Yushun Zhang

Improvement of inflammatory responses associated with NF-κB pathway in kidneys from diabetic rats

Abstract.Objective:The effects of fenofibrate on the kidneys of diabetic rats were investigated by measuring the inflammatory responses associated with transcription factor nuclear factor kappa-B (NF-κB) pathway.Methods:Male Wistar rats were randomly divided into 3 groups: normal control, diabetes control and diabetes + fenofibrate (10 in each group). The expression of NF-κB p65, plasminogen activator inhibitor-1 (PAI-1), and intercellular adhesion molecule-1 (ICAM-1) in renal cortex was detected by Western blot, RT-PCR, and immunohistochemistry, respectively. Blood lipid profiles, glucose, and urine albumin were measured as well.Results:The expression of NF-kB p65, PAI-1, and ICAM-1 was significantly higher in the diabetes control than those in the normal control, and treatment with fenofibrate inhibited the increased expression of these factors in kidneys by 48.18 %, 35.04 %, and 26.41 %, respectively when compared with the diabetes control, although they were still higher in diabetes + fenofibrate than those in the normal control. Correspondingly, the profiles of lipid were significantly elevated in the diabetes control compared with the normal control, and decreased significantly in diabetes + fenofibrate.Conclusions:Fenofibrate exhibited a downregulating effect on the NF-κB pathway in diabetic kidneys, implying that fenofibrate could be a potential treatment for diabetic nephropathy.

PARP-1 Mediates LPS-Induced HMGB1 Release by Macrophages through Regulation of HMGB1 Acetylation

The high-mobility group box protein 1 (HMGB1) is increasingly recognized as an important inflammatory mediator. In some cases, the release of HMGB1 is regulated by poly(ADP-ribose) polymerase-1 (PARP-1), but the mechanism is still unclear. In this study, we report that PARP-1 activation contributes to LPS-induced PARylation of HMGB1, but the PARylation of HMGB1 is insufficient to direct its migration from the nucleus to the cytoplasm; PARP-1 regulates the translocation of HMGB1 to the cytoplasm through upregulating the acetylation of HMGB1. In mouse bone marrow–derived macrophages, genetic and pharmacological inhibition of PARP-1 suppressed LPS-induced translocation and release of HMGB1. Increased PARylation was accompanied with the nucleus-to-cytoplasm translocation and release of HMGB1 upon LPS exposure, but PARylated HMGB1 was located at the nucleus, unlike acetylated HMGB1 localized at the cytoplasm in an import assay. PARP inhibitor and PARP-1 depletion decreased the activity ratio of histone acetyltransferases to histone deacetylases that elevated after LPS stimulation and impaired LPS-induced acetylation of HMGB1. In addition, PARylation of HMGB1 facilitates its acetylation in an in vitro enzymatic reaction. Furthermore, reactive oxygen species scavenger (N-acetyl-l-cysteine) and the ERK inhibitor (FR180204) impaired LPS-induced PARP activation and HMGB1 release. Our findings suggest that PARP-1 regulates LPS-induced acetylation of HMGB1 in two ways: PARylating HMGB1 to facilitate the latter acetylation and increasing the activity ratio of histone acetyltransferases to histone deacetylases. These studies revealed a new mechanism of PARP-1 in regulating the inflammatory response to endotoxin.

Neutrophil to lymphocyte ratio predicts persistent organ failure and in-hospital mortality in an Asian Chinese population of acute pancreatitis.

Abstract Neutrophil to lymphocyte ratio (NLR) has frequently been reported as a significant indicator of systemic inflammation in various medical conditions. The association underlying NLR and outcomes in patients with acute pancreatitis (AP) has not been evaluated after the publication of revised Atlanta classification. This was a single-center retrospective diagnostic accuracy study and a cohort outcome study. From 2009 to 2015, Asian Chinese patients with a diagnosis of AP presented within 72 hours from symptom onset and underwent neutrophil, lymphocyte assessment at presentation were included in this study. The outcomes were the occurrence of persistent organ failure (POF), intensive care unit (ICU) stay >7 days, and in-hospital mortality. The relationships of baseline neutrophil, lymphocyte count, and NLR with outcomes were assessed with multivariate Cox regression model. A total of 974 consecutive AP patients were clinically eligible. The mean neutrophils, lymphocytes, and NLR for the entire population were 10.23 ± 4.76  × 109/L, 1.05 ± 0.49  × 109/L, and 12.88 ± 11.25. Overall, 223 (22.9%) of the patients developed with POF, 202 (20.7%) spent more than 7 days in ICU, and 58 (6.0%) died during hospitalization. The NLR had a superior predictive performance than neutrophils and lymphocytes. Using an NLR cutoff of 11, the area under the curves (AUC) were 0.76 for POF, 0.74 for longer ICU stay, and 0.79 for death during hospitalization. After multivariate analysis, NLR ≥ 11 was further identified as an independent prognostic factor (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.00–1.89; HR 1.44, 95% CI 1.03–2.00; HR 2.75, 95% CI 1.12–6.76; all P value < 0.05). Following stratification according to quartiles of NLR, positive trends for the association across increasing NLR quartiles and the 3 outcomes were observed (P values for trends across quartiles were 0.007, 0.016, and 0.028, respectively). The adjusted HRs for highest NLR quartile versus the lowest were 2.80 (95% CI 1.42–5.51) (POF), 2.79 (95% CI 1.37–5.70) (ICU > 7 days), and 2.22 (95% CI 0.49–10.05) (mortality), respectively. Our data show for the first time that an increased NLR is an independent risk factor for POF, longer ICU stay, and in-hospital mortality in AP.

The Reduction of Peripheral Blood CD4+ T Cell Indicates Persistent Organ Failure in Acute Pancreatitis.

Objective Few data are available on the potential role of inflammatory mediators and T lymphocytes in persistent organ failure (POF) in acute pancreatitis (AP). We conducted a retrospective study to characterize their role in the progression of POF in AP. Methods A total of 69 AP patients presented within 24 hours from symptom onset developing organ failure (OF) on admission were included in our study. There were 39 patients suffering from POF and 30 from transient OF (TOF). On the 1st, 3rd and 7th days after admission, blood samples were collected for biochemical concentration monitoring including serum IL-1β, IL-6, TNF-α and high-sensitivity C-reactive protein (hs-CRP). The proportions of peripheral CD4+ and CD8+ T lymphocytes were assessed based on flow cytometry simultaneously. Results Patients with POF showed a significantly higher value of IL-1β and hs-CRP on day 7 compared with the group of TOF (P < 0.05). Proportions of CD4+ T cells on days 1, 3, 7 and CD4+ / CD8+ ratio on day 1 were statistically lower in the group of POF patients (P < 0.05). A CD4+ T cell proportion of 30.34% on day 1 predicted POF with an area under the curve (AUC) of 0.798, a sensitivity with 61.54% and specificity with 90.00%, respectively. Conclusions The reduction of peripheral blood CD4+ T lymphocytes is associated with POF in AP, and may act as a potential predictor.

Serum calcium as an indicator of persistent organ failure in acute pancreatitis

Aim Decreased level of serum calcium was commonly seen in critical illness. Hypocalcemia was significantly more frequent in patients with severe form of acute pancreatitis (AP), and a negative correlation was observed between endotoxemia and serum calcium in AP. AP patients with persistent organ failure (POF) show an extremely high mortality. The association underlying calcium and POF in AP has not been characterized. Methods We conducted a retrospective cohort study of adult patients who presented within 72 hours from symptom onset of AP at our center between January 2014 and May 2015. Demographic parameters on admission, organ failure assessment, laboratory data and in‐hospital mortality were compared between patients with and without POF. Uni‐and multi‐variate logistic regression analyses were utilized to evaluated the predictive ability of serum calcium. Results A total of 128 consecutive AP patients, including 29 with POF, were included. Compared to patients without POF, patients with POF showed a significantly lower value of serum calcium on admission (2.11 ± 0.46 vs. 1.55 ± 0.36 mmol/L, P < 0.001). After multivariate logistic analysis, serum calcium remained an independent risk factor for POF (Hazard ratio 0.21, 95% confident interval: 0.08–0.58; P = 0.002). A calcium value of 1.97 mmol/L predicted POF with an area under the curve (AUC) of 0.888, a sensitivity with 89.7% and specificity with 74.8%, respectively. Conclusion Our results indicate that serum calcium on admission is independently associated with POF in AP and may serve as a potential prognostic factor.

Serum lactate dehydrogenase is predictive of persistent organ failure in acute pancreatitis

Purpose: Elevated serum lactate dehydrogenase (LDH) has been reported in a serious of clinical diseases. However, the relationship between LDH and the incidence of persistent organ failure (POF) in acute pancreatitis (AP) has not been characterized. Materials and methods: A total of 105 patients with AP who presented within 72 h from symptom onset between 2014 and 2015 were included in this retrospective study. Demographic parameters and laboratory data on admission were compared between patients with and without POF. Multivariable logistic regression analyses were utilized to evaluate the prognostic value of LDH for predicting POF. Results: 21 patients were diagnosed with POF. Compared to non‐POF, patients with POF showed a significantly higher value of serum LDH on admission (741.57 ± 331.72 vs. 296.08 ± 135.73 U/L, P < 0.001). After multivariate logistic analysis, LDH remained an independent risk factor for POF (Hazard ratio 4.38, 95%CI: 1.42–13.47; P = 0.010). A LDH value of 647 U/L predicted POF with an area under the curve (AUC) of 0.876, a sensitivity with 76.2% and specificity with 98.8%, respectively. Conclusions: Our results indicate that serum LDH on admission is independently associated with POF in AP and may serve as a potential prognostic factor.

Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis

Objective To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis. Methods Clinical data of 1308 patients with acute pancreatitis (AP) were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases) and test group (201 cases). Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity. Results The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively. Conclusions The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.

Inverted U-Shaped Relationship between Central Venous Pressure and Intra-Abdominal Pressure in the Early Phase of Severe Acute Pancreatitis: A Retrospective Study

Objective Many studies have indicated that intra-abdominal pressure (IAP) is positively correlated with central venous pressure (CVP) in severe cases. However, although elevated IAP is common in patients with severe acute pancreatitis (SAP), its relationship with CVP remains unclear. Our study aimed to investigate the association of IAP with CVP in early-phase SAP patients. Methods In total, 116 SAP patients were included in this retrospective study. On the first day of hospitalization, blood samples were collected for biochemical examination and cytokine concentration monitoring. Additionally, a urinary catheter and right subclavian vein catheter were inserted for IAP and CVP measurement, respectively. Other routine clinical data were also recorded. Results Within 24 hours after hospitalization, CVP fluctuated and increased with increasing IAP up to 15.7 mmHg (P = 0.054) but decreased with increasing IAP when the IAP was > 15.7 mmHg (P < 0.001). After adjusting for abdominal perfusion pressure (APP) and mean arterial pressure (MAP), a similar distribution was observed. An inverted U-shaped trend between IAP and CVP was also present in the groups classified according to the patient’s sex, local complications, ascites, and serum amylase levels. Conclusions CVP and IAP have an inverted U-shaped relationship, with a peak at an IAP of 15.7 mmHg in the early phase of SAP. After this peak, CVP decreases as IAP increases. These results have crucial implications for clinical fluid resuscitation in SAP patients. In particular, because one CVP value might be correlated with different IAP values in patients with the same CVP, the volume of fluid needed might be different.

The influence of gravity levels on soot formation for the combustion of ethylene-air mixture

The reduced mechanism coupled with 2D flame code using CHEMKIN II to investigate the effect of gravity on flame structure and soot formation in diffusion flames. The results show that the gravity has a rather significant effect on flame structure and soot formation. The visible flame height and peak soot volume fraction in general increases with the gravity from 1g decreased to 0g. The peak flame temperature decreases with decreasing gravity level. Comparing the calculated results from 1g to 0g, the flame shape becomes wider, the high temperature zone becomes shorter, the mixture velocity has a sharp decrease, the soot volume fraction has a sharp increase and CO and unprovided species distribution becomes wider along radial direction. At normal and half gravity, the flame is buoyancy controlled and the axial velocity is largely independent of the coflow air velocity. At microgravity (0g), the flame is momentum controlled.

Implantation of radioactive 125 I seeds improves the prognosis of locally advanced pancreatic cancer patients: A retrospective study

Locally advanced pancreatic cancer is associated with a very poor prognosis. This study was performed to evaluate whether patients with locally advanced pancreatic cancer benefit from 125I seed implantation. This retrospective study included 224 patients with locally advanced pancreatic cancer, with 137 patients (61.2%) in the implantation (IP) group and 87 (38.9%) in the non-implantation (NIP) group. The survival status, complications and objective curative effects were compared between the groups. The average operative time in the IP group was significantly longer than that in the NIP group (243±51 vs. 214±77 min). The tumor response rates were 9.5% and 0 at the 2nd month after surgery in the IP and NIP groups, respectively (P<0.05). The IP group exhibited a trend toward pain relief at the 6th month after surgery. The global health status scores of the IP group were higher than those of the NIP group at the 3rd and 6th month after surgery. The median survival time in the IP group was significantly longer than that in the NIP group. In conclusion, patients with locally advanced pancreatic cancer can benefit from 125I seed implantation in terms of local tumor control, survival time, pain relief and quality of life.SummaryLocally advanced pancreatic cancer is associated with a very poor prognosis. This study was performed to evaluate whether patients with locally advanced pancreatic cancer benefit from 125I seed implantation. This retrospective study included 224 patients with locally advanced pancreatic cancer, with 137 patients (61.2%) in the implantation (IP) group and 87 (38.9%) in the non-implantation (NIP) group. The survival status, complications and objective curative effects were compared between the groups. The average operative time in the IP group was significantly longer than that in the NIP group (243±51 vs. 214±77 min). The tumor response rates were 9.5% and 0 at the 2nd month after surgery in the IP and NIP groups, respectively (P<0.05). The IP group exhibited a trend toward pain relief at the 6th month after surgery. The global health status scores of the IP group were higher than those of the NIP group at the 3rd and 6th month after surgery. The median survival time in the IP group was significantly longer than that in the NIP group. In conclusion, patients with locally advanced pancreatic cancer can benefit from 125I seed implantation in terms of local tumor control, survival time, pain relief and quality of life.