• Volume 27,Issue 7,2018 Table of Contents
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    • >指南与共识
    • Guidelines for diagnosis and treatment of groin hernia in adults (2018 edition)

      2018, 27(7):803-807. DOI: 10.3978/j.issn.1005-6947.2018.07.001

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      Abstract:The “Guidelines for diagnosis and treatment of groin hernia in adults (2018 edition)” was completed on the basis of the previous edition by the joint discussion and consultation of more than 50 experts and scholars in China, after making an overview of the related etiology, pathology, classification and typing of groin hernia across the world, and combined considerations of the clinical practice in our country. In the current edition, the diagnosis, differential diagnosis, surgical treatment and other aspects of inguinal hernia are systematically expounded, and the viewpoints, measures and methods supported by evidence-based medicine are also pointed out. The relevant medical institutions and professionals in China are requested to use this document as a reference in clinical practice.

    • Guidelines for diagnosis and treatment of abdominal wall incisional hernia (2018 edition)

      2018, 27(7):808-812. DOI: 10.3978/j.issn.1005-6947.2018.07.002

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      Abstract:The abdominal wall incisional hernia is an iatrogenic condition and its clinical treatment is complicated, in which, many respects are involved, such as etiology, pathophysiology, classification, typing, and surgical methods. The compilation of “Guidelines for diagnosis and treatment of abdominal wall incisional hernia (2018 edition)” was completed on the basis of “Guidelines for diagnosis and treatment of abdominal wall incisional hernia (2014 edition)” by the joint discussion and amendments of more than 50 experts and scholars in China, according to the clinical practice in our country in the recent 4 years. In the current edition, the definition, etiology, pathophysiology, classification, typing, diagnosis, differential diagnosis, treatment and other related aspects are systematically updated, and the viewpoints, measures and methods supported by evidence-based medicine are pointed out. The relevant medical institutions and professionals in China are requested to use this document as a reference in clinical practice.

    • >指南解读
    • Interpretation of essential points of the updates of EASL clinical practice guidelines for management of hepatocellular carcinoma (2018)

      2018, 27(7):813-817. DOI: 10.3978/j.issn.1005-6947.2018.07.003

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      Abstract:Due to increased incidence and mortality rates of hepatocellular carcinoma (HCC), enhancing early detection efforts, improving early diagnosis rates and personalized therapy guided by precise staging are of great importance for management of HCC at present. In April 2018, the European Society for the Study of the Liver (EASL) released the updated clinical practice guidelines for HCC, focusing on HCC monitoring, diagnosis, staging, and treatment related issues, which comprehensively updated the recommendations for the HCC staging system and the treatment strategies for patients in various stages. Based on the main points of the guidelines for the diagnosis and treatment of primary liver cancer in China (2017) and latest evidence-based research resources, the authors interpret the essential points of the updates, so as to provide help for the clinical decision makers to appropriately apply the guidelines for HCC management.

    • >专题研究
    • Clinical application of 3D technology in preoperative surgical planning for central liver tumor

      2018, 27(7):818-825. DOI: 10.3978/j.issn.1005-6947.2018.07.004

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      Abstract:Objective: To investigate the application value of 3D visualization technique in the preoperative planning of patients with central liver tumor. Methods: The clinical data of 28 patients with central liver tumor that underwent preoperative evaluation by 3D visualization technique during January 2016 to November 2017 were analyzed retrospectively. Before operation, the two-dimensional CT images of the patients were obtained and imported into 3D visualization software. In the liver, hepatic artery system, portal vein system, hepatic venous system and tumor, image segmentations and 3D reconstructions were performed respectively. Then the subsection of the liver, the classification of the central liver tumor and calculation of the individual liver volume were performed. Based on the results of 3D reconstruction, the surgical planning was made, and the rational surgical approaches and procedures were selected. Results: The 3D visualization model was successfully established in all of the 28 patients. The anatomies of the intrahepatic vascular system and the exact site, size and adjacent relations of the tumor were displayed, and the individual liver segmentation and classification of the central liver tumor were made through 3D technique. The median total liver volume was 1 532 (1 025–1 864) mL, volume of liver tumor was 466 (45–558) mL and volume of virtual resection liver was 595(108~806) mL. Radical resection of tumor was performed in all of the 28 patients. The coincidence rate between the actual surgical approaches and preoperative surgical planning was 100%. The median intraoperative blood loss and amount of blood transfusion were 700 (100–2 000) mL and 600 (0–1400) mL, the rate of blood transfusion was 71.42% (20/28) and the incidence of complications was 28.57% (8/28). No postoperative liver failure occurred and the in-hospital mortality rate was 0. Conclusion: 3D visualization technique can calculate the volume of residual liver, improve the accuracy and safety of the preoperative planning of hepatectomy for central liver tumor, and is helpful for the precise operation during surgery.

    • Application of digital 3D reconstruction technique in precise hepatectomy for liver cancer

      2018, 27(7):826-833. DOI: 10.3978/j.issn.1005-6947.2018.07.005

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      Abstract:Objective: To investigate the clinical application of digital three-dimensional reconstruction technique in precise hepatectomy for liver cancer. Methods: Twenty one patients with primary liver cancer (tumor diameter >5 cm) treated from October 2015 to October 2017 were selected. All patients underwent plain and contrast enhanced CT scan of the liver before operation. Three-dimensional reconstruction of the liver was performed by Myrian reconstruction software. The intrahepatic vessels, location and size of the tumor and their relationship in the patients were analyzed, and the total liver volume (TLV), standard liver volume (SLV), functional liver volume (FLV), tumor volume (TuV), virtual resection liver volume (vRLV), virtual resection specimen volume (vRSV) and residual liver volume (RLV) were calculated. The intraoperative actual specimen weight (aRSW) and actual specimen volume (aRSV) were determined. After that, the accuracy of vRSV was examined and analyzed and the correlations among vRSV, aRSV and aRSW were analyzed. Results: In the 21 patients, the TLV was (1 827.9±314.8) cm3, TuV was (593.4±283.2) cm3, vRLV was (511.2±180.0) cm3 and vRSV was (1 104.6±292.3) cm3; the aRSW obtained after operation was (1 212.9±278.46) g. There was no significant difference between vRSV and aRSV (P=0.76). Pearson test showed that there were significantly positive correlation between aRSV and vRSV, aRSW and vRSV and aRSW and aRSV (r=0.9 964, 0.9 201, 0.9 345, all P<0.0 001). The preoperative virtual surgery simulations were consistent with the actual surgical protocols. None of the 21 patients had hepatic encephalopathy or liver failure after operation, and no death occurred during the perioperative period. Conclusion: The three-dimensional reconstruction of liver combined with liver function assessment before operation has great value for surgical procedure selection of precise liver cancer resection, for its precise tumor positioning, automatic segmentation and quantitative analysis, especially liver volume calculation and virtual liver resection.

    • Application of concept of enhanced recovery after surgery in laparoscopic resection of small hepatocellular carcinoma

      2018, 27(7):834-839. DOI: 10.3978/j.issn.1005-6947.2018.07.006

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      Abstract:Objective: To investigate the clinical value of using the concept of enhanced recovery after surgery (ERAS) in perioperative management of patients undergoing laparoscopic hepatectomy for small liver cancer. Methods: The clinical data of 50 patients undergoing laparoscopic resection for small liver cancer from January 2016 to December 2017 were analyzed. Of the patients, 24 cases received ERAS protocols during perioperative period (ERAS group) and 26 cases received conventional perioperative treatment (control group). The main clinical variables between the two groups of patients were compared. Results: The preoperative clinical data of the two groups of patients were comparable. In ERAS group compared with control group, the intraoperative blood loss and operative time showed no significant difference (both P>0.05), while the time to postoperative anal gas passage and length of postoperative hospital stay were significantly shortened, the total hospitalization cost was significantly reduced and the incidence of complications was significantly decreased (all P<0.05); the QoR-15 scores for recovery quality and C-reactive protein levels on postoperative day 1, 3 and 5 in ERAS group were significantly better than those in control group (all P<0.05). Conclusion: Using ERAS concept during perioperative period in patients undergoing laparoscopic hepatectomy for small liver cancer can effectively reduce surgical trauma, shorten hospital stay, reduce hospitalization costs and surgical complications, and thereby accelerate the patient's recovery.

    • Value of preoperative neutrophil to lymphocyte ratio for prediction of microvascular invasion in patients with small hepatocellular carcinoma

      2018, 27(7):840-846. DOI: 10.3978/j.issn.1005-6947.2018.07.007

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      Abstract:Objective: To evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting microvascular invasion (MVI) in patients with small hepatocellular carcinoma (HCC). Methods: The clinical data of 50 patients diagnosed as small HCC with MVI from June 2012 to June 2017, and 90 patients by random pick from those diagnosed as small HCC without MVI in the same period were retrospectively analyzed. The cut-off value of NLR for diagnosis of MVI was calculated by using receiver operating characteristic (ROC) curve. The risk factors for MVI in patients with small HCC were determined by univariate and unconditional Logistic regression analyses. Results: The cut-off value of NLR for diagnosis of MVI was 3.27, with sensitivity of 0.480, specificity of 0.767 and area under the curve (AUC) of 0.613 (95% CI=0.511 0.715, P=0.027). Univariate analysis showed that the proportions of cases with AFP>25 ng/mL, maximum tumor diameter larger than 3 cm and NLR>3.27 in patients with MVI were singinifcantly higher than those in patients without MVI (all P<0.05); unconditional logistic regression analysis revealed that NLR, AFP level and maximum tumor diameter were independent risk factors for small HCC with complicated MVI (all P<0.05). In addition, the variables that included AFP, neutrophil, lymphocyte, blood platelet, albumin and maximum tumor diameter in patients with NLR≤3.27 were significantly superior to those in patients with NLR>3.27 (all P<0.05). Conclusion: Preoperative NLR value is one of the independent risk factors for complicated MVI in patients with small HCC, and it can be a simple to use and practicable indicator in clinical practice. Patients with NLR>3.27 may have a higher likelihood of MVI.

    • Diagnostic value of serum Golgi protein 73 for HBV-related hepatocellular carcinoma: a Meta-analysis

      2018, 27(7):847-858. DOI: 10.3978/j.issn.1005-6947.2018.07.008

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      Abstract:Objective: To evaluate the diagnostic value of serum Golgi protein 73 (GP73) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: A computer-based systematic search of publically published literature of relevant studies in China and abroad was performed. The indexes for diagnostic accuracy were pooled, and the area under carve (AUC) of the summary receiver operating characteristic carve (SROC) and Q* index were calculated by using Meta-Disc1.4 software. The post-test probability was calculated, and Fagan’s nomograms were drawn to assess the application value of GP73 by using Stata 14.0 software. Results: A total of 14 studies were finally included, with a total sample size of 3 953 subjects. The pooled sensitivity and specificity of GP73 in diagnosis of HBV-related HCC were 0.70 (95% CI=0.68 0.73) and 0.75 (95% CI=0.73–0.77) respectively, and the pooled positive likelihood ratio and negative likelihood ratio were 3.37 (95% CI=2.75–4.13) and 0.36 (95% CI=0.29 0.45), respectively. The summary diagnostic odds ratio (DOR) was 9.67 (95% CI=6.72–13.91), and the AUC and Q* index were 0.826 and 0.759, respectively. For a pre-test probability of 50%, the post-test probabilities for positive and negative test of GP73 were 78% and 26%, respectively. Conclusion: GP73 has certain value in diagnosis of HBV-related HCC, but the value of its lone use for confirmation or exclusion of this disease is limited and other combined examinations are required.

    • Surgical resection combined with hyperthermic intraperitoneal chemoperfusion for spontaneous rupture/hemorrhage of hepatocellular carcinoma in children: a report of one case and literature review

      2018, 27(7):857-861. DOI: 10.3978/j.issn.1005-6947.2018.07.009

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      Abstract:Objective: To investigate the safety and feasibility of hyperthermic intraperitoneal chemoperfusion (HIPEC) in treatment of spontaneous rupture/hemorrhage of hepatocellular carcinoma in children. Methods: The clinical and follow-up data of one pediatric patient with spontaneous rupture/hemorrhage of hepatocellular carcinoma were retrospectively analyzed and the relevant literature was reviewed. Results: The 10-year old female patient underwent emergency interventional embolization therapy for hemostasis due to rupture of intrahepatic tumor in other hospital, and received cholecystectomy and hemihepatectomy combined with HIPEC (10 mg pirarubicin diluted in 3 000 mL 5% glucose, circulated for 40 min at 41 °C) 6 days later in the Department of Hepatobiliary Surgery of Hunan Provincial People’s Hospital. The operation was uneventfully performed and no complications occurred during the perioperative period. The postoperative pathology confirmed a grade III hepatocellular carcinoma with R0 resection margin. Subsequently, the patient was transferred to the Department of Pediatric Hematological Oncology and received chemotherapy using a FOLFOX4 regimen. Follow-up examinations at 11 months after operation showed that the AFP was 9.56 ng/mL, the HBV-DNA was under 100 IU/mL, and no tumor recurrence occurred as evidenced by upper abdominal MRI. Conclusion: Surgical resection combined with HIPEC is safe and feasible for the treatment of spontaneous rupture/hemorrhage of hepatocellular carcinoma in children, with satisfactory short-term results.

    • >基础研究
    • Analysis of miR-1180 expression in hepatocellular carcinoma tissue and its clinical significance based on bioinformatics

      2018, 27(7):862-869. DOI: 10.3978/j.issn.1005-6947.2018.07.010

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      Abstract:Objective: To analyze the expression of miR-1180 in hepatocellular carcinoma (HCC) tissue and its clinical significance through bioinformatics data analysis. Methods: The relevant data sets from GEO (Gene Expression Omnibus) and TCGA (Cancer Genome Atlas) database were downloaded, and then the expression levels of miR-1180 in HCC tissues and cancer adjacent liver tissues were compared, and the relations of miR-1180 expression level with clinicopathologic characteristics and prognosis of the patients were also analyzed. The prediction of potential target genes of miR-1180 and functional enrichment analyses of the target genes were performed by bioinformatics analysis. Furthermore, the key target genes of miR-1180 were screened based on survival analysis. Results: The expression levels of miR-1180 were significantly up-regulated in HCC tissues compared with the cancer adjacent tissues, which had good diagnostic efficiencies for HCC (AUC>0.8, all P<0.05). The miR-1180 expression level was significantly associated with age, family history of cancer, degree of tumor differentiation and AFP of the patients (all P<0.05). Survival analysis showed that miR-1180 overexpression was independent risk factor for diagnosis in HCC patients (P<0.05). Enrichment analyses revealed that the target genes of miR-1180 were mainly enriched in the pathways associated with lipid metabolism, cell migration, transcriptional regulation and fatty acid degradation. PPARGC1A, ALDH2, SARDH, HMGCS2, ESR1 and ETS2 were the key target genes of miR-1180, with significantly decreased down-regulation in HCC tissue (all P<0.05), and patients with low expressions of these genes had relatively poor prognosis (all P<0.05). Conclusion: The miR-1180 expression is increased in HCC tissue. It may participate in the occurrence and development of HCC as an oncogenic miRNA, and also has potential value as a diagnostic biomarker, prognostic indicator and therapeutic target for HCC.

    • Meta-analysis of relationship between alcohol dehydrogenase 1C polymorphisms and susceptibility to alcoholic liver cirrhosis

      2018, 27(7):870-879. DOI: 10.3978/j.issn.1005-6947.2018.07.011

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      Abstract:Objective: To assess the relations of alcohol dehydrogenase 1C (ADH1C) gene polymorphisms with the susceptibility to alcoholic liver cirrhosis (ALC) through Meta-analysis. Methods: The relevant case-control studies were retrieved by searching several national and international databases from their inception to October 2017. Statistical analyses were performed by using Stata 12.0 software. Results: A total of 14 case-control studies were included, involving 1 457 patients in case group and 2 715 subjects in control group. Results of the entire group showed that the risk of ALC was significantly increased in allele model (OR=1.17, 95% CI=1.02–1.34, P=0.013), heterozygous model (OR=1.39, 95% CI=1.16–1.66, P=0.035), homozygous model (OR=1.27, 95%CI=1.02–1.58, P=0.036) and dominant model (OR=1.37, 95% CI=1.16–1.63, P=0.027), but had no significant change in recessive model (OR=1.19, 95% CI=0.98–1.44, P=0.052). Results of subgroup analysis showed that the risk of ALC among Asian populations was increased in allele model (OR=1.43, 95% CI=1.07–1.90, P=0.037), heterozygous model (OR=1.53, 95%CI=1.14–2.04, P=0.034), homozygous model (OR=1.52, 95% CI=1.05–2.18, P= 0.036), dominant model (OR=1.52, 95% CI=1.14–2.03, P=0.039) and recessive model (OR=1.51, 95% CI=1.08–2.11, P=0.016), while an increased risk of ALC was only found in heterozygous model (OR=1.31, 95% CI=1.04–1.64, P=0.038) and dominant model (OR=1.30, 95% CI=1.05–1.60, P=0.022) among Caucasian populations. Conclusion: ADH1C gene polymorphism is closely related to ALC susceptibility, and those with heterozygous mutation, homozygous mutation and mutant allele genotype may have increased risk of ALC.

    • >临床研究
    • Comparison of using infrahepatic inferior vena cava clamping versus controlled low central venous pressure in complex hepatectomy

      2018, 27(7):880-885. DOI: 10.7659/j.issn.1005-6947.2018.07.012

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      Abstract:Objective: To compare the safety and efficacy of using infrahepatic inferior vena cava (IIVC) clamping and controlled low central venous pressure (CLCVP) technique in complex hepatectomy. Methods: The clinical data of 103 patients with hepatocellular carcinoma undergoing complex hepatectomy between March 2016 and December 2017 were retrospectively analyzed. Pringle maneuver was used for hepatic inflow control in all patients, of whom, 56 cases underwent IIVC clamping (IIVC clamping group) and 47 cases underwent CLCVP (CLCVP group) for reducing the central venous pressure (CVP). The changes of CVP and blood loss during parenchymal transection, total intraoperative blood loss, intraoperative urine volume, rate of blood transfusion and incidence of postoperative complications, as well as postoperative liver and renal functions between the two groups of patients were compared. Results: The general data showed no significant differences between the two groups of patients (all P>0.05). The CVP levels in both groups were decreased significantly during parenchymal transection, but the decreasing amplitude in IIVC clamping group was greater than that in CLCVP group, and blood loss during parenchymal transection, the total intraoperative blood loss, ALT level on postoperative day (POD) 3 and TBIL level on POD 3 and 7 in IIVC clamping group were significantly lower than those in CLCVP group (all P<0.05). There were no significant differences in intraoperative urine volume, blood transfusion rate, incidence of postoperative complications and renal function parameters between the two groups (all P>0.05). Conclusion: The operation of IIVC clamping combined with Pringle maneuver is simple and convenient, and it has advantages of less influence on systemic hemodynamics, faster recovery of liver function and easier CVP reduction for controlling bleeding in the cutting surface of the liver compared with CLCVP. So this method is helpful for improving the safety of complex hepatectomy.

    • Intra-abdominal infection after hepatectomy: analysis of pathogens and antimicrobial resistance

      2018, 27(7):886-892. DOI: 10.3978/j.issn.1005-6947.2018.07.013

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      Abstract:Objective: To investigate the distribution of pathogens isolated from patients with intra-abdominal infection after hepatectomy and their antimicrobial resistances as well as the relations of the clinicopathologic profiles of the patients with the type of infection. Methods: The clinical data and microbiological profiles of 95 patients with intra-abdominal infection after hepatectomy from January 2013 to December 2017 were retrospectively analyzed. The relationship between the clinical data of the patients and types of infections were determined by univariate and multivariate Logistic regression analyses. Results: Of the 95 patients, a total of 170 non-duplicate bacterial strains were isolated from culture media, 55 cases (57.9%) had single infection and 40 cases (42.1%) had mixed infection, including 80 Gram-negative bacteria (47.1%), 83 Gram-positive bacteria (48.8%) and 7 fungi (4.1%). The top five common pathogens isolated were Escherichia coli (15.3%), Enterococcus faecium (14.7%), Klebsiella pneumonia (12.4%), Enterococcus faecalis (11.2%), and Coagulase-negative staphylococci (8.2%), respectively. Antimicrobial susceptibility testing showed that the detection rate of extended-spectrum β-lactamases (ESBLs) in Escherichia coli and Klebsiella pneumonia was 76.9% and 37.5%, respectively. The susceptible rate of Escherichia coli and Klebsiella pneumonia to cefperazone-sulbactam was 66.7% and 70.0%, and to imipeniem was 100.0% and 79.2%, respectively. The susceptible rate of Acinetobacter baumannii to major antibiotics was lower than 30% except tigecycline (susceptible rate 100%). No resistance to vancomycin was found in the 44 isolates of Enterococcus faecium/faecalis, and their susceptible rate to vancomycin was 92.0% and 89.5%, respectively. All the 14 isolates of coagulase-negative staphylococci were methicillin-resistant coagulase-negative staphylococci and their susceptible rates to vancomycin and linezolid were maintained at 100%. Logistic regression analysis results showed that occurrence of postoperative intraperitoneal complications was an independent risk factor for mixed infection (P=0.006). Conclusion: Gram-positive bacteria, especially the Enterococcus species are dominant pathogens associated with intra-abdominal infection after hepatectomy. Of gram-negative bacteria, the proportion of Carbapenem-resistant Enterobacteriaceae shows an increasing trend with severe multidrug resistance problems. Occurrence of postoperative intraperitoneal complications is an independent risk factor for mixed infection.

    • Comparison of different hepatic blood occlusion methods in external capsule excision for hepatic cystic echinococcosis

      2018, 27(7):893-898. DOI: 10.3978/j.issn.1005-6947.2018.07.014

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      Abstract:Objective: To compare the clinical effects of different hepatic blood occlusion procedures in external capsule excision for hepatic cystic echinococcosis. Methods: Fifty-six patients with hepatic cystic echinococcosis undergoing external capsule excision were enrolled. Of the patients, 31 cases underwent hepatic blood inflow occlusion by Glisson’s pedicle ligation (Glisson’s pedicle occlusion group), and 25 cases underwent hepatic blood inflow occlusion by Pringle’s procedure (Pringle group). The main clinical variables between the two groups of patients were compared. Results: The preoperative data were comparable between the two groups of patients. There were no significant differences in operative time, occlusion time, intraoperative blood loss, amount of postoperative drainage and hospitalization cost between the two groups of patients (all P>0.05), but the time to postoperative anal gas passage and length of postoperative hospital stay in Glisson’s pedicle occlusion group were significantly shorter than those in Pringle group (both P<0.05). As for the liver function parameters, the postoperative alanine transaminase and aspartate transaminase levels in Glisson’s pedicle occlusion group were significantly lower than those in Pringle group (both P<0.05), but no significant difference were noted in postoperative total bilirubin levels between the two groups (P>0.05). There were no significant differences in prothrombin time and stress response indicators such as C-reactive protein, HOMA-IR index and tumor necrosis factor α between the two groups (all P>0.05). Conclusion: Hepatic blood inflow occlusion by method of Glisson’s pedicle ligation can promote the postoperative liver function recovery in patients with hepatic cystic echinococcosis undergoing external capsule excision compared with that by Pringle’s procedure.

    • >文献综述
    • Research progress associated with microRNAs in hepatocellular carcinoma

      2018, 27(7):899-909. DOI: 10.3978/j.issn.1005-6947.2018.07.015

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      Abstract:Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the third of cancer related death worldwide, which has become one of the most common serious threats to people’s lives and health in China. Understanding the molecular mechanism for the occurrence and development of HCC is very important for its prevention, diagnosis and treatment. MicroRNAs (miRNAs) comprise a family of non-coding regulatory RNAs, and can regulate the expressions of 1/3 human genes. miRNAs participate in a series of important process, and play important roles in the pathogenesis of cancer. Here, the authors review the research progress about the expression, biological function and clinical applications of miRNAs in HCC.

    • Research progress on mechanisms for occurrence of liver cancer and its treatment status

      2018, 27(7):910-923. DOI: 10.3978/j.issn.1005-6947.2018.07.016

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      Abstract:Primary liver cancer is a malignant tumor with poor prognosis and high morbidity and mortality. So far, the mechanisms for the occurrence and development of primary liver cancer have not been fully understood, and multidisciplinary comprehensive therapy is the main modality for the treatment of primary liver cancer. Here, the authors overview the research progress on pathogenesis of primary liver cancer and its treatment, so as to provide better strategies for its diagnosis and treatment.

Governing authority:

Ministry of Education People's Republic of China

Sponsor:

Central South University Xiangya Hospital

Editor in chief:

WANG Zhiming

Inauguration:

1992-03

International standard number:

ISSN 1005-6947(Print) 2096-9252(Online)

Unified domestic issue:

CN 43-1213R

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