Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination External Rotation Type IV Ankle Injury.

BACKGROUND Lateral malleolus fractures, typically from trauma, sports, or accidents, are common, with supination external rotation (SER) injuries being most prevalent. SER injuries involve complex joint mechanics and often necessitate surgical intervention for instability. This study compares intramedullary nail and plate fixation for fibula fractures in SER type IV ankle injuries, considering their biomechanical properties and influence on fracture healing. MATERIAL AND METHODS A prospective, randomized study was conducted between January 2021 and December 2021. A total of 81 patients with SER injuries were included in the study. Surgical procedures were performed using either intramedullary nails or plates. The following parameters were recorded and analyzed: postoperative complications, operation times, bone healing times, American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores for pain, and ankle range of motion. RESULTS Out of the 81 cases, 42 were treated with intramedullary nails, while 39 received plate fixation. Statistical analysis revealed a significantly lower rate of postoperative complications in the intramedullary nail group than in the the plate fixation group (9.52% vs 30.77%, P<0.0164). However, there were no significant differences between the 2 groups in terms of operation time, bone healing time, AOFAS scores, VAS scores, and functional evaluations (P>0.05). CONCLUSIONS Plate fixation and intramedullary nail fixation are effective techniques for treating fibula fractures in SER type IV injuries. However, intramedullary nail fixation demonstrates a lower rate of complications. Therefore, intramedullary nails may be preferable to plate fixation for the management of fibula fractures in SER type IV ankle injuries.

Biomaterial-Based Gene Delivery: Advanced Tools for Enhanced Cartilage Regeneration.

Gene therapy has emerged as a promising and innovative approach in cartilage regeneration. Integrating biomaterials into gene therapy offers a unique opportunity to enhance gene delivery efficiency, optimize gene expression dynamics, modulate immune responses, and promote tissue regeneration. Despite the rapid progress in biomaterial-based gene delivery, there remains a deficiency of comprehensive discussions on recent advances and their specific application in cartilage regeneration. Therefore, this review aims to provide a thorough overview of various categories of biomaterials employed in gene delivery, including both viral and non-viral vectors, with discussing their distinct advantages and limitations. Furthermore, the diverse strategies employed in gene therapy are discussed and summarized, such as the utilization of growth factors, anti-inflammatory cytokines, and chondrogenic genes. Additionally, we highlights the significant challenges that hinder biomaterial-based gene delivery in cartilage regeneration, including immune response modulation, gene delivery efficiency, and the sustainability of long-term gene expression. By elucidating the functional properties of biomaterials-based gene therapy and their pivotal roles in cartilage regeneration, this review aims to enhance further advances in the design of sophisticated gene delivery systems for improved cartilage regeneration outcomes.

RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer.

Background: Colorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC. Methods: Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation. Results: This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC. Conclusion: Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.

Functional metabolomics revealed functional metabolic-characteristics of chronic hepatitis that is significantly differentiated from acute hepatitis in mice.

Diagnosis and therapeutics of acute- and chronic- hepatitis (A-H and C-H) cannot be distinguished during clinical practice because functional molecular-characteristics of two conditions remains elusive. Here, we employed a functional metabolomics strategy to discover functional metabolites that can readily distinguish C-H from A-H in CCl4 treated mice. Metabolic-differentiation between A-H and C-H was identified as A-H was largely characterized by the dysregulated purine cycle and amino acid metabolism, while the disorders of hepatic taurine-conjugated bile acids and glycerolipid biosynthesis were observed with C-H. Excitingly, we found that the enhanced conversation of C18-22 PUFA-containing TAGs to MUFA-containing TAGs promoted the development of C-H, which was also closely associated with the changes of TCA intermediates regulated by gut microbiota (Muribaculaceae and Prevotellaceae). Such metabolic discovery on hepatitis was validated by the functional annotation of metabolic genes, as the decreased expressions of Slc27a2, Acaa1a and Acaa1b mostly account for the dysregulation of purine degradation with AH, then the lowered expressions of Cyp2e1, Cat, Slc27a5 and Klb are significantly related to the dysregulated bile acids with C-H. Collecting clinical samples from the patients with hepatitis to compare serum metabolomes with A-H and C-H mice, the determinant functional metabolites were identified to significantly distinguish C-H from A-H in both experimental and clinical settings, suggesting metabolic discovery with CCl4 treated mice could be further efficiently explored to guide clinical research of A-H and C-H. Collectively, our study is providing novel insight into distinctive metabolic-characteristics of A-H and C-H underlying the innovative diagnosis and therapeutics of hepatitis.

Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic bile duct stones into intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with poor prognosis. Intrahepatic bile duct stone (IBDS) is one of the key causes to ICC occurrence and can increase morbidity rate of ICC about forty times. However, the specific carcinogenesis of IBDS is still far from clarified. Insight into the metabolic phenotype difference between IBDS and ICC can provide potential mechanisms and therapeutic targets, which is expected to inhibit the carcinogenesis of IBDS and improve the prognosis of ICC. METHODS: A total of 34 participants including 25 ICC patients and 9 IBDS patients were recruited. Baseline information inclusive of liver function indicators, tumor biomarkers, surgery condition and constitution parameters etc. from patients were recorded. ICC and IBDS pathological tissues, as well as ICC para-carcinoma tissues, were collected for GC-MS based metabolomics experiments. Multivariate analysis was performed to find differentially expressed metabolites and differentially enriched metabolic pathways. Spearman correlation analysis was then used to construct correlation network between key metabolite and baseline information of patients. RESULTS: The IBDS tissue and para-carcinoma tissue have blurred metabolic phenotypic differences, but both of them essentially distinguished from carcinoma tissue of ICC. Metabolic differences between IBDS and ICC were enriched in linoleic acid metabolism pathway, and the level of 9,12-octadecadienoic acid in IBDS tissues was almost two times higher than in ICC pathological tissues. The correlation between 9,12-octadecadienoic acid level and baseline information of patients demonstrated that 9,12-octadecadienoic acid level in pathological tissue was negative correlation with gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) level in peripheral blood. These two indicators were all cancerization marker for hepatic carcinoma and disease characteristic of IBDS. CONCLUSION: Long-term monitoring of metabolites from linoleic acid metabolism pathway and protein indicators of liver function in IBDS patients has important guiding significance for the monitoring of IBDS carcinogenesis. Meanwhile, further insight into the causal relationship between linoleic acid pathway disturbance and changes in liver function can provide important therapeutic targets for both IBDS and ICC.

Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial.

BACKGROUND: Marginal resection frequently occurred in hepatectomy for hepatocellular carcinoma (HCC), leading to increased local recurrence, especially among patients with microvascular invasion (MVI). Stereotactic body radiotherapy (SBRT) showed effectiveness in controlling tumour and tumour thrombosis. This study aimed to investigate the efficacy of SBRT, targeting on suboptimal resection margin, as adjuvant setting in MVI-positive HCC. METHODS: This was a single-centre randomised controlled trial conducted in Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Participants with MVI-positive HCC receiving marginal resection were randomly assigned to the postoperative adjuvant SBRT or surgery alone (SA) group. SBRT was delivered by the CyberKnife® system with marker tracking devices, targeting on resection margin one month after surgery. The disease-free survival (DFS) and overall survival (OS) were compared between the groups, and the adverse events (AEs) were monitored. This trial was registered on ClinicalTrials.gov, NCT04891874. FINDINGS: A total of 76 participants were enrolled, with 38 in each group. The one-, three-, and five-year DFS rates were 92.1%, 65.8%, and 56.1% in SBRT group versus 76.3%, 36.8%, and 26.3% in SA group, respectively (p = 0.005). The one-, three-, and five-year OS rates were 100%, 89.5%, and 75.0% in SBRT group versus 100.0%, 68.4%, and 53.7% in SA group, respectively (p = 0.053). The total dose of SBRT for single participant was 35 Gy, and the biological effective dose (BED) was 59.5 Gy. The overall incidence of radiotherapy-related AE was 31.6% (12/38), and no grade 3 or higher grade AE was developed. INTERPRETATION: SBRT on the resection margin provides a safe therapeutic modality of adjuvant setting in MVI-positive HCC with suboptimal resection margin. It prevents local recurrence and improves DFS. TRIAL REGISTRATION NUMBER: NCT04891874.

miR-93 regulates liver tumor initiating cells expansion and predicts chemotherapeutic response of patients.

Tumor initiating cells (T-ICs) play an important role in tumorigenesis, progression, metastasis, recurrence and drug resistance, but the underlying mechanism was not clearly elucidated. In our study, we found that miR-93 was highly expressed in liver T-ICs. Self-renewal and tumorigenesis ability of liver T-ICs were enhanced by miR-93 overexpression and attenuated by miR-93 interference. Mechanically, miR-93 regulated liver T-ICs by binding to 3'-UTR of myotubularin-related protein 3 (MTMR3). In addition, miR-93 was found highly expressed in cisplatin or sorafenib-resistant liver cancer tissues. Interference of miR-93 sensitizes hepatoma cells to cisplatin or sorafenib treatment. Clinical cohort analysis showed that Hepatocellular carcinoma (HCC) patients with low miR-93 were benefit more from TACE or sorafenib treatment. In conclusion, our study demonstrates a new regulation mechanism of liver T-ICs, a new target for HCC, and a biomarker for postoperative TACE or sorafenib.

circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression.

In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involvement of circFN1 in sorafenib resistance and how circFN1 is associated with the miR-1205/E2F1 pathway, which have been demonstrated to mediate this resistance in HCC cells. We investigated the expression of circRNAs in five paired sorafenib-sensitive HepG2 cells and sorafenib-resistant (SR)-HepG2 cells by microarray analysis. The quantitative real-time PCR analysis was used to investigate the expression pattern of circFN1 in HCC patient tissues and cell lines. Then, the effects of circFN1 on sorafenib resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. In this study, circFN1 was observed to be upregulated in HCC patient tissues and cell lines. Overexpression of circFN1 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. Our in vivo and in vitro data indicated that inhibition of circFN1 enhances the sorafenib sensitivity of HCC cells. Mechanistically, we found that circFN1 could promote the expression of E2F1 by sponging miR-1205. In summary, our study demonstrated that circFN1 contributes to sorafenib resistance by regulating the miR-1205/E2F1 signaling pathway. These results indicate that circFN1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.

LncRNA FOXD2-AS1 as a competitive endogenous RNA against miR-150-5p reverses resistance to sorafenib in hepatocellular carcinoma.

The current study elucidated the role of a long non-coding RNA (lncRNA), FOXD2-AS1, in the pathogenesis of hepatocellular carcinoma (HCC) and the regulatory mechanism underlying FOXD2-AS1/miR-150-5p/transmembrane protein 9 (TMEM9) signalling in HCC. Microarray analysis was used for preliminary screening of candidate lncRNAs in HCC tissues. qRT-PCR and Western blot analyses were used to detect the expression of FOXD2-AS1. Cell proliferation assays, luciferase assay and RNA immunoprecipitation were performed to examine the mechanism by which FOXD2-AS1 mediates sorafenib resistance in HCC cells. FOXD2-AS1 and TMEM9 were significantly decreased and miR-150-5p was increased in SR-HepG2 and SR-HUH7 cells compared with control parental cells. Overexpression of FOXD2-AS1 increased TMEM9 expression and overcame the resistance of SR-HepG2 and SR-HUH7 cells. Conversely, knockdown of FOXD2-AS1 decreased TMEM9 expression and increased the sensitivity of HepG2 and Huh7 cells to sorafenib. Our data also demonstrated that FOXD2-AS1 functioned as a sponge for miR-150-5p to modulate TMEM9 expression. Taken together, our findings revealed that FOXD2-AS1 is an important regulator of TMEM9 and contributed to sorafenib resistance. Thus, FOXD2-AS1 may serve as a therapeutic target against sorafenib resistance in HCC.

Derepression of LOXL4 inhibits liver cancer growth by reactivating compromised p53.

TP53 is the most frequently mutated gene in human cancer, whereas tumors with wild-type TP53 develop alternative strategies to survive. Identifying new regulators of p53 reactivation would greatly contribute to the development of cancer therapies. After screening the entire genome in liver cancer cells, we identified lysyl oxidase-like 4 (LOXL4) as a novel regulator for p53 activation. We found that 5-azacytidine (5-aza-CR) induces LOXL4 upregulation, with LOXL4 subsequently binding the basic domain of p53 via its low-isoelectric point region. The interaction between LOXL4 and p53 induces the reactivation of compromised p53, resulting in cell death. Furthermore, the nude mouse xenograft model showed that the 5-aza-CR-dependent LOXL4-p53 axis reduces tumor growth. A positive correlation between LOXL4 expression and overall survival in liver cancer patients with wild-type p53 tumors was observed. In conclusion, we found that 5-aza-CR-induced LOXL4 upregulation reactivates wild-type p53 and triggers cell death, which blocks liver cancer development.

MicroRNA-26b-5p regulates cell proliferation, invasion and metastasis in human intrahepatic cholangiocarcinoma by targeting S100A7.

The present study aimed to investigate the effects of microRNA expression in intrahepatic cholangiocarcinoma (ICC). It was identified that the expression of microRNA-26b-5p (miR-26b-5p) was downregulated in ICC tissues compared with matched adjacent non-tumor tissues. Furthermore, miR-26b-5p expression was downregulated in metastatic ICC tumor tissues and invasive ICC cell line subpopulations compared with non-metastatic tumor tissue and the parental ICC cells. In vitro studies demonstrated that transfection with an miR-26b-5p mimic inhibited the proliferation, migration and invasion of RBE and HCCC-9810 cells, whereas an miR-26b-5p inhibitor promoted these abilities. S100 calcium-binding protein A7 (S100A7) was predicted as a direct target of miR-26b-5p. Transfection with an miR-26b-5p mimic decreased S100A7 expression, whereas an miR-26b-5p inhibitor increased S100A7 expression. The result of a dual luciferase reporter assay also indicated this interaction. S100A7 was therefore confirmed as a direct target of miR-26b-5p in ICC. The knockdown of S100A7 abrogated the effect of miR-26b-5p on cell migration in RBE and HCCC-9810 cells. In conclusion, the present study demonstrated that miR-26b-5p suppresses the proliferation, migration and invasion of ICC cells by suppressing S100A7.

PEG10 is imperative for TGF-ß1-induced epithelial­mesenchymal transition in hepatocellular carcinoma.

Substantial evidence indicates that transforming growth factor-beta 1 (TGF-ß1) plays a vital role in epithelial-mesenchymal transition (EMT). PEG10 has been shown involved in invasion and metastasis of tumors. The present study investigated the role of PEG10 in TGF-ß1-triggered EMT in hepatocellular carcinoma (HCC) progression. Immunohistochemistry and real-time PCR were used to measure the expression level of PEG10 in clinical HCC tissues with or without lymph node metastasis, and normal tissues. The results showed that PEG10 expression is higher in HCC tissues and associated with overall survival (OS) and lymph node metastasis. Moreover, PEG10 expression level was remarkably higher in hepatic cancer cells than the normal hepatic cell line L02. In the present study, we constructed an adenovirus vector containing the coding area of PEG10 (Ad-PEG10) and infected HepG2 cells and found that overexpression of PEG10 promoted the cell migration, invasion ability and EMT of HepG2 cells. TGF-ß1 acted on HepG2 cells by enhancing cell migration, invasion, EMT and upregulating PEG10 expression level. However, cells pretreated with adenovirus vector of PEG10 shRNAs (Ad-shRNA1 and Ad-shRNA2) did not occur EMT prior to TGF-ß1 stimulation. Moreover, TGF-ß1 did not increase the migration and invasion of cells with PEG10 knockdown and overexpression of PEG10 confers chemoresistance to HepG2 cells. Accordingly, sufficient PEG10 expression level is essential for TGF-ß1 induced EMT and associated with the chemoresistance in HepG2 cells.

Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429.

Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients. Functional experiments showed that GIHCG promotes HCC cells proliferation, migration, and invasion in vitro, and promotes xenografts growth and metastasis in vivo. Mechanistically, we demonstrated that GIHCG physically associates with EZH2 and the promoter of miR-200b/a/429, recruits EZH2 and DNMT1 to the miR-200b/a/429 promoter regions, upregulates histone H3K27 trimethylation and DNA methylation levels on the miR-200b/a/429 promoter, and dramatically silences miR-200b/a/429 expression. Furthermore, the biological functions of GIHCG on HCC are dependent on the silencing of miR-200b/a/429. Collectively, our results demonstrated the roles and functional mechanisms of GIHCG in HCC, and indicated GIHCG may act as a prognostic biomarker and potential therapeutic target for HCC. KEY MESSAGE: lncRNA-GIHCG is upregulated in HCC and associated with poor survival of patients. GIHCG significantly promotes tumor growth and metastasis of HCC. GIHCG physically associates with EZH2. GIHCG upregulates H3K27me3 and DNA methylation levels on the miR-200b/a/429 promoter. GIHCG epigenetically silences miR-200b/a/429 expression.

MicroRNA-147 suppresses human hepatocellular carcinoma proliferation migration and chemosensitivity by inhibiting HOXC6.

Patients with hepatocellular carcinoma (HCC) experience poor prognosis and low survival rates. In this study, we explored the molecular mechanism of microRNA-147 (miR-147) in regulating human HCC. We firstly used quantitative RT-PCR (qRT-PCR) to compare the expression levels of miR-147 between 7 HCC and two normal liver cell lines, as well as 10 paired primary HCC tissues and their adjacent non-carcinoma tissues. We found miR-147 was down-regulated in both HCC cell lines and primary HCCs tissues. HCC cell lines HepG2 and HuH7 were transfected with lentiviral vector of miR-147 mimics. We found overexpressing miR-147 significantly inhibited HCC in vitro proliferation and migration, increased 5-FU chemosensitivity, and reduced in vivo tumorigenicity. Luciferase, qRT-PCR and western blot assays showed that HOXC6 was the downstream target of miR-147, and both gene and protein levels of HOXC6 were down-regulated by miR-147 in HCC cells. SiRNA mediated HOXC6 knockdown inhibited in vitro proliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCC in vitro proliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.

Potential Role of MicroRNA-210 as Biomarker in Human Cancers Detection: A Meta-Analysis.

We conducted this meta-analysis aimed to evaluate diagnostic accuracy of miR-210 in human cancers. A total of 673 cancer patients and 606 cancer-free individuals from 13 studies were contained in this meta-analysis. The overall diagnostic results in our study showed that the pooled sensitivity was 0.70, specificity was 0.76, and the AUC was 0.80. In addition, the PLR and NLR were 2.9 and 0.39, with DOR of 8. After the outliner exclusion detected by sensitivity analysis, these parameters had minimal change, which confirmed the stability of our work. The results in our studies showed that the miR-210 assay yielded relatively moderate accuracy in cancer patients and cancer-free individual differentiation. More basic researches are needed to highlight its role as supplement in clinical treatment.

The treatment of vasopressin V2-receptor antagonists in cirrhosis patients with ascites: a meta-analysis of randomized controlled trials.

BACKGROUND: Ascites is the most common complication of cirrhosis. It may lead to the consequence of poor prognosis and the deterioration of quality of life. Asopressin V2 receptor antagonists is a kind of vaptans, and it has been proved to be effective in hyponatremia patients. We conducted a meta-analysis about treatment of vaptans in cirrhosis patients with ascites. METHODS: Following our selection criteria, we collected a total of 14 studies containing 16 randomized controlled trials (2620 patients) from a series of database about the treatment with vaptans for cirrhosis with ascites patients. The included studies compared the treatment effect of lixivaptan (VPA 985), or RMJ-351647, or satavaptan, or tolvaptan with placebo. RESULTS: The included vaptans (asopressin V2 receptor antagonists) showed significant effect of increasing the serum sodium concentration for cirrhosis patients (WMD = 2.11 mmol/L, p < 0.00001). Patients also could acquire significant improvement of ascites, as this kind of aquaretics can significantly reduce ascites patients' weight (WMD = -1.53, p < 0.00001), abdominal girth (WMD = -2.04, p < 0.00001), and the ratio of worsening ascites (RR = 0.51, p = 0.001). Though the drug did not produce more total adverse events (RR = 1.04, p = 0.09) and the total serious events (RR = 1.04, p = 0.42), the emergence of excessive correction of serum sodium concentrations (>145 mmol/L) was more frequently noted in patients under the employment of vaptans (RR = 2.14, 95 % CI [1.45, 3.16], p = 0.0001). Whether with the administration of vaptans for short-term or long-term, no survival benefit was detected from the selected studies. CONCLUSIONS: Asopressin V2 receptor antagonists could play an effective and safe role in symptomatic treatment for cirrhosis patients with ascites, especially for refractory ascites patients who presented insufficient response to conventional diuretics.

Overexpression of miR-218 inhibits hepatocellular carcinoma cell growth through RET.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with poor prognosis. Here, we investigated the role of microRNA 218 (miR-218) in regulating human HCC development. Quantitative PCR (qPCR) was used to compare the expression levels of miR-218 between eight HCC and a normal liver cell lines, as well as nine primary HCC tissues and adjacent non-carcinoma tissues. HCC cell lines MHCC97L and Huh7 were transfected with lentiviral vector of miR-218 mimics. The effect of miR-218 overexpression on cancer cell growth, both in vitro and in vivo, as well as cancer cell invasion was examined. A bioinformatic method was used to predict the binding of miR-218 to RET proto-oncogene (RET). Small interfering RNA (SiRNA)-mediated genetic knock-down of RET was performed in MHCC97L and Huh7 cells, and its modulatory effect on miR-218-mediated HCC development was examined. miR-218 was found to be downregulated in HCC cell lines and primary HCC tissues. Overexpression of miR-218 in MHCC97L or Huh7 cells resulted in significant decrease in cell proliferation and invasion capability. Overexpression of miR-218 also reduced the tumor growth of xenografted Huh7 cells in vivo. The expression of endogenous RET was found to be upregulated by miR-218, and siRNA-induced RET downregulation resulted in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) upregulation and reversal of the inhibitory effect of miR-218 upregulation on HCC proliferation. Our results indicate that miR-218 modulates HCC development, and this effect may be through RET and PTEN.

Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV.

Hepatocellular carcinoma (HCC) was among the most common solid tumors which rated third in cancer-related mortality worldwide. Hepatitis B viral (HBV) infection represents an important risk factor for HCC. Long non-coding RNAs (lncRNAs) were a class of newfound non-coding RNAs widely depicted in the genome currently. Nevertheless, the potential roles of them in human cancers were not well comprehended. Through this study, we aimed at exploring the expression profile and the potential clinical value of two lncRNAs (lncRNA-uc003wbd and lncRNA-AF085935) in differentiating HCC from both HBV patients and the healthy specimens. Serum samples were extracted from 104 HBV patients, 137 HCC patients, and 138 healthy controls. The lncRNA levels of all the subjects were assayed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). We differentiated the three groups by the receiver operating characteristic (ROC) curve of each group. Statistical analyses were conducted by GraphPad software. Two-tailed P value less than 0.05 was considered to be statistically significant. The level of serum lncRNA-uc003wbd and lncRNA-AF085935 was significantly upregulated in HCC patients and HBV patients compared with that in normal controls. LncRNA-AF085935 showed a relatively higher accuracy for HCC screening (area under the curve (AUC) = 0.96, 95 % confidence interval (CI) = 0.93-0.99) than lncRNA-uc003wbd (AUC = 0.86, 95 % CI = 0.82-0.91) from healthy controls, as well as for HCC screening (AUC = 0.86, 95 % CI = 0.80-0.91) which is more accurate than lncRNA-uc003wbd (AUC = 0.70, 95 % CI = 0.63-0.76) from HBV patients. When differentiating HBV patients from the normal group, the descriptive value of lncRNA-AF085935 (AUC = 0.77, 95 % CI = 0.71-0.83) was almost as equal to lncRNA-uc003wbd (AUC = 0.76, 95 % CI = 0.70-0.82). In addition, higher expressions of lncRNAs were observed in HCC patients than in HBV patients. LncRNA-uc003wbd and lncRNA-AF085935 were observed with an aberrant serum level in HCC and HBV patients, which is showing that both lncRNA-uc003wbd and lncRNA-AF085935 are able to be potential biomarkers for HCC and HBV screening.

[Application of total hemihepatic vascular exclusion in liver resection for patients with hepatocellular carcinoma and impaired liver function].

OBJECTIVE: To study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function. METHODS: The data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group. RESULTS: Total blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012). CONCLUSIONS: THHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.