that stimulates the clearance of clinically important bacterial pathogens such as Pseudomonas aeruginosa. However, the P. aeruginosa factors responsible for the production of PTX3 have not been elucidated. In this study, we found that P. aeruginosa DnaK, a homolog of heat shock protein 70, induced PTX3 production. Induction was mediated by intracellular signals transmitted through the Toll-like receptor 4 (TLR4) signaling pathway. Following receptor engagement, the stimulatory signals were relayed initially through the nuclear factor kappa B (NF-κB) signaling pathway and subsequently by extracellular signal-regulated kinases (ERK), which are mitogen-activated protein kinases. However, ERK activation was negatively controlled by NF-κB, implying the existence of negative crosstalk between the NF-κB and the ERK pathways. These data suggest that P. aeruginosa DnaK acts as a pathogen-associated molecular pattern to trigger modulation of host defense responses via production of PTX3.

Association of Complement-Related Proteins in Subjects With and Without Second Trimester Gestational Diabetes.

Introduction: Gestational Diabetes Mellitus (GDM) development is related to underlying metabolic syndrome that is associated with elevated complement C3 and C4. Elevated C3 levels have been associated with preeclampsia and the development of macrosomia. Methods: This case-control study included 34 pregnant women with GDM and 16 non-diabetic (ND) women in their second trimester. Complement-related proteins were measured and correlated with demographic, biochemical, and pregnancy outcome data. Results: GDM women were older with a higher BMI (p<0.001); complement C3, C4 and Factor-H were significantly elevated (p=0.001, p=0.05, p=0.01, respectively). When adjusted for age and BMI, Complement C3 (p=0.04) and Factor-H (p=0.04) remained significant. Partial correlation showed significant correlation between C4 with serum alanine aminotransferase (ALT) (p<0.05) and 2nd term diastolic blood pressure (p<0.05); Factor-H and C-reactive protein (CRP; p<0.05). Pearson bivariate analysis revealed significant correlations between C3, C4, and Factor-H and CRP; p<0.05; C3 and gestational age at delivery (GA; p<0.05); C4 and ALT and second-trimester systolic blood pressure (STBP) (p=0.008 and p<0.05, respectively); Factor-H and glycated hemoglobin (HbA1c) (p<0.05). Regression analysis showed that the elevation of C3 could be accounted for by age, BMI, GA and CRP, with CRP being the most important predictor (p=0.02). C4 elevation could be accounted for by ALT, CRP and STBP. CRP predicted Factor-H elevation. Conclusion: The increased C3, C4 and Factor-H during the second trimester of pregnancy in GDM are not independently associated with GDM; inflammation and high BMI may be responsible for their elevation. The elevation of second trimester C3 in GDM is associated with earlier delivery and further work is needed to determine if this is predictive.

Comparison of high-sensitivity C-reactive protein vs. C-reactive protein for diagnostic accuracy and prediction of mortality in patients with acute myocardial infarction.

BACKGROUND: The role of chronic inflammation in the pathogenesis of atherosclerosis has been unequivocally proven. However, the prognostic impact of C-reactive protein, a marker of inflammatory response in patients with acute myocardial infarction has not been fully clarified. Furthermore, there is no direct comparison of the diagnostic accuracy of C-reactive protein and high sensitivity C-reactive protein in the acute myocardial infarction population. METHODS: In this prospective observational cohort study, 344 patients with acute myocardial infarction were enrolled. All-cause mortality was a primary endpoint. Patients were followed prospectively for a median of six years. RESULTS: The correlation between high sensitivity C-reactive protein and C-reactive protein (r = 0.99; P < 0.001) and the diagnostic accuracy (98.6%) was high. The ROC analysis revealed that C-reactive protein and high sensitivity C-reactive protein had a low AUC for prediction of mortality (C-reactive protein: 0.565, 95% CI [0.462-0.669], vs. high sensitivity C-reactive protein: 0.572, 95% CI [0.470-0.675]) or major adverse cardiac events (C-reactive protein: AUC 0.607, 95% CI [0.405-0.660], vs. high sensitivity C-reactive protein: AUC 0.526, 95% CI [0.398-0.653]) when assessed at time point of acute myocardial infarction. In contrast, longitudinal inflammatory risk assessment with serial C-reactive protein measurements in the stable phase of the disease revealed a 100% specificity, 100% negative predictive value, 32% sensitivity and 12% positive predictive value of C-reactive protein to predict long-term mortality. The Kaplan Meier analysis showed a significant survival benefit for patients at low residual inflammatory risk (P = 0.014). CONCLUSION: C-reactive protein and high sensitivity C-reactive protein provide a similar diagnostic accuracy, highlighting that C-reactive protein might replace high sensitivity C-reactive protein in routine assessments. Furthermore, low inflammatory status during the stable phase after acute myocardial infarction predicts favourable six-year survival.

Thermovaccination: Thermoheliox as an Immune Response Stimulant. Kinetics of Antibodies and C-Reactive Protein Synthesis in Coronaviral Infection.

The high efficiency of using thermoheliox (inhalation with a high-temperature mixture of helium and oxygen) in the treatment of patients affected by COVID-19 was shown. The dynamics of accumulation of IgG, IgM, and C-reactive protein (CRP) in patients with coronavirus infection in the "working" and control groups was studied experimentally. It was shown that thermoheliox intensifies the synthesis of IgG, IgM, and CRP antibodies, while eliminating the induction period on the kinetic curves of the synthesis of specific antibodies in the IgG form and transfers the synthesis of CRP to a fast phase. The results of experiments confirm the previously obtained data based on the analysis of the kinetic model of the development of coronaviral infection in the human body.

The effect of anesthesia on the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colorectal cancer in the context of an enhanced recovery pathway: A prospective cohort study.

ABSTRACT: There are reports that the use of regional anesthesia (RA) may be associated with better perioperative surgical stress response in cancer patients compared with general anesthetics (GA). However, the role of anesthesia on the magnitude of the postoperative systemic inflammatory response (SIR) in colorectal cancer patients, within an enhanced recovery pathway (ERP), is not clear.The aim of the present study was to examine the effect of anesthesia, within an enhanced recovery pathway, on the magnitude of the postoperative SIR in patients undergoing elective surgery for colorectal cancer.Database of 507 patients who underwent elective open or laparoscopic colorectal cancer surgery between 2015 and 2019 at a single center was studied. The anesthetic technique used was categorized into either GA or GA + RA using a prospective proforma. The relationship between each anesthetic technique and perioperative clinicopathological characteristics was examined using binary logistic regression analysis.The majority of patients were male (54%), younger than 65 years (41%), either normal or overweight (64%), and were nonsmokers (47%). Also, the majority of patients underwent open surgery (60%) and received mainly general + regional anesthetic technique (80%). On univariate analysis, GA + RA was associated with a lower day 4 CRP (≤150/>150 mg/L) concentration. On day 4, postoperative CRP was associated with anesthetic technique [odds ratio (OR) 0.58; confidence interval (CI) 0.31-1.07; P = .086], age (OR 0.70; CI 0.50-0.98; P = .043), sex (OR 1.15; CI 0.95-2.52; P = .074), smoking (OR 1.57; CI 1.13-2.19; P = .006), preoperative mGPS (OR 1.55; CI 1.15-2.10; P = .004), and preoperative dexamethasone (OR 0.70; CI 0.47-1.03; P = .072). On multivariate analysis, day 4 postoperative CRP was independently associated with anesthetic technique (OR 0.56; CI 0.32-0.97; P = .039), age (OR 0.74; CI 0.55-0.99; P = .045), smoking (OR 1.58; CI 1.18-2.12; P = .002), preoperative mGPS (OR 1.41; CI 1.08-1.84; P = .012), and preoperative dexamethasone (OR 0.68; CI 0.50-0.92; P = .014).There was a modest but an independent association between RA and a lower magnitude of the postoperative SIR. Future work is warranted with multicenter RCT to precisely clarify the relationship between anesthesia and the magnitude of the postoperative SIR.

Decreased serum Annexin A1 levels in Kawasaki disease with coronary artery aneurysm.

BACKGROUND: Kawasaki disease (KD) is an acute and systemic vasculitis whose etiology remains unclear. The most crucial complication is the formation of coronary artery aneurysm (CAA). Annexin A1 (ANXA1) is an endogenous anti-inflammatory agent and pro-resolving mediator involved in inflammation-related diseases. This study sought to investigate the serum ANXA1 levels in KD patients and further explore the relationship between ANXA1 and CAA, as well as additional clinical parameters. METHODS: Serum samples were collected from 95 KD patients and 39 healthy controls (HCs). KD patients were further divided into two groups: KD with CAAs (KD-CAAs) and KD non-CAAs (KD-NCAAs). Serum levels of ANXA1 and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. RESULTS: Serum ANXA1 levels in the KD group were significantly lower than in the HC group. In particular, serum ANXA1 levels were substantially lower in the KD-CAA groups. Moreover, serum ANXA1 levels were positively correlated with N%, C-reactive protein (CRP), and IL-6 but negatively correlated with L% in the KD group. Positive correlations between serum ANXA1 levels and erythrocyte sedimentation rate (ESR), IL-6, and D-dimer (DD) were observed in the KD-CAA group. CONCLUSIONS: ANXA1 may be involved in the development of KD, and downregulation of ANXA1 may lead to the hypercoagulability seen in KD. IMPACT: For the first time, it was demonstrated that serum ANXA1 levels were significantly decreased in Kawasaki disease with coronary artery aneurysms. ANXA1 might be involved in the acute phase of Kawasaki disease. Low serum concentrations of ANXA1 might lead to the hypercoagulability stage in Kawasaki disease. ANXA1 might be a potential therapeutic target for patients with Kawasaki disease.

Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke.

Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute-phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET-1 or L-Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP-positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood-brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel-based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte-derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof-of-concept that PTX3 could be a therapeutic target for white matter-related diseases, including stroke.