A nomogram to predict conversion of laparoscopic surgery to laparotomy for Choledocholithiasis.

BACKGROUND: Laparoscopic surgery is effective for treating common bile duct (CBD) stones. However, it has high requirements for surgeons and the risk of conversion to laparotomy cannot be ignored. However, when conditions during surgery are not favorable, persisting with laparoscopic procedures blindly can lead to serious complications. Our study aimed to establish a nomogram model for predicting conversion of laparoscopic to laparotomy for choledocholithiasis. MATERIALS AND METHODS: A total of 867 patients who were diagnosed with choledocholithiasis and underwent laparoscopic surgery were randomly divided into a training group (70%, n = 607) and a validation group (30%, n = 260). A nomogram was constructed based on the results of logistic regression analysis. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram. RESULTS: Previous upper abdominal surgery, maximum diameter of stone ≥12 mm, medial wall of the duodenum stone, thickening of the gallbladder wall, thickening of CBD wall, stone size/CBD size ≥0.75, and simultaneous laparoscopic hepatectomy were included in the nomogram. The AUC values were 0.813 (95% CI: 0.766-0.861) and 0.804 (95% CI: 0.737-0.871) in the training and validation groups, respectively. The calibration curve showed excellent consistency between the nomogram predictions and actual observations. DCA showed a positive net benefit for the nomogram. CONCLUSIONS: We constructed a nomogram with a good ability to predict conversion to open surgery in laparoscopic surgery for choledocholithiasis, which can help surgeons to make a reasonable operation plan before surgery and timely convert to laparotomy during operation to reduce potential harm to the patient.

Bi Nanosheets on Porous Carbon Cloth Composites for Ultrastable Flexible Nickel-Bismuth Batteries.

The use of bismuth (Bi) as an anode material in nickel-metal batteries has gained significant attention due to its highly reversible redox reaction and suitable operating conditions. However, the cycling stability and flexibility of nickel-bismuth (Ni//Bi) batteries need to be further improved. This paper employs a facile electrodeposition technique to prepare Bi nanosheets uniformly grown on a porous carbon cloth (PCC), denoted as Bi-PCC electrodes. The Bi-PCC electrode portrays a specific surface area and good wettability that enable fast charge transfer and ion transport channels. Consequently, the Bi-PCC electrode demonstrates a high specific capacity of up to 297.1 mAh g-1 at 2 A g-1, with a capacity retention of up to 71.5% at 2-40 A g-1 and an impressive capacity retention of 79.9% after 1000 cycles at 2-40 A g-1. More importantly, the flexible rechargeable Ni//Bi battery (denoted as Ni(OH)2-PCC//Bi-PCC) with Bi-PCC as the anode and Ni(OH)2-PCC as the cathode has excellent electrochemical performance. The Ni(OH)2-PCC//Bi-PCC battery boasts a remarkable capacity retention of 93.6% after 3000 cycles at 10 A g-1. Further, the cell presents a maximum energy density of 73.1 Wh kg-1 and an impressive power density of 11.9 kW kg-1.

Brain Network Reorganization During Visual Search Task Revealed by a Network Analysis of Fixation-Related Potential.

Visual search is ubiquitous in daily life and has attracted substantial research interest over the past decades. Although accumulating evidence has suggested complex neurocognitive processes underlying visual search, the neural communication across the brain regions remains poorly understood. The present work aimed to fill this gap by investigating functional networks of fixation-related potential (FRP) during the visual search task. Multi-frequency electroencephalogram (EEG) networks were constructed from 70 university students (male/female = 35/35) using FRPs time-locked to target and non-target fixation onsets, which were determined by concurrent eye-tracking data. Then graph theoretical analysis (GTA) and a data-driven classification framework were employed to quantitatively reveal the divergent reorganization between target and non-target FRPs. We found distinct network architectures between target and non-target mainly in the delta and theta bands. More importantly, we achieved a classification accuracy of 92.74% for target and non-target discrimination using both global and nodal network features. In line with the results of GTA, we found that the integration corresponding to target and non-target FRPs significantly differed, while the nodal features contributing most to classification performance primarily resided in the occipital and parietal-temporal areas. Interestingly, we revealed that females exhibited significantly higher local efficiency in delta band when focusing on the search task. In summary, these results provide some of the first quantitative insights into the underlying brain interaction patterns during the visual search process.

Piperine alleviates acute pancreatitis: A possible role for FAM134B and CCPG1 dependent ER-phagy.

BACKGROUND: Acute pancreatitis was a common acute abdominal disease characterized by pancreatic acinar cell death and inflammation. Endoplasmic reticulum autophagy (ER-phagy) coud maintain cell homeostasis by degrading redundant and disordered endoplasmic reticulum and FAM134B and CCPG1 was main ER-phagy receptors. As a natural alkaloid, piperin is found in black pepper and has anti-inflammatory properties, whose effect on ER-phagy in pancreatitis has not been studied. PURPOSE: The objective of this study was to demonstrate the pivotal role of FAM134B and CCPG1 dependent ER-phagy for alleviating acute pancreatitis and explore the molecular mechanism of piperine in alleviating acute pancreatitis. METHOD: In this study we investigated the role of ER-phagy in acute pancreatitis and whether piperine could alleviate pancreatitis through ER-phagy regulation. We first detected endoplasmic reticulum stress (ER-stress) and ER-phagy in different degrees of acute pancreatitis. Then we used ER-stress and autophagy regulators to explore the relationship between ER-stress and ER-phagy in acute pancreatitis and their regulation of cell death. Through using FAM134B-/- and CCPG1-/-, we investigated the mechanism of piperine in the treatment of acute pancreatitis. RESULTS: In this study, we confirmed that with the progression of acute pancreatitis, the pancreatic endoplasmic reticulum stress increased continuously, but the ER-phagy increased first and then was inhibited. Meanwhile, in acute pancreatitis, ER-stress and ER-phagy interacted: endoplasmic reticulum stress can induce ER-phagy, but serious ER-stress would inhibit ER-phagy; and ER-phagy could alleviate ER-stress. Next, we found that piperine reduced ER-stress by enhancing FAM134B and CCPG1 dependent ER-phagy, thereby alleviating pancreatic injury. CONCLUSION: Impaired ER-phagy was both a cause and a consequence of ER-stress in AP mice, which contributed to the transition from AP to SAP. Piperine targeting ER-phagy provided a new insight into the pharmacological mechanism of piperine in treating AP.

Novel sonification designs: Compressed, iconic, and pitch-dynamic auditory icons boost driving behavior.

With the development of connected vehicles, in-vehicle auditory alerts enable drivers to effectively avoid hazards by quickly presenting critical information in advance. Auditory icons can be understood quickly, evoking a better user experience. However, as collision warnings, the design and application of auditory icons still need further exploration. Thus, this study aims to investigate the effects of internal semantic mapping and external acoustic characteristics (compression and dynamics design) on driver performance and subjective experience. Thirty-two participants (17 females) experienced 15 types of warnings - (3 dynamics: mapping 0 vs. 1 vs. 2) × (5 warning types: original iconic vs. original metaphorical vs. compressed iconic vs. compressed metaphorical auditory icon vs. earcon) - in a simulator. We found that compression design was effective for rapid risk avoidance, which was more effective in iconic and highly pitch-dynamic sounds. This study provides additional ideas and principles for the design of auditory icon warnings.

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma.

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.

Development of cancer prognostic signature based on pan-cancer proteomics.

Utilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. And the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has generated extensive proteomics data of the vast majority of tumors. Based on CPTAC, we can perform a proteomic pan-carcinoma analysis. We collected the proteomics data and clinical features of cancer patients from CPTAC. Then, we screened 69 differentially expressed proteins (DEPs) with R software in five cancers: hepatocellular carcinoma (HCC), children's brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). GO and KEGG analysis were performed to clarify the function of these proteins. We also identified their interactions. The DEPs-based prognostic model for predicting over survival was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model in training cohort. Then, we used the time-dependent receiver operating characteristics analysis to evaluate the ability of the prognostic model to predict overall survival and validated it in validation cohort. The results showed that the DEPs-based prognostic model could accurately and effectively predict the survival rate of most cancers.

Endometrial polyp-like perivascular epithelioid cell neoplasm associated with TFE3 translocation: report of one case.

This article reports the pathologic features and malignant biological behavior of a perivascular epithelioid cell neoplasm (PEComa) with the clinical manifestation being endometrial polyps. The case was cured with curettage in a local hospital one year ago. The postoperative diagnosis was "endometrial polyps". This time, due to "irregular bleeding", we carried out another curettage in our hospital. After the operation, 3 pieces of polyps were inspected with diameters of 0.3 cm, 0.5 cm and 0.6 cm, respectively. The tumor consisted of epithelioid cells with alveolar and nesting pattern and showed a diffuse strong expression of HMB45, Melan-A and TFE3. The patient then underwent a hysterectomy and the "polyps" were sent for pathological examination. The result showed that tumor cells infiltrated the deep muscle layer, close to the outer membrane, suggesting a malignant biologic behavior. TFE3-related PEComa is different from general PEComa. This neoplasm and Melanotic Xp11 renal carcinoma have similar clinicopathologic features, histology, immunity and molecular phenotypes, belonging to the same type of tumor. It has been suggested in the literature naming this neoplasm as 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm'. Our case has expanded our understanding of PEComa characteristics and increased data for TFE3 translocation-related PEComa, reminding us to avoid misdiagnosis when PEComa manifests as small polyps.

Applied anatomy of pelvic lymph nodes and its clinical significance for prostate cancer:a single-center cadaveric study.

BACKGROUND: Pelvic lymph node dissection (PLND) is one of the most important steps in radical prostatectomy (RP). Not only can PLND provide accurate clinical staging to guide treatment after prostatectomy but PLND can also improve the prognosis of patients by eradicating micro-metastases. However, reports of the number of pelvic lymph nodes have generally come from incomplete dissection during surgery, there is no anatomic study that assesses the number and variability of lymph nodes. Our objective is to assess the utility of adopting the lymph node count as a metric of surgical quality for the extent of lymph node dissection during RP for prostate cancer by conducting a dissection study of pelvic lymph nodes in adult male cadavers. METHODS: All 30 adult male cadavers underwent pelvic lymph node dissection (PLND), and the lymph nodes in each of the 9 dissection zones were enumerated and analyzed. RESULTS: A total of 1267 lymph nodes were obtained. The number of lymph nodes obtained by limited PLND was 4-22 (14.1 ± 4.5), the number obtained by standard PLND was 16-35 (25.9 ± 5.6), the number obtained by extended PLND was 17-44 (30.0 ± 7.0), and the number obtained by super-extended PLDN was 24-60 (42.2 ± 9.7). CONCLUSIONS: There are substantial inter-individual differences in the number of lymph nodes in the pelvic cavity. These results have demonstrated the rationality and feasibility of adopting lymph node count as a surrogate for evaluating the utility of PLND in radical prostatectomy, but these results need to be further explored.

Heterogeneous Fenton ferroferric oxide-reduced graphene oxide-based composite microjets for efficient organic dye degradation.

A global water pollution on account of organic dye waste poses serious heath threat to human beings. Graphene-based micromotors have recently attracted considerable attentions for efficient water remediation. However, a secondary catalytic degradation is required for completely destroying persistent organic dyes after their adsorption by graphene and its derivatives. Here, we immobilized ferroferric oxide (Fe3O4) nanoparticles (NPs) with reduced graphene oxide (rGO)-based micromotors in order to synthesize heterogeneous Fenton Fe3O4-rGO/Pt composite microjets and to improve their catalytic performance. The as-prepared composite microjets are well propelled in contaminated waters by Pt catalyzing hydrogen peroxide. Combining the attractive properties of reduced graphene oxide (rGO) and Fe3O4 NPs along with fascinating motor movement, the composite microjets offer an efficient removal of methylene blue in short time. This outstanding catalytic performance is ascribed to the synergistic effect of Fe3O4 and rGO during the heterogeneous Fenton-like reaction and the enhanced localized mixing effect during the motion. Moreover, the Fenton composite microjets are able to magnetically recovered and reused for further decontamination processes. Our proposed Fenton composite microjets with extraordinary catalytic capability and good recyclability holds considerable promise for diverse environmental applications.

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a case report and review of the literature.

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is an extremely rare lung sarcoma that is characterized in most cases by recurrent balanced chromosomal translocation t(2;22)(q33;q12) leading to the oncogenic fusion gene EWSR1-CREB1. CASE PRESENTATION: We report a case of PPMS with molecular confirmation using fluorescence in situ hybridization (FISH) and DNA sequencing in a 45-year-old female patient. Computer tomography (CT) scanning revealed a peripheral circumscribed solid mass of 2.1 × 2 cm in the right lung superior lobe. Histologically, the tumor cells ranged from stellate, polygonal to chondrocyte-like or physaliferous-like, forming reticular network of delicate lace-like cellular strands and cords in abundant myxoid stroma. The tumor cell immunophenotype was positive for vimentin, EMA and negative for CK-pan, TTF-1, CAM5.2, S-100, calponin, SMA, desmin, ALK, CD31 and CD34. Molecular analysis demonstrated EWSR1-CREB1 gene fusion in this tumor. During 38 months of follow-up, the patient was alive with no clinical or radiological evidence of recurrence or metastasis. CONCLUSION: PPMS is a rare low-grade sarcoma with distinct histological and genetic features. We add another case to the literature of this rare tumor and report for the first time occurrence of chondrocyte-like and physaliferous-like tumor cells in this tumor, thus enriching its morphologic and cytologic spectrum.

Restoration of miRNA-148a in pancreatic cancer reduces invasion and metastasis by inhibiting the Wnt/ß-catenin signaling pathway via downregulating maternally expressed gene-3.

Various microRNAs (miRNA) have been recognized potential novel tumor markers and have a critical role in cancer development and progression. Recently, methylation of miRNA-148a was identified as a crucial biochemical process in the progression of cancer. However, its potential role and in pancreatic cancer as well as the underlying mechanisms have remained largely elusive. The present study investigated the potential antitumor effect of miR-148a as well as its impact on invasion and metastasis in pancreatic cancer. It was found that the expression of miRNA-148a and the potential predictive biomarker maternally expressed gene-3 (MEG-3) were obviously decreased in human pancreatic cancer tissues compared with those in adjacent non-tumorous tissues. Furthermore, miR-148a was found to be downregulated in pancreatic cancer cell lines compared with normal pancreatic cells through promoter methylation. An MTT assay and a clonogenic assay demonstrated that restoration of miRNA-148a inhibited the proliferation and colony formation of pancreatic cancer cells. In addition, miR-148a transduction led to the upregulation of MEG-3 expression and promoted apoptosis of pancreatic cancer cells. Western blot analysis revealed that transduction of miR-148a markedly decreased the expression levels of C-myc, cyclin D1 and ß-catenin in pancreatic cancer cells. Methylation of miR-148a not only decreased the endogenous ß-catenin levels but also inhibited the nuclear translocation of ß-catenin to delay cell cycle progression. Furthermore, ectopic miR-148a methylation inhibited pancreatic cancer cell migration and invasion via causing an upregulation of MEG-3 expression. Most importantly, ectopic overexpression of miR-148a in pancreatic cancer cells inhibited tumor formation in an animal experiment. Taken together, miR-148a methylation is a crucial regulatory process to inhibit the proliferation and invasion of pancreatic cancer cells, and transduction of miR-148a suppressed the proliferation of pancreatic cancer cells through negative regulation of the Wnt/ß-catenin signaling pathway. The findings of the present study suggested that miRNA-148a acts as a tumor suppressor in pancreatic cancer and may contribute to the development of novel treatments for pancreatic cancer.

Role of interleukin-17 in the pathogenesis of perianal abscess and anal fistula: a clinical study on 50 patients with perianal abscess.

BACKGROUND: To investigate the role of interleukin (IL)-17 in tissue and peripheral blood of perianal abscess and anal fistula. METHODS: Patients with primary perianal abscess (n = 50) admitted to Jinhua Municipal Central Hospital between March 2003 and August 2004 were enrolled. Fifty patients with mixed haemorrhoids, who showed no perianal abscess or anal fistula, were also recruited as the control. After surgery, patients were followed up for 6 months. Protein and gene expression of IL-17 was determined in surgically harvested anal tissues and peripheral blood, respectively. The relationship between IL-17 and clinical pathological features were analysed. RESULTS: As shown by immunohistochemistry of anorectal tissues, the positive rate of IL-17 protein was higher in the perianal abscess group than in the control group. In patients with perianal abscess, the expression of IL-17 significantly correlated with the diameter of the abscess (P = 0.013), the wound surface healing time (P = 0.010) and the progression into anal fistula (P = 0.003). For the gene expression of IL-17 in peripheral blood cells, the level was significantly higher in patients with perianal abscess comparing to the control group (0.4350 ± 0.1190 versus 0.1785 ± 0.1230, P ≤ 0.001). Comparing to the recovery group, patients with their perianal abscess progressed to anal fistula showed higher levels of IL-17 gene expression (P = 0.014). CONCLUSIONS: Expression of IL-17 was increased in the anorectal tissues and peripheral blood of patients with perianal abscess and anal fistula. IL-17 may play an important role in the pathogenesis of perianal abscess and anal fistula.

A Prediction Model for Recognizing Strangulated Small Bowel Obstruction.

INTRODUCTION: Early and accurate diagnosis of strangulated small bowel obstruction (SSBO) is difficult. This study aimed to devise a prediction model for predicting the risk of SSBO. MATERIALS AND METHODS: A database of 417 patients who had clinical symptoms of intestinal obstruction confirmed by computed tomography (CT) were evaluated for inclusion in this study. Symptoms and laboratory and radiologic findings of these patients were collected after admission. These clinical factors were analyzed using logistic regression. A logistic regression model was applied to identify determinant variables and construct a clinical score that would predict SSBO. RESULTS: Seventy-six patients were confirmed to have SSBO, 169 patients required surgery but had no evidence of intestinal ischemia, and 172 patients were successfully managed conservatively. In multivariate logistic regression analysis, body temperature ≥ 38.0°C, positive peritoneal irritation sign, white blood cell (WBC) count > 10.0 × 10^9/L, thick-walled small bowel ≥3 mm, and ascites were significantly associated with SSBO. A new prediction model with total scores ranging from 0 to 481 was developed with these five variables. The area under the curve (AUC) of the new prediction model was 0.935. CONCLUSIONS: Our prediction model is a good predictive model to evaluate the severity of SBO.

Primary pericardial primitive neuroectodermal tumor: a case report and review of literature.

Primitive neuroectodermal tumor (PNET) is a rare, high-grade malignant tumor that most commonly occurs in the peripheral nervous system, bone, and deep soft tissues. It is extremely rare in the pericardium. To the best of our knowledge, only two patients with primary PNET of the pericardium have been reported so far in the literature. We report a case of PNET of the pericardium in a 13-year-old female patient, who was referred to our hospital for dyspnea and edema of lower extremities. Computer tomography (CT) scanning revealed a soft tissue mass in the pericardium which was surgically removed. The diagnosis of PNET was confirmed by histology, immunohistochemistry and molecular study. The patient was alive and well at follow up 8 months after surgery.

Genetically engineered recombinant adenovirus expressing interleukin­2 for hepatocellular carcinoma therapy.

Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin­2 (IL­2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL­2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL­2 (rAd­IL­2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients. In the present study, the ability of IL­2 to stimulate an immune response and the ability of recombinant adenovirus to inhibit tumor cell growth in HCC was investigated in a HCC tumor model. It was demonstrated that the regulatory and effector cell­mediated tumor suppression by antitumor cluster of differentiation (CD)4+ and CD8+ T cells stimulated by rAd­IL­2 is tumor­specific. Furthermore, rAd­IL­2 significantly stimulated tumor­specific cytotoxic T lymphocyte responses, increased interferon­Î³ release and enhanced antitumor immunity by inducing CD4+ and CD8+ T cell recruitment into the tumor, and additionally induced memory to protect tumor­bearing mice against tumor challenge. Treatment with rAd­IL­2 led to tumor regression and long­term survival of mice in the 120­day treatment period. Tumor challenge experiments demonstrated that rAd­IL­2 induced memory, protecting against reinfection. In conclusion, rAd­IL­2 may promote tumor­associated effector and regulatory T cell expansion and may be a potential therapeutic agent for clinical immunotherapy application in the treatment of cancer.

[Hypoxia-inducible factor-1α and CD133 predicts pathological complete response and survival for locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy].

Objective: To investigate the expression of hypoxia-inducible factor 1α (HIF-1α) and CD133 in predicting pathologic remission and survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods: One hundred and fourteen patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and immunohistochemistry methods were used to detect the mRNA and protein expression of HIF-1α and CD133 before and after chemoradiotherapy. Spearman rank correlation was used to analyze the correlation between HIF-1α and CD133 mRNA expression. Univariate and logistic multivariate analyses were used to determine the factors related to pathological complete response (pCR). Logistic regression analysis and Cox's proportional hazard model were used to determine factors related to overall survival and recurrence-free survival. Results: The expression of HIF-1α and CD133 mRNA was correlated with pT, ypTNM, pCR, recurrence and metastasis of rectal cancer, while not correlated with sex, age and BMI of patients. HIF-1α mRNA expression was positively correlated with CD133 mRNA expression ( α=0.579, P=0.000). Immunohistochemistry analysis showed that residual cancer cells strongly expressing HIF-1α also expressed CD133 strongly. Univariate analysis showed that HIF-1α mRNA and CD133 mRNA were significantly correlated with pCR ( P=0.001, P=0.022, respectively). Multivariate analysis showed that HIF-1α and CD133 mRNA expression were independent prognostic factors of pCR ( P=0.012, P=0.047, respectively). Cox regression analysis showed that the expression of HIF-1α mRNA and CD133 mRNA were independent predictors of recurrence-free survival and overall survival ( P=0.025, P=0.033, respectively). Conclusion: The study indicates that HIF-1α and CD133 can predict pathological complete remission and survival of patients with locally advanced rectal cancer.

Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway.

The antidiabetic drug metformin has been shown to possess antitumor functions in many types of cancers. Although studies have revealed its beneficial effects on the prognosis of hepatocellular carcinoma (HCC), the detailed molecular mechanism underlying this event remains largely unknown. In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells. We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC.