Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis.

OBJECTIVE: Infectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitis METHODS: This study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed. RESULTS: We observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%). CONCLUSION: This study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.

Comparison between auto-trilevel and bilevel positive airway pressure ventilation for treatment of patients with concurrent obesity hypoventilation syndrome and obstructive sleep apnea syndrome.

PURPOSE: Our study aims to compare the difference in clinical efficacy between auto-trilevel positive airway pressure (auto-trilevel PAP) ventilator and conventional fixed bilevel positive airway pressure (BiPAP) ventilator for obesity hypoventilation syndrome (OHS) patients with coexisting moderate or severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Twenty-three OHS patients with moderate or severe OSAHS enrolled between January 2015 and September 2017 underwent ventilation by three different modes of positive airway pressure (PAP) for 8 h per night. A single variable mode was applied at the first night followed by two nights when no PAP therapy was carried out as a washout period between each mode. The inspiratory positive airway pressure (IPAP) decided by PaCO2 was consistently used for modes 1, 2, and 3. In mode 1, the expiratory positive airway pressure (EPAP) issued by BiPAP was decided by the minimal PAP levels for cessation of snoring. However, in mode 2, the EPAP was fixed at 3 cmH2O higher than this value. With the use of auto-trilevel PAP in mode 3, the EPAP was set to initially match that of mode 1 but the end of EPAP (EEPAP) was automatically regulated to be elevated according to upper airway patency condition. We also compared the following parameters including apnea hypopnea index (AHI), minimal SpO2 (miniSpO2), arousal index, and sleep efficiency during sleep; PaCO2 in the morning and Epword sleepiness score (ESS) at daytime were measured prior to and during PAP treatment as well as between three selected PAP modes. RESULTS: Compared with the parameters before ventilation therapies, all three variable modes of ventilation were associated with a higher nocturnal miniSpO2 and sleep efficiency (all P < 0.01). Among the three variable modes, mode 3 resulted in not only the lowest arousal index and daytime ESS but also the highest sleep efficiency. Compared to mode 1, mode 2 demonstrated a significantly reduced AHI and an elevated miniSpO2 and morning PaCO2 (all P < 0.05), while mode 3 was associated with a decreased AHI, an increased miniSpO2 (all P < 0.05), and no statistical change of PaCO2 following the end of PAP treatment (P > 0.05). Comparison between mode 2 and mode 3 revealed that mode 3 had a significantly lower PaCO2 (P < 0.05), but displayed no remarkable changes of AHI and miniSpO2 (all P > 0.05). CONCLUSION: Compared to fixed BiPAP ventilation, auto-trilevel PAP ventilation could more effectively correct hypercapnia, achieve lower index of nocturnal apnea and hypopnea, more improved sleep quality, and lower daytime sleepiness score. Auto-trilevel PAP ventilation is therefore more efficacious than conventional BiPAP ventilation in non-invasive ventilation therapy for OHS patients with concurrent moderate or severe OSAHS.

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients.

PURPOSE: Although bilevel positive airway pressure (Bilevel PAP) therapy is usually used for overlap syndrome (OS), there is still a portion of OS patients in whom Bilevel PAP therapy could not simultaneously eliminate residual apnea events and hypercapnia. The current study was expected to explore whether auto-trilevel positive airway pressure (auto-trilevel PAP) therapy with auto-adjusting end expiratory positive airway pressure (EEPAP) can serve as a better alternative for these patients. METHODS: From January of 2014 to June of 2016, 32 hypercapnic OS patients with stable chronic obstructive pulmonary diseases (COPD) and moderate-to-severe obstructive sleep apnea syndrome (OSAS) were recruited. Three variable modes of positive airway pressure (PAP) from the ventilator (Prisma25ST, Weinmann Inc., Germany) were applicated for 8 h per night. We performed the design of each mode at each night with an interval of two nights with no PAP treatment as a washout period among different modes. In Bilevel-1 mode (Bilevel-1), the expiratory positive airway pressure (EPAP) delivered from Bilevel PAP was always set as the lowest PAP for abolishment of snoring. For each patient, the inspiratory positive airway pressure (IPAP) was constantly set the same as the minimal pressure for keeping end-tidal CO2 (ETCO2) ≤45 mmHg for all three modes. However, the EPAP issued by Bilevel PAP in Bilevel-2 mode (Bilevel-2) was kept 3 cmH2O higher than that in Bilevel-1. In auto-trilevel mode (auto-trilevel) with auto-trilevel PAP, the initial part of EPAP was fixed at the same PAP as that in Bilevel-1 while the EEPAP was automatically regulated to rise at a range of ≤4 cmH2O based on nasal airflow wave changes. Comparisons were made for parameters before and during or following treatment as well as among different PAP therapy modes. The following parameters were compared such as nocturnal apnea hypopnea index (AHI), minimal SpO2 (minSpO2), arousal index, sleep structure and efficiency, morning PaCO2, and daytime Epworth Sleepiness Scale (ESS). RESULTS: Compared with the parameters before PAP therapies, during each mode of PAP treatment, significant reduction was detected in nocturnal AHI, arousal index, morning PaCO2, and daytime ESS while significant elevation was revealed in nocturnal minSpO2 and sleep efficiency (all P < 0.01). Comparison among three PAP modes indicated that under the same IPAP, the auto-trilevel PAP mode could result in the lowest arousal index, daytime ESS, and the highest sleep efficiency. Compared with Bilevel-1, it was detected that (a) AHI was lower but minSpO2 was higher in both Bilevel-2 and auto-trilevel (all P < 0.05) and (b) morning PaCO2 showed no statistical difference from that in auto-trilevel but displayed higher in Bilevel-2 (P < 0.05). Compared with Bilevel-2, in auto-trilevel, both AHI and minSpO2 showed no obvious changes (all P > 0.05) except with a lower morning PaCO2 (P < 0.05). CONCLUSION: Auto-trilevel PAP therapy was superior over conventional Bilevel PAP therapy for hypercapnic OS patients with their OSAS moderate to severe, since auto-trilevel PAP was more efficacious in synchronous elimination of residual obstructive apnea events and CO2 retention as well as in obtaining a better sleep quality and milder daytime drowsiness.

Fluid shear stress promotes osteoblast proliferation via the Gαq-ERK5 signaling pathway.

Fluid shear stress (FSS) is a ubiquitous mechanical stimulus that potently promotes osteoblast proliferation. Previously, we reported that extracellular signal-regulated kinase 5 (ERK5) is essential for FSS-induced osteoblast proliferation. However, the precise mechanism by which FSS promotes osteoblast proliferation via ERK5 activation is poorly understood. The aim of this study was to determine the critical role of Gαq in FSS-induced ERK5 phosphorylation and osteoblast proliferation, as well as the downstream targets of the Gαq-ERK5 pathway. MC3T3-E1 cells were transfected with 50 nM Gαq siRNA, treated with 5 mM XMD8-92 (a highly selective inhibitor of ERK5 activity), and/or exposed to FSS (12 dyn/cm(2)). Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression levels of Gαq, P-ERK5, ERK5, Cyclin B1, and CDK1 were analyzed by Western blot. Physiological FSS exposure for 60 min remarkably promoted MC3T3-E1 cell proliferation, however, this effect was suppressed by siRNA-mediated Gαq knockdown or inhibition of ERK5 activity by XMD8-92 treatment, suggesting that Gαq and ERK5 might modulate FSS-increased osteoblast proliferation. Furthermore, ERK5 phosphorylation was dramatically inhibited by Gαq siRNA. In addition, our study further revealed that FSS treatment of MC3T3-E1 cells for 60 min markedly upregulated the protein expression levels of Cyclin B1 and CDK1, and this increased expression was predominantly blocked by Gαq siRNA or XMD8-92 treatment. We propose that FSS acts on the Gαq-ERK5 signaling pathway to upregulate Cyclin B1 and CDK1 expression, thereby resulting in MC3T3-E1 cell proliferation. Thus, the Gαq-ERK5 signaling pathway may provide useful information regarding the treatment of bone metabolic disease.

Removal of BTEX from water system by synergistic flocculation of biosurfactant and iron salt.

The adsorption micelle flocculation (AMF) effect of biosurfactants (rhamnolipids, RL) and polymerized ferric sulfate (PFS) on the removal of low molecular weight benzoic acid (benzoic acid and p-methyl benzoic acid) and phenol (2,4-dichlorophenol and bisphenol A) organics was investigated. The coexistence system of RL and organic matter was constructed, and the effects of pH, Fe concentration, RL concentration and initial concentration of organic matter on the removal effect were discussed. For benzoic acid and p-methyl benzoic acid, the increase of Fe and RL concentrations was beneficial to their removal rates under weak acidic conditions, and the removal rate of the coexistence system was higher for methyl benzoic acid (87.7 %) than for benzoic acid (78.6 %), which might be attributed to the stronger hydrophobicity of the coexistence system for methyl benzoic acid; while for 2,4-dichlorophenol and bisphenol A, pH and Fe concentration changes had less effect on the removal rate, but the increase in RL concentration was favorable to the removal rate, which was 93.1 % and 86.7 % for BPA and 2,4-dichlorophenol, respectively. These findings provide feasible ideas and directions for the removal of organics by AMF using biosurfactants.

Serum metabolomics study for acute attack of chronic pancreatitis.

BACKGROUND & AIMS: Chronic pancreatitis (CP) is an inflammatory disease characterized by irreversible changes. However, acute CP attacks can lead to various complications and affect patient prognosis. Therefore, this study aimed to identify reliable candidate metabolic biomarkers for diagnosing acute CP attacks and complement candidate diagnostic markers for CP. METHODS: A total of 139 serum specimens were prospectively included in three consecutive exploratory, identification, and validation studies. All samples were analyzed for candidate diagnostic biomarkers and metabolic pathways using a liquid chromatography-mass spectrometer. RESULTS: Serum metabolic profiles differed between patients with CP and non-pancreatic disease controls, and 239 potential metabolic biomarkers for diagnosing CP were identified. Based on identification and validation studies, Diacylglycerol(16:0/18:4), 16-F1-PhytoP, N-(hexacosanoyl)-tetradecasphing-4-enine, carnosic acid, and Auxin b were identified as biomarkers for distinguishing acute attacks from non-acute attacks in patients with CP. The area under the curve of the Diacylglycerol(16:0/18:4) was 0.969 (95% confidence interval, 0.869-1) in the validation study. CONCLUSIONS: To the best of our knowledge, this is the first prospective cohort study to identify and validate a metabolomic signature in serum for diagnosing acute attacks of CP. In addition, our study identified 239 potential biomarkers for CP diagnosis.

Sialoglycoproteins isolated from the eggs of Carassius auratus alleviates CCL4-induced liver injury via downregulation of the IRE-α/NF-κB signaling pathway.

Chemical liver injury is a common cause of liver disease primarily characterized by oxidative stress and inflammation. Sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) have been proved to exhibit the antioxidant effect. However, the effect of Ca-SGP on liver injury remains unclear. Thus, this study was aimed to determine the effect of Ca-SGP on CCL4-induced chronic chemical liver injury and explore the underlying molecular mechanism. Results showed that Ca-SGP mitigated the elevated levels of serum alanine aminotransferase and aspartate aminotransferase, inhibited the systemic oxidative stress, and reduced the levels of pro-inflammatory factors TNF-α and IL-1ß. Histologic results showed that Ca-SGP supplements alleviated hepatocyte necrosis and liver macrophage infiltration. Further, Ca-SGP supplement decreased endoplasmic reticulum stress-related proteins expression, including BiP, IRE-α, p-IRE-α, and TRAF2, and further inhibited the trigger of the NF-κB pathway. In summary, Ca-SGP might be a novel agent for liver injury treatment, and its potential mechanism was related to the inhibition of liver inflammation induced by the endoplasmic reticulum. PRACTICAL APPLICATION: The fish egg is an important by-product in fish processing. Carassius auratus is a common freshwater fish with large catches and low prices. However, the eggs of C. auratus are usually direct discard or processed into salted roe products, and the quality and value of these salted products are unsatisfactory. In this current study, we confirmed that sialoglycoproteins isolated from the C. auratus eggs have the potential for the treatment of liver injury and determined that its mechanism is related to the endoplasmic reticulum and inflammation, which put forward a new idea for solving the by-product of fish processing.

Correction: Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation.

[This corrects the article DOI: 10.1371/journal.pone.0167744.].

Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases, such as atherosclerosis. HHcy promotes atherogenesis by modifying the histone methylation patterns and miRNA regulation. In this study, we investigated the effects of homocysteine (Hcy) on the expression of enhancer of zeste homolog 2 (EZH2), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased EZH2 expression, which is regulated by miR-92a. The levels of EZH2 and H3K27me3 were increased in the aorta of ApoE-/- mice fed a high-methionine diet for 16 weeks, whereas miR-92a expression was decreased. Over-expression of EZH2 increased H3K27me3 level and the accumulation of total cholesterol and triglycerides in the foam cells. Furthermore, upregulation of miR-92a reduced EZH2 expression in the foam cells. These data suggested that EZH2 plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-92a may be a novel therapeutic target in Hcy-related atherosclerosis.