COMPARISON AMONG PRESEPSIN, PROCALCITONIN, AND C-REACTIVE PROTEIN IN PREDICTING BLOOD CULTURE POSITIVITY AND PATHOGEN IN SEPSIS PATIENTS.

ABSTRACT: Background: Sepsis is caused by the invasion of the bloodstream by microorganisms from local sites of infection, leading to high mortality. This study aimed to compare the predictive ability of the biomarkers presepsin, procalcitonin (PCT), and C-reactive protein for bacteraemia. Methods: In this retrospective, multicentre study, a dataset of patients with sepsis who were prospectively enrolled between November 2017 and June 2021 was analyzed. The performances of the biomarkers for predicting positive blood cultures and infection with specific pathogens were assessed by the areas under the receiver operating characteristic curves (AUCs). The independent effects of the pathogen and foci of infection on presepsin and PCT levels were assessed by linear logistic regression models. Results: A total of 577 patients with 170 positive blood cultures (29.5%) were enrolled. The AUC achieved using PCT levels (0.856) was significantly higher than that achieved using presepsin (0.786, P = 0.0200) and C-reactive protein (0.550, P < 0.0001) levels in predicting bacteraemia. The combined analysis of PCT and presepsin levels led to a significantly higher AUC than the analysis of PCT levels alone for predicting blood culture positivity (0.877 vs. 0.856, P = 0.0344) and gram-negative bacteraemia (0.900 vs. 0.875, P = 0.0216). In a linear regression model, the elevated concentrations of presepsin and PCT were both independently related to Escherichia coli , Klebsiella species, Pseudomonas species, and Streptococcus species infections and Sequential Organ Failure Assessment score. Presepsin levels were also associated with Acinetobacter species and abdominal infection, and PCT levels were positively associated with other Enterobacteriaceae and negatively associated with respiratory infection. Combined analysis of presepsin and PCT levels provided a high sensitivity and specificity in identifying E. coli or Klebsiella species infection. Conclusions: Presepsin and PCT were promising markers for predicting bacteraemia and common pathogens at the time of sepsis onset with a synergistic effect.

The effect of cerebral blood perfusion on the correlation between cerebral stroke onset time and synthetic T2 mapping: a pilot study.

Background: In patients with acute stroke with an unknown onset time, the T2 relaxation time (qT2) in the region of diffusion restriction is associated with the time from symptom onset. We hypothesized that cerebral blood flow (CBF) status assessed using arterial spin labeling magnetic resonance (MR) imaging would influence the association between qT2 and stroke onset time. The purpose of this study was to preliminarily investigate the effects of diffusion-weighted imaging-T2-weighted fluid-attenuated inversion recovery (DWI-T2-FLAIR) mismatch and T2 mapping value changes on the accuracy of stroke onset time in patients with different CBF perfusion statuses. Methods: A total of 94 patients with acute ischemic stroke (symptom onset time ≤24 h) admitted to the Liaoning Thrombus Treatment Center of Integrated Chinese and Western Medicine, Liaoning, China, were enrolled in this cross-sectional retrospective study. MR image compilation (MAGiC), DWI, 3-dimensional (3D) pseudo-continuous arterial spin labeling perfusion (pcASL), and T2-FLAIR images were acquired. The T2 map was directly generated from MAGiC. The CBF map was assessed using 3D pcASL. Patients were divided into the good CBF group (CBF >25 mL/100 g/min) and the poor CBF group (CBF ≤25 mL/100 g/min). The T2 relaxation time (qT2), T2 relaxation time ratio (qT2 ratio), and T2-FLAIR signal intensity ratio (T2-FLAIR ratio) between the ischemic and nonischemic region of the contralateral side were calculated. The correlations between the qT2, qT2 ratio, T2-FLAIR ratio, and stroke onset time were statistically analyzed in the different CBF groups. Results: In DWI-restricted areas, the time from symptom onset correlated with the qT2 and T2-FLAIR ratio. We identified an interaction between this association and CBF status. In the poor CBF group, stroke onset time most significantly correlated with the qT2 ratio (r=0.493; P<0.001), followed by the qT2 (r=0.409; P=0.001) and the T2-FLAIR ratio (r=0.385; P=0.003). In the total patient group, the stroke onset time moderately correlated with the qT2 ratio (r=0.438; P<0.001) but weakly correlated with the qT2 (r=0.314; P=0.002) and the T2-FLAIR ratio (r=0.352; P=0.001). In the good CBF group, no obvious correlations were found between stroke onset time and all MR quantitative indicators. Conclusions: In patients with reduced cerebral perfusion, the stroke onset time correlated with changes in the T2-FLAIR signal and qT2. The stratified analysis showed that the qT2 ratio had a higher correlation with stroke onset time than with the qT2 and T2-FLAIR ratio.

Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development.

Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.

Plasma metabolomics and lipidomics signatures of motoric cognitive risk syndrome in community-dwelling older adults.

Introduction: Motoric cognitive risk syndrome (MCR) is characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Metabolomics and lipidomics may potentiate disclosure of the underlying mechanisms of MCR. Methods: This was a cross-sectional study from the West China Health and Aging Trend cohort study (WCHAT). The operational definition of MCR is the presence of SCCs and SG without dementia or mobility disability. The test and analysis were based on untargeted metabolomics and lipidomics, consensus clustering, lasso regression and 10-fold cross-validation. Results: This study enrolled 6,031 individuals for clinical analysis and 577 plasma samples for omics analysis. The overall prevalence of MCR was 9.7%, and the prevalence of MCR-only, assessed cognitive impairment-only (CI-only) and MCR-CI were 7.5, 13.3, and 2.1%, respectively. By consensus clustering analysis, MCR-only was clustered into three metabolic subtypes, MCR-I, MCR-II and MCR-III. Clinically, body fat mass (OR = 0.89, CI = 0.82-0.96) was negatively correlated with MCR-I, and comorbidity (OR = 2.19, CI = 1.10-4.38) was positively correlated with MCR-III. Diabetes mellitus had the highest ORs above 1 in MCR-II and MCR-III (OR = 3.18, CI = 1.02-9.91; OR = 2.83, CI = 1.33-6.04, respectively). The risk metabolites of MCR-III showed relatively high similarity with those of cognitive impairment. Notably, L-proline, L-cystine, ADMA, and N1-acetylspermidine were significantly changed in MCR-only, and PC(40:3), SM(32:1), TG(51:3), eicosanoic acid(20:1), methyl-D-galactoside and TG(50:3) contributed most to the prediction model for MCR-III. Interpretation: Pre-dementia syndrome of MCR has distinct metabolic subtypes, and SCCs and SG may cause different metabolic changes to develop MCR.

Effect of roasting temperature and time on volatile compounds, total tocopherols, and fatty acids of flaxseed oil.

Roasting affects the physicochemical and nutritional qualities of flaxseed oil (FSO). The FSO samples were extracted from the roasting flaxseeds at 10-, 20-, and 30-min points and at different temperatures (140°C, 160°C, and 180°C). A total of 61 volatile compounds were identified, and the quantity of the volatile compounds increased significantly (p < 0.05) after roasting. The maximum aldehyde (25.83%) and heterocyclic content (29.26%) was obtained from the samples roasted at 200°C for 20 and 30 min, respectively. The predominant fatty acid in FSO samples was linolenic acid (46.01%-49.35%), which changed dynamically during roasting. The loss of α-, γ-, and δ-tocopherol after roasting was 28.73, 109.78, and 6.67 mg/100 g, respectively. The principal component analysis and hierarchical cluster analysis results showed good discrimination of the different FSO samples into three groups, which were mainly related to the roasting time. Therefore, it can be concluded that roasting time has a stronger effect on the volatile composition of FSO than the temperature during the roasting process. This work provides a basis for improving the aroma of FSO. PRACTICAL APPLICATION: The roasting process is used to extract flaxseed oil (FSO) from flaxseeds. Studying the physicochemical properties and quality characteristics of FSO under diverse roasting conditions is an important step in producing FSO in the food industry, which can give precise instructions to produce flaxseed oil in factories. The results of this study document the volatile constituents generated in FSO samples extracted from flaxseeds during roasting, which may help manufacturers, who are trying to develop natural and artificial FSO flavors.

Higher uric acid serum levels are associated with sarcopenia in west China: a cross-sectional study.

BACKGROUND: Sarcopenia is the decline in muscle strength and mass attributed to aging. The pathogenesis of sarcopenia may be triggered by oxidative stress and uric acid (UA) has strong antioxidant properties. The aim of this study was to investigate the relationship between UA and sarcopenia in community-dwelling adults of West China using the baseline data of West China Health and Aging Trend (WCHAT) study. DESIGN: A cross-sectional study. METHODS: 4236 adults aged 50 years or older in communities of west China were enrolled in this study. We applied Asian Working Group for Sarcopenia (AWGS) 2019 criteria to define sarcopenia. Muscle mass was measured using skeletal muscle index (SMI) based on bioimpedance analysis (BIA). Handgrip strength (HGS) and gait speed (GS) were recorded, respectively. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. General linear model was done to investigate the relationship between UA and HGS/GS/SMI, adjusting age, ethnic groups, sleeping quality, education level, cognitive function, smoking history, drinking history, ADL score, and chronic disease. RESULTS: Participants were grouped according to UA quartiles by gender. After adjusting for potential confounders, a negative association between serum UA levels and sarcopenia was shown both in men and women. And a significant association between serum UA levels and HGS in women was shown as an inverted J shape. Besides, a positive association between the UA quartiles and SMI was observed, irrespective of gender. CONCLUSIONS: Our results showed that higher uric acid levels were significantly correlated with higher muscle mass and grip strength among Chinese adults aged over 50. Higher UA serum levels might slow down the progression of sarcopenia.

Comorbid anxiety and depression, depression, and anxiety in comparison in multi-ethnic community of west China: prevalence, metabolic profile, and related factors.

OBJECTIVES: To identify the prevalence, lifestyle factors, chronic disease status, and assessing the metabolic profile, comparing key differences in a cohort of subjects aged at least 50 years old among depression combined anxiety, depression and anxiety in a multi-ethnic population in west China. METHODS: A large multi-ethnic sample of 6838 participants aged 50 years old (mean age 62.4 ± 8.3 years) from West China Health and Aging Trend (WCHAT) study was analyzed. We categorized all participants into four groups: (a) comorbid anxiety and depression symptomology (CAD), (b) anxiety only, (c) depression only, or (d) neither depression nor anxiety. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). GDS-15 scores ≥5 indicate depression. Anxiety status was assessed using Generalized Anxiety Disorder (GAD-7) instrument and the scores ≥5 was considered as having anxiety. Different variables like anthropometry measures, life styles, cognitive function and chronic disease comorbidities were collected and serum parameters were tested. Multivariable logistic regression adjusted for age, sex, and ethnicity was done to compare between those with the mental outcomes and without. RESULTS: The proportions of CAD, anxiety and depression were 9.0%, 12.8% and 10.6% respectively with ethnic diversity. The 'comorbid' group shown greater frequency of being female, having a lower educational level, higher prevalence of being single/divorced/widowed, drinking alcohol and smoking, more chronic disease profile and cognitive decline compared with individuals with only one disorder. And the metabolic profile showed differences in albumin, total protein, creatinine, uric acid, thyroid hormones in comparing CAD symptomology and the 'neither symptomology'. CONCLUSIONS: Yi, Qiang and Uyghur ethnic groups have a higher prevalence of mental disease compared with Han in west China. And these mental disease had a distinct risk factor profile in age, sex, educational level, chronic disease and cognitive function. Vitamin D levels were lower among those with mental disease compared to those without.

Predictive value of serum cystatin C for risk of mortality in severe and critically ill patients with COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. COVID-19 is clinically categorized into mild, moderate, severe, and critical illness. Acute kidney injury is an independent risk factor for poor prognosis in patients with. Serum cystatin C (sCys C) is considered a more sensitive biomarker for early renal insufficiency than conventional indicators of renal function. Early detection of risk factors that affect the prognosis of severe and critically ill patients while using active and effective treatment measures is very important and can effectively reduce the potential mortality rate. AIM: To determine the predictive value of sCys C for the prognosis of patients with COVID-19. METHODS: The clinical data of 101 severe and critically ill patients with COVID-19 at a designated hospital in Wuhan, Hubei Province, China were analyzed retrospectively. According to the clinical outcome, the patients were divided into a discharge group (64 cases) and a death group (37 cases). The general information, underlying diseases, and laboratory examination indexes of the two groups were compared. Multivariate Cox regression was used to explore the relationship between sCys C and prognosis. The receiver operating characteristic (ROC) curve was used to demonstrate the sensitivity and specificity of sCys C and its optimal cut-off value for predicting death. RESULTS: There were significant differences in age, sCys C, creatinine, C-reactive protein, serum albumin, creatine kinase-MB, alkaline phosphatase, lactate dehydrogenase, neutrophil count, and lymphocyte count between the two groups (P < 0.001). Multivariate logistic regression analysis showed that sCys C was an independent risk factor for death in patients with COVID-19 (Odds ratio = 1.812, 95% confidence interval [CI]: 1.300-2.527, P < 0.001). The area under the ROC curve was 0.755 (95%CI: 1.300-2.527), the cut-off value was 0.80, the specificity was 0.562, and the sensitivity was 0.865. CONCLUSION: sCys C is an independent risk factor for death in patients with COVID-19. Patients with a sCys C level of 0.80 mg/L or greater are at a high risk of death.

The impact of functional status on LOS and readmission in older patients in geriatrics department: a cohort study.

BACKGROUND: Length of hospital stay (LOS) and readmission are important outcomes for older inpatients. The association between functional status on admission and outcomes has not been well investigated in Chinese elderly. OBJECTIVES: To detect the impact of function impairments on LOS and 90-day readmission in a population of Chinese elderly inpatients. METHODS: This is a prospective cohort study. All new patients over 60 years in geriatrics department of a university hospital in Western China from June to August 2016 were enrolled. Activities of daily living (ADL) and Instrumental ADL (IADL) on admission were evaluated with Barthel Index and Lawton IADL. Outcomes were LOS and 90-day readmission. LOS was calculated as the total days of hospital stay. Readmission was investigated through telephone interviews after discharge. Pearson Chi-square test was used to detect the associations. Binary logistic regression was used to detect the association of function status on admission with LOS and readmission. RESULTS: A total of 225 patients were enrolled. Mean age 82.41 (± 7.316; 63-99), 31.1% were females. Overall, 64.9% of the patients were hospitalized longer than 14 days and 33.30% experienced a 90-day readmission. Following an adjustment for age, gender, marital status, education level, smoking, alcohol, nutrition status, and admission location, the binary logistic regression models showed that both ADL impairment (OR 2.03; 95% CI 1.06-3.87) and IADL impairment (OR 2.54; 95% CI 1.28-5.01) were independent predictors for LOS. ADL impairment was an independent predictor for 90-day readmission (OR 2.26; 95% CI 1.14-4.47), while IADL impairment was not associated with readmission (OR 1.43; 95% CI 0.68-3.02). CONCLUSION: Functional status on admission is the predictor of LOS and 90-day readmission in Chinese older inpatients from the geriatric department of a university hospital.

Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells.

Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investigated the effects of Ox40 on the conversion and function of DNT in vitro and in vivo without IL-2. We found that OX86 (an Ox40 agonist) increased the conversion rate of DNT but failed to enhance the suppressive function of DNT. Ox40 deficiency profoundly decreased the conversion rate and suppressive function of DNT. This suppression decline was caused by effects of Ox40 on proliferation and apoptosis independent of Perforin, Granzyme B and Fas ligand. Ox40 deficiency influenced the regulatory function of DNT through multiple signals, such as Cxcr3, Cd160 and Cd30, independently of Prf, Gzmb and Fasl. In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.

Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells.

CD4+ T-cell-converted CD4-CD8- double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that the OX40 molecule was highly expressed on cDNT. The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. OX40 promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-κB cell signaling played an important role in the transmission of essential division and survival signals through OX40 in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of the OX40 molecule. IL-2 promoted OX40 expression via downregulating the PPARα expression. In conclusion, we elucidated that OX40 is a key molecule that regulates cDNT proliferation and survival. IL-2 promoted OX40 expression by downregulating the PPARα binding to the OX40 promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT.

The Protection of Midazolam Against Immune Mediated Liver Injury Induced by Lipopolysaccharide and Galactosamine in Mice.

Objectives: Liver macrophages agitated by Lipopolysaccharide (LPS) can enhance immuno-inflammatory responses in the liver which mediate liver injury and result in dysfunction. Midazolam has been reported to have inhibitory effects on activated immunity and escalated inflammation, however, what the effects of midazolam on the liver injury caused by excessive immuno-inflammatory response in sepsis, and what influence it will exert on inflamed liver macrophages need to be elucidated. Methods: In the present study, LPS and galactosamine-induced acute liver injury mice were used to observe the effect of midazolam in vivo. LPS-stimulated bone marrow cells were used to evaluate the influence of midazolam on monocytes in vitro. Results: Midazolam prevented liver tissue injury and decreased serum alanine transaminase (ALT) level in LPS plus galactosamine treated mice. Mechanistically, midazolam suppressed tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) produced by LPS stimulated liver macrophages in vivo and bone marrow monocytes in vitro, and reduced the expression of major histocompatibility complex class II (MHC II), cluster of differentiation 40 and 86 (CD40 and CD86) on the cell surface. These results could be reversed by PK-11195, a peripheral benzodiazepine receptor (PBR) blocker. Conclusion: Midazolam can prevent liver from LPS-induced immune mediated liver injury by inhibiting inflammation and immune activation in liver macrophages.

A case report of blunt gastric perforation treated with endoscopic clip closure.

RATIONALE: Gastroscopymay not only allow identification of gastric injury, but may also facilitate prompt repair. PATIENT CONCERNS: A 39-year-old male patient was admitted 3 hours after abdominal injury caused by penetration of a screwdriver. Physical examination and computed tomography showed no evidence of gastric injury. However, 3000 mL fresh blood was vomited during the subsequent observation period. DIAGNOSES: Gastroscopy identified a ruptured artery and gastric perforation. INTERVENTIONS: Repaired immediately using titanium clips. OUTCOMES: After operation, the patient recovered well without complications. No more bleeding was observed after the operation. LESSON SUBSECTIONS ASPER STYLE: Interventional endoscopy has evolved as an effective alternative to primary surgery for treating gastrointestinal perforation.

Taurine Promotes the Cartilaginous Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Vitro.

Taurine has been reported to influence osteogenic differentiation, but the role of taurine on cartilaginous differentiation using human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) remains unclear. In this study, we investigated the effect of taurine (0, 1, 5 and 10 mM) on the proliferation and chondrogenesis of hUC-MSCs by analyzing cell proliferation, accumulation of glycosaminoglycans and expression of cartilage specific mRNA. The results show though taurine did not affected the proliferation of hUC-MSCs, 5 mM of taurine is sufficient to enhanced the accumulation of glycosaminoglycans and up-regulate cartilage specific mRNA expression, namely collagen type II, aggrecan and SOX9. Taurine also inhibits chondrocyte dedifferentiation by reducing expression of collagen type I mRNA. Taken together, our study reveals that taurine promotes and maintains the chondrogenesis of hUC-MSCs.