Up-regulation of circular RNA hsa_circ_01844 induces apoptosis and suppresses proliferation and migration of glioblastoma cells.

BACKGROUND: Previous studies have demonstrated that various circular RNAs are involved in the malignant proliferation of cancers, such as liver cancer, lung cancer, breast cancer, and others. The potential role of circular RNAs in glioblastoma, however, is still uncertain. In this study, we aimed to study the potential role of hsa_circ_01844 in glioblastoma. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) method, hsa_circ_01844 expression was measured in five glioblastoma samples and five normal brain samples. To evaluate the potential function of hsa_circ_01844 in glioblastoma, hsa_circ_01844 was overexpressed in glioblastoma cell lines (U251 and U87 cells). Using these two cell lines, in vitro experiments including the flow cytometry assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Transwell assay, and cell apoptosis assay were performed to investigate the role of hsa_circ_01844 in glioblastoma. Student t test and one-way analysis of variance were used for statistical analysis. RESULTS: The expression of circular RNA hsa_circ_01844 was lower in glioblastoma tissues when compared with the normal brain tissues by RT-PCR method (0.034 ±â€Š0.036 vs. 1.630 ±â€Š0.891, P < 0.001). Using two glioblastoma cell lines, we found that overexpression of hsa_circ_01844 in glioblastoma cells suppressed their proliferation, colony formation, migration, and increased the apoptotic rate compared with empty vector group and blank control group (all P < 0.05). CONCLUSION: Hsa_circ_01844 shows decreased expression in glioblastoma and its overexpression induces apoptosis and inhibits proliferation, migration, and invasion of glioblastoma cells.

Parenchymal-sparing versus extended hepatectomy for colorectal liver metastases: A systematic review and meta-analysis.

AIMS: To assess the safety and efficacy of parenchymal-sparing hepatectomy (PSH) as a treatment of colorectal liver metastases (CLM). METHODS: A comprehensive medical literature search was performed. Perioperative and long-term survival outcomes were pooled. Subgroup analysis and meta-regression analysis were performed to identify potential sources of heterogeneity. RESULTS: A total of 18 studies comprising 7081 CLM patients were eligible for this study. The PSH was performed on 3974 (56.1%) patients. We found that the OS (overall survival; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.94-1.08) and RFS (recurrence-free survival; HR = 1.00, 95% CI: 0.94-1.07) were comparable between non-PSH and PSH group. The perioperative outcomes were better in PSH than in non-PSH group. Non-PSH group was significantly associated with longer operative time (standard mean difference [SMD] = 1.17, 95% CI: 0.33-2.00), increased estimated blood loss (SMD = 1.36, 95% CI: 0.64-2.07), higher intraoperative transfusion rate (risk ratio [RR] = 2.27, 95% CI: 1.60-3.23), and more postoperative complications (RR = 1.39, 95% CI: 1.16-1.66). Meta-regression analyses revealed that no variable influenced the association between surgical types and the survival outcomes. CONCLUSIONS: This study shows that PSH is associated with better perioperative outcomes without compromising oncological outcomes. Given the increasing incidence of hepatic parenchyma, the PSH treatment offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. It should be considered as an effective surgical approach for CLM.

Feasibility of using marginal liver grafts in living donor liver transplantation.

Liver transplantation (LT) is one of the most effective treatments for end-stage liver disease caused by related risk factors when liver resection is contraindicated. Additionally, despite the decrease in the prevalence of hepatitis B virus (HBV) over the past two decades, the absolute number of HBsAg-positive people has increased, leading to an increase in HBV-related liver cirrhosis and hepatocellular carcinoma. Consequently, a large demand exists for LT. While the wait time for patients on the donor list is, to some degree, shorter due to the development of living donor liver transplantation (LDLT), there is still a shortage of liver grafts. Furthermore, recipients often suffer from emergent conditions, such as liver dysfunction or even hepatic encephalopathy, which can lead to a limited choice in grafts. To expand the pool of available liver grafts, one option is the use of organs that were previously considered "unusable" by many, which are often labeled "marginal" organs. Many previous studies have reported on the possibilities of using marginal grafts in orthotopic LT; however, there is still a lack of discussion on this topic, especially regarding the feasibility of using marginal grafts in LDLT. Therefore, the present review aimed to summarize the feasibility of using marginal liver grafts for LDLT and discuss the possibility of expanding the application of these grafts.

The choose of different surgical therapies of hepatic alveolar echinococcosis: A single-center retrospective case-control study.

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.

Cost-effectiveness analysis of transcatheter arterial chemoembolization with or without sorafenib for the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) and TACE in combination with sorafenib (TACE-sorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model. METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib. Transition probabilities and utilities were obtained from systematic literature reviews, and costs were obtained from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated. Sensitive analysis was performed by varying potentially modifiable parameters of the model. RESULTS: The base-case analysis showed that TACE cost $26 951 and yielded survival of 0.71 QALYs, and TACE-sorafenib cost $44 542 and yielded survival of 1.02 QALYs in the entire treatment. The ICER of TACE-sorafenib versus TACE was $56 745 per QALY gained, which was above threshold for cost-effectiveness in China. Sensitivity analysis revealed that the major driver of ICER was the cost post TACE-sorafenib therapy with stable state. CONCLUSION: TACE is a more cost-effective strategy than TACE-sorafenib for the treatment of unresectable HCC.

Two-stage hepatectomy for multiple giant alveolar echinococcosis.

Alveolar echinococcosis is a chronically progressive and potentially fatal disease. Patients with multiple giant alveolar echinococcosis have a poor prognosis when radical resection cannot be achieved, but curative resection can be limited by low future remnant liver volumes. In these cases, 2-stage liver resection may be a better choice: after a first-stage hepatectomy with partial resection, liver regeneration is allowed in the residual liver before proceeding to the second-stage hepatectomy. In this study, we therefore retrospectively reviewed and evaluated the safety and feasibility of two-stage hepatectomy in patients with multiple giant alveolar echinococcosis.We reviewed the data for all patients who underwent 2-stage hepatectomy for multiple giant alveolar echinococcosis between August 2013 and December 2015 at either the West China Hospital of Sichuan University or the Hospital of Ganzi Tibetan Autonomous Prefecture.We identified 7 patients in whom 2-stage hepatectomy was completed. During the first-stage hepatectomy, 4 patients underwent right-sided hepatectomy and the other 3 underwent left-sided hepatectomy. The second-stage hepatectomies were successfully performed 3 months after the first-stage procedures. All patients had follow-up durations of >1 year; there were no cases of operation-related mortality, and no patients experienced disease recurrence.Two-stage hepatectomy is safe and feasible for patients with multiple giant alveolar echinococcosis.

Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy.

BACKGROUND: Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with recurrent HCC who receive a second hepatectomy is unknown. METHODS: We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. RESULTS: The median overall survival was comparable between the first and second hepatectomy groups, 34 (3-84) mo versus 27 (3-57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive-positive or negative-positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. CONCLUSIONS: A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy.

Second Hepatectomy Improves Survival in Patients With Microvascular Invasive Hepatocellular Carcinoma Meeting the Milan Criteria.

Microvascular invasion (MVI) is a strong risk factor for patients with hepatocellular carcinoma (HCC) meeting the Milan criteria and who have received curative hepatectomy. The relevance of a second hepatectomy in patients with MVI-positive recurrent HCC remains controversial. We had 329 cases of HCC hepatectomy meeting the Milan criteria and compared data on patient demographics, liver function, and tumor pathology between MVI-positive and MVI-negative group. We analyzed potential risk factors of overall survival (OS) and disease-free survival (DFS). Furthermore, newly developed pathological features following the second hepatectomy were also analyzed.The median OS and DFS were significantly superior in the MVI-negative group than in the MVI-positive group, 61 (10-81) versus 49 (11-82) months (P < 0.01) and 41 (7-75) versus 13 (3-69) months (P <  0.01), respectively. The presence of MVI and a total tumor diameter >3 cm were independent risk factors associated with both OS and DFS. Overall survival was significantly improved by a second hepatectomy in the MVI-positive group compared with the original MVI-positive group, 60 (26-82) versus 49 (11-82) months, respectively. This was now comparable to the MVI-negative group, 60 (26-82) versus 61 (10-81) months (P = 0.72). A second hepatectomy was consistently associated with better survival in the MVI-negative group as compared to the MVI-positive group. A second hepatectomy improves survival in patients with MVI HCC meeting the Milan criteria. The biology of MVI may change following a second hepatectomy. The absence of MVI is a good prognostic sign for patients undergoing second hepatectomy.

Ultrasonic integrated backscatter in assessing liver steatosis before and after liver transplantation.

BACKGROUND: Liver steatosis affects 20%-30% of adults. Because of the increasing gap between graft supplies and demands, livers with steatosis are frequently used in liver transplantation. But severely steatotic liver grafts are associated with a high risk of intraoperative and postoperative complications. Accurate assessment of fat content of donor livers and monitoring of the extent of steatosis in recipients are required for liver transplantation. The present study aimed to determine the correlation between liver echogenicity and fat content, and to evaluate the use of an ultrasonic integrated backscatter system (IBS) in the assessment of changes in fat content after liver transplantation. METHODS: Seventy-nine consecutive patients receiving liver grafts from living donors were evaluated in our center. Of these recipients, 67 survived for more than two years and were included in this study. Each liver graft was evaluated with IBS and ultrasound before operation and the fat content was estimated. The fat content of the grafts in the recipients was again assessed with ultrasound at 18 months after surgery. RESULTS: A correlation was detected between each graft's IBS value and its fat content (P=0.001). The IBS value in fatty grafts with various degrees of steatosis was significantly decreased in 3 (P=0.02), 12, 15 and 18 (P=0.001) months after orthotopic liver transplantation. The IBS value returned to normal in all patients in 18 months after liver transplantation. CONCLUSIONS: Decreased fat content in steatotic grafts can be observed in all recipients. Ultrasonic IBS is useful in determining the steatotic degree of grafts in donors as well as in monitoring the grafts after liver transplantation.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients.

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection. METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence, and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at 1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase (before 2 years; n=164) and late phase (after 2 years; n=83). Cox's multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status (P=0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1 of the 2 early recurrence risk factors (multiplicity of tumors ≥ 2 and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6, respectively). CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

Tissue engineered esophagus scaffold constructed with porcine small intestinal submucosa and synthetic polymers.

Acellular porcine small intestinal submucosa (SIS) has been successfully used for reconstructing esophagus with half circumferential defects. However, repairing full circumferential esophageal defects with SIS has been restricted due to the latter's poor mechanical properties. In the present study, synthetic polyesters biomaterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(lactide-co-glycolide) (PLGA) have been used to improve the mechanical properties of SIS. Feasibility of SIS/PHBHHx-PLGA composite material scaffold for esophageal tissue engineering has been assessed through a series of testing. The appropriate mixing ratio of PHBHHx and PLGA polymers has been determined as 5:5 by mechanical testing and in vitro degradation experiment. The morphology of constructed membranous and tubular scaffolds was also characterized. As confirmed by enzyme-linked immunosorbent assay, the contents of VEGF and TGF-ß have respectively reached 657 ± 18 ng mL(-1) and 130 ± 4 pg mL(-1) within the SIS/PHBHHx-PLGA specimens. Biocompatibility of the SIS/PHBHHx-PLGA specimens with rat bone marrow mesenchymal stem cells (MSCs) was also evaluated by scanning electron microscopy and a live-dead cell viability assay. Actin filaments of MSCs on the composite materials were labeled. Biological safety of the extract from SIS/PHBHHx-PLGA specimens, measured as hemolysis rate, was all lower than 5%. Compared with SIS and SIS/PHBHHx-PLGA specimens, inflammatory reaction provoked by the PHBHHx-PLGA specimens in rats was however more severe. Our results have suggested that SIS/PHBHHx-PLGA composite material can offer a new approach for esophageal tissue engineering.

An accurate predictor of liver failure and death after hepatectomy: a single institution's experience with 478 consecutive cases.

AIM: To establish a reliable definition of postoperative liver failure (PLF) and allow the prediction of outcomes after hepatectomy. METHODS: The clinical data of 478 consecutive patients who underwent hepatectomy were retrospectively analyzed. The examined prognostic factors included the ratio of total bilirubin (TBIL) on postoperative day (POD) X to TBIL on POD 1 (TBIL-r1) and the ratio of the international normalized ratio (INR) on POD X to the INR on POD 1 (INR-r1) for PODs 3, 5 and 7. Student's t test, the χ(2) test, logistic regression, survival analysis and receiver operating curve analysis were used to evaluate risk factors and establish the definition of postoperative liver failure (PLF). RESULTS: Fourteen patients (2.9%) died of liver failure within 3 mo of surgery. Significant differences were found between patients who died of liver failure and the remaining patients in terms of TBIL-r1 and INR-r1 on PODs 3, 5 and 7. The combination of TBIL-r1 and INR-r1 on POD 5 showed strong predictive power for liver failure-related death (sensitivity 92.9% and specificity 90.1%). The hepatic damage score (HDs), which was derived from TBIL-r1 and INR-r1, was used to define the degree of metabolic functional impairment after resection as mild (HDs = 0), reversible hepatic "dysfunction" (HDs = 1) or fatal hepatic failure (HDs = 2). Furthermore, the indocyanine green retention rate at 15 min (ICG-R15) and the number of resected segments (RSs) were identified as independent predictors of the HDs. A linear relationship was found between ICG-R15 and RSs in the HDs = 2 group. The regression equation was: RSs = -0.168 × ICG-R15 + 5.625 (r (2) = 0.613, F = 14.257, P = 0.004). CONCLUSION: PLF can be defined by the HDs, which accurately predicts liver failure-related death after liver resection. Furthermore, the ICG-R15 and RSs can be used as selection criteria for hepatectomy.

Intracisternal administration of SB203580, a p38 mitogen-activated protein kinase inhibitor, attenuates cerebral vasospasm via inhibition of tumor-necrosis factor-α.

Tumor-necrosis factor-α (TNF-α) is critical to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Hence, therapeutic strategies targeting TNF-α can attenuate cerebral vasospasm. This study investigated the effects of SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on TNF-α concentration in the cerebral arteries and the cerebrospinal fluid (CSF) after SAH and on subsequent cerebral vasospasm. Twenty-three rabbits were divided into four groups: (i) control (without SAH), (ii) SAH (SAH only), (iii) dimethylsulfoxide (DMSO, vehicle), and (iv) SB203580. The severity of vasospasm and the immunoreactivities of TNF-α and phosphorylated p38 MAPK in the brain vessels were determined in all animals, and the concentrations of TNF-α in the CSF were also assessed. Severe vasospasm was observed in the rabbits from the SAH and DMSO groups. SB203580 reversed vasospasm after SAH. Lower immunoreactivities of TNF-α and phosphorylated p38 MAPK were found in the basilar artery in the SB203580 group than in the DMSO group. The concentration of TNF-α in the CSF increased after SAH, but treatment with SB203080 after SAH suppressed this increase. Our data show that SB203580 reversed cerebral vasospasm by inhibiting the phosphorylation of p38 MAPK in the basilar artery and by suppressing the increase in TNF-α in the basilar artery and CSF after SAH. SB203580 could therefore potentially be used for the treatment of cerebral vasospasm after SAH.

[Expression of vigilin in cell lines and human hepatocellular carcinoma].

OBJECTIVE: To explore the expression status of Vigilin (high density lipoprotein binding protein) in various cell lines and human hepatocellular carcinoma (HCC) tissues. METHODS: The expression of Vigilin was measured semiquantitatively with western blot in hepatic cancer, cervical cancer and normal cell lines. The samples of 59 hepatocellular carcinoma tissues, 59 adjacent liver tissues and 33 distant non-tumor liver tissues were collected, Vigilin expression in the above samples was detected by immunohistochemistry. RESULTS: Vigilin expressed in all cell lines, but no expression was found in peripheral blood lymphocytes. The expression levels of Vigilin in tumor cell lines were higher than those in normal cell lines (P < 0.05). Most of the hepatic cells expressed Vigilin, but the expression levels were different (tumor tissues: 0.2226 +/- 0.054, adjacent tissues: 0.2060 +/- 0.056, distant tissues: 0.1820 +/- 0.038, P < 0.001). Highly expression of Vigilin was observed in 54% of tumor tissues, 35% adjacement tissues, and 6% of distant non-tumor tissues, respectively. CONCLUSION: Vigilin may have relationship with HCC progression and proliferation.

Potential contribution of nuclear factor-kappaB to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

Nuclear factor-kappaB (NF-kappaB) plays a key role in inflammation, which is involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study, we assessed the potential role of NF-kappaB in regulation of cerebral vasospasm. Nuclear factor-kappaB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 micromol/L), an inhibitor of NF-kappaB. Forty-two rabbits were divided into three groups: control, SAH, and PDTC groups (n=14 for each group). The caliber of the basilar artery was evaluated. Nuclear factor-kappaB DNA-binding activity and the gene expression levels of cytokines and adhesion molecules in the basilar artery were measured. Immunohistochemical study was performed to assess the expression and localization of tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-kappaB DNA-binding activity was significantly increased by treatment with hemolysate in cultured VSCMs, but this increase was suppressed by pretreatment with PDTC. Severe vasospasm was observed in the SAH group, which was attenuated in the PDTC group. Subarachnoid hemorrhage could induce increases of NF-kappaB DNA-binding activity and the gene expression levels of TNF-alpha, interleukin (IL)-1 beta, ICAM-1, and vascular cell adhesion molecule (VCAM)-1, which were reduced in the PDTC group. Immunohistochemical study demonstrated that the expression levels of TNF-alpha, ICAM-1, and MPO were all increased in the SAH group, but these increases were attenuated in the PDTC group. Our results suggest that NF-kappaB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.