Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

High concentrations of environmental ammonia induced changes in large-scale loach (Paramisgurnus dabryanus) immunity.

High concentrations of environmental ammonia can cause reduced immunity and death in fish, causing enormous economic losses. Air-breathing fish usually have a high ammonia tolerance and are very suitable for high-density fish farming. However, research on the effects of environmental ammonia on air-breathing fish immunity is lacking. Therefore, this study investigated the effects of environmental ammonia on the immunity of large-scale loach (Paramisgurnus dabryanus) by exposing fish to 30 mmol/L NH4Cl solution and subsequently analyzing the changes in serum and liver immune indicators, including total protein, albumin, globulin, immunoglobulin (Ig) M, lysozyme, complement component (C) 3 and C4, heat shock protein (HSP) 70, HSP90, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12. Results revealed that ammonia exposure significantly affected the total protein, albumin, globulin, IgM, complement C3 and C4, HSP70, HSP90, and inflammatory cytokine contents in the body, indicating that ammonia exposure induced a significant immune response and lowered bodily immunity. However, most of the immune indicators significantly decreased in the later stages of the experiment, suggesting a weakened immune response, which may be due to the species-specific ammonia detoxification ability of large-scale loach that reduces ammonia toxicity in the body.

Impact of combined ischemic preconditioning and remote ischemic perconditioning on ischemia-reperfusion injury after liver transplantation.

Ischemic preconditioning (IPC) and remote ischemic perconditioning (RIPer) confer protective effects against liver ischemia-reperfusion injury (IRI), but data about RIPer applying in liver transplantation is lacking. The study aimed to evaluate whether the combination of IPC and RIPer provides reinforced protective effects. C57BL/6 mice (160 pairs) were allocated into four groups: control, subjected to liver transplantation only; IPC, donor hilar was clamped for 10 min followed by 15 min of reperfusion; RIPer, three cycles of occlusion (5 min) and opening (5 min) of femoral vascular bundle were performed before reperfusion; IPC + RIPer, donors and recipients were subjected to IPC and RIPer respectively. Liver tissues were obtained for histological evaluation, TUNEL staining, malondialdehyde assays, GSH-Px assays, and NF-κB p65 protein and Bcl-2/Bax mRNA analyses. Blood samples were used to evaluate ALT, AST, TNF-α, NOx levels and flow cytometry. We found that protective efficacy of RIPer is less than IPC in terms of ALT, TNF-α, GSH-Px and NOx at 2 h postoperation, but almost equivalent at 24 h and 72 h postoperation. Except for Suzuki scores, ALT, Bcl-2/Bax mRNA ratio, other indices showed that combined treatment brought enhanced attenuation in IRI, compared with single treatment, through additive effects on antioxidation, anti-apoptosis, modulation of microcirculation disturbance, and inhibition of innate immune response. This study suggested a combined strategy that could enhance protection against IRI in clinical liver transplantation, otherwise, provided a hint that RIPer's mechanism might be partly or totally different from IPC in humoral pathway.

Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns.

Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.

Drainage fluid and serum amylase levels accurately predict development of postoperative pancreatic fistula.

AIM: To investigate potential biomarkers for predicting postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). METHODS: We prospectively recruited 83 patients to this study. All patients underwent PD (Child's procedure) at the Division of Hepatobiliary and Pancreas Surgery at the First Bethune Hospital of Jilin University between June 2011 and April 2015. Data pertaining to demographic variables, clinical characteristics, texture of pancreas, surgical approach, histopathological results, white blood cell count, amylase and choline levels in the serum, pancreatic/gastric drainage fluid, and choline and amylase levels in abdominal drainage fluid were included in the analysis. Potential correlations between these parameters and postoperative complications such as, POPF, acute pancreatitis, hemorrhage, delayed gastric emptying, and biliary fistula, were assessed. RESULTS: Twenty-eight out of the 83 (33.7%) patients developed POPF. The severity of POPF was classified as Grade A in 8 (28%) patients, grade B in 16 (58%), and grade C in 4 (14%), according to the pancreatic fistula criteria. On univariate and multivariate logistic regression analyses, higher amylase level in the abdominal drainage fluid on postoperative day (POD)1 and higher serum amylase levels on POD4 showed a significant correlation with POPF (P < 0.05). On receiver operating characteristic curve analysis, amylase cut-off level of 2365.5 U/L in the abdominal drainage fluid was associated with a 78.6% sensitivity and 80% specificity [area under the curve (AUC): 0.844; P = 0.009]. A cut-off serum amylase level of 44.2 U/L was associated with a 78.6% sensitivity and 70.9% specificity (AUC: 0.784; P = 0.05). CONCLUSION: Amylase level in the abdominal drainage fluid on POD1 and serum amylase level on POD4 represent novel biomarkers associated with POPF development.

Sodium cantharidinate induces HepG2 cell apoptosis through LC3 autophagy pathway.

The function of sodium cantharidinate on inducing hepatocellular carcinoma cell apoptosis was investigated for the first time. Sodium cantharidinate inhibits HepG2 cell growth mainly by LC3 autophagy pathway. MTT results show that sodium cantharidinate effectively inhibits the proliferation of HepG2 cells in a dose- and time-dependent manner and induce cell apoptosis by caspase-3 activity. The further western blotting and FACS detection show that sodium cantharidinate initiates HepG2 cell autophagy program by LC3 pathway. Autophagy-specific inhibitor 3-MA reduce sodium cantharidinate-induced caspase-3 activity and HepG2 cell apoptosis. Silence of the LC3 gene in HepG2 cell lines also reduce sodium cantharidinate-induced cell apoptosis. Collectively, our data indicate that sodium cantharidinate induces HepG2 cell apoptosis through LC3 autophagy pathway. Sodium cantharidinate has potential for development as a new drug for treatment of human HCC.

Burn-Related Dysregulation of Inflammation and Immunity in Experimental and Clinical Studies.

The purpose of this study was to evaluate burn-related variations of inflammation and immunity. Fifty-five mice were divided randomly into sham burn and burn groups. Eighty-seven hospitalized burn patients were also reviewed. In mice, neutrophils and monocytes were elevated significantly on post burn day (PBD 1). Lymphocytes were reduced on PBDs 1 and 3. Levels of serum tumor necrosis factor-α and interleukin-6 were highest on PBD 1. Interleukin-1ß levels were the highest on PBD 3. On PBD 3, CD4CD25T regulatory cells/CD4 cells in spleen were higher. On PBDs 1, 3, 7, and 14, percentage of splenic dendritic cells were significantly lower than the sham burn group. In patients, neutrophils and monocytes were significantly elevated on PBD 1. Levels declined but remained elevated at most days to PBD 7. Lymphocytes in burn groups 1 and 2 were reduced on PBDs 1 and 3, respectively. Our results exhibited that severe burn injury initiated a hyperinflammatory response and immunosuppression. PBDs 1 to 3 were important for changes in inflammation and immunosuppression.

Successful salvage treatment of acute graft-versus-host disease after liver transplantation by withdrawal of immunosuppression: a case report.

Acute graft-versus-host disease (GVHD) following liver transplantation is a rare but fatal complication. The correct diagnosis and management of GVHD after liver transplantation are still major challenges. Herein, we reported successful salvage treatment of acute GVHD by withdrawal of immunosuppression in a patient who presented with fever, skin rashes, and decreased blood cell counts after liver transplantation. This case highlights the need for awareness of drug-induced liver injury if liver function tests are elevated during treatment, especially in patients taking multiple potentially hepatotoxic drugs, such as broad-spectrum antibiotics. When occurs, an artificial liver support system is a useful tool to provide temporary support of liver function for the patient in the event of drug-induced liver injury.

Ischemic preconditioning and remote ischemic preconditioning provide combined protective effect against ischemia/reperfusion injury.

AIMS: Our objective was to compare the protective efficacy of ischemic preconditioning (IPC) and remote ischemic preconditioning (RIPC) against liver ischemia/reperfusion injury (IRI) and to evaluate their combined protective effect in mouse liver transplantation (MLT). MATERIALS AND METHODS: Mice were randomly allocated to sham, IPC, RIPC, or IPC+RIPC groups. The animals were sacrificed at 2h, 24h, and 3 days after reperfusion. Blood samples were collected to evaluate alanine aminotransferase, TNF-α, and innate immune response. Liver tissue samples were obtained for histological evaluation, terminal deoxynucleotidyltransferased UTP nick end labeling, malondialdehyde (MDA) assay. KEY FINDINGS: Mice given preconditioning measures had significantly lower increase in transaminase, TNF-α expression, MDA formation, liver injury scores, and apoptosis index at 2h, 24h and 3 days after liver transplantation. The percentages of CD11b(+), CD11b(+)CD16/32(+) and CD11b(+) CD16/32(high) in white blood cells at 3 days after MLT were significantly lower than in the sham group. The results of factorial analysis demonstrated no synergistic effect for IPC and RIPC, except for MDA formation 2h after reperfusion (p=0.038). SIGNIFICANCE: Based on the synergistic and addictive effect on liver IRI induced by MLT between IPC and RIPC, the study suggested ways in which combined preconditionings could be elicited in patients undergoing planned procedures complicated by IRI to support better outcomes.

Clinical Significance of UCA1 to Predict Metastasis and Poor Prognosis of Digestive System Malignancies: A Meta-Analysis.

Purpose. Urothelial carcinoma-associated 1 (UCA1) has been reported to be overexpressed and correlated with progression in various cancers. However, the association between UCA1 expression and some clinicopathological features of digestive system malignancies, such as metastasis and survival, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of UCA1 in digestive system malignancies. Methods. Relevant literatures were searched in PubMed, Web of Science, Cochrane Library, and Embase databases updated to May 2016. Results. A total of 1089 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that digestive system malignancy patients with UCA1 overexpression were significantly more susceptible to developing lymph node metastasis (LNM) (OR = 1.85, 95% CI: 1.28-2.67) and distant metastasis (DM) (OR = 3.14, 95% CI: 1.77-5.58) and suffer from poor overall survival (OS) (HR = 2.31, 95% CI: 1.89-2.82, univariate analysis; HR = 2.24, 95% CI: 1.69-2.98, multivariate analysis) and poor disease-free survival (DFS) (HR = 2.65, 95% CI: 1.59-4.43, univariate analysis; HR = 2.50, 95% CI: 1.62-3.86, multivariate analysis). Conclusion. UCA1 overexpression was correlated with LNM, DM, poor OS, and poor DFS. UCA1 may serve as an indicator for metastasis and poor prognosis in digestive system malignancies.

A new method of wound treatment: targeted therapy of skin wounds with reactive oxygen species-responsive nanoparticles containing SDF-1α.

OBJECTIVE: To accelerate wound healing through promoting vascularization by using reactive oxygen species (ROS)-responsive nanoparticles loaded with stromal cell-derived factor-1α(SDF-1α). METHODS: The ROS-reactive nanomaterial poly-(1,4-phenyleneacetone dimethylene thioketal) was synthesized, and its physical and chemical properties were characterized. ROS-responsive nanoparticles containing SDF-1α were prepared through a multiple emulsion solvent evaporation method. The loading capacity, stability, activity of the encapsulated protein, toxicity, and in vivo distribution of these nanoparticles were determined. These nanoparticles were administered by intravenous infusion to mice with full-thickness skin defects to study their effects on the directed chemotaxis of bone marrow mesenchymal stem cells, wound vascularization, and wound healing. RESULTS: The synthesized ROS-reactive organic polymer poly-(1,4-phenyleneacetone dimethylene thioketal) possessed a molecular weight of approximately 11.5 kDa with a dispersity of 1.97. ROS-responsive nanoparticles containing SDF-1α were prepared with an average diameter of 110 nm and a drug loading capacity of 1.8%. The encapsulation process showed minimal effects on the activity of SDF-1α, and it could be effectively released from the nanoparticles in the presence of ROS. Encapsulated SDF-1α could exist for a long time in blood. In mice with full-thickness skin defects, SDF-1α was effectively released and targeted to the wounds, thus promoting the chemotaxis of bone marrow mesenchymal stem cells toward the wound and its periphery, inducing wound vascularization, and accelerating wound healing.

Effects of Ras homolog gene family, member C gene silencing combined with rapamycin on hepatocellular carcinoma cell growth.

The aim of the present study was to investigate the combined effects of inhibiting the Ras homolog gene family, member C (RhoC)/Rho kinase and phosphoinositide 3 kinase/Akt/mammalian target of rapamycin (mTOR) pathways on hepatocellular carcinoma cell growth. The RhoC gene was silenced by RNA interference (RNAi) and mTOR was inhibited by rapamycin (RAPA). Subsequently, an MTT assay for cell growth detection, western blot analysis for gene expression analysis, silver nitrate staining for cell proliferation, Wright's staining for analysis of the apoptotic rate analysis, soft agar clonogenic assay for the determination of cell growth characteristics and a Transwell assay for cell migration were performed. RhoC expression in hepatoma cell lines was lower than that in the HL7702 normal human liver cell line. The level of cell proliferation in the RNAi + RAPA group was lower than that in the RNAi, RAPA and Scramble groups. The levels of cyclin­dependent kinase 2 in the RNAi + RAPA group were lower than those in the other groups, while the levels of P16 in the RNAi + RAPA group were higher than those in the other experimental groups. No significant difference was found between the RNAi + RAPA and the normal HL7702 group. The number of silver nitrate­stained particles was reduced in the RNAi + RAPA group compared with that in the other groups. No significant difference was found between the RNAi + RAPA and HL7702 groups. Wright's staining for apoptosis demonstrated that apoptosis in the Scramble group was rare, while the RAPA and RNAi groups contained a large number of apoptotic cells, which displayed nuclear condensation, fragmentation, deepened staining, as well as a wrinkled membrane. B­cell lymphoma­2 (Bcl­2) expression in the RNAi + RAPA group was lower than that in the other groups, while the gene expression of Bcl­2­associated X protein in the RNAi + RAPA group was increased compared with that in the other groups. No cell colony formation was observed in the soft agar cloning experiment in the RNAi + RAPA and HL7702 group, while in the other groups, visible cell clones appeared. In the Transwell assay the number of migrated cells in the RNAi + RAPA group was lower than that in the other groups. The gene expression of matrix metalloproteinase (MMP)2, MMP­9 and vascular endothelial growth factor in the RNAi + RAPA group was lower than that in the other experimental groups. In conclusion, RhoC gene silencing combined with RAPA was able to significantly inhibit the growth of hepatocellular carcinoma cells.

Comparison of Laparoscopic Distal Pancreatectomy with or without Splenic Preservation.

Laparoscopic distal pancreatectomy (LDP) has gained large popularity in recent years, although the choice of whether to preserve the spleen has remained inconsistent. The aim of our study was to report our experiences with LDP and to provide evidence for the safety of the operative technique and an evaluation index of splenic function. We retrospectively evaluated all LDPs performed at our institution between March 2008 and February 2012. Cases were divided into a laparoscopic spleen-preserving distal pancreatectomy (LSPDP) group (n = 14) and an LDP with splenectomy (LDPS) group (n = 19). Parametric and nonparametric statistical analyses were used to compare perioperative and oncologic outcomes. Demographic characteristics, operating time, length of stay, estimated blood loss, transfusion requirement, pathologic diagnosis, and complication rate were similar between groups. Patients who underwent LDPS tended to have larger masses and lower pancreatic fistula rates, but these differences were not significant. White blood cell (WBC) counts were significantly higher in the LDPS group than in the LSPDP group on postoperative days 1 and 7. To avoid splenectomy-associated complications, preservation of the spleen and especially the splenic vessels are preferred. This procedure can be performed safely and feasibly. Lower postoperative WBC counts may imply better splenic function.

Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma.

Sclerosing cholangitis (SC) is a rarely reported morbidity secondary to transcatheter arterial chemoembolization (TACE) with bleomycin-iodinated oil (BIO) for liver cavernous hemangioma (LCH). This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO. Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts. Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy. Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy. Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area. Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy. Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC.

In vitro regulation of hepatocellular carcinoma cell viability, apoptosis, invasion, and AEG-1 expression by LY294002.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and is characterized by advanced clinical stages at diagnosis and very poor prognosis. SUBJECTS AND METHODS: This study investigated the effects of PI3K inhibitor, LY294002, on suppression of astrocyte elevated gene-1 (AEG-1) and regulation of HCC cell viability, apoptosis, and invasion in vitro. Cell lines derived from normal liver and HCC were treated with LY294002 and evaluated by RT-PCR, western blot, cell viability, migration, and invasion assays. RESULTS: The data showed that AEG-1 mRNA and protein were overexpressed in HCC cells, compared to the normal liver cells. LY294002 treatment of HCC cells significantly reduced tumor cell viability, but promoted apoptosis. Tumor cell migration and invasion assays showed that LY294002 treatment also decreased the capacity of HCC cell migration and invasion. Molecularly, LY294002 treatment down-regulated AEG-1 expression, AKT and GSK3ß phosphorylation, and expression of cyclinD1, CDK4, VEGF and Bcl2, but up-regulated Bax and c-Myc expression. CONCLUSION: The data from this study demonstrated usefulness of LY294002 for effective control of HCC. Future studies should investigate the effects of LY294002 on HCC cells in vivo before initiating clinical trials in HCC patients.

[Association between serum homocysteine and in-hospital death in patients with acute pulmonary embolism].

OBJECTIVE: To explore the association between serum homocysteine (Hcy) level and in-hospital death in patients with acute pulmonary embolism. METHODS: A total of 186 acute pulmonary embolism patients [ (66.8 ± 12.7) years, 89 male] hospitalized in our department between June 2008 and June 2011 were included in this prospective study. Patients were divided into high Hcy group (Hcy ≥ 15.2 µmol/L, n = 95) and low Hcy group (Hcy < 15.2 µmol/L, n = 91). Patients were followed-up for 1 year for the incidence rate of early death associated with acute pulmonary embolism. The Cox proportional hazard model was used to analyze the relationship between serum Hcy level and early death in acute pulmonary embolism patients. RESULTS: Patients were hospitalized for 1-37 days [(10 ± 6) days]. In-hospital death rate was 14.5% (27/186) and was significantly higher in high Hcy group than in low Hcy group [25.3% (24/95) vs. 3.3% (3/91) , P = 0.001]. Univariate Cox regression analysis indicated that admission heart rate, oxygen saturation, enlargement of right ventricle, Hcy ≥ 15.2 µmol/L, serum creatinine level, peak TnT level and deep venous thrombosis (P < 0.05) were independent risk factors for in-hospital death. Multivariate Cox regression analysis showed that Hcy ≥ 15.2 µmol/L (HR = 4.10, 95%CI:3.00-4.98, P = 0.017), admission heart rate (HR = 1.10, 95%CI:1.01-1.20, P = 0.031) , deep venous thrombosis (HR = 1.65, 95%CI:1.45-1.76, P = 0.034) and age (HR = 1.10, 95%CI:1.02-1.19, P = 0.010) were independent predictors of in-hospital death for acute pulmonary embolism patients. One-year follow up was finished in 142 patients (89.3%). There were 19 deaths ( 5 due to repeat pulmonary embolism, 4 due to decompensated respiratory and /or cardiac diseases, 6 due to malignant tumors, 2 due to fatal bleeding and 2 due to pneumonia) . Death rate was similar between the two groups during follow up. CONCLUSION: Higher serum homocysteine is an independent for in-hospital death for patients with acute pulmonary embolism.

Laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel conservation: a retrospective study of 20 cases.

BACKGROUND/AIMS: To compare the outcomes and potential morbidities of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation in patients with benign or low-grade malignant pancreatic lesions. METHODOLOGY: Twenty patients who underwent spleen-preserving distal pancreatectomy were retrospectively analyzed. All the patients had benign or low-grade malignant pancreatic lesions that had not invaded the spleen. Twelve patients underwent Kimura's procedure and eight patients underwent Warshaw's. Perioperative data, and procedure-specific complications were compared between the two groups. RESULTS: Age, gender, and body mass index were comparable between the two groups. Operative time and intraoperative blood loss were significantly lower for patients who underwent Warshaw's procedure than for those who received Kimura's (p <0.05 for both). There were no significant differences between the two groups with regard to perioperative blood transfusions, length of postoperative hospital stays, or complication rates. Splenic infarction and gastric varices developed only in patients who underwent Warshaw's procedure (one case each). CONCLUSIONS: Our results suggest that the Kimura technique should be the first choice for patients with benign or low-grade malignant pancreatic lesions. Warshaw's technique was associated with a higher incidence of several complications. However, Warshaw's can increase the success rate of splenic preservation in some cases.

Role of inhibition of p38 mitogen-activated protein kinase in liver dysfunction after hemorrhagic shock and resuscitation.

BACKGROUND: The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. MATERIALS AND METHODS: C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1ß) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. RESULTS: p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1ß mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. CONCLUSIONS: p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver.