Icariin promotes osteogenic differentiation through the mmu_circ_0000349/mmu-miR-138-5p/Jumonji domain-containing protein-3 axis.

Circular RNAs (circRNAs) regulate Jumonji domain-containing protein-3 (JMJD3) by sponging with microRNAs (miRNAs). This study aimed to investigate the role of icariin on specific circRNA/miRNA/JMJD3 axis in osteogenic differentiation of MC3T3-E1 cells. CircRNA sequencing was performed on the MC3T3-E1 cells induced by osteogenic differentiation medium for 1 d (negative control (NC) group) and 14 d (osteogenesis group). And mmu_circ_0000349 was verified using Sanger sequencing, ribonuclease R degradation, and actinomycin D assay. The function of mmu_circ_0000349 was validated by detecting the expressions of osteogenic differentiation markers, alkaline phosphatase (ALP), and runt-related transcription (RUNX2), via real-time quantitative PCR (qPCR) and Western blotting or ALP and alizarin red staining assay. Dual luciferase reporter gene assay confirmed the relationship between mmu_circ_0000349 and mmu-miR-138-5p (or mmu-miR-138-5p and JMJD3). Meanwhile, the JMJD3 binding to mmu_circ_0000349 was screened using an RNA pull-down assay. qPCR and Western blotting confirmed the effect of icariin on the mmu_circ_0000349/mmu-miR-138-5p/JMJD3 axis and osteogenic differentiation. As MC3T3-E1 osteogenic differentiation progressed, the JMJD3 expression level increased. A total of 361 circRNAs exhibited differences between the NC and osteogenesis groups. After validation, mmu_circ_0000349 was further analyzed as it exhibited the largest expression. And mmu_circ_0000349 was identified as a stable circular structure. Overexpression of mmu_circ_0000349 increased the expression levels of ALP and RUNX2, enhanced ALP activity, and increased the number of mineralized nodules; contrarily, inhibition of mmu_circ_0000349 exerted opposite effects. The data also confirmed that mmu_circ_0000349 regulated JMJD3 by sponging with mmu-miR-138-5p. With the increase in icariin concentration and time for treatment, the expression levels of mmu_circ_0000349, JMJD3, ALP, and RUNX2 also increased, whereas that of mmu-miR-138-5p decreased. In conclusion, Icariin promoted osteogenic differentiation by regulating the mmu_circ_0000349/mmu-miR-138-5p/JMJD3 pathway. Therefore, this provides a theoretical basis for the treatment of diseases related to osteogenic differentiation.

Effect of thread depth and thread pitch on the primary stability of miniscrews receiving a torque load : A finite element analysis.

PURPOSE: We have been developing a new type of miniscrew to specifically withstand orthodontic torque load. This study aimed to investigate the effect of thread depth and thread pitch on the primary stability of these miniscrews if stressed with torque load. METHODS: Finite element analysis (FEA) was used to evaluate the primary stability of the miniscrews. For thread depth analysis, the thread depth was set to 0.1-0.4 mm to construct 7 models. For thread pitch analysis, the thread pitch was set to 0.4-1.0 mm to construct another 7 models. A torque load of 6 Nmm was applied to the miniscrew, and the other parameters were kept constant for the analyses. Maximum equivalent stress (Max EQV) of cortical bone and maximum displacement of the miniscrews (Max DM) were the indicators for primary stability of the miniscrew in the 14 models. RESULTS: In the thread depth analysis, Max DM increased as the miniscrew thread depth increased, while Max EQV was smallest in model 3 (thread depth = 0.2, Max EQV = 8.91 MPa). In the pitch analysis, with an increase of the thread pitch, Max DM generally exhibited a trend to increase, while Max EQV of cortical bone showed a general trend to decrease. CONCLUSION: Considering the data of Max DM and Max EQV, the most appropriate thread depth and thread pitch of the miniscrews in our model was 0.2 and 0.7 mm, respectively. This knowledge may effectively improve the primary stability of newly developed miniscrews.

Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review).

Intrahepatic cholangiocarcinoma (ICC) is a primary malignant liver tumour whose incidence is second only to that of hepatocellular carcinoma. ICC is a highly heterogeneous disease arising from neoplastic transformation of intrahepatic biliary epithelial cells (cholangiocytes), and it is characterized by a very poor prognosis. Signal transducer and activator of transcription 3 (STAT3) is an important oncogene that is widely expressed in numerous cancers. STAT3 is a candidate target for the treatment of ICC. However, studies on STAT3 and the occurrence and development of ICC require improvements. Therefore, the present review summarized the mechanism of STAT3 in ICC and provided a theoretical basis for STAT3 to become an effective target for determining the prognosis and treatment of ICC.

SOX9/MKLN1-AS Axis Induces Hepatocellular Carcinoma Proliferation and Epithelial-Mesenchymal Transition.

SOX9, as a transcript factor, has been confirmed to boost proliferation and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC), but the underlying mechanism remains incompletely elucidated. A bioinformatics analysis web, Jaspar, manifested that SOX9 can transcriptionally regulate an lncRNA, MKLN1-AS. To determine the role of MKLN1-AS in HCC, this study measured MKLN1-AS expression in HCC and the paracancerous tissues and conducted a series of assays, including MTT, colony formation, and transwell assays, in vitro. EMT of HCC was evaluated by E-cadherin and vimentin protein levels. The regulatory effect of SOX9 on MKLN1-AS was determined using dual luciferase reporter and ChIP assays. Both MKLN1-AS and SOX9 were up-regulated in HCC tissues compared to paracancerous tissues. SOX9 promoted cell viability, proliferation, invasion, and EMT of HCCs, but these promoting effects of SOX9 were attenuated after the knockdown of MKLN1-AS. Overexpression of SOX9 increased MKLN1-AS in HCCs, whereas silencing SOX9 decreased MKLN1-AS expression. According to dual luciferase reporter and ChIP assays, SOX9 can bind to the promoter of MKLN1-AS gene to stimulate the expression. MKLN1-AS is transcriptionally regulated by SOX9 and mediates the effects of SOX9 on the proliferation and EMT of HCCs.

Evidence for quasar fast outflows being accelerated at the scale of tens of parsecs.

Quasar outflows may play a crucial role in regulating the host galaxy, although the spatial scale of quasar outflows remain a major enigma, with their acceleration mechanism poorly understood. The kinematic information of outflow is the key to understanding its origin and acceleration mechanism. Here, we report the galactocentric distances of different outflow components for both a sample and an individual quasar. We find that the outflow distance increases with velocity, with a typical value from several parsecs to more than one hundred parsecs, providing direct evidence for an acceleration happening at a scale of the order of 10 parsecs. These outflows carry ∼1% of the total quasar energy, while their kinematics are consistent with a dust-driven model with a launching radius comparable to the scale of a dusty torus, indicating that the coupling between dust and quasar radiation may produce powerful feedback that is crucial to galaxy evolution.

LncRNA SNHG3 Facilitates the Malignant Phenotype of Cholangiocarcinoma Cells via the miR-3173-5p/ERG Axis.

BACKGROUND: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is an oncogenic lncRNA that has been reported in many cancers, but the role of SNHG3 in cholangiocarcinoma (CCA) remains largely unknown. Bioinformatic analysis revealed a regulatory relationship among SNHG3, miR-3173-5p, and ERG. miR-3173-5p is a tumour suppressive miRNA, while ERG is an oncogene. In the present study, we focused on the regulatory effects and molecular mechanisms of SNHG3 in CCA. METHOD: The expression of SNHG3 and miR-3173-5p was evaluated using qRT-PCR analysis. Knockdown of SNHG3 was achieved by shRNA. Cell viability was assessed by MTT assay. Migration and invasion were determined by Transwell assay. Flow cytometry was used to assess cell apoptosis. Western blots were applied to quantify protein levels. Furthermore, using RNA pulldown and dual luciferase assays, the interactions between SNHG3 and miR-3173-5p and between miR-3173-5p and ERG in CCA cells were validated. RESULTS: SNHG3 was significantly upregulated in CCA cells compared with normal human intrahepatic biliary epithelial cells. Knockdown of SNHG3 inhibited the proliferation and migration of CCA cells. Mechanistically, SNHG3-sponged miR-3173-5p, thus releasing the repression of ERG by miR-3173-5p. Rescue experiments showed that the miR-3173-5p/ERG axis mediated the oncogenic effect of SNHG3. CONCLUSION: Taken together, our data suggest that SNHG3 is a pleiotropic oncogenic lncRNA in CCA. Knockdown of SNHG3 expression suppressed malignant phenotypes in CCA cells via the miR-3173-5p/ERG axis.

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer.

Purpose: The aim of the study was to investigate the effect of hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) combined with radical surgery and capecitabine on stage III gallbladder cancer. Method: Seventy-eight patients with stage III gallbladder cancer treated in our hospital between December 2015 and April 2019 were retrospectively enrolled. Depending on the treatment approach, the patients were divided into the control group (radical surgery and capecitabine) and the HIPEC group (hyperthermic intraperitoneal perfusion chemotherapy combined with radical surgery and capecitabine). The patients were followed up by outpatient or through telephone until April 1, 2020. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using the Kaplan-Meier method and parallel log-rank test. Results: There were 43 cases in the control group and 35 cases in the HIPEC group. There were no significant differences in operation time, lymph node metastasis, microvascular infiltration, and nerve invasion; there was no significant difference in postoperative complications between the two groups (P > 0.05). The average hospitalization time of the HIPEC group was 23.0 ± 6.9 days, which was longer than the 20.0 ± 5.8 days of the control group (P < 0.05). The body temperatures of HIPEC group patients at 0 h and 6 h after operation were higher than those of patients in the control group (P < 0.05); however, the body temperature of the two groups gradually became the same at 12-24 h after operation. There was no liver and kidney damage in the two groups after surgery. The platelets in the HIPEC group were less than those in the control group (P < 0.05). The median survival time of HIPEC was 19.2 months, which was longer than 15.3 months in the control group. The 1-year survival rates of the two groups were 91.43% vs. 76.71%, and the 2-year survival rates were 26.29% vs. 17.53%, respectively (P < 0.05). Conclusion: HIPEC combined with radical surgery and capecitabine for stage III gallbladder cancer can effectively prolong survival time without increasing surgery-related complications.

[Corrigendum] HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin.

Following the publication of the above article, the authors have realized that the Funding section of the Declarations on p. 7 was written incorrectly: The text here should have appeared as follows: 'This work was supported by the Research Fund Subsidy Project of Hunan Provincial Committee on Health Commission (grant no. 20200179) and Xiang Wei Medical Administration Medical Office Memorandum (2019) No. 118 and the Research Fund of Hunan Provincial Department of Education (grant no. 20C1163)'. The authors regret their oversight in providing this incorrect information in the Funding section of their paper. They thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership of the Journal and to the inappropriately credited funding bodies in question for any inconvenience caused. [the original article was published in Molecular Medicine Reports 23: 343, 2021; DOI: 10.3892/mmr.2021.11982].

Long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) is a potential diagnostic and prognostic biomarker and therapeutic target for hepatocellular carcinoma.

BACKGROUNDS/AIMS: Hepatocellular carcinoma is recognized as the most common subtype of hepatic cancer. Muskelin 1 antisense RNA (MKLN1-AS) shows prognostic value in hepatitis B virus-hepatocellular carcinoma. The aim of this study is to investigate the detailed biological role of MKLN1-AS and Yes-associated transcriptional regulator 1 (YAP1)-related mechanisms. METHODS: Based on online databases (GEPIA, TCGA, and GEO), the expression of MKLN1-AS and YAP1 in patients with hepatocellular carcinoma was analyzed. The IntaRNA algorithm was used to predict complementary sites between MKLN1-AS and YAP1 mRNA. Hepatocellular carcinoma tumor tissues and cells were collected for the quantification of MKLN1-AS and YAP1. FISH was performed to explore the location of MKLN1-AS in cells. The effects of MKLN1-AS and YAP1 on proliferation, migration and invasionof hepatocellular carcinoma were determined in vitro and in vivo. Actinomycin D and RNA immunoprecipitation were resorted to confirm the regulatory role of MKLN1-AS in YAP1 expression. RESULTS: The up-regulation of MKLN1-AS contributed to the poor prognosis of patients with hepatocellular carcinoma. MKLN1-AS and YAP1 were overexpressed in hepatocellular carcinoma tissues and cells. MKLN1-AS positively modulated YAP1 expression through targeting and stabilizing YAP1 mRNA.MKLN1-AS was predominantly located in the cytoplasm of the cells. MKLN1-AS intensified proliferation, migration and invasion of hepatocellular carcinoma cells via YAP1. MKLN1-AS also caused hepatocarcinogenesis through inducing YAP1 expression in vivo. CONCLUSIONS: MKLN1-AS overexpression enhances the stability of YAP1 mRNA, which is necessary for the oncogenic activity of MKLN1-AS. MKLN1-AS can be utilized in the diagnosis and prognosis of hepatocellular carcinoma as an upstream factor of YAP1.

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin.

Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase­2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA­HK2 or pCDNA3.1­HK2, followed by GA treatment. A Cell Counting Kit­8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription­quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2­knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated­AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.

LncRNA NEAT1 promotes cell proliferation, migration, and invasion via the miR-186-5p/PTP4A1 axis in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly aggressive and malignant tumor. In this study, the effect and molecular mechanism of nuclear enriched abundant transcript 1 (NEAT1) in CCA were elucidated. The expressions of NEAT1, microRNA-186-5p (miR-186-5p), and PTP4A1 were measured by quantitative real-time PCR. The protein levels were measured by Western blotting. Kaplan-Meier analysis was performed to create survival curves. The interactions between NEAT1, miR-186-5p, and PTP4A1 were assessed through the dual luciferase reporter assay. Additionally, the cell proliferation, apoptosis, migration, and invasion were measured by colony formation, flow cytometry, the Transwell assay, and the wound healing assay, respectively. NEAT1 and PTP4A1 were significantly upregulated in CCA tissues and cells, but miR-186-5p was downregulated. NEAT1 expression was negatively correlated with the survival of CCA patients and has remarkable correlation with serum CA199 levels and lymph node metastasis. Besides, NEAT1 could act as a molecular sponge for miR-186-5p to upregulate PTP4A1 expression. More importantly, the knockdown of NEAT1 or overexpression of miR-186-5p inhibited the proliferation, migration and invasion of CCA cells, and the inhibition of miR-186-5p reversed the effects of the knockdown of NEAT1. In addition, NEAT1 could also activate the PI3K/AKT signaling pathway and regulate the epithelial-mesenchymal transition (EMT) through the miR-186-5p/PTP4A1 axis. In conclusion, NEAT1 was involved in cell proliferation, migration and invasion in CCA, and the NEAT1/miR-186-5p/PTP4A1/PI3K/AKT axis indicated novel regulatory mechanisms and therapeutics for the treatment of CCA.

Effects of Cangfu Daotan Decoction on obese polycystic ovary syndrome and its mechanism.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. Cangfu Daotan Decoction (CFDTT) is one of the prescriptions in the stagnation of obesity-type PCOS. Our previous study showed that CFDTT treatment of obese PCOS was correlated with organic anion transporting polypeptides (OATPs). METHODS: Here, we studied the effects of CFDTT on obese PCOS and its underlying mechanism. We built an obese PCOS rat model and treated the rats with CFDTT. Then, we detected the serum levels of TCHO, TG, LDL-c, HDL-c, luteinizing hormone (LH), follicle stimulating growth hormone (FSH), testosterone (T), estradiol (E2), IL-1ß, IL-6, and TNF-α in each group and adopted RT-PCR, western blotting and immunohistochemical staining to investigate the effects of CFDTT treatment on the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. In addition, we compared the pregnancy outcomes of each group. RESULTS: We found that CFDTT decreased the serum levels of TCHO, TG, LDL-c, LH, T, IL-1ß, IL-6, and TNF-α and increased the levels of HDL-c, FSH and E2 in a dose-dependent manner. CFDTT could induce the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. Moreover, CFDTT could improve pregnancy outcomes. CONCLUSION: These data suggested that the therapeutic mechanism of Cangfu Daotan Decoction on PCOS may be correlated with regulating lipid metabolism, sex hormone secretion and the inflammatory response and increasing OATP2B1 and OATP3A1 expression. Cangfu Daotan Decoction can be developed as a PCOS treatment drug.

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the Gentianella acuta, is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out. AIM: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC. MATERIALS AND METHODS: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings. RESULTS: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM). CONCLUSION: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.

Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.

BACKGROUND: The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. CASE PRESENTATION: A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. CONCLUSIONS: We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Effect of rNA interference on Oatp3a1 gene expression on biological characteristics and immune factors of ovarian granulosa cells in rats with PCOS.

Polycystic ovary syndrome (PCOS) is a common endocrinal metabolic disease, and its pathogenesis has not yet been thoroughly studied. The purpose of this experiment was to investigate the effect of RNA interference on Oatp3a1 gene expression on the biological viability and immune factors of ovarian granulosa cells in rats with PCOS. First, rats were intragastrically administered 1 mg/kg letrozole to successfully construct PCOS model. Western blot, qRT-PCR, CCK8 and flow cytometry were used to detect the gene expression, immune factor protein expression, cell proliferation and apoptosis in ovarian granulosa cells transfected with siRNA Oatp3a1 in rats with PCOS, respectively. The results showed that follicle stimulating hormone receptor (FSHR) was located on the cell membrane of rat ovarian granulosa cells, and letrozole successfully induced PCOS rat model. In PCOS rat ovarian granulosa cells, the mRNA expression level of Oapta1 was higher than that in normal rat ovarian granulosa cells. At the same time, compared with the sham group, the protein expression of NF-κB, TGF-ß1 and VEGF in si-Oatp3a1 group was significantly down-regulated (P < 0.05), and the cell proliferation rate was significantly decreased in si-Oatp3a1 group (P < 0.05) in comparison with the sham group. The apoptotic rate was increased obviously (P < 0.05), which was about 2.5 times that of the sham group. This indicates that in the ovarian granulosa cells of rats with PCOS, the interference of Oatp3a1 gene expression can significantly inhibit cell proliferation and promote apoptosis, while inhibiting the expression of immune factors TGF-ß1 and VEGF can reduce the expression of NF-κB protein, thereby suppressing the activation of the NF-κB signaling pathway.

Thread shape affects the stress distribution of torque force on miniscrews: a finite element analysis.

This study aimed to investigate the effect of miniscrews thread shape on the stress distribution receiving a torque load. Seven thread shapes (S,V1,V2,B1,B2,R1,R2) models were constructed and a 6 Nmm-torque load was applied. The order of maximum equivalent stress (EQV) value was V1 > V2 > B1 > R1 > R2 > B2 > S. The order of maximum displacement of miniscrew (Max DM) value was S > B2 > R1 = V1 > B1 > V2 > R2. Model R2 may be the most appropriate thread shape affording a torque force.

Application of Laparoscopic Radical Resection for Type III and IV Hilar Cholangiocarcinoma Treatment.

BACKGROUND: This study is aimed at investigating the feasibility and safety of the laparoscopic radical resection for treating type III and IV hilar cholangiocarcinoma (III/IV Hilar C). METHODS: Six patients with III/IV Hilar C were enrolled in our hospital. All patients underwent total laparoscopic surgery, including basic surgery (laparoscopic gallbladder, hilar bile duct, and common bile duct resection and hepatoduodenal ligament lymph node dissection) combined with left hepatic and caudate lobe resection/portal resection. The tumor size, operation time, intraoperative blood loss, and postoperative complications were observed. The follow-up of the patients after discharge was recorded. RESULTS: Surgery was successfully completed in 6 patients. We found that the tumor size of 6 patients ranged from 1.5 to 3.6 cm, with 4 lymph nodes. The operation time was 540-660 minutes, and the blood loss was 300-500 ml. One patient developed bile leakage after surgery, healed within 2 weeks after drainage. The postoperative hospital stay was 16 (13-24) days. There were 4 cases of negative bile duct margin tumor, 1 case was positive, and 1 case was not reported. All 6 patients were discharged smoothly without perioperative death. Regular examinations were conducted every 3 months after discharge, and the median duration was 7 months. Only 1 patient had a marginal dysplasia, and 5 patients had no obvious signs of recurrence. CONCLUSIONS: Application of laparoscopic radical resection for III/IV Hilar C is safe and feasible and has good short-term efficacy with adequate preoperative evaluation, appropriate case selection, and precise operative strategy.

Long non-coding RNA UCA1 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells through targeting microRNA-122.

Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed. In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.