Percutaneous CT-guided radiofrequency ablation for patients with extrahepatic oligometastases of hepatocellular carcinoma: long-term results.

BACKGROUND: The aim of this study was to evaluate the therapeutic outcome of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for extrahepatic oligometastases of hepatocellular carcinoma (HCC). METHODS: Institutional review board approval was obtained for this retrospective study, and all patients provided written informed consent. Between April 2004 and December 2015, 116 oligometastases (diameter, 5-50 mm; 20.3 ± 10.4) in 79 consecutive HCC patients (73 men and 6 women; average age, 50.3 years ±13.0) were treated with RFA. We focussed on patients with 1-3 extrahepatic metastases (EHM) confined to 1-2 organs (including the lung, adrenal gland, bone, lymph node and pleura/peritoneum) who were treated naïve with curative intent. Survival, technical success and safety were evaluated. The log-rank test and Cox proportional hazards regression models were used to analyse the survival data. RESULTS: No immediate technical failure occurred, and at 1 month, the technique effectiveness rate was determined to be 95.8%. After a median follow-up time of 28.0 months (range, 6-108 months), the 1-, 2- and 3-year overall survival (OS) rates were 91, 70 and 48%, respectively, with a median survival time of 33.5 months. Time to unoligometastatic progression (TTUP) of less than 6 months (p < 0.001) and a Child-Pugh score of more than 5 (p = 0.001) were significant indicators of shorter OS. The 1-, 2- and 3-year disease free survival (DFS) rates were 34, 21 and 8%, respectively, with a median DFS time of 6.8 months. DFS was better for those with lung metastases (p = 0.006). Major complication occurred in nine (9.5%, 9/95) RFA sessions without treatment-related mortality. CONCLUSIONS: CT-guided RFA for oligometastatic HCC may provide favourable efficacy and technical success with a minimally invasive approach.

Toxicity of Water-Accommodated Fractions (WAF), Chemically Enhanced WAF (CEWAF) of Oman Crude Oil and Dispersant to Early-Life Stages of Zebrafish (Danio rerio).

This study focused on comparing the lethal and sublethal toxicity of water-accommodated fractions (WAF) and chemically enhanced WAF (CEWAF) of crude oil to zebrafish (Danio rerio) on early life stages (ELS). Results showed that the addition of GM-2 dispersant caused an increase in the levels of total petroleum hydrocarbons (TPHs) and total priority polycyclic aromatic hydrocarbons (ΣPAHs). Based on ΣPAHs, the LC20 estimates for WAF and CEWAF were 4.88 µg L-1 and 1.19 µg L-1, respectively, indicating that CEWAF was approximately four times more toxic. CEWAF exposure caused markedly lower hatching rates and higher malformation frequencies than WAF. Meanwhile, the general morphology score (GMS) values in CEWAF were about fourfold lower than that in WAF, indicating that CEWAF exposure induced more significant developmental delay. The results suggested that chemical dispersant enhanced the toxicity of crude oil to zebrafish on ELS and its application could increase the exposure of fishes to crude oil.

Percutaneous CT-guided Radiofrequency Ablation for Lymph Node Oligometastases from Hepatocellular Carcinoma: A Propensity Score-matching Analysis.

Purpose To assess the effectiveness and safety of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for lymph node (LN) oligometastases from hepatocellular carcinoma (HCC). Materials and Methods This retrospective study was approved by the institutional ethics committee, and all patients provided written informed consent. From January 2004 to December 2013, 119 consecutive patients with HCC and LN oligometastases (115 men [mean age, 51.3 years; age range, 16-83 years] and four women [mean age, 38.2 years; age range, 23-47 years]) were included in this study. A matched cohort composed of 46 patients from each group was selected after adjustment with propensity score matching. The median follow-up time was 14.0 months in the RFA group and 13.8 months in the non-RFA group. The overall survival (OS), local control rate, and complications were evaluated. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results Eighty-seven patients had LN metastases located in the regional site, and 32 patients had LN metastases in the distant site. No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. The RFA group showed higher 6-month and 1-year OS rates compared with the non-RFA group (87.0% and 58.3% vs 62.4% and 17.9%, respectively; P = .001). The 3-month local control rate after RFA was 84.4%, including complete response in 71.1% of patients and partial response in 13.3%. The complications of RFA were short-term abdominal pain and self-limited local hematoma, which occurred in 10 patients (21.7%) and five patients (10.9%), respectively. Conclusion Percutaneous CT-guided RFA may be a safe and effective treatment for the LN oligometastases generated by HCC. © RSNA, 2016.

Water-accommodated fractions of crude oil and its mixture with chemical dispersant impairs oxidase stress and energy metabolism disorders in Oryzias melastigma embryos.

In this study, marine medaka (Oryzias melastigma) embryos were exposed to different concentrations of water-accommodated fractions (WAFs) and chemically enhanced water-accommodated fractions (CEWAFs) of Oman crude oil for 14 d by semi-static exposure methods. The effects on growth and development and energy metabolism process were evaluated. Results showed that embryo survival and hatchability were decreased in a dose-dependent manner with an increase in the concentration of petroleum hydrocarbon compounds, whereas the malformation exhibited a dose-dependent increase. Compared to the control, the adenosine triphosphate (ATP) content and Na+-K+-ATPase (NKA) activities of embryos exposed to both WAFs and CEWAFs were reduced, while intracellular reactive oxygen species (ROS) levels and NADH oxidase (NOX) activities were increased. Our study demonstrated that exposure to crude oil dispersed by chemical dispersant affected the growth and development of marine medaka embryos, caused oxidative stress while produced a series of malformations in the body and dysregulation in energy metabolism. In comparison, the toxic effects of chemically dispersed crude oil might be more severe than the oil itself in the equivalent diluted concentration treatment solution. These would provide more valuable and reliable reference data for the use of chemical dispersants in oil spills.

Predictive value of circulating immune cell changes in response to PD-1 blockade and TKI therapy in patients with hepatocellular carcinoma.

PURPOSE: This study investigated the dynamic changes in circulating immune cells following immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), and interventional therapy in hepatocellular carcinoma (HCC). METHODS: HCC patients undergoing transarterial chemoembolization (TACE), TKI, and ICI treatment were included in the treatment group. Peripheral blood samples were collected from these patients before each cycle of PD-1 blockade treatment. Flow cytometry analysis was conducted to assess the composition of peripheral immune cells and identify PD-1-expressing T cells. RESULTS: The treatment group showed a median time-to-tumor progression (TTP) of 8 months and an overall survival (OS) of 19 months. In comparison, the control group had 6 months and 15 months respectively. These differences were statistically significant (P = 0.029 for TTP and P = 0.020 for OS). In HCC patients receiving Lenvatinib, more circulating natural killer (NK) cells were noted. After 1-2 cycles of PD-1 antibody treatment, a general decline in the proportion of circulating PD-1+T cells was found, indicating individual variations in response. CONCLUSION: Circulating immune cells have the potential to serve as indicators of the response to immunotherapy, providing a means to monitor dynamic changes and optimize treatment for HCC.

Percutaneous CT-guided radiofrequency ablation as supplemental therapy after systemic chemotherapy for selected advanced non-small cell lung cancers.

OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) as a supplemental therapy after systemic chemotherapy for selected patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 220 patients with advanced NSCLC who were treated with platinum-doublet chemotherapy between January 2000 and January 2012. Among them, 49 patients underwent RFA as a supplemental therapy for tumors in partial response or stable diseases after first-line chemotherapy. The progression-free survival (PFS) was evaluated by Kaplan-Meier method. RESULTS: There were nine women and 40 men (median age, 60 years; range, 24-82 years), including 28 patients with stage IIIb cancer and 21 with stage IV cancer. All 49 patients (partial response, 23 patients; stable disease, 26 patients) underwent 67 RFA sessions for 61 targeted tumors after systemic chemotherapy. There were no procedure-related deaths. Pneumothorax requiring chest tubes developed in eight sessions (11.9%). Thirty-one patients (63.3%) had complete response, 12 patients (24.5%) had partial response, six patients (12.2%) had stable disease, and no patients had progressive disease. The median follow-up period was 19 months (range, 6-34), and the median PFS was 16 weeks (95% CI, 14.5-17.5). CONCLUSION: Percutaneous CT-guided RFA can be performed as a feasible minimally invasive supplemental therapy with satisfactory PFS after systemic chemotherapy for patients with advanced NSCLC.

Oxidative stress responses in the respiratory tree and the body wall of sea cucumber Apostichopus japonicus (Selenka) to high temperature.

Sea cucumber Apostichopus japonicas (Selenka) is one of the important aquaculture species distributed in northern China. In recent years, global warming caused frequent high temperature weather in summer in northern China, resulting in dramatic losses of the sea cucumber aquaculture industry. In the present study, we focused on the effect of oxidative stress in Apostichopus japonicus (Selenka) subjected to high temperature stress. Sea cumbers were exposed to the control (16 °C), and high temperature treatments (20 °C, 24 °C, and 28 °C) for 7 days. Then, reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity, catalase (CAT) activity, peroxidase (POD) activity, reduced glutathione (GSH) content, malondialdehyde (MDA) content and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in the respiratory tree and body wall were detected, respectively. Results showed that 24 °C and 28 °C acute exposure induced the elevation of ROS level, SOD, CAT, POD activities, GSH content, MDA content and 8-OHdG level in the respiratory tree of sea cucumber. In contrast, no significant changes were observed for ROS and 8-OHdG levels in the body wall of sea cucumber, while the antioxidants including SOD, CAT, POD, and GSH decreased to some extent. Moreover, MDA content exhibited a noticeable increase in the body wall, similarly to that in the respiratory tree, indicating that high temperature could induce severe lipid peroxidation in two tissues. Considering the differences in various biomarkers measured in two tissues, respiratory tree might be more susceptible to the high temperature changes compared to the body wall. Our findings may help understand the oxidative stress response to high temperature in the respiratory tree and the body wall in A. japonicus.

Percutaneous CT-guided radiofrequency ablation for unresectable hepatocellular carcinoma pulmonary metastases.

PURPOSE: This study aimed to evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) for unresectable hepatocellular carcinoma pulmonary metastases (HCCPM) and to identify the prognostic factors for survival. MATERIALS AND METHODS: We reviewed the medical records of 320 patients with HCCPM treated between January 2005 and January 2012. Among them, 29 patients with 68 lesions of unresectable HCCPM underwent 56 RFA sessions. Safety, local efficacy, survival and prognostic factors were evaluated. Survival was analysed using the Kaplan-Meier method. Univariate analyses were evaluated by the log-rank test. RESULTS: Pneumothorax requiring chest tube placement occurred in five (8.9%, 5/56) RFA sessions. During the median follow-up period of 23 months (range 6-70), 18 patients (62.1%, 18/29) died of tumour progression and 11 (37.9%, 11/29) were alive. The 1-, 2- and 3-year overall survival rates were 73.4%, 41.1% and 30%, respectively. The median progression-free survival was 18 months (95% confidence interval (CI) 9.8-26.2) and the median overall survival time was 21 months (95%CI, 9.7-32.3). The maximum tumour diameter ≤3 cm (p = 0.002), the number of pulmonary metastases ≤3 (p = 0.014), serum AFP level ≤400 ng/mL (p = 0.003), and the controlled status of intrahepatic tumour after lung RFA (p = 0.001) were favourable prognostic factors for overall survival. CONCLUSIONS: Our study indicates that percutaneous CT-guided RFA, as an alternative treatment procedure to pulmonary metastasectomy, can be a safe and effective therapeutic option for unresectable HCCPM.

[Value of CIK in the treatment of TACE combined with RFA for HCC in long-term survival and prognostic analysis].

OBJECTIVE: To assess the long-term efficacy and investigate the prognostic factors of cytokine-induced killer (CIK) combined with the sequential transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC). METHOD: A total of 95 HCC patients with the informed consents received TACE combined with RFA, 48 cases of which accepted the CIK via intravenous drop infusion for more than 6 times (study group) while the other 47 cases were enrolled in control group. The following-up duration was more than 3 years. Primary endpoint was the overall survival (OS) and the secondary endpoint was the disease-free survival (DFS). RESULTS: 76 patients in all (38 in study group, 38 in control group) complied with the study and follow-up (44 months in median, 10-88 months). No mortality and serve complications were observed in both groups. The ratio for patients with DFS over 1-year, 3-year and 5-year were 79%, 26% and 16% (28 months in median and 32.3 months in mean) while 71%, 21% and 8% (22 months in median and 23.1 months in mean) for the control group. There was significant difference between the two groups (P=0.001). For the OS, the ratio for 1-year, 3-year and 5-year in the study group were 92%, 53% and 26% (38 months in median and 42.5 in mean) and 89%, 42% and 24% (35 months in median and 37 in mean). No significant difference was observed in both groups. ECOG performance status, Hepatitis B virus infection and treatment were the prognostic factors for DFS while ECOG performance status was the only prognosis for OS. CONCLUSION: CIK infusion basing on the TACE combined with RFA can control the recurrence of HCC, decrease the times of TACE or RFA.

Percutaneous transcatheter super-selective renal arterial embolization with N-butyl cyanoacrylate for iatrogenic renal hemorrhage.

Background: To evaluate the safety and efficacy of percutaneous transcatheter super-selective renal arterial embolization (SRAE) with N-butyl cyanoacrylate (NBCA) for iatrogenic renal hemorrhage. Methods: Between January 2014 and December 2019, 45 patients (including 18 patients with coagulopathy), who underwent percutaneous transcatheter SRAE with NBCA for iatrogenic renal hemorrhage at our institution, were retrospectively reviewed. The technical success rate, clinical success rate, and embolization-related complications were analyzed. The values of estimated glomerular filtration rate (eGFR), serum creatinine (sCr), and serum urea (sUr) were analyzed at the time of pre-SRAE, post-SRAE, and last follow-up to evaluate the effects of NBCA-based SRAE on renal function. Results: Diagnostic renal arteriography revealed contrast extravasation in 18 patients and pseudoaneurysms in 27 patients. NBCA mixed with iodized oil in a 1:2-1:4 ratio was the sole embolic agent. No procedure-related mortality or major complications occurred. The technical and clinical success rates were both 100%. The values of eGFR, sCr and sUr were not found to be significantly different between pre-SRAE, post-SRAE and last follow-up (eGFR: 91.52 â€‹± â€‹21.17 vs. 90.98 â€‹± â€‹22.11 vs. 92.14 â€‹± â€‹23.51 â€‹mL/min/1.73 â€‹m2, p â€‹= â€‹0.729; sCr: 74.73 â€‹± â€‹11.08 vs. 75.27 â€‹± â€‹12.43 vs. 73.95 â€‹± â€‹10.14 â€‹µmol/L, p â€‹= â€‹0.543; sUr: 5.69 â€‹± â€‹0.84 vs. 5.71 â€‹± â€‹0.96 vs. 5.70 â€‹± â€‹0.79, p â€‹= â€‹0.515, respectively). Conclusions: Percutaneous transcatheter SRAE with NBCA is a safe and effective treatment modality for iatrogenic renal hemorrhage with no deterioration of renal function.

Exposure of adult sea urchin Strongylocentrotus intermedius to stranded heavy fuel oil causes developmental toxicity on larval offspring.

Heavy fuel oil (HFO) spills pose serious threat to coastlines and sensitive resources. Stranded HFO that occurs along the coastline could cause long-term and massive damage to the marine environment and indirectly affect the survival of parental marine invertebrates. However, our understanding of the complex associations within invertebrates is primarily limited, particularly in terms of the toxicity effects on the offspring when parents are exposed to stranded HFO. Here, we investigated the persistent effects on the early development stage of the offspring following stranded HFO exposure on the sea urchin Strongylocentrotus intermedius. After 21 d exposure, sea urchins exhibited a significant decrease in the reproductive capacity; while the reactive oxygen species level, 3-nitrotyrosine protein level, protein carbonyl level, and heat shock proteins 70 expression in the gonadal tissues and gametes significantly increased as compared to the controls, indicating that HFO exposure could cause development toxicity on offspring in most traits of larval size. These results suggested that the stranded HFO exposure could increase oxidative stress of gonadal tissues, impair reproductive functions in parental sea urchins, and subsequently impact on development of their offspring. This study provides valuable information regarding the persistent toxicity effects on the offspring following stranded HFO exposure on sea urchins.

[Comparison of safety and efficacy for transcatheter arterial chemoembolization alone and plus radiofrequency ablation in the treatment of single branch portal vein tumor thrombus of hepatocellular carcinoma and their prognosis factors].

OBJECTIVE: To compare the transcatheter arterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in the treatment of single branch portal vein tumor thrombus(PVTT)in patients with hepatocellular carcinoma (HCC) so as to evaluate the safety, control rate, prognostic factors and overall survival. METHODS: From January 2004 to December 2007, 50 HCC patients (< 5 cm in diameter and 3 parenchymal lesions) with concurrent PVTT were enrolled and treated by TACE alone or TACE plus RFA randomly (TACE, n = 25; TACE-RFA, n = 25). In TACE group, the intra-hepatic lesions received TACE sequentially with RFA; in TACE-RFA group, PVTT and intra-hepatic lesions were treated with TACE sequentially with RFA separately. Strict follow-up was conducted by computed tomography and alpha-fetoprotein (AFP) assay. The survival time was analyzed by the Kaplan-Meier method and Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Of all 50 HCC patients with single branch PVTT with TACE or RFA, 47 patients (TACE, n = 24; TACE-RFA, n = 23) received all the scheduled procedures and completed the follow-up. Two patients (8.3%) in TACE group had liver dysfunction versus none in TACE-RFA group, 2 patients (8.7%) developed bile duct injury in TACE-RFA group related with the RFA procedure. The OR (overall response) for PVTT was 54.2% (complete response (CR) 8.3%, partial response (PR) 45.8%) in TACE group while 87.0% (CR 60.9%, PR 26.1%) in TACE-RFA group during the follow-up. From the definite diagnosis of HCC, the median survival was 8 months. And the 1-, 2- & 3-year survival rates were 33.3%, 12.5%, 8.3% in TACE group. And 26 months, 65.2%, 47.8%, 30.4% in TACE-RFA group respectively. The difference between two groups was significant. From the definite diagnosis of PVTT, the respective data were 7 months, 12.5% and 4.2%, 0 in TACE group versus 22 months, 52.2%, 34.8%, and 8.7% in TACE-RFA group with a significant P value. In multivariate analysis, only therapy (TACE or TACE-RFA) showed a protective value (hazard rate 0.430 vs 0.345, P < 0.05). Survival was not correlated with age, intra-hepatic tumor status, liver functions and AFP level for all patients. CONCLUSION: RFA is both safe and efficacious to prolong survival in the treatment of single branch PVTT plus TACE in selected HCC patients. It may provide rationales for further studies of evaluating the outcome of RFA plus other therapies in the treatment of HCC with single branch PVTT.

Anlotinib followed by transarterial chemoembolization and radiofrequency ablation is a safe and effective initial treatment for hepatocellular carcinoma patients with portal vein tumor thrombus: A retrospective case series study.

BACKGROUND: Portal vein tumor thrombus (PVTT) remains a poor prognostic factor occurring in about 10%-40% of patients with hepatocellular carcinoma (HCC) for the optimal treatment is controversial. Anlotinib is an novel small molecule inhibitor that has a broad spectrum of inhibitory activities on tumor angiogenesis and growth. However, so far, no studies have reported the use of anlotinib in the treatment of HCC patients with PVTT. Here, we evaluated the safety and efficacy of anlotinib, followed by transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for the treatment of patients with HCC and PVTT. MATERIALS AND METHODS: A total of 145 consecutive HCC patients who underwent TACE in combination with RFA were enrolled in the retrospective study. Twenty-eight patients were diagnosed with PVTT and received anlotinib as basic treatment. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs Version 4.0. Time to tumor progression (TTP) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: The most common toxicities related to anlotinib were pharyngalgia (53.6%), fatigue (42.9%), and hand-foot skin reaction (39.3%). The median OS was 13 months (range: 3-18 months) with 1-year OS rate of 64.3%. The median TTP was 7 months (range: 1-12 months) with 6-month rate of 46.4%. CONCLUSION: Anlotinib followed by TACE and RFA is a safe and effective initial treatment modality for HCC patients with PVTT. Anlotinib may be a promising therapeutic option for relieving and/or stabilizing HCC with PVTT.

Sex-Specific Differences in the Toxic Effects of Heavy Fuel Oil on Sea Urchin (Strongylocentrotus intermedius).

The purpose of this study was to explore and compare the sex-specific differences in the toxic effects of water-accommodated fractions of 380# heavy fuel oil (HFO WAF) on the sea urchin Strongylocentrotus intermedius. Sea urchins were acutely exposed to HFO WAF at different nominal concentrations (0%, 10% and 20%) for seven days. The results showed that females had a higher polycyclic aromatic hydrocarbons (PAHs) bioaccumulation in gonad tissues and that both the total antioxidant capacity (TAC) and lipid peroxidation (LPO) levels in the gonad tissues of females were much higher than those of males. The PAHs bioaccumulation in gametes indicated that parents' exposure could lead to a transfer of PAHs to their offspring, and eggs had higher TAC and LPO than sperms. After maternal and paternal exposure to HFO WAF, the frequency of morphological abnormalities of the offspring was increased when compared to the control. Overall, these results indicated that maternal exposure to HFO WAF could cause more significantly toxic effects on sea urchins than paternal exposure could, which could lead to more significantly negative effects on their offspring.

Phenotypic and transcriptomic consequences in zebrafish early-life stages following exposure to crude oil and chemical dispersant at sublethal concentrations.

To further understand the underlying mechanisms involved in the developmental toxicity of crude oil and chemically dispersed crude oil on fish early-life stages (ELS), zebrafish (Danio rerio) embryos were exposed to GM-2 chemical dispersant (DISP), low-energy water-accommodated fractions (LEWAF), and chemically enhanced WAF (CEWAF) of Merey crude oil at sublethal concentrations for 120 h. We employed the General Morphology Score (GMS) and General Teratogenic Score (GTS) systems in conjunction with high-throughput RNA-Seq analysis to evaluate the phenotypic and transcriptomic responses in zebrafish ELS. Results showed that ΣPAHs concentrations in LEWAF and CEWAF solutions were 507.63 ± 80.95 ng·L-1 and 4039.51 ± 241.26 ng·L-1, respectively. The GMS and GTS values indicated that CEWAF exposure caused more severe developmental delay and higher frequencies of teratogenic effects than LEWAF exposure. Moreover, no significant change in heart rate was observed in LEWAF treatment, while CEWAF exposure caused a significant reduction in heart rate. LEWAF and CEWAF exposure exhibited an overt change in eye area, with a reduction of 4.0% and 25.3% (relative to the control), respectively. Additionally, no obvious impact on phenotypic development was observed in zebrafish embryo-larvae following DISP exposure. Significant changes in gene expression were detected in LEWAF and CEWAF treatments, with a total of 957 and 2062 differentially expressed genes (DEGs), respectively, while DISP exposure altered only 91 DEGs. Functional enrichment analysis revealed that LEWAF and CEWAF exposure caused significant perturbations in the pathways associated with phototransduction, retinol metabolism, metabolism of xenobiotics by cytochrome P450, and immune response-related pathways. Our results provide more valid evidence to corroborate the previous suggestion that ocular impairment is an equal or possibly more sensitive biomarker than cardiotoxicity in fish ELS exposed to oil-derived PAHs. All these findings could gain further mechanistic insights into the effects of crude oil and chemical dispersant on fish ELS.

Combined Effects of Elevated Temperature and Crude Oil Pollution on Oxidative Stress and Apoptosis in Sea Cucumber (Apostichopus japonicus, Selenka).

Currently, global climate change and oil pollution are two main environmental concerns for sea cucumber (Apostichopus japonicus) aquaculture. However, no study has been conducted on the combined effects of elevated temperature and oil pollution on sea cucumber. Therefore, in the present study, we treated sea cucumber with elevated temperature (26 °C) alone, water-accommodated fractions (WAF) of Oman crude oil at an optimal temperature of 16 °C, and Oman crude oil WAF at an elevated temperature of 26 °C for 24 h. Results showed that reactive oxygen species (ROS) level and total antioxidant capacity in WAF at 26 °C treatment were higher than that in WAF at 16 °C treatment, as evidenced by 6.03- and 1.31-fold-higher values, respectively. Oxidative damage assessments manifested that WAF at 26 °C treatment caused much severer oxidative damage of the biomacromolecules (including DNA, proteins, and lipids) than 26 °C or WAF at 16 °C treatments did. Moreover, compared to 26 °C or WAF at 16 °C treatments, WAF at 26 °C treatment induced a significant increase in cellular apoptosis by detecting the caspase-3 activity. Our results revealed that co-exposure to elevated temperature and crude oil could simulate higher ROS levels and subsequently cause much severer oxidative damage and cellular apoptosis than crude oil alone on sea cucumber.

Kinesin family members KIF2C/4A/10/11/14/18B/20A/23 predict poor prognosis and promote cell proliferation in hepatocellular carcinoma.

Kinesin superfamily proteins (KIFs) comprise a family of molecular motors that transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner, with multiple roles in cancers. Little is known about the function of KIFs in hepatocellular carcinoma (HCC). Here, we investigate the roles of KIFs in the prognosis and progression of HCC. Upregulation of eight KIFs (KIF2C, KIF4A, KIF10, KIF11, KIF14, KIF18B, KIF20A, and KIF23) was found to be significantly associated with the tumor stage and pathological tumor grade of HCC patients. Additionally, a high expression of these eight KIFs was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) in patients with HCC. Cox regression analysis showed the mRNA expression levels of these eight KIF members to be independent prognostic factors for worse outcomes in HCC. Moreover, a risk score model based on the mRNA levels of the eight KIF members effectively predicted the OS rate of patients with HCC. Additional experiments revealed that downregulation of each of the eight KIFs effectively decreased the proliferation and increased the G1 arrest of liver cancer cells in vitro. Taken together, these results indicate that KIF2C/4A/10/11/14/18B/20A/23 may serve as prognostic biomarkers for survival and potential therapeutic targets in HCC patients.

Exposure to water-accommodated fractions of two different crude oils alters morphology, cardiac function and swim bladder development in early-life stages of zebrafish.

The present study investigated the developmental toxicity of water-accommodated fractions (WAFs) of Oman crude oil (OCO) and Merey crude oil (MCO) on zebrafish (Danio rerio) in early-life stages (ELS). Based on total petroleum hydrocarbons (TPH), LC50 values manifested that OCO WAF was 1.2-fold more lethal to zebrafish embryos than MCO WAF. As for hatching rate, EC50 value for OCO WAF was 5.7-fold lower than that for MCO WAF. To evaluate the sublethal morphological effects, semi-quantitative extended general morphological score (GMS) and general teratogenic score (GTS) systems were adopted. The GMS and GTS scores indicated that the WAFs caused remarkable developmental delay and high frequencies of malformation in a dose-dependent manner. Additionally, OCO and MCO WAFs exposure exhibited severe bradycardia (reduced heart rate) and overt reduction of stroke volume, with a concomitant decrease in the cardiac output. Meanwhile, the WAFs also induced dose-dependent down-regulated expressions of several key functional genes of excitation-contraction coupling in cardiomyocytes, including ryr2, atp2a2a, atp2a2b, ncx1h, and kcnh2. For key gene markers of swim bladder development, results showed that high dose of TPH induced significant down-regulation of hb9 and anxa5 with no obvious change of acta2, suggesting that the WAFs could affect the specification and development of epithelium and outer mesothelium of swim bladder in zebrafish ELS. A strong negative relationship between the failure of swim bladder inflation and cardiac dysfunction via cardiac output was found. All these findings provide novel insights into the complicated mechanisms of the developmental toxicity of crude oil on fish in ELS.

Interventions for Treating 3- or 4-part proximal humeral fractures in elderly patient: A network meta-analysis of randomized controlled trials.

BACKGROUND: The fractures of proximal humerus have a high incidence in elderly patients, especially 3- or 4-part fracture. There are 4 main treatments including nonoperation, open reduction and internal fixation(ORIF), hemiarthroplasty(HA) and reverse shoulder arthroplasty(RSA). However, which one is the optimal choice remains a controversial topic. METHODS: Through the search of three electronic databases (PubMed, Embase, and Cochrane), the randomized controlled trials of 3- or 4-part proximal humeral fracture, until the end of July 2017, which is concerned with the elderly patients, were identified. The quality evaluation of each study was evaluated, Constant score and reoperation rates were extracted and analyzed. We used R(R i386 3.3.2) and the package of gemtc to perform our network meta-analysis. RESULTS: Seven randomized controlled experiments with a total number of 347 patients were brought into our network meta-analysis. The rank probability plot of Constant score showed that the RSA had significantly the highest Constant score and lower reoperation than other treatments. The other way around, the efficacy of ORIF was the poorest. The rank for the Constant score was: RSA, HA, nonoperation and ORIF. The rank for the reduction in total reoperation rates was: RSA, nonoperation, HA and ORIF. CONCLUSIONS: The statistical result suggested that RSA has become a beneficial choice to treat displaced 3-or 4-part fracture in elderly patients, that might result in more favorable clinical outcomes and reduction of reoperation rates than other methods performed for the same indication. But the ORIF is the worst.