Screening differential circular RNA expression profiles and the potential role of hsa_circ_0085465 in liver cancer.

Aims: This study aimed to screen the circular RNAs (circRNAs) that are differentially expressed between liver cancer and paired paracarcinoma tissues and then elucidate their role in cancer progression. Materials and Methods: High-throughput sequencing of cancer and paired paracarcinoma tissues was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the parental genes of the differentially expressed circRNAs, which were also verified via real-time quantitative polymerase chain reaction analysis of the tissues. In addition, the function of selected circRNAs was determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium (MTS) and transwell assays. Results: Total 218 and 121 circRNAs were differentially upregulated and downregulated, respectively; these were mainly enriched with GO and KEGG terms related to biological functions. From five representatives of the differentially expressed circRNAs, we selected hsa_circ_0085465 for further analysis, discovering that its overexpression promoted the proliferation, migration, and invasion of 97 L cells. Conclusion: Taken together, our results suggest that hsa_circ_0085465 is relevant to liver cancer progression.

Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020 / 中华预防医学杂志

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Transjugular intrahepatic portosystemic shunt versus endoscopic therapy for prevention of variceal rebleeding in patients with hepatocellular carcinoma meeting the Milan criteria.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic therapy (ET) have been recommended to prevent variceal rebleeding due to cirrhotic portal hypertension. However, which one is better for patients with hepatocellular carcinoma (HCC) remains controversial. Hence, we aimed to compare the clinical outcomes of these two treatments for these subpopulation. METHODS: This retrospective study was approved by the institutional review board. The data of 98 consecutive patients with HCC meeting the Milan criteria (mean age 54.1 years) who had received TIPS placement (34 patients) or ET (64 patients) between June 2010 and December 2017 were reviewed. The clinical outcomes were evaluated and were calculated by the Kaplan-Meier method and compared by using the log-rank test. A matched cohort composed of 34 patients from each group was selected after adjustment with propensity score matching to verify the robustness of the results. RESULTS: The median follow-up time was 33.1 months. The rebleeding rate was significantly lower in TIPS group (P = 0.016). A matched cohort composed of 34 patients from each group after adjustment with propensity score matching showed that TIPS reduced the risk of rebleeding (P = 0.030) without increasing long-term overt hepatic encephalopathy (P = 0.151), while there was no significant difference in overall liver transplant-free survival (P = 0.120). Thereafter, 25 patients in TIPS group (73.5%) and 42 patients in ET group (65.6%) received locoregional therapies for HCC (P = 0.431). CONCLUSION: TIPS reduced the risk of rebleeding without improving survival. Locoregional therapies can be performed safely to manage HCC after sufficient prevention of variceal rebleeding.

Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis.

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-ß (TGF-ß) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-ß-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer via DNA damage.

Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] (D0402) on Kunming(KM) mice bearing tumor (H22 hepatic cancer) has been evaluated, and the results showed that the tumor weight of mice treated with 0.22 mg/(kg·day) D0402 via i.v. administration for 7 days decreased about 31.79% compared to the control group, while the body weight, as well as the thymus, spleen, liver, lung, and kidney indices of mice treated with D0402 observed almost no loss compared to the control group. Furthermore, the mechanism studies on anti-angiogenic showed that D0402 could inhibit the formation of angiogenesis in the transgenic Tg(fli1a: EGFP) zebrafish. After treated with D0402, the sub-intestinal vessels(SIVs) of the zebrafish became disordered and chaotic, and was dosage dependent. Moreover, the TUNEL analysis and comet assays revealed that D0402 can induce apoptosis of HepG2 cell through DNA damage, and this was further demonstrated by immunofluorescence analysis with the number of γ-H2AX increased following the increasing amount of D0402. Besides, in vivo toxicity of D0402 has also been investigated on the development of zebrafish embryo, and the results showed that there were no death or development delay occurred for zebrafish embryo treated with D0402 up to concentration of 60 µM. All in together, this study suggested that D0402 can be developed as a potential inhibitor against liver cancer through co-junction of anti-angiogenesis and apoptosis-inducing via DNA damage in the near future.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results.

PURPOSE: To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization (PE-TACE) for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1, 2015 and August 30, 2016. The complication rate, tumor response rate, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Adverse events were generally mild and included abdominal pain and fever, although a major complication was reported in 1 patient (1.8%). During a median follow-up of 10.0 months (range, 3.0-24.0 months), 14 patients (25.5%) achieved a complete tumor response, 25 (45.5%) had a partial response, 9 (16.4%) showed stable disease, and 7 (12.7%) had disease progression. The 1-month overall response rate was 70.9%, and the local tumor response rate was 89.0%. The 1-month tumor response rate was 100% for Barcelona Clinic Liver Cancer (BCLC) stage A or B disease and 62.8% for BCLC stage C disease. The median PFS was 6.1 months (95% confidence interval [95%CI], 3.4-8.8 months; range, 1.0-24.0 months). The median OS was 11.0 months (95%CI, 7.1-14.9 months; range, 2.0-24.0 months). Kaplan-Meier analysis (log-rank test) found significant differences in OS between patients grouped by tumor number (P = 0.006), tumor size (P = 0.035), and Eastern Cooperative Oncology Group (ECOG) score (P = 0.005). The tumor number (1 vs. ≥2) was the only factor independently associated with OS (hazard ratio [HR], 2.867; 95%CI, 1.330-6.181; P = 0.007). CONCLUSIONS: PE-TACE for unresectable HCC may be safe, with favorable tumor response rates and survival time, especially in patients with a single large tumor. Longer follow-up using a larger series is necessary to confirm these preliminary results.

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma.

BACKGROUND: Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients. METHODS: This study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs. RESULTS: The best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14-5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01-3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14-0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30-0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined. CONCLUSIONS: Our findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients.

Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: A meta-analysis.

BACKGROUND: The impact of high body mass index (BMI, >23/25 kg/m) on surgical outcomes and prognosis in patients with esophageal carcinoma (EC) after undergoing esophagectomy remains controversial. We herein conducted a systematic review and meta-analysis to determine the relationship between high BMI and surgical outcomes and prognosis in patients undergoing esophagectomy for EC. METHODS: The study search was conducted by retrieving publications from the PubMed, Embase, Web of Science, and CNKI (up to September 8, 2017). Nineteen studies with 13,756 patients were included in this meta-analysis. RESULTS: We found that high BMI was closely associated with a higher incidence of wound infection (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.97, P = .04), cardiovascular complications (OR: 2.51, 95% CI, 1.65-3.81, P < .0001), and anastomotic leakage (OR: 1.50, 95% CI, 1.21-1.84, P = .0002), but a lower incidence of chylous leakage (OR: 0.59, 95% CI, 0.40-0.88, P = .01) when compared with normal BMI. The high BMI group was not associated with better or worse overall survival (OS) (hazard ratio [HR]: 0.95, 95% CI, 0.85-1.07, P = .4) and disease-free survival (HR: 0.95, 95% CI, 0.72-1.25, P = .72) than the normal BMI group. However, in the subgroup analysis, the pooled result of HRs generated from multivariate analyses suggested that high BMI could improve OS in EC patients (HR: 0.84, 95% CI, 0.76-0.93, P < .01). CONCLUSIONS: Overweight patients with EC should not be denied surgical treatment, but intraoperative prevention and careful postoperative monitoring for several surgical complications must be stressed for this population. Besides, high BMI might be a prognostic predictor in EC patients; further studies are warranted.

[Effects of alien species Robinia pseudoacacia on plant community functional structure in hilly-gully region of Loess Plateau, China.] / 外来物种刺槐对黄土丘陵区植物群落功能结构的影响.

To investigate the effects of the introduction of Robinia pseudoacacia on the functional structure of plant communities, we selected paired-plots of R. pseudoacacia communities and native plant communities across different vegetation zones, i.e., steppe zone, forest-steppe zone, forest zone in hilly-gully region of Loess Plateau, China. We measured several functional characteristics and then compared the functional structures of R. pseudoacacia and native plant communities in different vegetation zones. The results showed that the variation of the functional traits across different vegetation zones were consistent in R. pseudoacacia community and native plant community, including leaf carbon concentration, leaf nitrogen concentration, leaf phosphorus concentration, specific leaf area, and leaf tissue density. The leaf carbon concentration, leaf nitrogen concentration, and specific leaf area of the R. pseudoacacia community were significantly higher than those of the native plant community. The trend of change that the functional diversity indices, i.e., FRic, FEve, FDiv, FDis, Rao of the R. pseudoacacia community and the native plant community with vegetation zones were different. The introduction of R. pseudoacacia enhanced the plant community functional diversity in the forest zone but reduced community functional diversity in the steppe zone.

Chiral ruthenium(ii) complex as potent radiosensitizer of 125I through DNA-damage-mediated apoptosis.

A chiral ruthenium(ii) complex, Λ-[Ru(bpy)2(o-tFMPIP)] (ClO4)2 (o-tFMPIP = 2'-trifluoromethylphenyl) imidazo [4,5-f][1,10]phenanthroline, was prepared and evaluated for its enhancement of the radiosensitivity of 125I seeds. The synthetic Ru(ii) complex, LR042, effectively enhanced growth inhibition against HepG2 human hepatocellular liver carcinoma cells induced by 125I seeds and consequently effectively promoted the apoptosis of tumor cells with increasing level of cleave-caspase-3. Furthermore, the results of immunofluorescence indicated that LR042 enhanced the phosphorylation of H2AX by 125I seeds vigorously in response to damaged DNA. LR042 improved DNA damage induced by 125I seeds, which resulted in apoptosis through the activation of the p53/AKT signal. In conclusion, synthetic LR042 can be further developed as a potential radiosensitizer of 125I seed radiotherapy for cancer therapy.

Misdiagnosis of a small cell lung cancer resulting from inaccurate pathology.

Currently, a biopsy provides the most reliable evidence for diagnosing a disease, and the majority of doctors do not question the diagnosis made by a pathologist. However, an inaccurate diagnosis may lead to serious consequences; for example, a benign tumor may be misdiagnosed as a malignancy, or a malignancy may be deemed to be benign. How to avoid these types of mistakes is a continuing issue of concern to all doctors. Here, we report a case of small cell lung cancer misdiagnosed as an inflammatory myofibroblastic tumor. Fortunately, we performed a mediastinoscopy on the patient and discovered the actual pathologic condition. This case is presented to caution against the possibility of the misdiagnosis of uncommon diseases in clinical practice.