Potential of Ablation Therapy during Hepatocellular Carcinoma.

BACKGROUND: This study explored the potential of ablation therapy on membrane fluidity changes in diethylnitrosamine (DEN) induced hepatic cancer. METHODS: Male Wistar rats were segregated into four groups viz., normal control, DEN treated, ablation therapy treated, and DEN ablation therapy treated. We assessed the viscosities as well as fluidity parameters in isolated brush border membranes using the membrane extrinsic fluorophore pyrene. RESULTS: DEN treatment successfully induced hepatic cancer in the livers of rats and ablation therapy worked well in terms of therapy. DEN treatment resulted in a significant rise in lipid peroxidation (LPO) and significant decrease in the, reduced glutathione levels (GSH). A significant decrease was also noticed in the activities of glutathione reductase (GR), glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) following DEN treatment. On the other hand, ablation therapy treatment to DEN-treated rats resulted in a significant decrease in the LPO levels but caused a significant rise in the levels of GSH. Moreover, the activities of GR, GST, SOD, CAT, and GPx showed significant improvement after ablation therapy treatment. The results further demonstrated a marked decrease in membrane microviscosity following DEN treatment. On the other hand, a significant increase was noticed in both excimer/monomer ratio and fluidity parameter in DEN-treated rats. However, membrane microviscosity and the fluidity alterations were significantly restored back to near normal with ablation therapy treatment. CONCLUSIONS: The study, therefore, concluded that ablation therapy holds good therapeutic potential against DEN-induced hepatic cancer.

Modified duct-to-mucosa versus conventional pancreaticoenterostomy for pancreaticoduodenectomy: a retrospective cohort study based on propensity score matching analysis.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common neopathy after pancreatoduodenectomy (PD). An ideal pancreaticoenterostomy (PE) which can effectively reduce the incidence of CR-POPF and its potential neopathy is needed. We aimed to assess the efficacy of our modified duct-to-mucosa PE in the PD. METHOD: From January 2011 to December 2017, 233 consecutive patients with PD were retrospectively included from Shenzhen People's Hospital. After propensity score matching (PSM), there were 82 patients in both the modified duct-to-mucosa PE group (group A) and the conventional end-to-side inserting PE group (group B), respectively. The clinical course and the incidence of postoperative neopathy were compared between groups. Logistic regression method was utilized to analyze the association between PE approach and CR-POPF. RESULTS: The PE time was shorter in group A (9.3 ± 1.8 min vs. 21.5 ± 2.8 min, P < 0.001). The group A had significantly lower incidence of severe neopathy (Clavien-Dindo grade > II) [7.3% (5/82) vs. 17.1% (14/82), P = 0.028] and incidence of CR-POPF [1.2% (1/82) vs. 19.5% (12/82), P < 0.001] than the group B. Our modified duct-to-mucosa PE technique was associated with a reduced risk for CR-POPF (OR, 0.11 [95% CI, 0.02-0.57]; P = 0.009) as compared with the conventional end-to-side inserting PE. CONCLUSION: Compared with conventional end-to-side inserting PE, our modified duct-to-mucosa PE technique can effectively reduce the incidences of postoperative neopathy and CR-POPF. TRIAL REGISTRATION: Researchregistry3877 . Registered 24 March 2018. Retrospectively registered.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.

OBJECTIVE: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). METHODS: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. RESULTS: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. CONCLUSION: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Early growth response factor 1 upregulates pro-fibrotic genes through activation of TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in high-glucose treated HK-2 cells.

Tubulointerstitial fibrosis (TIF) makes a key role in diabetic kidney disease (DKD). In this study, we revealed that the expressions of Egr1 and protease-activated receptor 1 (PAR1) were increased in renal tissues of DKD rats. In vitro experiments demonstrated that both Egr1 overexpression and high glucose (HG) condition could promote the expressions of PAR1, fibronectin (FN) and collagen I (COL I). Furthermore, HG stimulation enhanced the binding capacity of Egr1 to PAR1 promoter. Both HG condition and Egr1 upregulation could increase, and thrombin inhibitor did not affect activity of TGF-ß1/Smad pathway via PAR1. Collectively, Egr1 is involved in TIF of DKD partly through activating TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in HG treated HK-2 cells.

Role of the pre- to postoperative alpha-fetoprotein ratio in the prognostic evaluation of liver cancer after radiofrequency ablation.

OBJECTIVE: This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after radiofrequency ablation (RFA) in the prognosis of patients with liver cancer. METHODS: A total of 368 patients who underwent RFA for liver cancer in Shenzhen People's Hospital from 2010 to 2020 were randomly divided into the training group and the validation group. Levels of AFP before and after RFA were recorded and their ratios were calculated. RESULTS: Using the X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training group was 37.9. Both in the training group and the validation group, the relapse-free survival and overall survival of patients with an AFP ratio <37.9 (high-risk group) were significantly shorter than those with an AFP ratio >37.9 (low-risk group) (training group, relapse-free survival, P = 0.0003; overall survival, P = 0.0186; validation group, relapse-free survival, P = 0.0490, overall survival, P = 0.0031). An AFP ratio <37.9 was an independent risk factor for recurrence and survival of liver cancer after RFA. CONCLUSION: The AFP ratio can predict the prognosis of patients with liver cancer after RFA. An AFP ratio <37.9 is an independent risk factor for tumor recurrence and survival after RFA.

Outcomes of reoperation for hepatolithiasis with 3D imaging individualized preoperative planning technique: a single-center experience.

BACKGROUND: A detailed assessment of biliary tract anatomy is necessary for the successful reoperation for hepatolithiasis. This study aimed to evaluate the feasibility of preoperative individualized surgical planning with three-dimensional (3D) imaging technique for reoperation of hepatolithiasis. METHODS: This was a retrospective matched case-control study. From January 2011 to December 2018, 56 patients receiving reoperation according to the individualized preoperative plan based on 3D imaging at our center were included (group A). Meanwhile, 54 patients receiving traditional imaging guided reoperation matched by age, gender and distribution of hepatobiliary stones to each case were selected as controls (group B). The perioperative and long-term follow-up outcomes were compared between the two groups. RESULTS: There was no significant difference in demographic characteristics between groups. Compared with group B, the group A had a significantly shorter operation time (245.7±56.2 min vs. 305.2±79.9 min, P<0.001), a significantly higher surgical plan implementation rate (SPIR, 92.9% vs. 66.7%, P=0.001) and a lower incidence-of severe complications (Clavien-Dindo grade>II, 1.8% vs. 14.8%, P=0.015). The incidences of initial residual stone (7.1% vs. 44.4%, P<0.001) and repeated cholangitis (3.6% vs. 33.3%, P<0.001) were significantly lower in group A than in group B. After postoperative choledochoscopic lithotripsy, the incidence of final residual stones was significantly lower in group A than in group B. (1.8% vs. 20.4%, P=0.002). CONCLUSIONS: The preoperative 3D imaging assisted surgical planning is feasible and safe for reoperation of hepatolithiasis which can effectively improve surgical plan implementation rate and reduce the incidence of postoperative complications as compared with conventional surgical planning.

Role of long intergenic non-protein coding RNA 01857 in hepatocellular carcinoma malignancy via the regulation of the microRNA-197-3p/anterior GRadient 2 axis.

OBJECTIVE: This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis. METHODS: LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC. RESULTS: LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC. CONCLUSION: The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.

Role of procalcitonin as a predictor in difficult laparoscopic cholecystectomy for acute cholecystitis case: A retrospective study based on the TG18 criteria.

Difficult laparoscopic cholecystectomy (DLC) is difficult to precisely predict before operation. This observational cohort study aimed to evaluate the predictive value of procalcitonin (PCT) for DLC in patients with acute cholecystitis (AC). A total of 115 patients were included in the study from January 2017 to April 2018. Multiple logistic regression and receiver-operating characteristic (ROC) were performed to evaluate the predictive value of PCT levels in DLC. Patients with DLC had significantly higher Tokyo Guidelines 2018 (TG18) grade (P = 0.002) and levels of C-reactive protein (CRP) (P = 0.007) and PCT (P < 0.001). The cut-off value of PCT for predicting DLC was 1.50 ng/ml. The sensitivity and specificity were 91.3% (95% CI 78.3-97.1) and 76.8% (95% CI 64.8-85.8), respectively. The area under ROC curve was 92.7% (95% CI 88.2-97.3, P < 0.001). Our results suggested that PCT was a good predictor for DLC in the AC patients, but further research is necessary. Monitoring of PCT trends in AC patients may be useful for preoperative risk assessment.

MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-ß/Smad pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality worldwide. Early growth response factor 1 (Egr1) plays a crucial role in cancer progression. However, its precise role in HCC has not been clear. Here, we identified the aggravating role of Egr1 in cell proliferation of HCC firstly. The expression of Egr1 was significantly increased in HCC tissues. Functionally, overexpression of Egr1 enhanced, whereas silenced Egr1 expression attenuated HCC cells proliferation in vitro. Mechanistically, up-regulated Egr1 induced cell proliferation through activating Transforming growth factor (TGF)-ß1/Smad signaling pathway concomitantly with upregulation of p-Smad2 and p-Smad3. Secondly, miR-181a-5p was down-regulated in clinical HCC specimens and its expression was inversely correlated with Egr1 expression. Functionally, overexpression of miR-181a-5p inhibited, whereas decreased expression of miR-181a-5p promoted HCC cells proliferation in vitro. Furthermore, we demonstrated that miR-181a-5p overexpression directly suppressed Egr1, resulting in a down-regulated TGF-ß1/Smad pathway. Besides, the silenced Egr1 expression could rescue the enhanced cell proliferation induced by miR-181a-5p inhibitor. Thus, we concluded that miR-181a-5p is a negative regulator of Egr1 that can suppress tumor proliferation in HCC through targeting Egr1/TGF-ß1/Smad pathway, which may be a potential therapeutic approach of HCC.

Targeted delivery of anti-miR-155 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy.

INTRODUCTION: MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics. METHODS: In this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC. RESULTS: Results showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. CONCLUSION: Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.

High glucose down-regulates microRNA-181a-5p to increase pro-fibrotic gene expression by targeting early growth response factor 1 in HK-2 cells.

Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor ß1 (TGF-ß1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells. We then found that miR-181a-5p expression was down-regulated, accompanied by the corresponding up-regulation of Egr1, TGF-ß1, fibronectin and collagen I in renal tissues of type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty rats with DN, and that the expression of miR-181a-5p was negatively correlated with the level of Egr1 in HK-2 cells treated with high glucose. Furthermore, we identified that miR-181a-5p directly suppressed Egr1 to decrease the expressions of TGF-ß1, fibronectin and collagen I in HK-2 cells through targeting the 3' untranslated region of Egr1. The functional relevance of miR-181a-5p-induced Egr1 decrease was supported by inhibition and overexpression of miR-181a-5p in HK-2 cells. Thus, we concluded that aberrant Egr1 expression, which can be suppressed by miR-181a-5p directly, plays a crucial role in the progression of renal TIF in DN. This study indicates that targeting miR-181a-5p may be a novel therapeutic approach of DN.

Medial umbilical ligament flap reinforcement of the internal ring in children with indirect inguinal hernia.

OBJECTIVES: The objective of this study was to describe use of the medial umbilical ligament (MUL) as a reinforcing flap to cover the internal ring (IR) during laparoscopic herniorrhaphy in children with indirect inguinal hernia. METHODS: Laparoscopic high ligation of the IR was performed in a cohort (A) of 110 children with 140 indirect hernias between October 2001 and December 2004. We then developed "recurrence risk criteria" to explain four recurrences (2.8%). These criteria include previous recurrence, an IR ≥1.5 cm in diameter (anterior-posterior), and older children in their teenage years (13-18 years). From January 2005 to February 2010, we carried out similar repairs in 226 consecutive children (cohort B) with 307 indirect hernias, except that we reinforced the IR with an MUL flap if one of the three recurrence risk criteria were met (n=36). Of these children, 15 had an enlarged IR, 10 had recurrences, and 11 were teenagers. RESULTS: The median patient age was 6.2 and 6.5 years in Groups A and B, respectively; there were four recurrences of 140 repairs (2.8%) in Group A, with a mean follow-up of 55 months (2-110 months). There were no recurrences in Group B including 36 MUL reinforcements with a mean follow-up of 32 months (5-74 months). CONCLUSION: Indirect hernias closed with our technique of laparoscopic high ligation of the IR will recur in 2.8% of children. Based on risk factors that we have developed, children prone to recurrence can be selected for MUL flap reinforcement of the IR, which may bring the recurrence rate close to zero.