The TRIM28/miR133a/CD47 axis acts as a potential therapeutic target in pancreatic necrosis by impairing efferocytosis.

Efferocytosis, the clearance of apoptotic cells by macrophages, plays a crucial role in inflammatory responses and effectively prevents secondary necrosis. However, the mechanisms underlying efferocytosis in acute pancreatitis (AP) remain unclear. In this study, we demonstrated the presence of efferocytosis in injured human and mouse pancreatic tissues. We also observed significant upregulation of CD47, an efferocytosis-related the "do not eat me" molecule in injured acinar cells. Subsequently, we used CRISPR-Cas9 gene editing, anti-adeno-associated virus (AAV) gene modification, and anti-CD47 antibody to investigate the potential therapeutic role of AP. CD47 expression was negatively regulated by upstream miR133a, which is controlled by the transcription factor TRIM28. To further investigate the regulation of efferocytosis and reduction of pancreatic necrosis in AP, we used miR-133a-agomir and pancreas-specific AAV-shTRIM28 to modulate CD47 expression. Our findings confirmed that CD47-mediated efferocytosis is critical for preventing pancreatic necrosis and suggest that targeting the TRIM28-miR133a-CD47 axis is clinically relevant for the treatment of AP.

Paeonol protects against acute pancreatitis by inhibiting M1 macrophage polarization via the NLRP3 inflammasomes pathway.

The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1ß and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.

Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy.

To investigate the protein expression levels of cyclin-dependent kinase subunit 2 (CKS2) and the cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significance. A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumour, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analysed the clinical significance of the expression of the two factors. (1) The positivity rates for CKS2 in benign gastric tumour tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, that is, 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumour diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r = .625, P = .000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival (OS) rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the OS rate for patients in the CKS2 (+) group was significantly worse and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse OS (30.1% vs 60.5%, χ2  = 15.67, P = .000). (4) The OS rates of CKS2 (+) CD47 (+) group, CKS2 (+) CD47 (-) group, CKS2 (-) CD47 (+) group, and CKS2 (-) CD47 (-) group were 20.0% (13/65), 58.3% (7/12), 57.1% (8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2 (+) CD47 (+) group was significantly poor. High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

Apigenin regulates the migration, invasion, and autophagy of hepatocellular carcinoma cells by downregulating YAP.

Apigenin is an edible flavonoid with anticancer properties; however, the underlying mechanisms in hepatocellular carcinoma (HCC) remain to be clarified. In the present study, we demonstrated that apigenin decreased the viability of both SMMC-7721 and SK-Hep1 cells in a dose-dependent manner, and inhibited the migration and invasion of HCC cells with different metastatic potential by regulating actin cytoskeletal rearrangements. Moreover, we showed that apigenin decreased the expression of YAP, and subsequently reduced migration and invasion by modulating the expression of the epithelial-mesenchymal transition (EMT) markers, and promoted the autophagy of HCC cells by regulating the expression of autophagy-related genes. Collectively, the present findings might provide a novel mechanism for the therapeutic application of apigenin in HCC.

Emerin knockdown induces the migration and invasion of hepatocellular carcinoma cells by up-regulating the cytoplasmic p21.

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.

Effect of neoadjuvant treatment combined with radical gastrectomy on postoperative complications and prognosis of gastric cancer patients.

OBJECTIVE: To investigate the occurrence of postoperative complications in and factors influencing the prognosis of patients undergoing radical gastrectomy after neoadjuvant chemotherapy. METHODS: A total of 238 patients with gastric cancer were enrolled in this study. There were 194 patients who underwent neoadjuvant chemotherapy before surgery and 44 patients who underwent concurrent radiochemotherapy before surgery. The clinical data of patients and the incidence of postoperative complications were collected. Postoperative complications were graded based on the Clavien-Dindo classification. The impact of postoperative complications on the prognosis of patients was analysed. RESULTS: (1) The overall incidence of postoperative complications was 17.2% (41/238) among all patients. A total of 49 patients experienced postoperative complications, including 12 cases of grade I, 15 cases of grade II, seven cases of grade IIIa, three cases of grade IIIb, seven cases of grade IV, and four cases of grade V complications. A total of 21 patients experienced severe complications. Multivariate analysis indicated that age, body mass index (BMI), and scope of gastrectomy were independent risk factors for postoperative complications (p < .05). (2) The five-year survival rate for the entire group of patients was 58.4%. The five-year survival rate for the complication group and non-complication group were 31.7% and 51.7%, respectively, with a significant difference between the two groups (χ2=15.41p = .000). Based on the severity of complications, the subgroup analysis indicated that the five-year survival rate for patients with severe postoperative complications was 21.1% and that for patients with non-severe complications was 40.9%; the difference was significant (χ2=21.70, p = .000). (3) Multivariate analysis indicated that age, pathological tumour, node, and metastasis (ypTNM) stages II-III, operation time >3.5 h, total gastrectomy, and postoperative complications were independent risk factors affecting the prognosis of patients undergoing radical gastrectomy after neoadjuvant chemotherapy. Postoperative adjuvant therapy was an independent protective factor for patient prognosis (p < .05). CONCLUSION: The incidence of complications in patients undergoing radical gastrectomy after neoadjuvant chemotherapy is closely correlated with patient age and the scope of surgical resection, and the occurrence of severe complications has a significant adverse effect on patient prognosis.

S-doped reduced graphene oxide: a novel peroxidase mimetic and its application in sensitive detection of hydrogen peroxide and glucose.

This article presents a novel peroxidase mimetic by doping S atoms into reduced graphene oxide (rGO), which was synthesized through a facile hydrothermal reaction without any templates or surfactants. The peroxidase-like activity of S-doped rGO (S-rGO) is greatly boosted compared with the pristine rGO, demonstrating the peroxidase-like active sites are dominantly originated in sulfur-containing groups. The steady-state kinetic studies further indicate that S-rGO obeys the typical Michaelis-Menten curves and has a much smaller Michaelis constant (Km) for hydrogen peroxide (H2O2) and 3, 3', 5, 5'-tetramethylbenzidine (TMB). In view of the outstanding performance of S-rGO as a peroxidase mimetic, an efficient and sensitive colorimetric detection platform for H2O2 and glucose has been successfully established. The linear detection for H2O2 is obtained in a range of 0.1-1 µM with an extremely lower detection limit of 0.042 µM, and glucose can be measured in a linear range of 1-100 µM, giving a detection limit of 0.38 µM. This study not only provides a new avenue for the reasonable design of heteroatom-doped carbon-based nanomaterials but also offers meaningful reference for detecting the important biomolecules in biotechnology. Graphical abstract.

Adaptive Ultrasound Tissue Harmonic Imaging Based on an Improved Ensemble Empirical Mode Decomposition Algorithm.

Complete and accurate separation of harmonic components from the ultrasonic radio frequency (RF) echo signals is essential to improve the quality of harmonic imaging. There are limitations in the existing two commonly used separation methods, that is, the subjectivity for the high-pass filtering (S_HPF) method and motion artifacts for the pulse inversion (S_PI) method. A novel separation method called S_CEEMDAN, based on the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) algorithm, is proposed to adaptively separate the second harmonic components for ultrasound tissue harmonic imaging. First, the ensemble size of the CEEMDAN algorithm is calculated adaptively according to the standard deviation of the added white noise. A set of intrinsic mode functions (IMFs) is then obtained by the CEEMDAN algorithm from the ultrasonic RF echo signals. According to the IMF spectra, the IMFs that contain both fundamental and harmonic components are further decomposed. The separation process is performed until all the obtained IMFs have been divided into either fundamental or harmonic categories. Finally, the fundamental and harmonic RF echo signals are obtained from the accumulations of signals from these two categories, respectively. In simulation experiments based on CREANUIS, the S_CEEMDAN-based results are similar to the S_HPF-based results, but better than the S_PI-based results. For the dynamic carotid artery measurements, the contrasts, contrast-to-noise ratios (CNRs), and tissue-to-clutter ratios (TCRs) of the harmonic images based on the S_CEEMDAN are averagely increased by 31.43% and 50.82%, 18.96% and 10.83%, as well as 34.23% and 44.18%, respectively, compared with those based on the S_HPF and S_PI methods. In conclusion, the S_CEEMDAN method provides improved harmonic images owing to its good adaptivity and lower motion artifacts, and is thus a potential alternative to the current methods for ultrasonic harmonic imaging.

Association of the hypertriglyceridemic waist phenotype and severity of acute pancreatitis.

BACKGROUND: The aim of this study was to evaluate the effect of a simple visceral obesity phenotype, known as the hypertriglyceridemic waist phenotype and its quantitative indicator waist circumference index on the severity of acute pancreatitis. MATERIALS AND METHODS: Diagnosis and severity analysis of acute pancreatitis were determined according to the Atlanta classification guidelines, revised in 2012. We considered the hypertriglyceridemic waist phenotype as characterized by increased waist circumference and elevated triglyceride concentrations. We investigated the association between the acute pancreatitis severity and hypertriglyceridemic waist phenotype, including waist circumference index. RESULTS: The hypertriglyceridemic waist phenotype was significantly associated with systemic inflammatory response syndrome, organ failure, and severe acute pancreatitis. The median waist circumference index and demonstration of hypertriglyceridemic waist phenotype were positively correlated with acute pancreatitis severity. In addition, multivariate logistic analysis showed that patients with the hypertriglyceridemic waist phenotype had 1.664 times the risk of organ failure and 1.891 times the risk of systemic inflammatory response syndrome, compared with the other groups. CONCLUSION: Upon admission, the hypertriglyceridemic waist phenotype was strongly associated with acute pancreatitis in patients. This phenotype, including waist circumference index, might be a simple method for evaluating individuals at high risk of severe acute pancreatitis.

Prevalence and clinical characteristics of fatty pancreas in Yangzhou, China: A cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence and risk factors of fatty pancreas in Yangzhou, China. METHODS: This was a cross-sectional study. Initially, 2093 subjects were included in the study. After the exclusion of 865 subjects based on incomplete information, a total of 1228 subjects were selected for further analysis. The subjects were stratified into two groups (the fatty pancreas group and the non-fatty pancreas group) based on the results. Anthropometric and biochemical findings were compared between the groups. RESULTS: Among the 2093 study subjects, 56 (2.7%) had fatty pancreas. Overall, 53 out of 1228 subjects were diagnosed with fatty pancreas and included into the fatty pancreas group. Univariate analysis showed significant differences in age and the prevalence of general obesity, central obesity, alcohol consumption, metabolic syndrome and fatty liver between the two groups (all p < 0.01). The fatty pancreas group had higher levels of aspartate aminotransferase, alanine aminotransferase, serum uric acid, fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein, and lower levels of high-density lipoprotein than did the non-fatty pancreas group (all p < 0.05). Multivariate logistic regression analysis showed that age (p = 0.007), central obesity (p = 0.002) and fatty liver (p = 0.006) were independent risk factors for fatty pancreas, with odds ratios (ORs) of 1.034 (95% confidence interval (CI): 1.009-1.059), 5.364 (95% CI: 1.890-15.227), and 2.666 (95% CI: 1.332-5.338), respectively. CONCLUSION: The prevalence of fatty pancreas in the examined population is approximately 2.7%. Increased age, central obesity and fatty liver disease are independent risk factors for fatty pancreas.

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1ß) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Corrigendum to "Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway".

[This corrects the article DOI: 10.1155/2018/3048532.].

High-dose wogonin exacerbates DSS-induced colitis by up-regulating effector T cell function and inhibiting Treg cell.

Wogonin exerts anti-tumour activities via multiple mechanisms. We have identified that high-dose wogonin (50 or 100 mg/kg) could inhibit the growth of transplanted tumours by directly inducing tumour apoptosis and promoting DC, T and NK cell recruitment into tumour tissues to enhance immune surveillance. However, wogonin (20-50 µM) ex vivo prevents inflammation by inhibiting NF-κB and Erk signalling of macrophages and epithelial cells. It is elusive whether high-dose wogonin promotes or prevents inflammation. To investigate the effects of high-dose wogonin on murine colitis induced by dextran sodium sulphate (DSS), mice were co-treated with DSS and various doses of wogonin. Intraperitoneal administration of wogonin (100 mg/kg) exacerbated DSS-induced murine colitis. More CD4+ CD44+ and CD8+ CD44+ cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4+ CD25+ CD127- and CD4+ CD25+ Foxp3+ cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high-dose wogonin (50-100 µg/ml equivalent to 176-352 µM) could synergize with IL-2 to promote the functions of CD4+ and CD8+ cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF-κB and Erk but down-regulated STAT3 phosphorylation in the CD4+ T cells. Wogonin down-regulated Erk and STAT3-Y705 phosphorylation in the regulatory T cells but promoted NF-κB and STAT3-S727 activation. Our study demonstrated that high-dose wogonin treatments would enhance immune activity by stimulating the effector T cells and by down-regulating regulatory T cells.

Induction of TGF-ß and IL-10 production in dendritic cells using astilbin to inhibit dextran sulfate sodium-induced colitis.

Astilbin, a major bioactive compound from Rhizoma smilacis glabrae, has been reported to possess anti-inflammatory properties. Our study first evaluated astilbin on dextran sulfate sodium (DSS)-induced acute colitis in mice. By intraperitoneal injection of astilbin, the severity of colitis was attenuated, and the serum levels of IL-10 and TGF-ß were increased. Using flow cytometry, a higher number of IL-10(+) dendritic cells (DCs) and TGF-ß(+) DCs and a lower number of CD86(+) DCs, IL-12 p40(+) DCs, and IL-1ß(+) DCs were detected in the spleen of mice with colitis after astilbin treatment. The administration of astilbin also resulted in the upregulation of CD103(+) expression in colonic DCs. In a coculture system, murine bone marrow-derived DCs pretreated with astilbin resulted in an enhanced production of CD4(+)CD25(+)Foxp3(+) T cells. The results of this study show that astilbin could be a candidate drug for inflammatory bowel disease by mediating the regulatory functions of DCs.

[Bilateral regulation of luteolin on spleen cells and sarcoma S180 cells of ICR mice: an experimental study].

OBJECTIVE: To study the regulation of luteolin on spleen cells and sarcoma S180 cells in normal ICR mice. METHODS: Spleen cells and S180 cells were incubated with different concentrations of luteolin (50, 100, 200, and 400 µmol/L). The effect of luteolin on spleen cells and sarcoma S180 cells was determined by MTT assay. The apoptosis was detected using propidium iodide staining flow cytometry. Intracellular reactive oxygen species (ROS) was determined by flow cytometric analysis. Activities of free radicals scavenging were determined by hydroxyl radical and DPPH tests. RESULTS: Compared with the solvent control group, 200 and 400 µmol/L luteolin increased the spleen cells viability (P < 0.05). Luteolin at 100, 200, and 400 µmol/L decreased activities of S180 cells (P < 0.01). The proportion of sub-G1 phase spleen cells was reduced after treated with 200 and 400 µmol/L luteolin (P < 0.05). The proportion of sub-G1 phase S180 cells was elevated after treated with 200 and 400 µmol/L luteolin (P < 0.05). Compared with the solvent control group, levels of intracellular ROS in spleen cells of ICR mice all increased; levels of intracellular ROS in S180 cells all decreased after treated with 50, 100, 200, and 400 µmol/L luteolin (P < 0.05). Luteolin scavenged hydroxyl radical and DPPH in a dose dependent manner. CONCLUSION: Luteolin had bilateral regulation on viability and apoptosis of spleen cells and S180 cells (promoting the viability of spleen cells, inhibiting apoptosis of spleen cells, inhibiting the viability of S180 cells, and promoting apoptosis of S180 cells), which was worth further study and exploration.

Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis.

Damage to pancreatic acinar cells (PAC) and intracellular metabolic disturbances play crucial roles in pancreatic necrosis during acute pancreatitis (AP). Phosphoglycerate kinase 1 (PGK1) is a crucial catalytic enzyme in glycolysis. However, the impact of PGK1-involving glycolysis in regulating metabolic necrosis in AP is unclear. Transcriptome analysis of pancreatic tissues revealed significant changes in the glycolysis pathway and PGK1 which positively correlated with the inflammatory response and oxidative stress injury in AP mice. Furthermore, we observed a substantial increase in PGK1 expression in damaged PAC, positively correlating with PAC necrosis. Treatment with NG52, a specific PGK1 inhibitor, ameliorated pancreatic necrosis, inflammatory damage, and oxidative stress. Transcriptomic data before and after NG52 treatment along with the Programmed Cell Death database confirmed that NG52 protected against PAC damage by rescuing impaired autophagy in AP. Additionally, the protective effect of NG52 was validated following pancreatic duct ligation. These findings underscore the involvement of PGK1 in AP pathogenesis, highlighting that PGK1 inhibition can mitigate AP-induced pancreatic necrosis, attenuate inflammatory and oxidative stress injury, and rescue impaired autophagy. Thus, the study findings suggest a promising interventional target for pancreatic necrosis, offering novel strategies for therapeutic approaches to clinical AP.

A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype.

BACKGROUND: The integrin α6 subunit is part of the integrin α6ß1 and α6ß4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. METHODS: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. RESULTS: The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group. CONCLUSIONS: Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.

CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice.

The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.

Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis.

INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.

Ultrasound simulation of blood with different red blood cell aggregations and concentrations.

BACKGROUND: Considerable progress of ultrasound simulation on blood has enhanced the characterizing of red blood cell (RBC) aggregation. OBJECTIVE: A novel simulation method aims at modeling the blood with different RBC aggregations and concentrations is proposed. METHODS: The modeling process is as follows: (i) A three-dimensional scatterer model is first built by a mapping with a Hilbert space-filling curve from the one-dimensional scatterer distribution. (ii) To illustrate the relationship between the model parameters and the RBC aggregation level, a variety of blood samples are prepared and scanned to acquire their radiofrequency signals in-vitro. (iii) The model parameters are determined by matching the Nakagami-distribution characteristics of envelope signals simulated from the model with those measured from the blood samples. RESULTS: Nakagami metrics m estimated from 15 kinds of blood samples (hematocrits of 20%, 40%, 60% and plasma concentrations of 15%, 30%, 45%, 60%, 75%) are compared with metrics estimated by their corresponding models (each with different eligible parameters). Results show that for the three hematocrit levels, the mean and standard deviation of the root-mean-squared deviations of m are 0.27 ± 0.0026, 0.16 ± 0.0021, 0.12 ± 0.0018 respectively. CONCLUSION: The proposed simulation model provides a viable data source to evaluate the performance of the ultrasound-based methods for quantifying RBC aggregation.