Silencing of GDF11 suppresses hepatocyte apoptosis to relieve LPS/D-GalN acute liver failure.

In this paper, we generated a short hairpin RNA growth differentiation factor-11 (sh-GDF11) and evaluated the effects of sh-GDF11 on the pathogenesis of acute liver failure (ALF) in vitro and in vivo. Through bioinformatics study, the key gene related to ALF was assayed. Lipopolysaccharide (LPS) and D-galactoamine (D-GalN) were applied to establish the mouse model of LPS/D-GalN-induced liver injury, and TNF-α and D-Gal were used to construct an in vitro cell model, followed by treatment of sh-GDF11 for analysis of liver cell proliferation. Bioinformatics analysis showed that the protective effect of sh-GDF11 on ALF may be mediated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The results of in vitro study found that sh-GDF11 could promote cell proliferation and inhibit death by blocking the PI3K/Akt/mTOR signaling pathway. In vivo animal experiments further confirmed that sh-GDF11 could suppress hepatocyte apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway. sh-GDF11 relieved LPS/D-GalN-induced ALF by blocking the PI3K/Akt/mTOR signaling pathway, emphasizing its critical role in LPS/D-GalN-induced ALF treatment.

Clinicopathological and prognostic significance of SMAD4 in non-small cell lung cancer: A meta-analysis and database validation.

BACKGROUND: The relationship between SMAD family member 4 (SMAD4) and the clinicopathological and prognostic significance of non-small cell lung cancer (NSCLC) patients is unclear. Our aim was to investigate the association between SMAD4 expression and clinicopathological parameters and NSCLC prognosis. METHODS: We searched articles in databases from inception to July 2022 to retrieve literature related to SMAD4 expression and the clinicopathological and/or prognostic significance of NSCLC patients. Odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. We evaluated the expression of SMAD4 and overall survival (OS) in NSCLC using the Kaplan-Meier plotter database. RESULTS: Eight articles with 1461 NSCLC patients were included. SMAD4 expression was related to tumor differentiation (OR = 0.359, 95% CI: 0.238-0.543, P = .000), lymph node metastasis (OR = 0.469, 95% CI: 0.04-0.725, P = .001), tumor node metastasis stage (OR = 0.238, 95% CI: 0.156-0.362, P = .000) and good OS (HR = 0.592, 95% CI: 0.332-0.853, P = .000) in NSCLC. There was no significant association between SMAD4 expression and age (OR = 0.822, 95% CI: 0.515-1.312, P = .411) or sex (OR = 1.056, 95% CI: 0.675-1.653, P = .811). Furthermore, SMAD4 expression was lower in NSCLC, and a good prognosis in NSCLC (HR = 0.6, 95% CI = 0.51-0.72, P = 4.2 e-9) was shown to correlate with higher SMAD4 expression using the Kaplan-Meier Plotter database. CONCLUSION: SMAD4 expression is lower in NSCLC and correlated with lymph node metastasis, tumor differentiation, tumor node metastasis stage and good OS for NSCLC patients.

Differentiation and prediction of pneumoconiosis stage by computed tomography texture analysis based on U-Net neural network.

BACKGROUND AND OBJECTIVE: The progressive worsening of pneumoconiosis will ensue a hazardous physical condition in patients. This study details the differential diagnosis of the pneumoconiosis stage, by employing computed tomography (CT) texture analysis, based on U-Net neural network. METHODS: The pneumoconiosis location from 92 patients at various stages was extracted by U-Net neural network. Mazda software was employed to analyze the texture features. Three dimensionality reduction methods set the best texture parameters. We applied four methods of the B11 module to analyze the selected texture parameters and calculate the misclassified rate (MCR). Finally, the receiver operating characteristic curve (ROC) of the texture parameters was analyzed, and the texture parameters with diagnostic efficiency were evaluated by calculating the area under curve (AUC). RESULTS: The original film was processed by Gaussian and Laplace filters for a better display of the segmented area of pneumoconiosis in all stages. The MCR value obtained by the NDA analysis method under the MI dimension reduction method was the lowest, at 10.87%. In the filtered texture feature parameters, the best AUC was 0.821. CONCLUSIONS: CT texture analysis based on the U-Net neural network can be used to identify the staging of pneumoconiosis.

Prediction Model for Infectious Disease Health Literacy Based on Synthetic Minority Oversampling Technique Algorithm.

Objective: Improving health literacy in infectious diseases is a direct manifestation of the solid advance in disease control and prevention. Our study is aimed at exploring applying synthetic minority oversampling technique (SMOTE) in the prediction assessment of whether residents and business employees have infectious disease health literacy. Methods: The Chinese resident infectious disease health literacy evaluation scale was used to investigate the associated variables. The screened variables were input variables and the presence or absence of infectious diseases health literacy as outcome variables. Logistic regression, random forest, and support vector machine (SVM) models were built in the data sets before and after treatment by the SMOTE algorithm, respectively, and the performance of the models was evaluated by receiver operating characteristic curves (ROC). Results: Logistic regression, random forest, and SVM achieved accuracies of 0.828, 0.612, and 0.654 before SMOTE algorithm processing, and the areas under the ROC curves (AUCs) of the three models were 0.754, 0.817, and 0.759, respectively. The accuracies were 0.938, 0.911, and 0.894 after SMOTE algorithm processing, and the AUCs of the three models were 0.913, 0.925, and 0.910, respectively. Conclusions: The random forest model based on the SMOTE has high application value in assessing whether residents versus enterprise employees have infectious disease health literacy.

Inhibitive Effect of Luteolin on Sevoflurane-Induced Neurotoxicity through Activation of the Autophagy Pathway by HMOX1.

Luteolin is a flavone compound occurring in a variety of medicinal plants, which is reported to have neuroprotective properties. In this study, we aimed to explore the effects of luteolin in alleviating sevoflurane-induced neurotoxicity. GeneCards and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were employed to screen luteolin, sevoflurane, and neurotoxicity-related genes. Subsequently, we isolated primary neurons from the hippocampus of 1-day-old C57BL/6J mice and tested for cytotoxicity after treatment of different concentrations of luteolin. Next, we measured the expression of apoptosis by flow cytometry and assessed inflammation-related factors, including heme oxygenase-1 expression detected by immunohistochemical staining and neuronal apoptosis. Finally, water maze, open field, and fear conditioning tests were conducted to observe the interaction between luteolin and sevoflurane in cognitive impairment of mice. Luteolin had the lowest cytotoxicity at concentrations of 30 or 60 µg/mL; we selected 30 µg/mL for drug administration experiments in vitro. Luteolin inhibited sevoflurane-induced neuronal apoptosis and inflammatory responses through the autophagic pathway and thus ameliorated sevoflurane-induced cognitive impairment in mice. Mechanistically, luteolin up-regulated heme oxygenase-1 expression, which activated the autophagy pathway in vitro. This was confirmed by subsequent histological experiments in mice and behavioral results showing rescue cognitive impairment. Our findings uncovered an inhibitory role of luteolin in sevoflurane-induced neuronal apoptosis and inflammatory response through activation of autophagy arising from up-regulation of heme oxygenase-1, thereby alleviating sevoflurane-induced cognitive impairment in mice.

Differential expression of TgMIC1 in isolates of Chinese 1 Toxoplasma with different virulence.

BACKGROUND: The predominant genotype of Toxoplasma in China is the Chinese 1 (ToxoDB#9) lineage. TgCtwh3 and TgCtwh6 are two representative strains of Chinese 1, exhibiting high and low virulence to mice, respectively. Little is known regarding the virulence mechanism of this non-classical genotype. Our previous RNA sequencing data revealed differential mRNA levels of TgMIC1 in TgCtwh3 and TgCtwh6. We aim to further confirm the differential expression of TgMIC1 and its significance in this atypical genotype. METHODS: Quantitative real-time PCR was used to verify the RNA sequencing data; then, polyclonal antibodies against TgMIC1 were prepared and identified. Moreover, the invasion and proliferation of the parasite in HFF cells were observed after treatment with TgMIC1 polyclonal antibody or not. RESULTS: The data showed that the protein level of TgMIC1 was significantly higher in high-virulence strain TgCtwh3 than in low-virulence strain TgCtwh6 and that the invasion and proliferation of TgCtwh3 were inhibited by TgMIC1 polyclonal antibody. CONCLUSION: Differential expression of TgMIC1 in TgCtwh3 and TgCtwh6 may explain, at least partly, the virulence mechanism of this atypical genotype.

Remifentanil up-regulates HIF1α expression to ameliorate hepatic ischaemia/reperfusion injury via the ZEB1/LIF axis.

Ischaemia/reperfusion (I/R)-induced hepatic injury is regarded as a main reason of hepatic failure after transplantation or lobectomy. The current study aimed to investigate how the opioid analgesic remifentanil treatment affects I/R-induced hepatic injury and explore the possible mechanisms related to HIF1α. Initially, an I/R-induced hepatic injury animal model was established in C57BL/6 mice, and an in vitro hypoxia-reoxygenation model was constructed in NCTC-1469 cells, followed by remifentanil treatment and HIF1α silencing treatment. The levels of blood glucose, lipids, alanine transaminase (ALT) and aspartate transaminase (AST) in mouse serum were measured using automatic chemistry analyser, while the viability and apoptosis of cells were detected using CCK8 assay and flow cytometry. Our results revealed that mice with I/R-induced hepatic injury showed higher serum levels of blood glucose, lipids, ALT and AST and leukaemia inhibitory factor (LIF) expression, and lower HIF1α and ZEB1 expression (P < .05), which were reversed after remifentanil treatment (P < .05). Besides, HIF1α silencing increased the serum levels of blood glucose, lipids, ALT and AST (P < .05). Furthermore, hypoxia-induced NCTC-1469 cells exhibited decreased HIF1α and ZEB1 expression, reduced cell viability, as well as increased LIF expression and cell apoptosis (P < .05), which were reversed by remifentanil treatment (P < .05). Moreover, HIF1α silencing down-regulated ZEB1 expression, decreased cell viability, and increased cell apoptosis (P < .05). ZEB1 was identified to bind to the promoter region of LIF and inhibit its expression. In summary, remifentanil protects against hepatic I/R injury through HIF1α and downstream effectors.

Knockdown of P3H4 inhibits proliferation and invasion of bladder cancer.

The prolyl 3-hydroxylase family member 4 (P3H4) (alias SC65) is implicated in a variety of physiological and pathological processes. However, little is known about the role of P3H4 in tumors. This study aimed to investigate the role of P3H4 in bladder cancer (BC) and the regulatory mechanisms that influence its expression. P3H4 was highly expressed in BC tissues. Knockdown of P3H4 inhibited BC cell proliferation, cell cycle, migration and invasion in vitro, and inhibited BC growth in vivo. We also found that ETV4 bound directly to the promoter region of P3H4 and activated its transcription. Furthermore, overexpression of ETV4 rescued the inhibition of proliferation and invasion induced by PH4 silencing. ETV4 was significantly overexpressed in the BC tissues. In conclusion, P3H4 functioned an oncogene role in BC progression, and ETV4 bound directly to the P3H4 promoter region to regulate its transcription.

Theaflavins alleviate sevoflurane-induced neurocytotoxicity via Nrf2 signaling pathway.

Aim: Sevoflurane could induce apoptosis of rat hippocampal neurons, while theaflavins (TFs) have antioxidant and anti-inflammatory properties. This study aims to explore whether TFs could alleviate sevoflurane-induced neuronal cell injury.Materials and methods: Cells were treated by concentration gradient of sevoflurane and TFs. Cell viability, level of reactive oxygen species (ROS) and apoptosis rate were determined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Quantitative PCR (qPCR) and western blot were performed to determine mRNA and protein expressions.Results: TFs promoted viability of cells under the treatment of sevoflurane, while it suppressed apoptosis and down-regulated ROS level in a concentration-dependent manner. TFs could also down-regulate expression levels of caspase-3 and caspase-9 and cytosol and intranuclear nuclear factor E2-related factor 2 (Nrf2) in rat hippocampal nerve cells, while it up-regulated those of heme oxygenase 1 (HO-1), NADPH quinine oxidoreductase 1 (NQO1), glutamate cysteine ligase (GCL) and peroxiredoxin 1 (Prx1).Conclusions: Our study suggests that TFs exert protective effects on sevoflurane-induced neurocytotoxicity and therefore could be used as a potential drug for treatment of neuronal injury.

The association of preoperative atrial fibrillation with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.

OBJECTIVE: The purpose of this study was to assess the fibrinolytic status after cardiopulmonary bypass in rheumatic valvular heart disease patients, and detect the associated factors of post-cardiopulmonary bypass hyperfibrinolysis. METHODS: According to the fibrinolytic status after cardiopulmonary bypass, 203 rheumatic valvular heart disease patients were divided into two groups: hyperfibrinolysis group (H group, n = 78) and non-hyperfibrinolysis group (NH group, n = 125). The demographic characteristics, operative variables, and postoperative follow-ups were compared between these two groups. RESULTS: The incidence of hyperfibrinolysis was 38.4% after cardiopulmonary bypass. Patients in the H group had a significant higher incidence of preoperative atrial fibrillation than patients in the NH group (92.3% vs. 55.2%, P < 0.01). Furthermore, postoperative daily drainage (655.3 ±â€¯131.5 ml vs. 535.4 ±â€¯161.4 ml, P < 0.01), transfusion volume of fresh frozen plasma (621.8 ±â€¯220.2 ml vs. 455.2 ±â€¯208.5 ml, P < 0.01), and red blood cells (5.9 ±â€¯2.2 u vs. 4.7 ±â€¯2.8 u, P < 0.01) was greater in the H group than in the NH group. Moreover, the logistic regression analysis revealed that preoperative atrial fibrillation was associated with post-cardiopulmonary bypass hyperfibrinolysis (OR = 19.691, 95% CI = 6.849-56.612; P < 0.05). CONCLUSION: Preoperative artial fibrillation is associated with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.

Ureteroscopic lithotripsy in the Trendelenburg position for extracting obstructive upper ureteral obstruction stones: a prospective, randomized, comparative trial.

OBJECTIVE: To introduce a new position for ureteroscopic holmium laser lithotripsy for patients with upper ureteral calculi. MATERIALS AND METHODS: Between June 2014 and May 2017, 192 patients were enrolled in this study. Patients were randomly assigned to one of two groups: group A, ureteroscopic lithotripsy (URSL) in the Trendelenburg position; or group B, URSL in the standard position. Baseline information, including gender, age, body mass index (BMI), stone side, stone size and hydronephrosis grade, was collected and determined preoperatively. Stone-free rate (SFR) was evaluated 3 weeks after surgery and was defined by the absence of residual stones or the presence of residual stones <2 mm in diameter. Operation time, hospital stay, stone migration, operative complications and SFR were assessed and compared between the two groups. RESULTS: There were no statistically significant differences in gender, age, BMI, stone side, stone size, serum creatinine or hydronephrosis grade between the two groups (all p > 0.05). There were no significant differences in the postoperative hospital stay or postoperative complications between the two groups (all p > 0.05), but the differences in operative time, stone migration and SFR between the two groups were statistically significant (p < 0.05). CONCLUSION: This study introduced a new position for ureteroscopic holmium laser lithotripsy for patients with upper ureteral calculi. The Trendelenburg position can improve the SFR and may provide an optional surgical method for treating upper ureteral calculi.

[Plaque excision plus autologous perididymal patch grafting for Peyronie's disease].

OBJECTIVE: To investigate the clinical effect of plaque excision plus autologous perididymal patch grafting in the treatment of Peyronie's disease. METHODS: This study included 10 patients with Peyronie's disease received in our Department of Urology between January 2013 and December 2015, who had failed to respond to over 12 months of expectant drug therapy and remained stable for more than 6 months, none able to perform sexual intercourse due to penile curvature (>60°). All the patients underwent plaque excision plus autologous perididymal patch grafting. RESULTS: Postoperative follow-up ranged from 6 to 24 months. All the patients achieved normal penile erection, without testicular atrophy, torsion or necrosis at the surgery side and all were satisfied with the surgical results without complaining about obvious penile shortening. CONCLUSIONS: Plaque excision plus autologous perididymal patch grafting is a safe, simple, economic and effective method for the treatment of Peyronie's disease.

Effects of disodium cantharidinate on dendritic cells of patients with bladder carcinoma.

The present study explored the effects of disodium cantharidinate (DC) on the peripheral blood-derived dendritic cells of patients with bladder carcinoma. The peripheral blood mononuclear cells from the 15 cases of urinary bladder carcinoma of middle and advanced stage were separated, and dendritic cells were prepared. The morphological changes of dendritic cells were observed. Flow cytometry was used to detect the expression levels of CD1a and CD83 on dendritic cell surface. MTT assay was utilized to measure the proliferation ability of allogeneic lymphocyte stimulated by DC. Annexin V-FITC/propidium iodide (PI) double staining flow cytometry method was carried out to detect cell apoptosis after treatment with DC. The changes in caspase-3 and PARP expression levels were investigated by western blot method. The high-dose DC resulted in a significant increase in the expressions of dendritic cell phenotyptic molecules CDla and CD83 as compared to control group. In addition, the proliferation index of allogenic lymphocyte stimulated by DC was significantly higher than that of control group. Moreover, MTT assay showed significant inhibition of the growth of BIU-87 cells. After 24 h of DC treatment, double staining flow cytometry confirmed the ability of DC to induce cell apoptosis. Further, western blot method showed a significant elevation of caspase-3 and PARP protein expression after DC treatment. In conclusion, DC treatment could induce dendritic cell maturation of patient with carcinoma of urinary bladder and promote its functional changes. Furthermore, DC was able to inhibit the proliferation of cell BIU-87 and also has the ability to induce cell apoptosis.

The antitumor effect of the novel cancer-specific adenovirus Ad-VEGFR on bladder cancer in vitro and in vivo.

Bladder cancer is one of the most common cancers. Approaches that block tumor angiogenesis are a new therapeutic strategy for locally advanced or metastatic BC. VEGF/VEGFR signaling has been obviously and negatively correlated with the progression and invasion of cancer. In this study, we constructed the recombinant adenovirus vAd-VEGFR-3 to investigate its antitumor effector in vitro/vivo. First, we used the recombinant adenovirus vAd-VEGFR-3 to infect bladder cancer cells and then collected the cell culture supernatant to treat human umbilical vein endothelial cells (HUVECs). The proliferation, migration and apoptosis of HUVECs were respectively detected by MTT, transwell and Annexin V-FITC/PI double staining. In addition, mouse bladder mucosa was injured by trypsin, and the orthotopic transplantation model of human bladder cancer was successfully constructed to clarify the anti-tumor effect of Ad-VEGFR in vivo. The results showed that Ad-VEGFR could inhibit the cancer's proliferation and migration, while promoting the apoptosis of HUVECs in vitro. Moreover, Ad-VEGFR could significantly promote the apoptosis of bladder cancer cells and then prevent tumor growth in vivo. In addition, it also down-regulated the expression levels of CD31, an endothelial cell marker which is closely related to the angiogenesis. Taken together, it suggests that the infection of adenovirus-carrying VEGFR in bladder cancer cells may inhibit blood vessel formation and prevent tumor progression.

Lipoamide Inhibits NF1 Deficiency-induced Epithelial-Mesenchymal Transition in Murine Schwann Cells.

BACKGROUND AND AIMS: Neurofibromatosis type I (NF1) is one of the most common neurocutaneous syndromes characterized by development of adult neurofibromas which is mainly made up of Schwann cells. The disease is generally accepted to be caused by inactivation mutation of Nf1 gene. And Nf1 deficiency had been reported to lead to ROS overproduction and epithelial-mesenchymal transition (EMT) phenotype. This study was designed to investigate whether excessive ROS conferred to Nf1 deficiency-induced EMT in Schwann cells. METHODS: Colony formation, wound healing assay and transwell assay was used to evaluate the effects of stable Nf1 knockdown in SW10 Schwann cells. Western blot and ROS assay was conducted to explore the molecular mechanisms of Nf1 inactivation in tumorigenesis. Animal experiments were performed to assess the inhibitory effects of lipoamide, which is the neutral amide of α-lipoic acid and functions as a potent antioxidant to scavenge ROS, on Nf1-deficiency tumor growth in vivo. RESULTS: Nf1 knockdown enhanced the cellular capacities of proliferation, migration and invasion, promoted ROS generation, decreased the expression of epithelial surface marker E-cadherin, and up-regulated several EMT-associated molecules in Schwann cells. Moreover, lipoamide dose-dependently inhibited not only Nf1 deficiency-induced EMT but also spontaneous EMT. Furthermore, lipoamide markedly suppresses tumor growth in a mouse model of NF1-associated neurofibroma. CONCLUSIONS: Our results clearly reveal that ROS overproduction is responsible for Nf1 deficiency-induced EMT and plays a crucial role in NF1 tumor growth. The findings presented herein shed light on the potential of antioxidant therapy to prevent the progression of NF1-associated neurofibroma.

Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis.

The associations between CYP1A1 polymorphisms and risk of leukemia have been studied extensively, but the results have been inconsistent. Therefore, in this study, we performed a meta-analysis to clarify associations of three CYP1A1 polymorphisms (T3801C, A2455G, and C4887A) with the risks of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Medline, EMBASE, and China National Knowledge Infrastructure databases were searched to collect relevant studies published up to April 20, 2015. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated to quantify the associations. Overall, 26 publications were included. Finally, T3801C was associated with an increased risk of AML in Asians under the dominant model. For A2455G, the risk of ALL was increased among Caucasians in the recessive model and the allele-contrast model; A2455G was also associated with an increased risk of CML among Caucasians under the recessive model, dominant model, and allele-contrast model. For C4887A, few of the included studies produced data. In conclusion, the results suggest that Asians carrying the T3801C C allele might have an increased risk of AML and that Caucasians with the A2455G GG genotype might have an increased risk of ALL. Further investigations are needed to confirm these associations.

[Effect of ulinastatin pretreatment on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats with major hepatectomy and ischemia-reperfusion injury].

OBJECTIVE: To investigate the effect of pretreatment with ulinastatin on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats after 70% hepatectomy combined with ischemia-reperfusion injury. METHODS: A total of 120 normal male SD rats weighing 230-280 g were randomized into 3 groups (n=40), namely simple partial hepatectomy (PH) group, partial hepatectomy with ischemia-reperfusion (PHIR) group, and ulinastatin group. All the rats received resection of the left and middle liver lobes. In PHIR group, the remnant right lobes were subjected to blood flow occlusion for 30 min; in UTI group, the rats were given 50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant liver tissues were examined for regenerated liver weight, PCNA staining, TNF-α and IL-6, STAT-3, cyclin D1, and Cdk4 expressions. RESULTS: The regenerated liver weight and PCNA positivity rates were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h after the reperfusion (P<0.05). In ulinastatin group, the levels of TNF-α and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1 and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h (P<0.05). CONCLUSION: Ulinastatin can promote liver regeneration after major hepatectomy and ischemia-reperfusion injury, and the effect is possibly related with activation of IL-6/STAT-3 signal pathway, which promotes the synthesis of cyclin Dl-Cdk4 complex and hepatocyte proliferation.

[The impact of ischemic postconditioning on the tumor necrosis factor-α/IL-6/signal transducers and activators of transcription-3 signal pathway of liver regeneration].

OBJECTIVE: To investigate the impact of the ischemic postconditioning on the tumor necrosis factor (TNF)-α/IL-6/signal transducers and activators of transcription (STAT)-3 signal pathway of liver regeneration. METHODS: Ninety healthy clean grade male Sprague-Dawley rats weighting 230 to 280 g were selected and assigned into three groups randomly: group I subtotal hepatectomy (SH), group II ischemia reperfusion (IR), group III ischemic postconditioning (IPO). The left and middle liver was resected, and the remnant liver was treated as followed: the blood flow was not blocked in SH group, but blocked 30 minutes in IR group, then reperfused; IPO groups received three cycles of 30 s-30 s intermittent interruptions of blood flow at onset of reperfusion. At 1, 6, 12, 24, 48 h after reperfusion, the serum TNF-α, IL-6 was detected and the mRNA of cyclinD1, Cdk4, STAT-3 was assayed by real-time PCR as well as the protein expression of cyclinD1 and Cdk4 by Western blot. RESULTS: Compared with SH group, the expression of IL-6 declined at each set time point in IR group (t = 5.076 to 8.334, P = 0.000), but the content of TNF-α increased in early stage (1 to 12 h) (t = 2.972 to 7.215, P = 0.000 - 0.014). The expression of STAT-3, cyclinD1 and Cdk4 mRNA and protein of cyclinD1 and Cdk4 at 24 and 48 h after reperfusion were lower in IR group than in SH group (t = 2.857 to 6.684, P = 0.000 to 0.017). However, there was a significant decrease in TNF-α from 1 to 12 h after reperfusion (t = 2.995 to 4.112, P = 0.002 to 0.017), but a significant increase in IL-6 in IPO group than in IR group (t = 2.458 to 3.543, P = 0.005 to 0.034). The expression of STAT-3, cyclinD1, Cdk4 mRNA and protein of cyclinD1 and Cdk4 at 24 and 48 h after reperfusion were all increased in IPO group in comparison with in IR group (t = 2.383 to 6.803, P = 0.000 to 0.038). CONCLUSIONS: The ischemic postconditioning could promote the remnant liver regeneration after subtotal hepatectomy with ischemia reperfusion injury. Its mechanism relates with the activation of the TNF-α/IL-6/STAT-3 signal pathway of and the cyclinD1-Cdk4 complex which enhances the proliferation of hepatocyte.