Relationship between gut microbiota dysbiosis and immune indicator in children with sepsis.

Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman's rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3+ T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.

Application of Indocyanine Green Fluorescence Imaging Combined with Laparoscopic Ultrasound in Laparoscopic Microwave Ablation of Liver Cancer.

BACKGROUND The aim of this study was to assess the effect of indocyanine green (ICG) fluorescence imaging combined with laparoscopic ultrasound in laparoscopic microwave ablation of liver cancer. MATERIAL AND METHODS This study retrospectively analyzed 61 patients who underwent laparoscopic microwave ablation of liver cancer, including laparoscopic microwave ablation with and without ICG fluoroscopy. RESULTS The operative times, ablation times, postoperative hospital stay, postoperative complication rate, hospitalization cost, postoperative liver function changes, and postoperative overall survival were similar between the 2 groups, but there was a statistically significant difference in recurrence-free survival (P<0.05). A total of 5 lesions were found in the fluorescence laparoscopy group that were not found by preoperative imaging, while no new lesions were found in the ordinary laparoscopy group. Fluorescence laparoscopy has obvious advantages over ordinary laparoscopy in finding small lesions that were not found before surgery. In terms of complete ablation rate, 3 patients in the ordinary laparoscopy group and 1 patient in the fluorescence laparoscopy group were judged to be incompletely ablated and were ablated again at 1 month after the operation. CONCLUSIONS For small hepatocellular carcinoma with severe liver cirrhosis and located on the liver surface, fluorescence laparoscopy can better reveal the location and boundary of the tumor, and fluorescence laparoscopy can detect tiny lesions that cannot be detected by preoperative imaging. The combination of fluorescence laparoscopy and microwave ablation has a good effect on the treatment of small hepatocellular carcinoma located on the surface of the liver that is difficult to distinguish.

Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder.

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were observed at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant reduction in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metabolism disorder (decreased homovanillic acid) were observed in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addition, our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in association with improved ASD symptoms, including a hyper-serotonergic state and dopamine metabolism disorder.

Coupling between d-3-phosphoglycerate dehydrogenase and d-2-hydroxyglutarate dehydrogenase drives bacterial l-serine synthesis.

l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1. SerA catalyzes the stereospecific reduction of 2-ketoglutarate (2-KG) to d-2-HG, responsible for the major production of d-2-HG in vivo. SerA combines the energetically favorable reaction of d-2-HG production to overcome the thermodynamic barrier of d-3-PG dehydrogenation. We identified a bacterial d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent enzyme, that converts d-2-HG back to 2-KG. Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG metabolism through their capacity to transfer electrons from D2HGDH. Furthermore, while the mutant with D2HGDH deletion displayed decreased growth, the defect was rescued by adding l-serine, suggesting that the D2HGDH is functionally tied to l-serine synthesis. Substantial flux flows through d-2-HG, being produced by SerA and removed by D2HGDH, ETF, and ETFQO, maintaining d-2-HG homeostasis. Overall, our results uncover that d-2-HG-mediated coupling between SerA and D2HGDH drives bacterial l-serine synthesis.

Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p < 0.001). Positive expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection.

As the most predominant tumour-infiltrating immune cells, tumour-associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68-positive TAMs display dissimilarly polarized programmes comprising CD11c-positive pro-inflammatory macrophages (M1) and CD206-positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c-positive TAM density (P = 0.005) and low versus high CD206-positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.

Expression of Kindlin-1 in human hepatocellular carcinoma and its prognostic significance.

Kindlin-1 is a member of the Kindlin family of focal adhesion proteins and is implicated in cell adhesion, proliferation, polarity, and motility. Although expression of Kindlin-1 has recently been reported in a variety of human cancers, studies on its expression in human hepatocellular carcinoma (HCC) are currently lacking. This study aimed to determine the clinicopathological parameters and prognostic value of Kindlin-1 in HCC patients after surgical resection. The messenger RNA (mRNA) and protein levels of Kindlin-1 in 22 matched HCC specimens were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting assays. The clinical and prognostic significance of Kindlin-1 in 68 cases of HCC was determined by immunohistochemistry. Kindlin-1 expression was higher in HCC tumor tissues relative to that in adjacent normal tissue at the both mRNA and protein levels (p < 0.05). Immunohistochemical results revealed that overexpression of Kindlin-1 was detected in 37 of 68 (54.4 %) tumor tissues and in seven of 68 (10.3 %) adjacent non-tumor tissues (p < 0.05). Positive Kindlin-1 expression was significantly correlated with tumor size, tumor capsula, status of metastasis, and tumor-node-metastasis (TNM) stage. Additionally, Kaplan-Meier survival analysis showed that positive Kindlin-1 expression was associated with unfavorable overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified Kindlin-1 as an independent prognostic predictor for OS and DFS in HCC patients (p = 0.041 and 0.027, respectively). Taken together, our data suggest that Kindlin-1 could play an important role in HCC and might serve as a promising prognostic marker and potential target for HCC therapy.

Protective effect of S-adenosylmethionine on hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic HBV infection.

BACKGROUND: Although hepatectomy is often performed with the Pringle maneuver, the problem of hepatic ischemia-reperfusion injury (HIRI) can also be serious. Thus, the present study was designed to investigate the protective effect of S-adenosylmethionine (SAMe) on HIRI, especially for patients with hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection and cirrhosis. METHODS: Eighty-one HCC patients with chronic HBV infection, undergoing partial hepatectomy with inflow occlusion, were divided into three groups. In the pretreatment group (PR group, n = 26), patients were given SAMe two hours before surgery. In the post-treatment group (PO group, n = 25), patients were given SAMe six hours after surgery. And in the control group (control group, n = 30), patients received partial hepatectomy without any SAMe. All pre-, intra- and postoperative blood samples were collected to measure the plasma levels of transaminases, bilirubin and cytokines. The results were compared among the three groups. RESULTS: There were no statistically significant intergroup differences observed in age, gender, hepatic inflow occlusion time and the results of liver function tests. Preoperative administration of SAMe (PR group) significantly reduced the plasma levels of alanine transaminase (ALT), aspartate transferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) as compared to the other two groups. In the PO group, TBIL and DBIL were significantly lower than in the control group. Significant differences were also seen in IL-6 and TNF-α between the PR group and the other groups. In all groups, postoperative liver reserve function in the PR group as revealed by ICGR15 (Post ICGR15) was at its best before abdominal closure. Compared to the control group, the risk of complications and the hospital stay after surgery were significantly meliorated in the PR group. Additionally, patients with cirrhosis had a more acute rate of change in ALT and AST than non-cirrhotic patients. CONCLUSIONS: Taken together, our preliminary findings suggest that preoperative administration of SAMe is useful and safe for reducing the HIRI in partial hepatectomy, especially for HCC patients whose disease is associated with chronic HBV infection and cirrhosis.

STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells.

BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) is critical for the development of the invasion and metastasis in human cancers. Recently, signal transducer and activator of transcription 3 (STAT3) activation has been linked to EMT program in breast cancer. However, the actual association of STAT3 activation with EMT, and its mediated tumor invasion and metastasis remains elusive in hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between STAT3 activation and EMT, as well as the underlying mechanism involved in HCC progression. METHODOLOGY: We treated SMMC-7721 cells with a known STAT3 activator, epithelial growth factor (EGF); in the absence or presence of JSI-124, a selective STAT3 inhibitor. The EMT-associated morphologic and molecular changes of cells were analyzed. The EMT-mediated HCC cell invasion, migration and adhesion were evaluated. RESULTS: In this study, we found that STAT3 activation induced by EGF was associated significantly with morphologic changes, cytoskeleton rearrangement and molecular changes consistent with EMT in SMMC-7721 cells; STAT3 activation-mediated EMT may be transcriptionally induced by Twist. STAT3 activation-mediated EMT also promoted HCC cell invasion, migration and adhesion significantly. CONCLUSIONS: In summary, our study show for the first time that STAT3 activation may induce invasion and metastasis through the mediation of EMT in HCC cells. Activated STAT3 and EMT markers can serve as molecular targets for HCC treatment.

Overexpression of HOXA13 as a potential marker for diagnosis and poor prognosis of hepatocellular carcinoma.

HOXA13 is a member of homeobox genes that encode transcription factors regulating embryonic development and cell fate. Abnormal HOXA13 expression was reported in hepatocellular carcinoma (HCC), but its correlation with tumor angiogenesis and prognosis still remain unclear. This study was aimed to uncover the expression, diagnostic and prognostic significance of HOXA13 in HCC. Immunohistochemistry was performed to detect HOXA13 expression in HCC and corresponding paracarcinomatous tissues from 90 patients. Enzyme-linked immunosorbent assay was used to detect serum HOXA13 in 90 HCC patients and 20 healthy volunteers. Receiver operating characteristics was analyzed to calculate diagnostic accuracy of serum HOXA13, alpha-fetoprotein (AFP) and their combination. Immunoreactivity of HOXA13 was detected in 72.2% of HCC, and 12.2% of adjacent non-cancerous samples. HOXA13 expression was significantly associated with tumor size, microvascular invasion, pathological grade, tumor capsula status, AFP level, tumor-node-metastasis stage and positively correlated with VEGF (p < 0.001) and microvessel density (p < 0.001). The combination of serum HOXA13 and AFP had a markedly higher area under the curve than HOXA13 alone. HOXA13 expression was associated with unfavorable overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001). Multivariate analysis indicated that patients with HOXA13-expressing tumors had a significantly shorter OS (p = 0.030) and DFS (p = 0.005) than those with HOXA13-negative tumors. Thus, HOXA13 expression possibly plays an important role in tumor angiogenesis, progression and prognosis of HCC. Moreover, we demonstrate that serum HOXA13 may serve as a biomarker for early HCC diagnosing and predicting outcome.

Cystic Plate Approach Combined with Indocyanine Green（ICG） Fluorescence in Laparoscopic Anatomical Hepatectomy.

BACKGROUND: The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intra- and extra-hepatic vascular system more conveniently and accurately has been gradually emphasized. OBJECTIVE: Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy. MATERIALS AND METHODS: Based on the theory of cystic plate and hepatic portal plate, we have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy. RESULTS: A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates. CONCLUSION: This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.

Human induced pluripotent stem cell line (SDQLCHi064-A) derived from a patient with Canavan disease carrying c.556_559dup GTTC and c.919delA mutations in the ASPA gene.

Canavan disease (CD, OMIM# 271900) is an autosomal recessive neurodegenerative disorder caused by homozygous or compound heterozygous mutations in ASPA gene, which result in catalytic deficiency of the aspartoacylase enzyme and the accumulation of N-acetylaspartic acid (NAA). Clinical presentation varies according to the age of disease onset. Here, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi064-A from a 5-month old boy with CD carrying two novel frame shift mutations c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) of the ASPA gene, in order for us to better understanding the disease.

Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty.

Precocious puberty, a pediatric endocrine disorder classified as central precocious puberty (CPP) or peripheral precocious puberty (PPP), is influenced by diet, gut microbiota, and metabolites, but the specific mechanisms remain unclear. Our study found that increased alpha-diversity and abundance of short-chain fatty acid-producing bacteria led to elevated levels of luteinizing hormone and follicle-stimulating hormone, contributing to precocious puberty. The integration of specific microbiota and metabolites has potential diagnostic value for precocious puberty. The Prevotella genus-controlled interaction factor, influenced by complex carbohydrate consumption, mediated a reduction in estradiol levels. Interactions between obesity-related bacteria and metabolites mediated the beneficial effect of seafood in reducing luteinizing hormone levels, reducing the risk of obesity-induced precocious puberty, and preventing progression from PPP to CPP. This study provides valuable insights into the complex interplay between diet, gut microbiota and metabolites in the onset, development and clinical classification of precocious puberty and warrants further investigation.

Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial.

BACKGROUND/AIMS: Hepatectomy is associated with high rates of postoperative liver dysfunction in patients with cirrhosis. Since S-adenosyl-L-methionine (SAMe) can be used to treat liver disease, we performed a prospective clinical trial to investigate whether it could be used after hepatectomy to benefit residual liver function. METHODOLOGY: We studied 79 hepatitis-related chronic patients who underwent resection of hepatocellular carcinoma; 39 patients were randomly assigned to receive postoperative intravenous SAMe treatment, and 40 were randomly assigned to a control group. The postoperative SAMe treatment consisted of SAMe 1,000mg given intravenously for seven days. The other treatment was standardized. RESULTS: At inclusion into the trial no significant differences were observed between the two groups with respect to gender, age, Child classification, preoperative liver function tests, blood loss, total time of hepatic pedicle occlusion and the extent of liver resection. The overall frequency of postoperative liver insufficiency decreased from 42% in the control group to 31% in the SAMe group, although not statistically significant (p=0.121). When the patients who underwent hepatic pedicle occlusion by Pringle's maneuver over 15min were analyzed, the frequency of postoperative liver insufficiency (p=0.028), serum total bilirubin levels on days 5 (p=0.025) and 7 (p=0.032) preoperatively, and the maximum value of postoperative serum total bilirubin (p=0.040) were significantly greater in the control than in the SAMe group. CONCLUSIONS: The results indicate that the postoperative SAMe therapy can benefit residual liver function of the patients with cirrhosis, especially in those suffering greater ischemia reperfusion injury.

Experimental and numerical study on gas production decline trend under ultralong-production-cycle from shale gas wells.

It is of engineering interest to explore recovered shale gas composition and its effects on total gas production trend over a long-term extraction period. However, there are previous experimental studies mostly focused on short term development for small scaled cores, which is less convincing to mimic reservoir-scaled shale production process. In addition, the previous production models mostly failed to account for comprehensive gas nonlinear effects. As a result, in this paper, to illustrate the full-life-cycle production decline phenomenon for shale gas reservoir, dynamic physical simulation was performed for more than 3433 days to simulate shale gas transport out of the formations over a relatively long production period. Moreover, a five-region seepage mathematical model was then developed and was subsequently validated by the experimental results and shale well production data. Our findings show that for physical simulation, both the pressure and production declined steadily at an annual rate of less than 5%, and 67% of the total gas in the core was recovered. These test data supported earlier finding that shale gas is of low flow ability and slow pressure decline in the shale matrices. The production model indicated that free gas accounts for the majority of recovered shale gas at the initial stage. Based on a shale gas well example, free gas extraction makes up 90% of produced total gas. The adsorbed gas constitutes a primary gas source during the later stage. Adsorbed gas contributes more than 50% of the gas produced in the seventh year. The 20-year-cumulative adsorbed gas makes up 21% of the EUR for a single shale gas well. The results of this study can provide a reference for optimizing production systems and adjusting development techniques for shale gas wells throughout the combinations of mathematical modeling and experimental approaches.

Analysis of the safety and effectiveness of TACE combined with targeted immunotherapy in the treatment of intermediate and advanced hepatocellular carcinoma.

To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune and targeted therapy in unresectable hepatocellular carcinoma (HCC). Prospective analysis of 23 patients with intermediate or advanced primary HCC treated at the Department of Hepatic Surgery, The First Affiliated Hospital of the University of Science and Technology of China from July 2019, including 11 cases treated with TACE alone and 12 cases treated with TACE combined with targeted therapy. The basal indexes of patients in the two groups were compared, and the response during treatment was observed; regular follow-up was performed to assess the efficacy of tumor treatment. Compared with TACE treatment alone, the objective response rate (ORR) was significantly higher in the TACE combined with targeted treatment group (50.0% vs 36.4%), with a higher success rate of surgical conversion (33.3% vs 18.2%) and a significantly longer progression-free survival (PFS) (20.5 ± 2.9 months vs 11.6 ± 2.9 months). Multifactorial regression analysis identified tumor vascular invasion as an independent prognostic factor affecting HCC. No patient experienced catheter retention-related complications during treatment, and there were no intolerable adverse effects. TACE combined with targeted treatment for intermediate to advanced unresectable HCC was effective, with good tumor responsiveness, high surgical conversion rate, and safe and controllable adverse reactions during treatment.

Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis.

Osteopontin (OPN) has been implicated in tumor development and progression for several years. However, the prognostic value of OPN overexpression in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to assess the relationship between OPN overexpression and clinical outcome of HCC. A meta-analysis of seven studies (1,158 patients) was carried out to evaluate the association between OPN and overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between OPN and tumor vascular invasion or other invasion-related parameters was also assessed. Data were synthesized with random effect model of DerSimonian and Laird, hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that high OPN expression predicted poor OS (HR: 1.37, 95% CI: 1.21-1.55) and DFS (HR: 1.62, 95% CI: 1.24-2.11) of HCC. OPN overexpression tended to be associated with the presence of tumor vascular invasion (OR: 1.93, 95% CI: 0.97-3.84) and advanced tumor grade (OR: 1.74, 95% CI: 0.95-3.18). By this study, we conclude that OPN overexpression indicates a poor prognosis for patients with HCC, it may also have predictive potential for HCC invasion and metastasis.

Activation of STAT3 signal pathway correlates with twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance.

BACKGROUND: To examine the expression of signal transducer and activator of transcription 3 (STAT3) and its activated form (p-STAT3), Twist, and E-cadherin in hepatocellular carcinoma (HCC), and explore their correlations with HCC progression and prognosis. MATERIALS AND METHODS: The expression profiles of STAT3, p-STAT3, Twist, and E-cadherin were assessed on 100 clinical HCC samples and 10 normal liver tissues by using an immunohistochemical staining method, and their correlations with clinicopathologic parameters and survival of HCC patients were statistically analyzed. RESULTS: The results demonstrated that the positive rate of STAT3, p-STAT3, and Twist in HCC was significantly higher than that in normal liver tissues; furthermore, 52% of HCC lesions showed reduced E-cadherin expression. Correlation analysis indicated that p-STAT3 was positively correlated with Twist expression, whereas Twist was negatively correlated with E-cadherin expression; p-STAT3, Twist, or E-cadherin expression was significantly associated with HCC invasion and metastasis. Survival analysis showed that HCC patients with p-STAT3, Twist positive expression, or reduced E-cadherin expression had a significantly shorter survival duration than those with p-STAT3, Twist negative expression, or those with normal E-cadherin expression. Multivariate analysis identified p-STAT3, Twist, or E-cadherin expression as an independent prognostic factor for overall survival of HCC patients after surgery. CONCLUSIONS: By this study, we suggest that activated STAT3 signal may associate with Twist and E-cadherin expression and mediate HCC invasiveness and metastasis; abnormal p-STAT3/Twist/E-cadherin signal axis may predict poor prognosis of HCC patients.

Efficacy and feasibility of radiofrequency ablation for hepatocellular carcinoma patients.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is a new treatment which is used to treat hepatocellular carcinoma (HCC). We performed this clinical trial to investigate whether it could reduce the damage of residual liver function. METHODOLOGY: We studied 40 hepatitis-related chronic patients who underwent RFA for hepatocellular carcinoma. Indocyanine green (ICG) test was performed pre and postoperatively. RESULTS: There were 32 males and 8 females with an average age of 53.98+12.59 years who underwent RFA for HCC. The mean preoperative ICGR15 value of 40 of the patients was (10.17+9.54) lower than the postoperative ICG retention rate at 15 min (ICGR15) value (14.95+12.71).Differences between the preoperative ICGR15 and the postoperative ICGR15 values were not significantly different (p=0.074). The 1-, 2- and 3-year survival rates were 98.7%, 88.8% and 76.4%, respectively. CONCLUSIONS: The results indicate that RFA is a minimally invasive treatment which provides a possible treatment modality for HCC patients with poor liver function and the efficacy is as well as the surgical treatment for HCC patients within the Milan criteria.

[Prognosis after hepatectomy for primary liver cancer of segment 7 or 8].

OBJECTIVE: To investigate the results of surgical treatment for primary liver cancer of segment VII or VIII. METHODS: The clinical data of 149 patients with primary liver cancer who underwent hepatectomy between January 2005 and December 2010 was retrospectively analyzed. There were 120 male and 29 female patients, aging from 19 to 75 years with a mean of 53.1 years. Among 149 patients, tumors were located at segment VII, VIII or several segments containing VII or VIII (VII/VIII group) in 53 patients, located at other segments (non-VII/VIII group) in 96 patients. The results of surgical treatment for VII/VIII group and non-VII/VIII group were compared by using t test, χ(2) test, Kaplan-Meier survival analysis and Cox proportion hazard regression analysis. RESULTS: Right liver lobe was turned over completely in VII/VIII group, hepatic lobe which tumor was located at was not or partly turned over in non-VII/VIII group. Compared with non-VII/VIII group, VII/VIII group had longer operative time ((215 ± 68) min vs. (123 ± 36) min, t = 2.860, P = 0.01). No significant difference was found for tumor size, tumor number, tumor encapsulation, microvascular invasion, Edmondson grade, pTNM stage, intraoperative blood loss, blood transfusion rate, R0 resection rate and postoperative complication rate between two groups. The cumulative 1-, 3-, and 5-year overall survival rates were 74.6%, 42.3%, 15.4% respectively, in VII/VIII group, and 89.3%, 63.0%, 40.4% respectively, in non-VII/VIII group (χ(2) = 13.501, P = 0.000). Univariate and multivariate analysis of prognostic factors indicated that tumor location (tumor was located at segment VII or VIII) had unfavorable prognostic influence on overall survival (χ(2) = 10.329, P = 0.001; HR = 1.693, 95%CI: 1.232 - 2.694, P = 0.013). CONCLUSION: The results of surgical treatment for primary liver cancer located at segment VII or VIII are worse than that located at other segments.