Development and validation of a nomogram for predicting survival in patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a complex and heterogeneous disease. We aimed to design and validate a prognostic nomogram for improving the prediction of short-term survival in patients with AP. METHODS: The clinical data of 632 patients with AP were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The nomogram for the prediction of 30-day, 60-day and 90-day survival was developed by incorporating the risk factors identified by multivariate Cox analyses. RESULTS: Multivariate Cox proportional hazard model analysis showed that age (hazard ratio [HR]=1.06, 95% confidence interval [95% CI] 1.03-1.08, P<0.001), white blood cell count (HR=1.03, 95% CI 1.00-1.06, P=0.046), systolic blood pressure (HR=0.99, 95% CI 0.97-1.00, P=0.015), serum lactate level (HR=1.10, 95% CI 1.01-1.20, P=0.023), and Simplified Acute Physiology Score II (HR=1.04, 95% CI 1.02-1.06, P<0.001) were independent predictors of 90-day mortality in patients with AP. A prognostic nomogram model for 30-day, 60-day, and 90-day survival based on these variables was built. Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting 30-day, 60-day, and 90-day survival (area under the ROC curve: 0.796, 0.812, and 0.854, respectively; bootstrap-corrected C-index value: 0.782, 0.799, and 0.846, respectively). CONCLUSION: The nomogram-based prognostic model was able to accurately predict 30-day, 60-day, and 90-day survival outcomes and thus may be of value for risk stratification and clinical decision-making for critically ill patients with AP.

[Effect of serum containing Xihuang pill on proliferation of human breast cancer cell line MDA-MB-435 and MCF-7 Cells].

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (P<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (P<0.05), and the ratio of Bcl-2/Bax was decreased (P<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (P<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.

Significant sex-based outcome differences in severely injured Chinese trauma patients.

A body of experimental evidence suggests that the female sex is associated with a lower risk of mortality after trauma-hemorrhage. However, controversy remains regarding the mechanism responsible for these differences and if basic science findings correspond to clinical differences. Racial disparities in trauma outcomes have also been increasingly described. Until now, research on the association between sex and trauma patient outcomes mainly focused on patients in Europe and the United States. Our research attempted to determine whether the female sex is associated with a survival advantage among severely injured Chinese trauma patients. A retrospective analysis of data derived from the Emergency Intensive Care Unit of the Shanghai Sixth People';s Hospital Acute Trauma Center during 2010 to 2013 was performed to characterize differences in sex-based outcomes after severe blunt trauma. The patient study cohort (858 Asian subjects) was then stratified by age and injury severity (using the Injury Severity Score [ISS]). Crude and adjusted odds ratios (ORs) were calculated to evaluate the association between sex and nosocomial infection rate and hospitalized mortality, both overall and by age and ISS category subgroups. Among all trauma patients, females had a significantly lower risk of in-hospital mortality compared with males (OR, 0.41; 95% confidence interval [95% CI], 0.20 - 0.85). This difference was most apparent for patients younger than 50 years (OR, 0.31; 95% CI, 0.12 - 0.82) and the group with ISS scores of 25 or higher (OR, 0.39; 95% CI, 0.17 - 0.91). No differences in the development of nosocomial infections between sexes were seen among the overall patient group and subgroups. This study revealed a statistically significant association between sex and mortality among severe blunt trauma patients, particularly those patients younger than 50 years and with ISSs of 25 or higher. Women had significantly lower mortality than men after severe blunt trauma. These results highlight the important role of sex hormones and sex-based outcome differences after severe traumatic injury in the Chinese population.

Co-precipitation synthesis of nanostructured Cu3SbSe4 and its Sn-doped sample with high thermoelectric performance.

Large-scale fabrication of nanostructured Cu3SbSe4 and its Sn-doped sample Cu3Sb0.98Sn0.02Se4 through a low-temperature co-precipitation route is reported. The effects of hot-pressing temperatures, time and Sn doping on the thermoelectric properties of Cu3SbSe4 are explored. The maximum figure of merit ZTmax obtained here reaches 0.62 for the un-doped Cu3SbSe4, which is three times as large as that of Cu3SbSe4 synthesized by the fusion method. Due to the ameliorated power factor by optimized carrier concentration and the reduced lattice thermal conductivity by enhanced phonon scattering at grain interfaces, Sn doping leads to an improvement of thermoelectric performance as compared to Cu3SbSe4. The maximum ZT for Cu3Sb0.98Sn0.02Se4 is 1.05 in this work, which is 50% larger than the largest value reported.

A facile and universal way to fabricate superlattice nanowire arrays.

A facile and universal synthetic approach for preparing superlattice nanowire (SLNW) arrays is developed. In this method, two kinds of elements are alternately electrodeposited into the holes of the anodic alumina oxide (AAO) template, automatically in separate electrolytes by a programmed device. This method is not restricted by the relative values of the reduction potentials of the elements, and the deposition of each element can be controlled independently. Three kinds of representative SLNW arrays containing noble-metal material (Ag/Ni), thermoelectric material (Bi/Sb) and magnetic material (Ni/Cu) with adjustable segment length are fabricated successfully.

[Inhibitory effects of Aspisol on growth of transplanted breast cancer in C3H mice].

BACKGROUND & OBJECTIVE: Cyclooxygenase (COX) plays an important role in tumorigenesis and development. Many inhibitors of COX could inhibit proliferation and induce apoptosis of cancer cells. This study was to observe the inhibitory effect of Aspisol on growth of transplanted breast cancer in C3H mice and the effects of Aspisol on tumor cell apoptosis and the expression of Caspase-3 and COX-2, and explore the mechanisms. METHODS: The suspension of breast cancer cells was injected subcutaneously into forelimb axillas of C3H mice to establish xenograft models. From the next day, the mice received intraperitoneal injection of different concentrations of Aspisol once a day for 28 days; the mice received injection of 5-fluorouracil (5-FU) were used as positive controls, and the mice received injection of normal saline (NS) were used as negative controls. The inhibition rate of tumor growth was calculated. Tumor cell apoptosis was detected by TUNEL assay. The expression of Caspase-3 and COX-2 was detected by immunohistochemistry. RESULTS: The inhibition rate of tumor growth was 38.9% in 175 mg/kg Aspisol group, 48.2% in 350 mg/kg Aspisol group, 47.0% in 700 mg/kg Aspisol group, and 60.4% in 10 mg/kg 5-FU group. Typical apoptotic morphologic changes were seen in the 4 groups. Caspase-3 expression was significantly higher and COX-2 expression was significantly lower in Aspisol groups than in NS group. CONCLUSIONS: Aspisol may inhibit the growth of transplanted breast cancer in C3H mice, and induce tumor cell apoptosis. The mechanism may be correlated to down-regulation of COX-2 and up-regulation of Caspase-3.

[Effect of exogenous carbon monoxide on sequestration of polymorphonuclear neutrophils in the lung following limb ischemia-reperfusion: an experimental study].

OBJECTIVE: To investigate the effect of exogenous carbon monoxide (CO) in inhibiting the sequestration of polymorphonuclear neutrophils (PMNs) in the lung following limb ischemia-reperfusion (IR) and the mechanism thereof. METHODS: PMNs of peripheral blood were isolated from the venous blood of a healthy volunteer. Serum was collected from a patient undergoing bilateral knee joint replacement as IR serum. Human pulmonary microvascular endothelial cells (PMVECs) were cultured and divided into 4 groups: control group (cultured under the condition of room air containing 5% CO2 for 5 h and cultured in normal human serum instead of medium during the last 4 hours of experiment), IR group (cultured under the condition of air containing 5% CO2 for 5h and cultured in the serum of IR patient during the last 4 hours), IR + CO group (cultured under the condition of air containing 0.025% CO and 5% CO2 for 5 hours and cultured in IR serum during the last 4 hours), and control + CO group (cultured under the condition of air containing and 0.025% CO and 5% CO2 for 5 hours and cultured in normal human serum during the last 4 hours). Immunofluorescence flow cytometry was used to detect the expression of intercellular adhesion molecule (ICAM)-1 and integrin CD11b in the PMVECs. Human PMVECs were put into the wells of a 96-well plate and added with PMNs to calculate the PMVEC-PMN adhesion rate. Tourniquettes were bound at the bilateral hind thighs of 32 healthy male SD rats for 4 hours so as to establish a rate IR model. The rats were randomly divided into 4 equal groups: control group (undergoing the same operation without causing limb ischemia and exposed to room air), IR group (undergoing bilateral hind limb ischemia for 4 h and reperfusion for 4 h and exposed to room air), IR + CO group (exposed to the containing 0.025% CO one hour before reperfusion till 4 hours after reperfusion), and control + CO group (exposed to air containing 0.025% CO at the corresponding time point as that of the IR + CO group). Then the rats were killed and their middle pulmonary lobes were taken out for microscopy and calculation of the number of PMNs in alveolar septum. Western blotting was used to examine the ICAM-1 protein expression in the lung. RESULTS: The ICAM-1 expression and integrin CD11b expression of the IR group PMVECs were significantly stronger than those of the IR + CO group PMVECs (both P < 0.05) and there were no significant differences in the ICAM-1 expression and CD11b expression between the control + CO and control groups (both P > 0.05). The PMN-PMVEC adhesion rate of the IR group PMVECs was 30 +/- 2.9%, significantly higher than those of the IR + CO group and control group PMVECs (19.8 +/- 1.5% and 13.4 +/- 1.1% respectively, both P < 0.05) and there was no significant difference in the PMN-PMVEC adhesion rate between the CO + control group and control group (P > 0.05). The lung tissues of the IR group rats showed edema and hemorrhage. The number of PMNs in the alveolar septum was 60.6 +/- 1.7/10 high power fields, significantly higher than those of the IR + CO group and control group (36.4 +/- 1.6 and 22.5 +/- 1.6 respectively, both P < 0.05) and there was no significant difference between the latter 2 groups (P > 0.05). The ICAM-1 protein expression in the lung of the IR group was the strongest, followed by the IR + CO group, control + CO group, and control group. CONCLUSION: Exogenous CO inhibits the limb/IR-induced PMN sequestration in the lung, probably by the mechanism of down-regulation of the expression of adhesion molecules and suppression of the PMN\PMVEC adhesion following IR.

Change and role of heme oxygenase-1 in injured lungs following limb ischemia/reperfusion in rats.

OBJECTIVE: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. METHODS: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats. RESULTS: Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P<0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P<0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P<0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P<0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated. CONCLUSIONS: Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.

Melatonin reduces peroxynitrite-induced injury in aortic smooth muscle cells.

AIM: To study the protective role of melatonin (MT) in peroxynitrite-induced injury in cultured aortic smooth muscular cells (ASMC). METHODS: Peroxynitrite was synthesized chemically with a quenched flow reaction. Cells were exposed to peroxynitrite 500 micromol/L for 1 h in the absence or presence of various concentrations of MT 100, 300, and 500 micromol/L. Nitrotyrosine (NT), a specific "footprint"of peroxynitrite formation, was detected by immunohistochemical technique. The DNA damage was assayed by TUNEL technique. The levels of MDA in the medium and cell viability were measured. RESULTS: Incubation of ASMC with peroxynitrite 500 micromol/L for 1 h elicited the increase in the extent of immunostaining for NT, the rate of the TUNEL-positive cell, the content of MDA in the medium, and the number of dead cell. Pretreatment of ASMC with MT 100-500 micromol/L decreased these peroxynitrite-induced changes in a concentration-dependent manner. CONCLUSION: MT attenuated the injury induced by peroxynitrite in ASMC.

[Expression of heme oxygenase-1 in skeletal muscle after ischemia-reperfusion in rats].

OBJECTIVE: To observe the changes of heme oxygenase-1 (HO-1) expression in the skeletal muscle after ischemia-reperfusion of hind limb in rats. METHODS: A model of hind limb ischemia was made by clamping femoral artery with a microvascular clip. Soleus muscle was obtained from the animals received sham operation, 4 h ischemia without reperfusion and 2 h, 4 h, 8 h, 16 h, 24 h reperfusion after 4 h ischemia. Soleus histology and malondialdehyde (MDA) content were measured. The levels of HO-1 mRNA and protein were measured in different time by Northern blotting, Western blotting and immunohistochemistry technique. RESULTS: After ischemia-reperfusion of limb, HO-1 mRNA increased at the 2nd hour, reached a peak at the 8th hour, and returned toward baseline at the 24th hour. The change of protein level was essentially in agreement with that of mRNA. Immunohistochemical results showed that HO-1 expressed primarily in skeletal muscle cytoplasma. There were no positive signals of mRNA and protein in sham group and in ischemia group. After limb reperfusion, MDA contents in the soleus muscle increased significantly when compared with that in the sham group (P < 0.05). MDA content of the 8th after reperfusion decreased significantly when compared with that of the 4 h after reperfusion (P < 0.05). CONCLUSION: Ischemia-reperfusion can induce HO-1 expression in skeletal muscle in rats, which may provide protection for injured tissue.

[Effect of endogenous carbon monoxide on oxidant-mediated multiple organ injury following limb ischemia-reperfusion in rats].

OBJECTIVE: To determine the role of endogenous carbon monoxide(CO) in oxidant-mediated organ injury following limb ischemia-reperfusion (I/R) in rats. METHODS: Sixty-four SD rats were divided into 4 groups: Sham group, Sham + zinc protoporphyrin (ZnPP, an inhibitor of heme oxygenase activity), 2-hour ischemia followed by 4-hour reperfusion (I/R) group and I/R + ZnPP group. Carboxyhemoglobin (COHb) level in the artery blood, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung, heart, liver and kidney were detected. The 24-hour survival rate of rats was studied. RESULTS: Compared with the sham group, the COHb level and MDA content significantly increased, while the SOD activity and the survival rate significantly decreased in I/R group (P < 0.05). Compared with the I/R group, MDA content significantly increased, while the SOD activity, the 24-hour survival rate and COHb level significantly decreased in I/R + ZnPP group (P < 0.05, respectively). CONCLUSION: Limb I/R could lead to the oxidant-mediated multiple organ injury accompanied by the increase of CO level which play an important role in the defense against I/R-induced remote multiple organ injury in rats.