Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

[Application of a modified paramedian lower lip-submandibular approach in maxillary (subtotal) total resection].

OBJECTIVE: To investigate the clinical efficacy of a modified paramedian lower lip-submandibular approach for maxillary (subtotal) total resection. METHODS: Eleven patients of maxillary tumors underwent maxillary (subtotal) total resection through the modified paramedian lower lip-submandibular approach. Clinical follow-up visits were conducted to evaluate appearance restoration, facial nerve functional status, parotid gland functional status, and orbital region complication. RESULTS: During the follow-up period of 6-36 months, the appearance of all 11 patients recovered well. All cases presented hidden scars. No facial nerve and parotid duct injury, lower eyelid edema, lower eyelid ectropion, or epiphora in all cases was observed. CONCLUSIONS: Applying modified paramedian lower lip-submandibular approach to maxillary (subtotal) total resection effectively reduces incidence of orbital region complications including lower eyelid edema, lower eyelid ectropion, and epiphora, which often occur to traditional approach. The modified approach produces more subtle scars than other methods and should be applied to treatment of maxillary (subtotal) total resection.

microRNA-4270-5p inhibits cancer cell proliferation and metastasis in hepatocellular carcinoma by targeting SATB2.

Hepatocellular carcinoma (HCC) remains a lethal cancer type for both males and females. MicroRNAs (miRNAs) contribute to the initiation, development and metastasis of cancer. Although several miRNAs have been identified as drivers or suppressors of HCC, the molecular mechanisms of many miRNAs have not been investigated. Currently, we discovered that miR-4270-5p was a significantly downregulated miRNA in HCC. We revealed that miR-4270-5p overexpression inhibited cell proliferation and invasion of HCC cells. The data manifested that miR-4270-5p directly targeted SATB2, a key regulator of epithelial mesenchymal transition (EMT), in HCC cells and reversed the EMT process. The rescue experiments suggested that SATB2 overexpression reversed the biological function of miR-4270-5p in HCC cells. Clinical data indicated that SATB2 expression was negatively correlated with miR-4270-5p levels in HCC patients. Our findings provided potential targets for prognosis and treatment of patients with HCC.

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: Circulating microRNA-122 (miR-122) has been recognized as a marker of hepatocellular carcinoma (HCC). The current meta-analysis was performed to quantitatively evaluate the diagnostic performance of circulating miR-122 for HCC. METHODS: Related studies that evaluated the diagnostic performance of circulating miR-122 determined from pathophysiological examination for HCC were obtained by systematic searches of the PubMed and Embase databases. A randomized fixed effects model was applied according to the heterogeneity among studies. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) were calculated to evaluate the diagnostic accuracy. Publication bias was detected by Deeks' funnel plot asymmetry test. RESULTS: Thirteen studies providing data for 920 HCC patients and 1217 controls were included in the meta-analysis. The pooled sensitivities, specificities, and AUCs of serum miR-122 were 0.76, 0.75, and 0.82, respectively, for discriminating HCC patients from overall controls; 0.85, 0.83, and 0.91, respectively, for discriminating HCC patients from healthy controls; 0.79, 0.82, and 0.87, respectively, for discriminating HCC from HBV or HCV infection; and 0.65, 0.75, and 0.74, respectively, for discriminating HCC from liver cirrhosis or dysplastic nodule formation. No significant publication bias was detected. CONCLUSIONS: Serum miR-122 confers moderate efficacy for discriminating HCC patients from healthy controls or patients with HBV or HCV infection, but not for discriminating HCC patients from those with liver cirrhosis or dysplastic nodule formation.

RETRACTED: Neferine inhibits proliferation, migration and invasion of U251 glioma cells by down-regulation of miR-10b.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Panels from Figures 2A, 2C and 5D appear similar to the "Migrated cell" panels from Figure 2E and the panels "Migrated cell/mimic NC + pEX" and "Invasive cell/miR-122 mimic + pEX" from Figure 7D of the article that was previously published by Daliang Kong and Yang Wang in the Journal of Cellular Biochemistry 119 (2018) 1050-1061 https://doi.org/10.1002/jcb.26273. Also, panels from Figures 2A and 2C appear similar to the panels "sh-FOXM1" from Figure 5D and "sh-HULC" from Figure 2E of the article that was published by Qiu Hong Rui, Jian Bo Ma, Yu Feng Liao, Jin Hua Dai and Zhen Yu Cai in the Brazilian Journal of Medical and Biological Research 52(4) (2019) e7728 https://doi.org/10.1590/1414-431X20197728. Although this article was published earlier than the article from the Brazilian Journal of Medical and Biological Research, the Editor decided to retract this article given concerns about the reliability of the data.

The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition of Colorectal Adenocarcinoma.

BACKGROUND/AIMS: Since the combined actions of lncRNAs and miRNAs have been considered to be involved in the occurrence and development of various neoplasms, the main purpose of this study was to discover whether and how lncRNA H19 and miR-194 influenced the epithelial-mesenchymal transition (EMT) process of colorectal adenocarcinoma (CRA). METHODS: Totally 214 pairs of CRA and adjacent normal tissues were collected, and 5 human CRA cell lines (i.e. HCT116, HT-29, RKO SW280 and Lovo) were purchased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was adopted to quantify the H19 and miR-194-5p expressions in cells and tissues. The expressions of FoxM1, E-cadherin, vimentin, N-cadherin were determined using western blot. On the side, si-H19, si-NC, miR-194-5p mimic, miR-194-5p inhibitor and negative control (NC) were transfected into CRA cell lines. Meanwhile, the invasive, migratory and proliferative conditions of the cells were assessed through transwell, wound healing and colony-forming experiments, with final verification of the relationship between H19 and miR-194-5p employing dual-luciferase reporter gene assay. RESULTS: Highly-expressed H19, lowly-expressed miR-194-5p, low-grade differentiation and lymph node metastasis appeared as the independent predictors of unfavorable prognosis in CRA patients' (all P< 0.05). It indicated that FoxM1 expression displayed positive correlations with H19 expression, yet negative associations with miR-194-5p expression within CRA tissues (P< 0.05). In addition, transfection of H19-siRNA and miR-145-5p mimic triggered a conspicuous increase in E-cadherin expression, as well as an evidently down-regulation in vimentin and N-cadherin expressions within HT29 and RKO cells (P< 0.05). On the other hand, the invasive and migratory capacities of CRA cells were significantly hindered (P< 0.05). Moreover, the luciferase reporter gene assay confirmed that H19 modified miR-194-5p expression through directly targeting at it (P< 0.05). Ultimately, FoxM1 could reverse the role of miR-194-5p in inhibiting invasion, migration and EMT of CRA cells (P< 0.05). CONCLUSION: LncRNA H19/miR-194/FoxM1 axis could serve as a profound target for the diagnosis and treatment of CRA.

Copper chelation by trientine dihydrochloride inhibits liver RFA-induced inflammatory responses in vivo.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Radiofrequency ablation (RFA) is currently performed widely for managing HCC. RFA treatment causes damage around the ablation. Trientine dihydrochloride has been used to reduce the copper in liver. METHODS: The rats were treated with trientine dihydrochloride for 5 days before liver RFA. Liver function, copper concentration, inflammation biomarkers and MDA, SOD were analyzed after RFA treatment for 2 h, 2 and 5 days. RESULTS: The results indicated that trientine dihydrochloride reduced the copper in plasma and liver tissue significantly. And trientine dihydrochloride significantly inhibited RFA-induced inflammatory gene expression in liver. Similar inhibitory effects of trientine dihydrochloride were observed on ROS-induced malondialdehyde production in liver tissues. CONCLUSION: These results suggest that pre-treatment with the selective copper chelator trientine dihydrochloride can inhibit inflammatory response effectively during and after liver RFA in vivo. Chelation of copper to a lower level before liver RFA may be a novel strategy to prevent or ameliorate inflammatory responses in liver induced by RFA and to protect the parenchyma tissues in liver during and after RFA in HCC patients.

TrkB activation by 7, 8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer's disease.

We recently demonstrated that activation of tyrosine receptor kinase B (TrkB) by 7, 8-dihydroxyflavone (7, 8-DHF), the selective TrkB agonist, increased surface alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPARs) AMPA receptor subunit GluR1 (GluA1) subunit expression at the synapses of Fragile X Syndrome mutant mice. This present study investigated the effects of 7, 8-DHF on both memory function and synapse structure in relation to the synapse protein level of AMPARs in the Tg2576 Alzheimer's disease (AD) mouse model. The study found that chronic oral administration of 7, 8-DHF significantly improved spatial memory and minimized dendrite loss in the hippocampus of Tg2576 mice. A key feature of 7, 8-DHF action was the increased expression of both GluA1 and GluA2 at synapses. Interestingly, 7, 8-DHF had no effect on the attenuation of amyloid precursor protein or Aß exhibiting in the Tg2576 AD brains, yet it activated the phosphorylation of TrkB receptors and its downstream signals including CaMKII, Akt, Erk1/2, and cAMP-response element-binding protein. Importantly, cyclotraxin B (a TrkB inhibitor), U0126 (a Ras-ERK pathway inhibitor), Wortmannin (an Akt phosphorylation inhibitor), and KN-93 (a CaMKII inhibitor) counteracted the enhanced expression and phosphorylation of AMPAR subunits induced by 7, 8-DHF. Collectively, our results demonstrated that 7, 8-DHF acted on TrkB and resolved learning and memory impairments in the absence of reduced amyloid in amyloid precursor protein transgenic mice partially through improved synaptic structure and enhanced synaptic AMPARs. The findings suggest that the application of 7, 8-DHF may be a promising new approach to improve cognitive abilities in AD. We provided extensive data demonstrating that 7, 8-dihydroflavone, the TrkB agonist, improved Tg2576 mice spatial memory. This improvement is correlated with a reversion to normal values of GluA1 and GluA2 AMPA receptor subunits and dendritic spines in CA1. This work suggests that 7, 8-DHF is a suitable drug to potentiate in vivo Tropomyosin receptor kinase B (TrkB) signaling in the Alzheimer's disease mice model.

Influences of laparoscopic-assisted gastrectomy and open gastrectomy on serum interleukin-6 levels in patients with gastric cancer among Asian populations: a systematic review.

BACKGROUND: To compare the effects of laparoscopic-assisted gastrectomy (LAG) and open gastrectomy (OG) on serum interleukin-6 (IL-6) levels in gastric cancer (GC) patients from Asia. METHODS: The following scientific literature databases were searched for relevant clinical studies: PubMed, EBSCO, Ovid, Wiley, Web of Science, Cochrane library, EMBASE, WANFANG and VIP databases. The studies retrieved from database searches were screened based on stringent inclusion and exclusion criteria to select high quality cohort studies for the present meta-analysis. The data extracted from final selected studies were analyzed using STATA 12.0 software. RESULTS: A total of 54 studies were initially retrieved from database searches, and 11 clinical cohort studies were eventually enrolled in this meta-analysis. The 11 selected studies contained a combined total of 767 GC patients (427 patients in LAG group and 340 patients in OG group). Meta-analysis results demonstrated that postoperative serum IL-6 levels in GC patients in LAG group was significantly lower than the OG group (SMD = -2.16, 95% CI = -3.19 ~ -1.14, P < 0.001). The difference in serum IL-6 levels between the preoperative and postoperative GC patients was significantly lower in the LAG group compared to the difference found in the OG group (SMD = -3.44, 95% CI = -4.87 ~ -2.01, P < 0.001). Subgroup analysis based on country showed that, in both Chinese and Japanese GC patients, the postoperative increase in serum IL-6 levels in LAG group were significantly lower than the increase observed in the OG group (all P < 0.05). In Korean GC patients, the postoperative increase in serum IL-6 levels was not significantly different between the LAG group and OG group (all P > 0.05). CONCLUSION: Our results provide strong evidence that LAG is associated with significantly lower serum IL-6 levels, compared to OG. Thus, LAG carries markedly lower risk of adverse inflammatory reactions in GC patients among Asian population.

Comparison between better and poorly differentiated locally advanced gastric cancer in preoperative chemotherapy: a retrospective, comparative study at a single tertiary care institute.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality in China, and the long-term survival for locally advanced gastric cancer is very poor. Simple surgery cannot yield an ideal result because of the high recurrence rate after tumor resection. Preoperative chemotherapy could help to reduce tumor volume, improve the R0 resection rate (no residual tumor after surgery), and decrease the risk of local tumor recurrence. The aim of this study was to evaluate the influence of pathological differentiation in the effect of preoperative chemotherapy for patients with locally advanced gastric cancer. METHODS: Patients with locally advanced gastric cancer (n = 32) received preoperative chemotherapy under the XELOX (capecitabine plus oxaliplatin) regimen. According to pathological examination, patients' tumors were classified into better (well and moderate) and poorly differentiated (lower differentiated and undifferentiated) groups, and the clinical response rate, type of gastrectomy, and negative tumor residual rate were compared between the two groups of patients. Morphological changes and toxic reactions were monitored after chemotherapy. RESULTS: The results showed that the clinical response rate in the better differentiated group was significantly higher than that in the poorly differentiated group (100% versus 25%, P = 0.000). The partial gastrectomy rate in the better differentiated group was significantly higher than that in the poorly differentiated group (87.5% versus 25% P = 0.000). A significant shrinking of tumor and necrosis of tumor tissues caused by chemotherapy could be observed. CONCLUSIONS: In conclusion, the better differentiated group with locally advanced gastric cancer is suitable for preoperative chemotherapy under the XELOX regimen, and as a result of effective preoperative chemotherapy, much more gastric tissue can be preserved for the better differentiated group.

[Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil].

Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.

[Predictive value of tumor vessel density from enhanced spiral CT scan for lymph node and distant metastasis of colorectal cancer].

OBJECTIVE: To test whether the tumor vessel density (TVD) from the enhanced spiral CT can preoperatively predict nodal status and distant metastasis of colorectal cancer. METHODS: Forty cases of colorectal cancer patients who received surgical treatment were included in this study. The three dimensional tumor vessels were reconstructed by an enhanced CT 64-slice spiral CT and its AW4.4 image processing platform. The TVD was measured by the 1000 high-resolution color graphics pathological analysis system. The TVD level was compared between different tumor size, classification, and TNM stage. The postoperative pathological staging was taken as golden standard. RESULTS: The sensitivity, specificity and accuracy for direct prediction of lymph node metastasis by the enhanced CT 64-slice spiral CT was 74.1%(20/27), 53.8%(7/13) and 67.5%(27/40) respectively. The TVD from the reconstructed three dimensional tumor vessels in the group with lymph node metastasis was significantly higher than that without metastasis(0.070±0.046 vs. 0.037±0.013, P<0.05). The TVD in the distant metastasis group was significantly higher than that without distant metastasis (0.130±0.032 vs. 0.049±0.030, P<0.01). No difference of TVD was found between different tumor size, invasion depth, and differentiation type. CONCLUSION: TVD level from the reconstructed three dimensional tumor vessels can indicate lymph node and distant metastasis of colorectal cancer.

Laparoscopic versus open resection of gastric gastrointestinal stromal tumors.

The aims of this study were to explore whether laparoscopic surgical resections of gastric gastrointestinal stromal tumors (GISTs) would produce better perioperative and similar oncologic outcomes compared with open surgical resection in Chinese patients. Thirty-six gastric GISTs cases were divided into a minimally invasive laparoscopic group and open resection group, depending on the surgical approach that was used. The general preoperative information, operative time, incision length, intraoperative blood loss, postoperative time to first flatulence, postoperative complications, postoperative hospital stay, total hospitalization costs, and such follow-up data as recurrence, metastasis, and mortality rates were compared between two groups. Among the 36 gastric GISTs, 15 received laparoscopic surgical treatment (laparoscopy group, n=15), and 21 received routine open resection treatment (open resection group, n=21). The laparoscopy group and the open resection group showed statistically significant differences (P<0.05) in incision length (7.8±2.3 vs. 16.9±3.8 cm), postoperative time to first flatulence (3.8±1.3 vs. 5.1±2.1 d), postoperative hospitalization time (7.6±2.5 vs. 11.3±3.7 d), and total cost of hospitalization (RMB 28,239±5,521 vs. RMB 23,761±5,362). There were no statistically significant differences (P>0.05) between the laparoscopy group and the open resection group in operative time (147.8±59.3 vs. 139.2±62.1 min) and intraoperative blood loss (149.8±98.9 vs. 154.2±99.3 mL). Both groups had no postoperative complications, no recurrence and metastasis, and no postoperative mortality. There were no statistically significant differences between the two groups in postoperative complications, postoperative recurrence and metastasis, and postoperative mortality. In conclusion, compared with open resection, the laparoscopic resection of gastric GISTs offers the advantages of less trauma, faster recovery, and shorter hospital stay.

Colonic polyps: application value of computer-aided detection in computed tomographic colonography.

BACKGROUND: Colonic polyps are frequently encountered in clinics. Computed tomographic colonography (CTC), as a painless and quick detection, has high values in clinics. In this study, we evaluated the application value of computer-aided detection (CAD) in CTC detection of colonic polyps in the Chinese population. METHODS: CTC was performed with a GE 64-row multidetector computed tomography (MDCT) scanner. Data of 50 CTC patients (39 patients positive for at least one polyp of ≥ 0.5 cm in size and the other 11 patients negative by endoscopic detection) were retrospectively reviewed first without computer-aided detection (CAD) and then with CAD by four radiologists (two were experienced and another two inexperienced) blinded to colonoscopy findings. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of detected colonic polyps, as well as the areas under the ROC curves (Az value) with and without CAD were calculated. RESULTS: CAD increased the overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the colonic polyps detected by experienced and inexperienced readers. The sensitivity in detecting small polyps (5 - 9 mm) with CAD in experienced and inexperienced readers increased from 82% and 44% to 93% and 82%, respectively (P > 0.05 and P < 0.001). With the use of CAD, the overall false positive rate and false negative rate for the detection of polyps by experienced and inexperienced readers decreased in different degrees. Among 13 sessile polyps not detected by CAD, two were ≥ 1.0 cm, eleven were 5 - 9 mm in diameter, and nine were flat-shaped lesions. CONCLUSIONS: The application of CAD in combination with CTC can increase the ability to detect colonic polyps, particularly for inexperienced readers. However, CAD is of limited value for the detection of flat polyps.

[Expression of Aurora-B in human glioma tissue and its significance].

OBJECTIVE: To study the expression of Aurora-B in human glioma tissue and its significance. METHODS: The total RNA was extracted from 41 human glioma tissues and 11 normal brain tissues by Trizol reagent. After reverse transcription of the total RNA into cDNAs, Aurora-B mRNA expressions in these samples were detected by quantitative real-time PCR. The protein expression in these samples was detected using immunohistochemical staining. RESULTS: Aurora-B mRNA and protein expressions were significantly increased in glioma tissues as compared with those in normal brain tissues. CONCLUSION: Aurora-B mRNA and protein show markedly higher expressions in glioma tissue, suggesting that Aurora-B may be one of the malignant biomarkers in the pathogenesis and progression of human glioma.