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Circular RNAs (circRNAs) are stable and extensively distributed non-coding RNA molecules that are differentially expressed in liver cancer tissues in the human body. In this study, we aimed to investigate circRNA as a novel candidate biomarker for hepatocellular carcinoma (HCC). For three groups of HCC and neighboring healthy tissues, the differentially expressed circRNAs were identified through high-throughput sequencing analysis. Reverse transcription PCR (RT-PCR) and quantitative polymerase chain reaction (qPCR) were employed for the evaluation of circRNAs that show an elevated expression level in HCC. The obtained results revealed the significantly differential expression of hsa_circ_0006091 in HCC. Then we obtained their target genes through biological analysis, followed by verifying the underlined target genes, and the regulator of G-protein signaling 12 (RGS12) showed an elevated expression level in HCC tissues. Finally, receiver operating characteristic (ROC) curve analysis was conducted on AFP, RGS12, and hsa_circ_0006091, and combined analysis was performed. Furthermore, hsa_circ_0006091 is a novel candidate biomarker for HCC and could improve the diagnostic strategies, prediction, and follow-up of HCC patients. The joint diagnosis of the hsa_circ_0006091&AFP and hsa_circ_0006091&RGS12 has diagnostic significance and can be used as a molecular marker for HCC diagnosis. Abbreviations: AUC:area under the ROC curve; ROC:Receptor Operating Characteristics; bp:base pair;mRNA:Messenger Ribonucleic acid;ceRNA:Competing endogenous RNA; RT-qPCR: Real time-quantitativen PCR technology; circRNA: circular RNA; HCC:Hepatocellular carcinoma;miRNA:microRNA;KEGG:Kyoto Encyclopedia of Genes and Genomes; RGS12:regulator of G-protein signaling 12; AFP:alpha fetoprotein; ncRNAs:non-coding RNAs; GEO:Gene Expression Omnibus; FDR:false discovery rate

Background Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor clinical prognosis. Rupture of the fibrous capsule (FC) is a very important clinical phenomenon in the invasion and metastasis of HCC. FC is mainly composed of type I collagen (COL1A1). However, it is not clear what caused the FC rupture. In this study, we aimed to determine whether the rupture of FC in HCC patients was related to macrophage-derived MMP-9/MMP-2, and their clinical diagnostic value for FC rupture. Results By performing immunohistochemical and immunofluorescence staining of ruptured FC and intact FC, the results showed that the ruptured area of FC aggregated a large number of macrophages with MMP-9/MMP-2. Western blot analysis and Quantitative real-time PCR were used to assess the expression of MMP-9/MMP-2 in the ruptured and relatively intact area of FC in ruptured FC patients, and the results revealed a significantly different expression of MMP-9/MMP-2. ELISA experiments show that we could discriminate effectively between ruptured FC and intact FC by MMP-9/MMP-2. Conclusions Taken together, macrophage-derived MMP-9/MMP-2 were closely related to the rupture of the FC of HCC and subsequently led to the migration and invasion of the tumor cells into the ruptured area of FC to the para cancer. it is suggested that when performing surgical resection, it is necessary to expand the range of tumor resection for patients with ruptured FC and hence reduce the possibility of recurrence and metastasis in HCC patients.

Background The effect of socioeconomic status (SES) on hepatocellular carcinoma (HCC) is still unclear, and there is no nomogram integrated SES and clinicopathological factors to predict the prognosis of HCC. This research aims to confirm the effects of SES on predicting patients’ survival and to establish a nomogram to predict the prognosis of HCC. Methods The data of HCC patients were collected from the Surveillance, Epidemiology, and Final Results (SEER) database from 2011 to 2015. SES (age at diagnosis, race and sex, median family income, education level, insurance status, marital status, residence, cost of living index, poverty rate) and clinicopathological factors were included in univariate and multivariate Cox regression analysis. Nomograms for predicting 1‐, 3‐, and 5‐year cancer‐specific survival (CSS) and overall survival (OS) were established and evaluated by the concordance index (C‐index), the receiver operating characteristic curve (ROC), the calibration plot, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI). Results A total of 33,670 diagnosed HCC patients were involved, and nomograms consisting of 19 variables were established. The C‐indexes of the nomograms are higher than TNM staging system, which predicts the CSS (0.789 vs. 0.692, p, The impacts of socioeconomic status (SES), including: age at diagnosis, race and sex, median family income, education level, insurance status, marital status, residence, cost of living index, poverty rate on hepatocellular carcinoma (HCC) are still unclear. This research collected the data of 33,670 diagnosed HCC patients from the Surveillance, Epidemiology, and Final Results (SEER) database, and nomograms for 1‐, 3‐, and 5‐year survival rates based on the SES and clinical factors were constructed.

Ewing sarcoma (ES) is a rare disease that lacks a prognostic prediction model. This study aims to develop a nomogram and risk classification system for estimating the probability of overall survival (OS) of patients with ES. The clinicopathological data of ES were collected from the Surveillance, Epidemiology and Final Results (SEER) database from 2010 to 2018. The primary cohort was randomly assigned to the training set and the validation set. Univariate and multiple Cox proportional hazard analyses based on the training set were performed to identify independent prognostic factors. A nomogram was established to generate individualized predictions of 3- and 5-year OS and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration curve, the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Based on the scores calculated with the nomogram, ES patients were divided into three risk groups to predict their survival. A total of 935 patients were identified, and a nomogram consisting of 6 variables was established. The model provided better C-indices of OS (0.788). The validity of the Cox model assumptions was evaluated through the Schönfeld test and deviance residual. The ROC, calibration curve, IDI and NRI indicated that the nomogram exhibited good performance. A risk classification system was built to classify the risk group of ES patients. The nomogram compares favourably and accurately to the traditional SEER tumour staging systems, and risk stratification provides a more convenient and effective tool for clinicians to optimize treatment options.

The morbidity and mortality of pancreatic cancer have been continuously increasing, causing seven deaths per 100,000 individuals/year. At present, effective therapies are severely lacking, thus, highlighting the importance of developing novel therapeutic approaches. The present study aimed to investigate the inhibitory roles of the 2,3-oxidosqualene cyclase inhibitor, RO 48-8071 (RO), on pancreatic ductal adenocarcinoma. RO was used to treat the pancreatic cancer cell line (PANC-1) in vitro to examine the effects of RO on cell viability, as well as to determine its potential molecular mechanism. Moreover, experiments in a xenograft model of subcutaneous tumors generated by injecting PANC-1 cells hypodermically into nude mice were performed to observe the inhibition of RO on tumor growth. It was found that RO inhibited PANC-1 cell viability when treatment was given for 24, 48 and 72 h. The in vivo study demonstrated that RO markedly inhibited subcutaneous tumor growth in nude mice. Further studies revealed that RO could induce cell cycle arrest in the G1 phase by regulating p27, cyclin B1 and cyclin E expression to inhibit PANC-1 cell viability. Moreover, RO inactivated the JNK and ERK MAPK signaling pathway by decreasing the phosphorylation levels of JNK and ERK. Collectively, the present study demonstrated that RO served anti-pancreatic cancer roles in vitro and in vivo, which may provide new ideas and facilitate the development of novel treatment options for pancreatic cancer.

Background: Objective to evaluate the predictive value of preoperative fibrinogen and systemic inflammatory response index (F-SIRI) in the prognosis of patients with hepatocellular carcinoma after radical hepatectomy. Methods: the clinical data of 298 patients with hepatocellular carcinoma who underwent surgery and confirmed by postoperative pathology in our hospital from January 2015 to December 2017 were retrospectively analyzed. The F-SIRI score was calculated according to FIB and SIRI data of peripheral blood. The relationship between F-SIRI score and clinicopathological characteristics was analyzed. The survival analysis was performed by Kaplan Meier method, Cox regression analysis was used to analyze the prognostic factors. Results: preoperative F-SIRI score was correlated with tumor diameter, FIB and SIRI (PP>0.05). There were significant differences in the 5-year DFS rate and OS rate among patients with different preoperative F-SIRI scores(PP< 0.05), while preoperative tumor diameter, ALB and F-SIRI score as independent predictors of OS (P

Background We aimed to screen a specific secretory protein that could serve as blood diagnostic marker for cholangiocarcinoma (CCA). Methods Starting with the analysis of gene expression profiles in tumor tissues and matched normal tissues from cases with CCA and hepatocellular carcinoma (HCC), we identified peptidase inhibitor 15 (PI15) was a potential diagnostic marker for CCA. We demonstrated PI15 expression levels in CCA, HCC, and normal liver tissues. Furthermore, quantitative enzyme-linked immunosorbent assay (ELISA) assessed plasma PI15 levels in CCA (n = 61), HCC (n = 72), benign liver disease (n = 28), chronic hepatitis B (CHB) patients (n = 45), and healthy individuals (n = 45). The diagnostic value of PI15 was estimated by the area under the receiver operating characteristic (ROC) curve (AUC). Findings The positive rate of PI15 expression was 70% in CCA and only 9.1% in HCC; PI15 was not detected in normal liver tissue. High levels of plasma PI15 were evident in CCA patients, whereas only low levels were observed in cases involving HCC, benign liver disease, CHB patients, and healthy individuals. Plasma PI15 levels in CCA patients were obviously reduced (p = .0014) after surgery. The AUC of plasma PI15 for discriminating between CCA and HCC was 0.735. Furthermore, with a specificity of 94.44%, the combination of CA19–9 (>98.5 U/ml) and PI15 (>13 ng/ml) yielded a sensitivity of 80.39% for CCA and HCC. Interpretation PI15 exhibits promise as a novel marker for predicting the diagnosis and follow-up of CCA patients. Fund Natural Science Research Foundation of Anhui Province and Natural Science Foundation of China

IntroductionGallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.Methods and analysisThe Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers.Ethics and disseminationThe protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019–085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences.Trial registration numberNCT04140552, Pre-results.

TMB-related lncrnas and their clinical significance in liver cancer have not been explored.Combining the expression levels of these lncrnas, somatic mutation files and clinical information in patients with liver cancer,we identified 514 lncrnas that are closely related to TMB.Based on these lncrnas, a TMB-derived lncRNA Signature (TMBLncSig) was established. TMBLncSig categorized the patients into high-risk group and low-risk group. There was a significant difference in the prognosis of the patients between the two groups, which was further verified in the independent test set.TMBLncSig is associated with TMB level in liver cancer patients and has the potential to be used as a TMB level measurement tool. In summary this st provide new thought for further study on the role of lncRNA in the difference of TMB level in liver cancer patients.

Background Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. Tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results We found that the expression levels of dendritic cells activated, macrophages M2, and T cells regulatory (Tregs) in ICC were higher than normal tissues, and the expression levels of macrophages M1, monocytes, and T cells follicular helper in ICC were lower than normal tissues. Conclusion These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

Accumulating data indicate caspase-1 (CASP1), one of the inflammatory caspases, promotes hepatocellular carcinoma (HCC) progression in tumor proliferation, invasion, EMT phenotype and sorafenib resistance. However, the molecular basis of regulating caspase-1 expression and caspase-1/IL1B (interleukin-1β) pathway in HCC remains unclear. Here, we demonstrated the novel interplay between caspase-1/IL1B activation and cluster differentiation 44 standard isoform (CD44s) in HCC. In this study, we observed that CD44s is responsible for caspase-1/IL1B activation both in HCC tissues and five HCC cell lines. In normoxia conditions, CD44s knockdown repressed the activation of caspase-1/IL1B via stimulating AMPK-mediated autophagy. Moreover, our data suggested that p62-induced autophagic degradation of caspase-1 accounted for caspase-1/IL1B inactivation in CD44s deficient cells. Administration of recombinant human IL1B could rescue impaired proliferation, invasion, and EMT phenotype in CD44s deficient HCC cells. Lastly, hypoxia-mediated caspase-1/IL1B overexpression could be abolished by CD44s downregulation through decreasing HIF1A and enhancing autophagic activity. Overall, targeting CD44s is a novel inhibitory mechanism of caspase-1/IL1B expression, both in normoxia and hypoxia conditions.

Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma. c‑Maf inducing protein (CMIP) is involved in the c‑Maf signaling pathway, which was reported to serve an important role in human minimal change nephrotic syndrome and in human reading and language related behavior. However, the relationship between CMIP and human gastric cancer has not yet been reported. In the present study, CMIP protein levels in gastric cancer tissues and cells were measured using immunohistochemistry and western blot analysis; the expression of CMIP protein was significantly higher in gastric cancer tissues compared with normal gastric tissues. Expression was positively associated with poorer clinical parameters, relapse‑free survival and overall survival. Furthermore, using cell counting, Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, together with flow cytometry, CMIP depletion by RNA interference was observed to reduce the capacity of gastric cancer cells to proliferate and migrate in vitro. Furthermore, the upstream and downstream genes of CMIP were analyzed by luciferase reporter assay and reverse transcription quantitative polymerase chain reaction, which indicated that CMIP was a direct target of miR‑101‑3p. In addition, CMIP knockdown was observed to result in the downregulation of MDM2 and mitogen activated protein kinase (MAPK) expression at the mRNA level. In conclusion, CMIP demonstrated an oncogenic role in human gastric cancer cells. Furthermore, microRNA‑101‑3p, MDM2 and MAPK were involved in the CMIP signaling pathway in gastric cancer. CMIP could be a novel target for further investigation in the clinical therapeutic management of gastric cancer.

Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip. Two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to select significant CpGs. In the training phase, penalized Cox regression was used to further narrow CpGs into 140 samples. In the validation phase, candidate CpGs were validated using an internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector Operation and the Support Vector Machine-Recursive Feature Elimination algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase inhibitor 3 were highlighted as candidate predictors in the training phase. On the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was developed to classify patients into high- and low-risk recurrence groups in the training cohort ( P < .001). The performance of MSEH was validated in the internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, hepatitis B virus surface antigen, and antivirus therapy was generated to predict the 5-year recurrence-free survival in the training cohort, and it performed well in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, respectively). Conclusion MSEH, a three-CpG–based signature, is useful in predicting recurrence for patients with E-HCC.

Summary Background and objectives Transcatheter arterial chemoembolization (TACE) is the first-line treatment for unresectable hepatocellular carcinoma (HCC). It consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The comparative outcomes of the two methods remain controversial. The study aim to research the optimal TACE strategy for unresectable HCC. Methods A systematic search of keywords, including ‘HCC’ and ‘drug-eluting beads’ was performed including four electronic databases: PubMed, Embase, China Biological Medicine Database (CBM), and Cochrane library databases from the date of inception to December 25, 2015. Review Manager 5.3 was used to calculate the pooled relative risks (RRs) and 95% confident intervals (CIs). Results Sixteen cohort studies (4 RCTs, 3 prospective cohorts, 9 retrospective cohorts) were included comprising a total of 1832 patients: 822 patients with DEB-TACE therapy and 1010 patients undergoing cTACE. The 1-, 2-, and 3-year overall survival (OS) rates and 1- and 2-year relapse-free survival (RFS) rates were significantly higher in DEB-TACE group, with pooled RRs of 1.12 (95% CI = 1.03–1.23, P = 0.007), 1.26 (95% CI = 1.03–1.54, P = 0.02), 1.69 (95% CI = 1.00–2.84, P = 0.04), 1.21 (95% CI = 1.01–1.44, P = 0.03) and 1.68 (95% CI = 1.17–2.43, P = 0.005). There was no statistical significance in 3-year RFS, tumor response and treatment-related adverse events. Conclusion Compared with cTACE, DEB-TACE therapy significantly improved 1-, 2-, and 3-year OS rates and the 1- and 2-year RFS rates.

// Peng Chen 1, * , Xiaohu Zheng 2, * , Yonggang Zhou 2 , Yechuan Xu 1 , Lixin Zhu 3 , Yeben Qian 1 1 Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China 2 Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China 3 Center Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, China * These authors contributed equally to this work Correspondence to: Yeben Qian, email: qianyeben@hotmail.com Keywords: Talin-1, hepatocellular carcinoma, tumor growth and metastasis, ion transport, membrane depolarization Received: October 09, 2016 Accepted: January 09, 2017 Published: January 16, 2017 ABSTRACT Talin-1 is a known oncogene-associated protein. In this study, we set out to determine its role and mechanisms in hepatocellular carcinoma (HCC) progression. We found Talin-1 to be highly expressed in HCC cells relative to non-cancer liver epithelial cells and to promote tumor growth and metastasis. We used Whole Human Genome Oligo Microarray analysis with HCC cells and HCC cells in which Talin-1 was knocked down using shRNA to identify transcripts regulated by Talin-1. Of the 40,000 tested genes, 3099 were differentially expressed after Talin-1 knockdown; expression of 1924 genes was increased, while expression of 2175 was decreased. Gene ontology (GO) profiling indicated that Talin-1 promotes many HCC progression-related activities, including ion transport and membrane depolarization, cell growth, and cell adhesion. We also characterized the network of gene transcripts regulated by Talin-1 and their role in promoting HCC progression. Our findings confirm the role of Talin-1 in carcinogenesis and provided a set of novel therapeutic targets for the treatment of HCC.

Natural killer (NK) cells have crucial roles in tumor surveillance. We found that tumor-infiltrating NK cells in human liver cancers had small, fragmented mitochondria in their cytoplasm, whereas liver NK cells outside tumors, as well as peripheral NK cells, had normal large, tubular mitochondria. This fragmentation was correlated with reduced cytotoxicity and NK cell loss, resulting in tumor evasion of NK cell-mediated surveillance, which predicted poor survival in patients with liver cancer. The hypoxic tumor microenvironment drove the sustained activation of mechanistic target of rapamycin-GTPase dynamin-related protein 1 (mTOR-Drp1) in NK cells, resulting in excessive mitochondrial fission into fragments. Inhibition of mitochondrial fragmentation improved mitochondrial metabolism, survival and the antitumor capacity of NK cells. These data reveal a mechanism of immune escape that might be targetable and could invigorate NK cell-based cancer treatments.

Background: Accumulating data indicates caspase-1 (CASP1), one of inflammatory caspases, promotes hepatocellular carcinoma (HCC) progression including proliferation, invasion and sorafenib resistance. However, the molecular basis of caspase-1 expression and caspase-1/IL1B pathway in HCC remains unclear. Here, we aimed to identify the novel mechanism of caspase-1/IL1B activation controlled by cluster differentiation 44 (CD44) in HCC. Methods: Public data from UCSC Xena and GEPIA were extracted and used to evaluate the correlation between CD44 and caspase-1 related genes including CASP1, NLRP3 and IL1B. CD44 deficient HCC cell lines were established by well-designed siRNA or lentivirus shRNA treatment. Western blot, Q-PCR and caspase-1 assays were employed to determine the association of CD44 and caspase-1/IL1B both in normoxia and hypoxia conditions. Proliferation and invasion abilities were assessed by Edu assays, transwell experiments, immunofluorescences and HCC orthotopic mouse models. Autophagic activities in gene-manipulated HCC cells were measured by transmission electron microscope and LC3B-staining immunofluorescence. Clinical correlations of related proteins in HCC tissues were examined by public data and analysis of immunohistochemistry. Findings: In this study, we observed that CD44 is positively correlated to caspase-1/IL1B activation both in HCC tissues and five HCC cell lines. In normoxia conditions, downregulation of CD44 reduced the expression of caspase-1/IL1B via AMPK-medaited autophagy. Moreover, we demonstrated that the p62-mediated autophagic degradation of caspase-1 is responsible for suppression of caspase-1/IL1B in CD44 deficient cells. Administration of recombinated human IL1B could rescue impaired proliferation, invasion and EMT phenotype in CD44 deficient HCC cells. Lastly, hypoxia-mediated caspase-1/IL1B overexpression could be abolished by CD44 downregulation through decreasing Hif1a and enhancing autophagic activity. Interpretation: Targeting CD44 is a novel inhibitory mechanism of caspase-1/IL1B expression both in normoxia and hypoxia conditions by prompting p62-mediated selectively autophagic degradation of caspase-1. Funding Statement: National Youth Fund Training Program for the First Affiliated Hospital of Anhui Medical University (No.2019kj03); the Scientific Research of BSKY from Anhui Medical University (XJ201726); Anhui Provincial Natural Science Foundation (No.1908085QC131). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All procedures of animals adhered to guidelines provided by the Animal Ethics Committee of first affiliated hospital of Anhui Medical University.

Background: Patients undergoing surgical resection of hepatocellular carcinoma (HCC) are at risk of recurrence, but the mechanism remains poorly understood. Methods: Through the analysis of gene expression profiles in tumor tissues and matched normal tissues from patients with hepatocellular carcinoma (HCC), we identified difference in interlukine-11 (IL-11) expression. Besides, we utilized a genetic mouse model, orthotopic tumor model, chemically induced model, and orthotopic allograft model to study the correlation between IL-11 and postsurgical recurrence. Furthermore, a series of experiments including histology and immunohistochemistry analysis, three-dimensional culture, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and flow cytometry were conducted to investigate the role of IL-11- Signal transducer and activator of transcription 3 (STAT3) signaling in recurrence. Findings: We demonstrate that IL-11 levels increase after surgery and trigger HCC outgrowth. Accordingly, pharmacologically blocking IL-11- STAT3 signaling in these models significantly alleviates tumor cell proliferation and suppresses postsurgical recurrence. Interpretation: These data identify that IL-11 has a central role in postsurgical HCC recurrence and that inhibition of IL-11-STAT3 signaling is a potential therapeutic strategy to prevent recurrence. Funding Statement: This work was supported by the Natural Science Foundation of China (# 81788101). Declaration of Interests: The authors declare no potential conflict of interest. Ethics Approval Statement: The collection of all samples was in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements, and was approved by the ethical review board of the University of Science and Technology of China (No. USTCEC201600004). All of the experimental procedures involving animals were conducted in accordance with the National Guidelines for Animal Usage in Research (China) and permission for these animal studies was obtained from the Ethics Committee at the University of Science & Technology of China.

Background: Several studies have reported that medical robot-assisted method (RA) might be superior to conventional freehand method (FH) in orthopedic surgery. Yet the results are still controversial, especially in terms of femoral neck fractures surgery. Here, 2 methods were assessed based on current evidence. Methods: Electronic databases including Cochrane Library, PubMed, Web of Science. and EMBASE were selected to retrieved to identify eligible studies between freehand and RAs in femoral neck fractures, with 2 reviewers independently reviewing included studies as well as collecting data. Results: A total of 5 studies with 331 patients were included. Results indicated that 2 surgical methods were equivalent in terms of surgical duration, Harris score, fracture healing time, fracture healing proportion and complications, while RA showed clinical benefits in radiation exposure, intraoperative bleeding, total drilling times, and screw parallelism. Conclusions: Current literature revealed significantly difference between 2 techniques and suggested that RA might be beneficial for patients than freehand method.

As the coronavirus disease 2019 (COVID-19) spreads globally, hospital departments will need take steps to manage their treatment procedures and wards. The preparations of high-risk departments (infection, respiratory, emergency, and intensive care unit) were relatively well within this pandemic, while low-risk departments may be unprepared. The spine surgery department in The First Affiliated Hospital of Anhui Medical University in Hefei, China, was used as an example in this study. The spine surgery department took measures to manage the patients, medical staff and wards to avoid the cross-infection within hospital. During the outbreak, no patients or healthcare workers were infected, and no treatment was delayed due to these measures. The prevention and control measures effectively reduced the risk of nosocomial transmission between health workers and patients while providing optimum care. It was a feasible management approach that was applicable to most low-risk and even high-risk departments.

Thanks are due to you for this letter and we would like to respond regarding some questions raised about our meta-analysis. In this letter, the authors questioned the index used in the meta-analysis and recommended hazard ratio (HR) instead of relative risk (RR) [1]. HR is truly a good index for survival analysis of one disease because it considers the effects of time and it worked when extracting data from studies we selected; however, RR is appropriate for comparing the control group and treatment group (NAs group) here, as it has equal effects to OR. The total number of patients was the same only in 1-year and 3-year recurrence, but, in OS and DFS, the numbers were different [2]. Disease-free survival has been defined as no recurrence of HCC in our article [2]. Randomized trials were really what we wanted to study in our meta-analysis; however, due to a lack of enough studies and data, this was unfortunately not possible [2]. We are not sure if postoperative NAs therapy has no impact on patients' short-term survival, for the reason that HBV reactivation usually occurs one month after operations were performed [3], so that is why we performed this meta-analysis. And as our results show, we do not agree with the comment that NAs have no short-term effects on survival and recurrence [1]. We would like to thank again the authors for this valuable letter and also for their concerns. We would like to receive further suggestions on our study.

Background.The long-term prognosis after curative therapy for hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) remains unsatisfactory due to the high incidence of recurrence. The effect of treatment with nucleotide analogues (NAs) in patients with HBV-related HCC after curative therapy remains unclear.Objective.To assess the impact of using NAs after curative therapy.Method.A computerized literature search was performed; eligible studies were identified from databases. The pooled risk ratios (RRs) and 95% CIs were calculated using Review Manager 5.3.Result.The meta-analysis included a total of 15 studies with 8060 patients. The one-year and three-year recurrence (one-year recurrence: RR 0.41 [95% CI 0.28 to 0.61];P<0.00001; three-year recurrence: RR 0.63 [95% CI 0.43 to 0.94];P=0.001) and the one-, three-, and five-year overall survival (OS) and disease-free survival (DFS) were significantly better in the treatment group.Conclusion.NAs can reduce the recurrence and improve the prognosis of HBV-related HCC after curative therapy.

Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide; however, despite its significance, there is a lack of treatment methods and clear prognoses. MicroRNA-9 (miR-9) is known to play an important role in tumor tumorigenesis and progression. Talin-1, which plays a significant role in regulating the transmutation of carcinoma, has been demonstrated to be downregulated by miR-9 in epithelial ovarian cancer. In the present study, we researched the potential role of miR-9 in the prognosis of HCC. The expression levels of miR-9 and Talin-1 mRNA in HCC tissues (n = 60), adjacent non-cancerous tissues (n = 60), and normal liver tissues (n = 20) were detected using a real-time quantitative assay; protein expression levels of Talin-1 were detected using western blot. The expression levels of miR-9 were significantly higher in HCC tissues (P < 0.001) than in normal liver and adjacent non-cancerous tissues. These levels were significantly associated with tumor grade, tumor size, portal vein tumor thrombus, integral capsule, and 2.0-year disease-free survival rate (P < 0.05). High levels of miR-9 were strongly associated with the malignant progression of HCC, and overexpression of miR-9 is a risk factor that has a statistically significant effect on survival rate. miR-9 could play a role as an HCC tumor activator by regulating the expression of Talin-1; therefore, miR-9 might be a potentially valuable biomarker for the prognosis in HCC patients.

Objective To investigate the optimizing of operative techniques on cavernous hepatic hemangioma by comparing the effective of the two approaches (enucleation and hepatectomy).

To study on treating organ transplant rejection with low doses of CsA and CTLA4-Ig.We set up a rat's cardiac transplant rejection model by Ono's way. The experimental rats were divided into four groups: group A: without any treatment; group B: intraperitoneal injection of CsA at 10 mg / (-1) / (-1) 1 - 7 days; after operation group C: intraperitoneal injection of 100 microgram CTLA4-Ig after 2nd operative day; group D: intraperitoneal injection of CsA 2 mg / (-1) / (-1) 1- 7 days after operation. 50 microgram CTLA4-Ig was given intraperitoneally on the 2nd day postoperation. The survival days of allograft, serum concentration of IL-2, and histological changes were tested.The allograft survival time of the four groups was 7.2 +/- 0.7 (group A), 19.4 +/- 2.07 (group B), 31.6 +/- 1.8 (group C) and 24.6 +/- 2.07 (group D) respectively. There were significantly differences among the groups (P0.05). The survival time in group D was more prolonged than that in group B (P0.05). The concentration of IL-2 was significantly decreased after operation. Significant difference was observed between the control group and each treated group (P0.01). In group A, B, C and D allograft rejection was graded IV, II, I and I respectively.CTLA4-Ig had a stronger immunosuppression than did CsA. The low doses of CsA and CTLA4-Ig had show a synergistic immunosuppression in allograft transplantation.