[Risk assessment of Cronobacter sakazakii in infant formula powder].

Objective: To assess the risk of foodborne diseases caused by Cronobacter sakazakii in infant formula powder from retail to feeding and provide formulate suggestions for safe feeding of infants at home. Methods: This study used the special monitoring and risk monitoring data of infant formula powder in Heilongjiang Province and combined data at home and abroad. The @RISK software was used to evaluate the disease risk caused by Cronobacter sakazakii in the process of infant formula powder from retail to feeding. Results: According to the results of this quantitative risk assessment, the risk of foodborne diseases caused by Cronobacter sakazakii at the current consumption pattern in Heilongjiang Province was 5.158×10-5 persons/million (40.0 ℃ and 50.0 ℃), 1.072×10-7 persons/million (60.0 ℃), 5.544×10-14 persons/million (70.0 ℃). When the feeding time of infant formula powder was adjusted to 0-2 h and 2-3 h respectively, the above prediction results did not change. When it was adjusted to 3-4 h, the risk increased. If it was adjusted to 4-24 h, the number of Cronobacter sakazakii increased by 14-24 orders of magnitude at room temperature. If the initial pollution concentration (after flushing) was adjusted to 1 MPN/ml, the average disease risk per meal was 805.7 persons/million (40.0 ℃ and 50.0 ℃), 1.7 persons/million (60.0 ℃) and 9.1 × 10-7 persons/million (70.0 ℃). The results of sensitivity analysis showed that the water temperature (70.0 ℃), initial pollution concentration, room storage time and temperature were important factors of risk. Conclusion: Controlling the contamination level of Cronobacter sakazakii in infant formula powder, controlling the feeding time within 3 h, storing in refrigerator and mixing with water with temperature not lower than 70.0 ℃ are effective measures to prevent infants from eating infant formula powder infected by Cronobacter sakazakii.

First Observation of the Four-Proton Unbound Nucleus

^{18}Mg was observed, for the first time, by the invariant-mass reconstruction of ^{14}O+4p events. The ground-state decay energy and width are E_{T}=4.865(34) MeV and Γ=115(100) keV, respectively. The observed momentum correlations between the five particles are consistent with two sequential steps of prompt 2p decay passing through the ground state of ^{16}Ne. The invariant-mass spectrum also provides evidence for an excited state at an excitation energy of 1.84(14) MeV, which is likely the first excited 2^{+} state. As this energy exceeds that for the 2^{+} state in ^{20}Mg, this observation provides an argument for the demise of the N=8 shell closure in nuclei far from stability. However, in open systems this classical argument for shell strength is compromised by Thomas-Ehrman shifts.

[Liraglutide alleviates lipotoxic liver cell damage and promotes autophagy to improve non-alcoholic fatty liver].

Objective: To study the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on free fatty acid (FFA)-induced hepatocyte steatosis, and to explore its autophagic role in this process. Methods: Human hepatocytes were cultured in vitro to induce NAFLD cell model. Liraglutide (LRG) concentration gradient was added to observe the effect on cell survival rate and fatty degeneration of liver cells. The relationship between liraglutide and autophagy was investigated with chloroquine inhibition and rapamycin (RAPA) activation in hepatocyte steatosis. Experimental group: control group: a certain concentration of BSA was added to cells cultured in DMEM complete medium; FFA model group: fatty degeneration of hepatocytes was induced by 1mmol/L FFA (OA : PA=2 : 1); LRG group: FFA (1 mmol/L) and LRG (100 nmol/L) were added to the cells at the same time; autophagy inhibition group: FFA (1 mmol/L), LRG (100 nmol/L), and chloroquine (20 µmol/L) were added to the cells at the same time; autophagy activated group: FFA (1 mmol/L) and RAPA (1 µmol/L) were added to the cells at the same time. Oil red O staining and fully automated biochemistry analyzer were used to observe the intracellular lipidosis condition. Western blotting was used to detect the levels of autophagy-related proteins (Beclin1, P62, and LC3B). One-way analysis of variance was used to compare the means between multiple groups. Results: Within a certain concentration range, with the increase of LRG concentration, the hepatocytes survival rate was increased and the degree of intracellular lipidosis had continued to decrease. The best effect was achieved when LRG concentration reached 100nmol/L, and the difference was statistically significant when compared with the FFA group (P < 0.01). During the exploration of the relationship between the degree of hepatic steatosis and autophagy, LRG group intracellular triglyceride content was significantly lower than FFA group (P < 0.01), and the levels of Beclin1, LC3B-II/LC3B-I were higher than FFA group. Additionally, FFA group had reduced P62 level, and enhanced autophagy. Compared with the LRG group, autophagy inhibition group intracellular triglyceride content was increased (P < 0.01), while the levels of Beclin1, LC3B-II/LC3B-I was decreased, and P62 level was increased. Autophagy activated group RAPA had significantly reduced FFA-induced intrahepatic triglyceride deposition, and the changes in autophagy-related protein levels were consistent with the effect of LRG. Conclusion: GLP-1RAs can alleviates FFA-induced lipotoxic liver cell damage, and promote autophagy to improve fatty degeneration of hepatocytes in NAFLD.

[Use of alternative pancreatic fistula risk score system for patients with clinical relevant postoperative pancreatic fistula after laparoscopic pancreaticoduodenectomy].

Objective: To examine the application value of alternative pancreatic fistula risk score system(a-FRS) for patients with clinically relevant postoperative pancreatic fistula(CR-POPF) after laparoscopic pancreaticoduodenectomy(LPD). Methods: Clinical data of 400 patients who underwent LPD at Department of Hepatobiliary and Pancreatic Surgery,Jilin University First Hospital,from April 2015 to August 2019 were retrospectively analyzed.There were 217 males and 183 females, with age of (M(QR)) 58 (53) years (range:26 to 93 years) and body mass index of (23.0±2.7) kg/m2 (range:19.4 to 27.1 kg/m2).Preoperative CA19-9 was (171.6±212.7) U/ml (range:32.1 to 762.6 U/ml), and preoperative CA125 was (18.6±22.9) U/ml (range:9.0 to 112.3 U/ml).Univariate analysis and multivariate Logistic regression analysis were implemented to find independent risk factors in CR-POPF.According to 3 indicators of a-FRS system(pancreatic texture,main pancreatic duct diameter,and body mass index),receiver operator characteristic curve was used to prospectively analyze the clinical value of CR-POPF. Results: CR-POPF occurred in 60 patients(15.0%) among the 400 LPD patients,including 54 patients(13.5%) with grade B pancreatic fistula and 6 patients(1.5%) with grade C pancreatic fistula.Univariate and multivariate Logistic regression analysis results showed that soft pancreas,diameter of main pancreatic duct ≤3 mm,and body mass index>23 kg/m2 were the independent risk factors for CR-POPF after LPD.The incidence of CR-POPF was 1.9% in the group with low pancreatic fistula risk(0 to 5%),5.9% with moderate pancreatic fistula risk(>5% to 20%),and 80.7% with high pancreatic fistula risk(>20%).a-FRS prospectively predicted the sensitivity and specificity of CR-POPF after LPD was 76.7% and 96.8%,positive predictive value was 80.7%,negative predictive value was 95.9%,positive likelihood ratio was 23.66,negative likelihood ratio was 0.24,and area under the curve was 0.735(95%CI:0.668-0.799). Conclusion: a-FRS system has great clinical application value in predicting CR-POPF after LPD,which can provide basis for early risk prediction of CR-POPF and timely related clinical intervention.

Proton Shell Evolution below

The ß-delayed γ-ray spectroscopy of neutron-rich ^{123,125}Ag isotopes is investigated at the Radioactive Isotope Beam Factory of RIKEN, and the long-predicted 1/2^{-} ß-emitting isomers in ^{123,125}Ag are identified for the first time. With the new experimental results, the systematic trend of energy spacing between the lowest 9/2^{+} and 1/2^{-} levels is extended in Ag isotopes up to N=78, providing a clear signal for the reduction of the Z=40 subshell gap in Ag towards N=82. Shell-model calculations with the state-of-the-art V_{MU} plus M3Y spin-orbit interaction give a satisfactory description of the low-lying states in ^{123,125}Ag. The tensor force is found to play a crucial role in the evolution of the size of the Z=40 subshell gap. The observed inversion of the single-particle levels around ^{123}Ag can be well interpreted in terms of the monopole shift of the π1g_{9/2} orbitals mainly caused by the increasing occupation of ν1h_{11/2} orbitals.

[Advances in epidemiology and serum markers for the noninvasive diagnosis of nonalcoholic fatty liver disease].

The global prevalence rate of nonalcoholic fatty liver disease (NAFLD) has increased year by year, and it has become the number one cause for chronic liver disease in China. In addition, the trend of NAFLD has become more pronounced and evident in female gender and younger age group. The long-term persistence of fatty liver disease may cause serious consequences. There are no accepted diagnostic criteria for diagnosing noninvasive diagnosis of NAFLD. Alpha-ketoglutarate is a newly discovered serological marker of high diagnostic value and considered the most valuable potential biomarker along with cytokeratine-18 (CK-18).

Beam particle identification and tagging of incompletely stripped heavy beams with HEIST.

A challenge preventing successful inverse kinematics measurements with heavy nuclei that are not fully stripped is identifying and tagging the beam particles. For this purpose, the HEavy ISotope Tagger (HEIST) has been developed. HEIST utilizes two micro-channel plate timing detectors to measure the time-of-flight, a multi-sampling ion chamber to measure energy loss, and a high-purity germanium detector to identify isomer decays and calibrate the isotope identification system. HEIST has successfully identified 198Pb and other nearby nuclei at energies of about 75 MeV/A. In the experiment discussed, a typical cut containing 89% of all 198Pb80+ in the beam had a purity of 86%. We examine the issues of charge state contamination. The observed charge state populations of these ions are presented and, using an adjusted beam energy, are well described by the charge state model GLOBAL.

Estimation of Lower Developmental Threshold and Degree Days for Pupal Development of Different Geographical Populations of Chinese Citrus Fly (Diptera: Tephritidae) in China.

The lower developmental threshold (LDT) and the number of developmental degree days (DDs) are fundamental parameters used to build phenology models that can be used to predict the timing of biological events during insect development. The Chinese citrus fly, Bactrocera minax (Enderlein) (Diptera: Tephritidae) is one of the most destructive citrus pest in China and Bhutan. This species overwinters as diapausing pupae in the soil before emerging as adults in the spring. In this study, B. minax collected from three representative geographical populations in China (Guizhou, Hubei, and Shaanxi) was used to conduct LDT experiments under laboratory conditions. Emergence data collected from pupae exposed to 10 constant temperatures was used to estimate the LDT and DDs required to complete pupal development for the three populations. The results show that LDT and DDs values for the Hubei and Shaanxi population are 11.9°C, 447.3 DDs and 11.5°C, 511.3 DDs, respectively. However, the geographic variation in pupal developmental rates was not statistically significant between the two populations. In addition, the Guizhou population was identified as a mixture of B. minax and B. tsuneonis (Miyake). The LDT and DDs values for the Hubei and Shaanxi populations obtained in this study can be used to predict adult emergence of naturally occurring field populations of B. minax within the majority of the citrus-growing production areas of China. These data can also be used in models to predict the risk of establishment of this species in the United States or other citrus-growing regions.

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats.

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

[Effect of adrenomedullin on mesenteric microvessels and microlymphatics in rat].

The dilatant effect of adrenomedullin (ADM), a novel peptide of 52 amino acids, on the mesenteric microvessels and microlymphatics was investigated under microscopic observation. 10(-6) mol/L ADM could also ameliorate alteration of the hemorheology induced by 10(-5) mol/L norepinephrine (NE) or 10(-7) mol/L endothelin (ET). However, this ameliorative response was markedly inhibited in the presence of NG-nitro-L-arginine (L-NNA), an inhibitor for production of nitric oxide.

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats.

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

Mesenteric lymph reperfusion exacerbates spleen injury caused by superior mesenteric artery occlusion shock.

The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.

Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats.

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40 ± 2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca²âº were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca²âº at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179 ± 0.038 to 0.440 ± 0.177 g/mg, P<0.05) and Ca²âº (from 0.515 ± 0.043 to 0.646 ± 0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca²âº at various concentrations in the shock+drainage group (from 0.744 ± 0.187 to 0.570 ± 0.143 g/mg in Emax for NE and from 0.729 ± 0.037 to 0.645 ± 0.056 g/mg in Emax for Ca²âº, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

Mesenteric lymph reperfusion exacerbates spleen injury caused by superior mesenteric artery occlusion shock

The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.

Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca2+ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca2+ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca2+ (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca2+ at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in Emax for NE and from 0.729±0.037 to 0.645±0.056 g/mg in Emax for Ca2+, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.