Laparoscopic versus open surgery for hepatic caudate lobectomy: a retrospective study.

BACKGROUND: This study was designed to investigate the feasibility and safety of laparoscopic hepatic caudate lobectomy (LHCL) for treating liver tumor by comparing with the open hepatic caudate lobectomy (OHCL). METHODS: In the LHCL group, we included 24 patients with liver tumor received LHCL in Qilu Hospital of the Shandong University from January 2014 to January 2019. Meanwhile, 24 matched liver tumor patients underwent OHCL in our hospital served as control. Then we compared the patient characteristics, intraoperative parameters, and postoperative outcomes between LHCL group and OHCL group. RESULTS: There were no significant differences in gender, age, degree of cirrhosis, tumor size, preoperative liver function, Child-Pugh grading, proportion of liver cirrhosis, and tumor size between LHCL group and OHCL group (P > 0.05). No death was reported in both groups. The length of incision in LHCL group was significantly lower than that in OHCL group (4.22 ± 1.14 cm vs. 22.46 ± 4.40 cm, P < 0.001). The intraoperative blood loss in LHCL group was significantly lower than that of OHCL group (116.82 ± 71.61 ml vs. 371.74 ± 579.35 ml, P = 0.047). The total operation time, Pringle maneuver occlusion time, and blocking rate in LHCL group showed no statistical difference compared with those of the OHCL group (P > 0.05). The VAS scores at postoperative 24 and 48 h showed no statistical differences between LHCL group and OHCL group (P > 0.05). Compared with the OHCL group, significant decrease was noticed in the proportion of patients with severe pain 48 h after surgery (0 vs. 4.25 ± 0.46, P < 0.001) and dezocine consumption (90.45 ± 45.77 mg vs. 131.6 ± 81.30 mg, P = 0.0448) in the LHCL group. CONCLUSION: LHCL is effective and feasible for treating liver tumor, which is featured by reducing intraoperative blood loss and serious pain.

IL-22 relieves hepatic ischemia-reperfusion injury by inhibiting mitochondrial apoptosis based on the activation of STAT3.

INTRODUCTION: Interleukin-22 (IL-22) has been proven to exhibit a protective role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to explore the change of IL-22 and IL-22 receptor 1 (IL-22R1) axis in HIRI and its role in mitochondrial apoptosis associated with STAT3 activation. MATERIALS AND METHODS: I/R mice were examined for the expression of IL-22, IL-22R1 and IL-22BP. The roles of IL-22 in hepatic histopathology and oxidative stress injuries (ALT, MDA and SOD) were determined. Oxidative stress damages of AML-12 cells were induced by H2O2, and were indicated by apoptosis, Ca2+ concentration, and mitochondrial function. The effects of IL-22 on p-STAT3Try705 were analyzed. RESULTS: We found that the expression of IL-22, IL-22R1, and IL-22BP was elevated 24 h after I/R induction, while decreased 48 h after I/R induction. Furthermore, we also discovered that IL-22 rescued the morphological damages and dysfunction of hepatocytes induced by H2O2, which were antagonized by IL-22BP, an endogenous antagonist of IL-22. Additionally, increased levels of Ca2+ concentration, MDA, ROS, apoptosis and mitochondrial dysfunction were noticed in H2O2-treated hepatocytes. However, IL-22 ameliorated the effects of I/R or H2O2. The protective effects of IL-22 were reversed by AG490, a specific antagonist of STAT3. CONCLUSIONS: In conclusion, our results indicated that IL-22 inhibited I/R-induced oxidative stress injury, Ca2+ overload, and mitochondrial apoptosis via STAT3 activation.

CREB3L4 promotes hepatocellular carcinoma progression and decreases sorafenib chemosensitivity by promoting RHEB-mTORC1 signaling pathway.

This study was designed to explore the roles of CREB3L4 in the pathogenesis and drug resistance of hepatocellular carcinoma (HCC). The proliferation of HCC lines was determined in the presence of CREB3L4 over-expression and silencing. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay were performed to screen the potential target of CREB3L4 on mTORC1. Xenografted tumor model was established to define the regulatory effects of CREB3L4 in the tumorigenesis. Then we evaluated the roles of CREB3L4 in chemosensitivity to sorafenib treatment. CREB3L4 significantly induced the HCC cell proliferation by modulating the activation of mTROC1-S6K1 signaling pathway via binding with RHEB promoter. Moreover, CREB3L4 dramatically inhibited the chemosensitivity to sorafenib treatment via up-regulating RHEB-mTORC1 signaling. CREB3L4 promoted HCC progression and decreased its chemosensitivity to sorafenib through up-regulating RHEB-mTORC1 signaling pathway, indicating a potential treatment strategy for HCC through targeting CREB3L4.

Neoadjuvant immunotherapy improves outcomes for resectable gastroesophageal junction cancer: A systematic review and meta-analysis.

BACKGROUND: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. METHODS: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta-analyses were performed using Stata BE17 software. RESULTS: For these meta-analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36-0.54; pCR: ES = 0.26; 95% CI: 0.21-0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48-0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%-17%; nodal downstage to ypN0 rate: ES = 21%-29%). Safety was assessed using the treatment-related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60-0.70; 0.15-0.51; and 0, respectively). The reported resection rates of 85%-95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. CONCLUSION: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long-term effects of NAIT require further study.

TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing cholesterol efflux capacity in macrophage.

Cholesterol efflux capacity (CEC) dysfunction in macrophages is important in atherosclerosis. However, the mechanism underlying CEC dysfunction remains unclear. We described the characteristics of ATF4 and inflammasome activation in macrophages during atherosclerosis through scRNA sequencing analysis. Then model of hyperlipemia was established in ApoE-/- mice; some were treated with tauroursodeoxycholic acid (TUDCA). TUDCA decreased the ATF4, Hspa, and inflammasome activation, reduced plaque area of the artery, and promoted CEC in macrophages. Furthermore, TUDCA abolished oxLDL-induced foam cell formation by inhibiting activation of the PERK/eIF2α/ATF4 and AIM2 inflammasome in macrophages. Further assays revealed ATF4 binding to AIM2 promoter, promoting its transcriptional activity significantly. Then we discovered that ATF4 affected AIM2-mediated foam cell formation by targeting ABCA1, which could be blocked by TUDCA. Our study demonstrated that TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing CEC of macrophage, which provided possibilities for the development of therapies.

Oxytocin alleviates liver fibrosis via hepatic macrophages.

Background & Aims: Previous studies demonstrated oxytocin treatment effectiveness in reducing mortality and reversing liver fibrosis in mice. However, the underlying mechanism remains obscure, given the absence of oxytocin receptor expression in hepatic stellate cells, the primary liver fibrosis effector cells. Methods: A comprehensive map of cell populations in fibrotic liver was generated using single-cell sequencing. The map enabled our study of the target cells of oxytocin action in the liver in more dimensions. Furthermore, we elucidated the mechanism of the oxytocin signaling system in hepatic macrophages using oxytocin receptor-specific knockout mice and liver fibrosis animal models. Results: The carbon tetrachloride-induced hepatic fibrosis and bile duct ligation hepatic fibrosis mouse models demonstrated that oxytocin reversed hepatic fibrosis in mice. The mapped liver cell populations demonstrated that oxytocin promoted the phenotypic switch from Ly6high to Ly6Clow in myeloid-derived macrophages. The phenotypic control of oxytocin signaling system activation on this phenotypic switch was validated using myeloid-specific oxytocin receptor knockout mice. Subsequent studies demonstrated that the calcium inward flow induced by oxytocin receptor activation activated the key orphan nuclear receptor NR4A1, which controls macrophage phenotypic switching. Specifically, calcium ions activated CREB, a key target regulator of NR4A1 expression. Conclusions: The findings established hepatic macrophages as a hub responsible for the oxytocin-mediated alleviation of liver fibrosis. This study revealed a novel pathway where oxytocin regulates macrophage phenotype. Impact and implications: Previous studies revealed for the first time the expression of oxytocin receptors in the liver. The present study shows that oxytocin reverses hepatic fibrosis and that hepatic macrophages are the central hub of oxytocin-mediated alleviation of hepatic fibrosis by promoting a phenotypic switch in hepatic macrophages, transitioning from Ly6high to Ly6Clow expression. The present study reveals a novel pathway by which oxytocin regulates macrophage phenotype. In addition, the potential applications of oxytocin and its analogues, as traditional drugs for clinical application, in the treatment of liver fibrosis deserve to be further explored.

Protective effect of N-acetylserotonin against acute hepatic ischemia-reperfusion injury in mice.

The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

Trocar number and placement for laparoscopic sleeve gastrectomy and comparison of single-incision and conventional laparoscopic sleeve gastrectomy: a systematic review and meta-analysis.

BACKGROUND: Conventional laparoscopic sleeve gastrectomy (CLSG) has been conducted in multiple centers for treating morbid obesity, however, there are no standard criteria for (1) placing the trocar; and (2) how many trocars should be used. Single-incision laparoscopic sleeve gastrectomy (SLSG), a newly emerged technique in 2008, has been proposed as an alternative to CLSG in recent years, however, there is no definite evidence for this. MATERIALS AND METHODS: A systematic literature search was performed using the PubMed, Embase, Web of Science, and Cochrane Library databases for laparoscopic sleeve gastrectomy cases from January 2006 to October 2022. We then summarized the trocar numbers and placement patterns among these studies. A meta-analysis was conducted to compare the difference between SLSG and CLSG in the perioperative and postoperative indices. RESULTS: A total of 61 studies involving 20 180 patients who underwent laparoscopic sleeve gastrectomy for treating morbid obesity were included in the systematic review, including 11 on SLSG, 35 on CLSG, and 15 studies comparing SLSG and CLSG. A systematic review showed that the trocar number varied in different CLSG studies, mainly using four or five trocars. The trocars were mainly placed in position, presenting an inverted trapezoid pattern and a left-predominant pattern. Meta-analysis showed that the operative time in the SLSG was significantly higher than that in the CLSG, and the pain Visual Analog Scale rating on postoperative day 1 in the CLSG was significantly higher than in the SLSG. There were no statistical significances in the other complications or surgical efficiency. CONCLUSIONS: In the CLSG, the majority of the trocars were arranged in an inverted trapezoid pattern and were of the left-predominant type. Although SLSG is a feasible technique in selected patients, there is insufficient evidence to recommend its widespread use compared with CLSG. High-quality randomized controlled trials with large study populations and long follow-up periods will be required in the future.

Ac2­26 alleviates hepatic ischemia­reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF­κB/neutrophils.

Inflammation is one of the most crucial mechanism underlying hepatic ischemia-reperfusion injury (HIRI). Several studies have shown that Ac2-26, the active N-terminal peptide of Annexin A1, could modulate anti-inflammatory processes and protect the organs from ischemia-reperfusion injury (IRI). However the effects of Ac2-26 on an HIRI model have not been reported to date. The purpose of the present study was to determine whether Ac2-26 pretreatment could protect hepatocytes against acute HIRI by inhibiting neutrophil infiltration through regulation of the high mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. To this end, a total of 72 adult C57BL/6 mice were randomly divided into sham operation (sham), ischemia-reperfusion (I/R), I/R + Ac2-26 and Ac2-26 groups. The HIRI model was established by occluding the branch of the hepatic pedicle to the left and median liver lobes with an atraumatic vascular clamp for 45 min, followed by reperfusion for 24 h. The expression of HMGB1, TLR4, NF-κB, IκBα and lymphocyte antigen 6 complex locus G6D (Ly6G) was detected using reverse transcription-quantitative PCR, western blotting and immunohistochemical staining; serum levels of HMGB1 were evaluated using an enzyme-linked immunosorbent assay. Flow cytometry was used to detect the proportion of neutrophil. The results indicated that Ac2-26 preconditioning rescued hepatocyte dysfunctions induced by HIRI. In addition, HIRI was associated with a significant increase in HMGB1 expression and release, accompanied by increased expression of TLR4, which was significantly inhibited by Ac2-26. Furthermore, the expression of phosphorylated (p)-NF-κB and the ratio of p-NF-κB to NF-κB were markedly increased, while the expression of IκBα was decreased in the I/R group compared with those in the sham group; however, these effects were reversed by Ac2-26 administration. Additionally, Ac2-26 administration significantly inhibited neutrophil infiltration and resulted in low levels of neutrophils and Ly6G as well as reduced myeloperoxidase activity. Taken together, these results indicated that Ac2-26 pretreatment serves a protective role against HIRI by regulating the HMGB1/TLR4/NF-κB signaling pathway and inhibiting neutrophil infiltration.

Liver retraction using n-butyl-2-cyanoacrylate glue during laparoscopic cholecystectomy.

ABSTRACT: There might be a thick "protrusion" in the visceral surface of hepatic quadrate lobe during the laparoscopic cholecystectomy (LC), which affects the surgical fields and consequently triggers high risks of biliary tract injury. Although n-butyl-2-cyanoacrylate (NBCA) glue has been applied to laparoscopic upper abdominal surgery for liver retraction, there is still no consensus on its safety and feasibility in LC. In this study, we investigated the safety, feasibility, and effectiveness of liver retraction using NBCA glue for these patients which have the thick "protrusion" on the square leaf surface of the liver during LC.Fifty-seven patients presenting thick "protrusion" hepatic quadrate lobe were included in our retrospective study. We performed LC in the presence of NBCA glue (n = 30, NBCA group) and absence of NBCA glue (n = 27, non-NBCA group), respectively. NBCA was used to fix the thick "protrusion" of the liver leaves to the hepatic viscera surface, which contributed to the revelation of the gallbladder triangle. The operation time, blood loss, postoperative hospitalization, and liver function were compared between the 2 groups.Both the groups' patients accomplished the operation in the laparoscopy. There was no mortality and no additional incision during operation. No severe complications including bile duct injury were available after surgery and no postoperative NBCA-related complications occurred after 9- to 30 months' follow-up. The time of operation in NBCA group showed significant decrease compared with that of non-NBCA group (48.33 ±â€Š16.15 vs 65.00 ±â€Š22.15 minutes, P < .01). There were no significant differences in blood loss, postoperative hospital stays, and the preoperative and postoperative liver function between the two groups (P > .05). Besides, no significant differences were noticed in major clinical characteristics between the 2 groups (P > .05).Liver retraction using NBCA during LC for thick "protrusion" hepatic quadrate lobe patients is safe, effective, and feasible.

Serum KIAA1199 is an advanced-stage prognostic biomarker and metastatic oncogene in cholangiocarcinoma.

BACKGROUND: Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear. RESULTS: Analysis of cancer-related databases showed that KIAA1199 is overexpressed in CCA. ELISA, immunohistochemistry, Western blotting and qPCR indicated high expression levels of KIAA1199 in serum, CCA tissues and CCA cell lines. In the serum (n = 41) and large sample validation (n = 177) cohorts, higher KIAA1199 expression was associated with shorter overall survival and disease-free survival times. At the cellular level, KIAA1199 overexpression (OE) promoted CCA growth and metastasis. Subcutaneous tumor xenograft experiments showed that KIAA1199 enhances CCA cell proliferation. Additionally, the expression levels of components in the EMT-related TGF-ß pathway changed significantly after KIAA1199 upregulation and silencing. CONCLUSION: KIAA1199 is a promising new diagnostic molecule and therapeutic target in CCA. The serum KIAA1199 level can be used as a promising clinical tool for predicting the overall postoperative outcomes of patients with CCA. METHODS: CCA-related KIAA1199 data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. To assess the prognostic impact of KIAA1199, an enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of KIAA1199 in 41 patients who underwent surgical resection. Immunohistochemical staining, Western blotting and qPCR were used to verify and retrospectively review the expression levels of KIAA1199 in cancer tissue specimens from 177 CCA patients. The effect of KIAA1199 on CCA was evaluated by cell-based functional assays and subcutaneous tumor xenograft experiments. The expression levels of proteins associated with epithelial-mesenchymal transition (EMT) and activation of relevant signaling pathways were measured via Western blotting.

A novel technique to prepare a single cell suspension of isolated quiescent human hepatic stellate cells.

To explore a simple and easy-to-learn procedure for the isolation of human quiescent hepatic stellate cells (HSCs) that requires no advanced training. Thus reducing costs and increasing efficiency. This protocol will provide sufficient primary cells with minimal contaminants for future basic research on diseases associated with human HSCs. Normal liver tissues were isolated from patients undergoing hepatic hemangioma resection, and a single cell suspension of these tissues was prepared using the Gentle MACS tissue processor. By using this method, the difficulty of the procedure was reduced, fewer cells were lost during the preparation treatments, and the maximal activity of single cells was maintained. Following preparation of the cell suspension, the HSCs were further isolated using a Nycodenz density gradient. Cell viability was examined by trypan blue staining, and the purity of the quiescent human HSCs was determined by autofluorescence and oil red O staining. Activated and quiescent human HSCs were identified using immunofluorescence and Western blotting. The cell cycle distribution in activated and quiescent human HSCs was analyzed by flow cytometry.The recovery rate of the HSCs was approximately (2.1 ± 0.23) × 106 of tissue, with 94.43 ± 1.89% cell viability and 93.8 ± 1.52% purity. The technique used in this study is a simple, high-yield, and repeatable method for HSC isolation that is worthy of recommendation.

Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis.

Suppressor of variegation, Enhancer of Zeste, Trithorax and Myeloid-Nervy-DEAF1 domain-containing (SMYD) proteins are a set of lysine methyltransferases involved in a range of diverse biological functions, including gene expression, and regulation of skeletal and cardiac-muscle development. These proteins may additionally serve roles in a number of different types of cancer. However, the roles of the five SMYD proteins, SMYD 1/2/3/4/5, their expression patterns and prognostic value remain unclear. In the present study, the transcriptional expression levels of the five SMYD proteins were compared with the survival data of patients with breast carcinoma (BC) from the ONCOMINE dataset, Breast Cancer Gene-Expression Miner v4.0, Kaplan-Meier Plotter, The Cancer Genome Atlas and cBioPortal. An increase in the SMYD2/3/5 mRNA expression levels and a decrease in SMYD1/4 mRNA expression levels in BC tissues compared with normal tissues were identified. Increased SMYD3 mRNA and decreased SMYD5 mRNA expression levels were associated with decreased levels of histological differentiation, according to the Scarff-Bloom-Richardson grading system. Kaplan-Meier curves demonstrated that the increased SMYD1/4 and decreased SMYD2/3 mRNA expression levels were associated with good relapse-free survival (RFS) in patients with BC. Furthermore, SMYD2 mRNA expression levels were associated with the RFS of patients with BC with metastatic relapse, and SMYD4 may serve as a tumor suppressor in patients with BC, as patients with increased SMYD4 mRNA expression levels had significantly better RFS compared with decreased SMYD4 mRNA expression levels. The present data suggested that SMYD2 and SMYD3 may be potential biomarkers for diagnosis of BC. Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC.

Liver Retraction Using n-Butyl-2-Cyanoacrylate (NBCA) Glue during Laparoscopic Splenectomy and Azygoportal Disconnection in Cirrhotic Patients.

BACKGROUND: Although liver retraction using n-butyl-2-cyanoacrylate (NBCA) glue has been applied to laparoscopic upper abdominal surgery in noncirrhotic patients, there is still no consensus on its safety and feasibility for cirrhotic patients. In this study, we aimed to investigate the safety and effectiveness of liver retraction using NBCA glue during laparoscopic splenectomy and azygoportal disconnection (LSD) for gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension. METHODS: Thirty-nine gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension patients were included in our study. We performed LSD in the presence of NBCA glue (n = 22, NBCA group) and absence of NBCA glue (n = 17, n-NBCA group), respectively. The operation time, blood loss, postoperative hospitalization, and liver function were compared between the two groups. RESULTS: There was no mortality during the operation. One patient in non-NBCA group received open surgery due to parenchyma hemorrhage. Postoperative pleural effusion occurred in 2 cases of the NBCA group and 1 of the non-NBCA group. One showed left subphrenic abscess in the non-NBCA group. No postoperative bleeding occurred after 9-30 months of follow-up. The time of operation in NBCA group was significantly shorter than those in n-NBCA group (198.86±17.86 versus 217.81±20.25min, P<0.01). Blood loss in NBCA group was significantly lower than non-NBCA group (159.09±56.98 versus 212.50±88.51 ml, P<0.05). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased on day 1 after LSD and decreased to normal level on day 7 after LSD in both groups. There was no significant difference in postoperative hospitalization and liver function between the two groups. CONCLUSION: Liver retraction using NBCA glue during LSD for gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension is safe, effective, and feasible.

KIAA1199 overexpression is associated with abnormal expression of EMT markers and is a novel independent prognostic biomarker for hepatocellular carcinoma.

PURPOSE: To determined KIAA1199 expression and investigate its correlation with the clinicopathologic data and prognosis of hepatocellular carcinoma (HCC), as well as markers of epithelial-mesenchymal transition (EMT); N-cadherin, E-cadherin and vimentin. MATERIALS AND METHODS: Western blot, quantitative real-time PCR, and immunohistochemical staining were used to measure KIAA1199 expression in human HCC specimens. Subsequently, the correlation between KIAA1199 expression and the pathological characteristics of HCC patients was analyzed. Univariate and multivariate analyses were used to explore the risk factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: KIAA1199 expression was remarkably increased in hepatocellular carcinoma tissues compared to paracarcinomatous tissues. This phenomenon was accompanied by aberrant expression of EMT-associated markers. In addition, high KIAA1199 expression was associated with severe pathological symptoms, low DFS, and low OS. Results of the multivariate analysis showed that KIAA1199 expression may be an independent predictor of low disease-free survival and OS of HCC patients. CONCLUSION: KIAA1199 overexpression in HCC patients is associated with aberrant expression of EMT-associated markers and severe clinicopathological symptoms, and thus may function as a marker of poor prognosis in HCC.

Surgical Technique and Clinical Analysis of Twelve Cases of Isolated Laparoscopic Resection of the Hepatic Caudate Lobe.

OBJECTIVE: To describe the surgical procedures of laparoscopic caudate lobectomy and analyze its clinical efficiency for treating cancer. METHODS: Twelve consecutive patients of hepatocellular carcinoma, hepatic hemangioma, and focal nodular hyperplasia who received laparoscopic caudate lobectomy in Qilu Hospital of Shandong University from January 2013 to January 2017 were included in this study. The clinical data, intraoperative parameters, and postoperative outcomes were assessed. RESULTS: All 12 patients received totally laparoscopic technique. The operative time was 140.8 ± 95.34 minutes. The average estimated blood loss was 97.92 ± 90.54 ml, and no blood transfusions were required. The mean duration of hospital stay was 9.17 ± 2.88 days. There was no perioperative complication or patient mortality in this series. CONCLUSIONS: Laparoscopic caudate lobectomy is safe and feasible in the selected patients.

Bone marrow derived mesenchymal stem cells alleviated brain injury via down-regulation of interleukin-1ß in focal cerebral ischemic rats.

Interleukin-1ß (IL-1ß) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1ß, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1ß. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1ß). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1ß was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1ß. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1ß expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1ß expression, thus repair the injured brain in focal cerebral ischemic rats.

Microarray comparison of the gene expression profiles in the adult vs. embryonic day 14 rat liver.

The aim of the present study was to identify the differentially-expressed genes of embryonic day 14 (ED 14) rat liver in comparison to adult rat liver, which may provide specific information for the investigation of the hepatogenesis mechanism. The gene expression profiles of ED 14 and adult rat livers were investigated using microarray analysis (the Illumina RatRef-12 Expression BeadChip). Quantitative polymerase chain reaction (qPCR) analyses were conducted to confirm the gene expression. There were 787 genes upregulated in the embryonic liver. Based on the gene ontology classification system, which was analyzed by the database for annotation, visualization and integrated discovery software, a number of the upregulated genes were categorized into the distinct and differentially-expressed functional groups, including metabolism pathway, cell cycle, transcription, signal transduction, purine metabolism, cell structure, transportation and apoptosis. qPCR analyses confirmed the gene expression. Eleven upregulated genes were found in the ED 14 rat liver, which may provide specific information for the understanding of the molecular mechanisms that control hepatogenesis. These overexpressed genes are potential markers for identifying hepatic progenitor cells.

N-acetyl-serotonin protects HepG2 cells from oxidative stress injury induced by hydrogen peroxide.

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2 produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.