Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Upregulated LncRNA H19 Sponges MiR-106a-5p and Contributes to Aldosterone-Induced Vascular Calcification via Activating the Runx2-Dependent Pathway.

BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.

Thoracic perivascular adipose tissue inhibits VSMC apoptosis and aortic aneurysm formation in mice via the secretome of browning adipocytes.

Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.

Experimental realization of visible gas sensing technology based on spatial heterodyne spectroscopy.

Based on the characteristics of optical absorption gas sensing technology (OA-GST) and spatial heterodyne spectroscopy (SHS), a novel type of visual gas sensing technology (V-GST) can present the invisible gas information in the form of two-dimensional visual fingerprint, which has attracted people's attention. In this paper, we have realized the NO2 detection of V-GST in the laboratory environment for the first time. Experimental results show that: V-GST not only has different interferogram response to different spectra, but also has good response to different concentrations of NO2, which lays a foundation for the application of this technology in gas sensing. And the average classification recognition rate of the system for different band NO2 response data is over 80%, which verifies the effectiveness of the V-GST in gas detection.

Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy.

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)-enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α-SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3-MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.

A comparison study of percutaneous endoscopic decompression and posterior decompressive laminectomy in the treatment of thoracic spinal stenosis.

BACKGROUND: Percutaneous endoscopic decompression (PED) is considered a minimally invasive and safe procedure in lumbar degenerative disease. Few authors report the success of PED for thoracic spinal stenosis (TSS) with thoracic myelopathy. The objective of this study was to compare the outcome of PED versus posterior decompressive laminectomy (PDL) for TSS. METHODS: We retrospectively reviewed 30 consecutive patients who underwent surgery for single-level TSS from January 1, 2015 to May 1, 2019.These patients were divided into PED (n = 16) and PDL(n = 14) group. Preoperative demographic characteristics and perioperative outcomes were reviewed. Pre- and postoperative neurological status was evaluated using the modified Japanese Orthopaedic Association (mJOA) score and the recovery rate (RR). RESULTS: The patients' mean age was 57.3 years (27-76) in PED group and 58.8 years (34-77) in PDL group. No statistical difference was found between two groups with regards to neurological status at pre-operative and final follow-up. The RR in PED group achieved the same improvement as PDL group (87.5% vs 85.7%, P > 0.05), while the PED brought advantages in operative time(m) (86.4 vs 132.1, p < 0.05), blood loss (mL) (18.21 vs 228.57, p < 0.05),drainage volume(mL) (15.5 vs 601.4, p < 0.05), and hospital stay (d) (3.6 vs 5.6, p < 0.05). CONCLUSIONS: Both PED and PDL showed favorable outcome in the treatment of TSS. Besides, PED had advantages in reducing traumatization. In terms of perioperative quality of life, PED could be an efficient supplement to traditional posterior decompressive laminectomy in patients with TSS.

Oncological outcomes and predictors of radiofrequency ablation of colorectal cancer liver metastases.

BACKGROUND: Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis (CRLM) patients, but only a small number of patients are suitable for resection following diagnosis. Radiofrequency ablation (RFA) is an accepted alternative therapy for CRLM patients who are not suitable for resection. However, the relatively high rate of local tumor progression (LTP) is an obstacle to the more widespread use of RFA. AIM: To determine the oncological outcomes and predictors of RFA in CRLM patients. METHODS: A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases, who had received percutaneous RFA treatment at our institution from January 2013 to December 2018. Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations. The Kaplan-Meier method was used to calculate overall survival (OS) and LTP-free survival (LTPFS). The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes. RESULTS: There were no RFA procedure-related deaths, and the technique effectiveness of the treatment was 89.1% (123/138). The median follow-up time was 30 mo. The LTP rate was 32.6% (45/138), and the median OS was 36 mo. The 1-, 3-, and 5-year OS rates were 90.6%, 45.6%, and 22.9%, respectively. Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS, while extrahepatic disease (EHD), tumor number, and tumor size were the factors influencing OS. Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS, while tumor number greater than 1, size larger than 3 cm, and presence of EHD were the independent predictors of shorter OS. CONCLUSION: RFA is a safe and effective treatment method for CRLM. Tumor size and ablative margin are the important factors affecting LTPFS. Tumor number, tumor size, and EHD are also critical factors for OS.

Percutaneous transforaminal endoscopic decompression for lumbar spinal stenosis with degenerative spondylolisthesis in the elderly.

OBJECTIVES: Percutaneous transforaminal endoscopic decompression (PTED) under local anesthesia is rarely performed for lumbar spinal stenosis (LSS) with degenerative lumbar spondylolisthesis (DLS) because of the limited field of vision, inherent instability, etc. The objective of this study was to describe the procedure of the PTED technique and to demonstrate the early clinical outcomes. PATIENTS AND METHODS: From January 2017 to January 2019, 40 consecutive patients aged 60 and older were diagnosed with LSS with DLS in our institution and underwent PTED. All patient were followed up to 1 year postoperatively. The clinical outcomes were evaluated using the visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. RESULTS: The mean age was 70.2 ± 7.1 years. Follow-up ranged from 12 to 24 months. The mean ± SD values of the preoperative VAS leg pain and ODI scores were 7.5 ± 1.1 and 67.3 ± 9.3, respectively. The scores improved to 2.2 ± 1.1 and 20.7 ± 8.1 at 12 months postoperatively. The outcomes of the modified MacNab criteria showed that 87.5 % of patients obtained a good-to-excellent rate. The percent slippage of spondylolisthesis before surgery (10.8 ± 2.6 %) and at the end of follow-up (11.0 ± 2.4 %) was not significantly different. One patient had a dural tear and intracranial hypertension, and one patient had tibialis anterior weakness. CONCLUSION: PTED under local anesthesia could be an effective treatment method for LSS with DLS in elderly patients. However, potential complications still require further evaluation.

LncRNA-ATB promotes autophagy by activating Yes-associated protein and inducing autophagy-related protein 5 expression in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in many diseases, including hepatocellular carcinoma (HCC). Autophagy is a metabolic pathway that facilitates cancer cell survival in response to stress. The relationship between autophagy and the lncRNA-activated by transforming growth factor beta (lncRNA-ATB) in HCC remains unknown. AIM: To explore the influence of lncRNA-ATB in regulating autophagy in HCC cells and the underlying mechanism. METHODS: In the present study, we evaluated lncRNA-ATB expression in tumor and adjacent non-tumor tissues from 72 HCC cases by real-time PCR. We evaluated the role of lncRNA-ATB in the proliferation and clonogenicity of HCC cells in vitro. The effect of lncRNA-ATB on autophagy was determined using a LC3-GFP reporter and transmission electron microscopy. Furthermore, the mechanism by which lncRNA-ATB regulates autophagy was explored by immunofluorescence staining, RNA immunoprecipitation (RIP), and Western blot. RESULTS: The expression of lncRNA-ATB was higher in HCC tissues than in normal liver tissues, and lncRNA-ATB expression was positively correlated with tumor size, TNM stage, and poorer survival of patients with HCC. Moreover, ectopic overexpression of lncRNA-ATB promoted cell proliferation and clonogenicnity of HCC cells in vitro. LncRNA-ATB promoted autophagy by activating Yes-associated protein (YAP). Moreover, lncRNA-ATB interacted with autophagy-related protein 5 (ATG5) mRNA and increased ATG5 expression. CONCLUSION: LncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. Our data demonstrate a novel function for lncRNA-ATB in autophagy and suggest that lncRNA-ATB plays an important role in HCC.

Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation.

Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.

Ezetimibe Protects Endothelial Cells against Oxidative Stress through Akt/GSK-3ß Pathway.

Ezetimibe was reported to pharmacologically defend against oxidative stress. This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h. TUNEL assay and detectionfor the protein levels of cleaved caspase-3, Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis. Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence. The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay. The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining. Phosphorylation levels of glycogen synthase kinase-3p (p-GSK-3P) and Akt (p-Akt), as well as total GSK-3p and Akt were determined by Western blotting. The results showed that ezetimibe treatment inhibited HUVECs apoptosis, intracellular ROS production, and enhanced antioxidant enzyme activities elicited by oxLDL. HUVECs exposed to oxLDL alone had reduced mitochondrial function, while ezetimibe pre-intervention could significantly rescue the MMP. Furthermore, the protein levels of p-GSK-3p and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs. However, no significant effect on total GSK- 3P and Akt was found in ezetimibe-pretreated HUVECs. Taken together, it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP, which may be mediated by Akt-dependent GSK-3P phosphorylation.

Deferoxamine ameliorates adipocyte dysfunction by modulating iron metabolism in ob/ob mice.

OBJECTIVE: The mechanisms underlying obesity and anti-obesity processes have garnered remarkable attention as potential therapeutic targets for obesity-associated metabolic syndromes. Our prior work has shown the healing efficacy of iron reduction therapies for hepatic steatosis in a rodent model of diabetes and obesity. In this study, we investigated how iron depletion by deferoxamine (DFO) affected adipocyte dysfunction in the epididymal adipose tissues of ob/ob mice. METHODS: Male ob/ob mice were assigned to either a vehicle-treated or DFO-treated group. DFO (100 mg/kg body weight) was injected intraperitoneally for 15 days. RESULTS: We confirmed that iron deposits were statistically increased in the epididymal fat pad of 26-week-old ob/ob mice compared with wild-type (WT) mice. DFO significantly improved vital parameters of adipose tissue biology by reducing reactive oxygen species and inflammatory marker (TNFα, IL-2, IL-6, and Hepcidin) secretion, by increasing the levels of antioxidant enzymes, hypoxia-inducible factor-1α (HIF-1α) and HIF-1α-targeted proteins, and by altering adipocytic iron-, glucose- and lipid-associated metabolism proteins. Meanwhile, hypertrophic adipocytes were decreased in size, and insulin signaling pathway-related proteins were also activated after 15 days of DFO treatment. CONCLUSIONS: These findings suggest that dysfunctional iron homeostasis contributes to the pathophysiology of obesity and insulin resistance in adipose tissues of ob/ob mice. Further investigation is required to develop safe iron chelators as effective treatment strategies against obesity, with potential for rapid clinical application.

A Retrospective Study of Central Nervous System Invasive Fungal Disease after Allogeneic Stem Cell Transplantation: Risk Factors, Clinical Characteristics, and Outcomes.

There are limited reports of central nervous system (CNS) invasive fungal disease (IFD) in allogeneic stem cell transplantation (HSCT) recipients. We aimed to describe the clinical characteristics of and the risk factors for CNS-IFD. We retrospectively reviewed consecutive HSCT patients at Peking University Institute of Hematology during a 10-year period. A total of 29 patients were diagnosed with CNS-IFD. The median onset of CNS-IFD was 173 (range, 24 to 972) days after HSCT. The most frequent pathogen was Aspergillus, and the most common clinical symptoms and signs were space-occupying presentations. We found that prior pulmonary IFD (P < .001; hazard ratio, 62.746; 95% confidence interval, 14.28 to 275.27) was the only risk factor associated with occurrence of CNS-IFD. Poor response at 6 weeks after treatment (P = .045; hazard ratio, 2.574; 95% confidence interval, 1.021 to 6.487) was the only risk factor predicting the involvement of the CNS in pulmonary IFD. Overall survival was 24.2% at the last follow-up, with a median of 289 (range, 27 to 3341) days after transplantation. We conclude that patients with pulmonary IFD had higher risk of CNS-IFD, especially in those with poor response after 6 weeks of treatment. The prognosis of CNS-IFD was very poor after HSCT.

Mcl-1 as a potential therapeutic target for human hepatocelluar carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality in part due to its high resistance to chemotherapeutic drugs. The anti-apoptotic Mcl-1 expression has been reported as a resistance factor in various types of tumors. Here, we investigated the expression of Mcl-1 in hepatoma cells and HCC tissues and its relationship with p53, and analyzed the possibility of the gene as a molecular target for HCC therapy. HCC specimens of 30 patients were examined by immunohistochemistry for Mcl-1 and p53 expression. Mcl-1 expression in hepatoma cell lines was measured by RT-PCR and Western blotting. The suppression of Mcl-1 by RNA interference or specific phosphatidylinositol-3 kinase (PI3K) inhibitor, LY294002, was evaluated as monotherapy, and it was combined with mitomycin C (MMC) in treating hepatoma cell line HepG2. Cell viability and apoptosis were assessed by MTT and FACS analysis. Finally, changes of Mcl-1 or p53 expression in various hepatoma cell lines were examined after transfection with Mcl-1 siRNA, the Mcl-1 expression plasmid, or the wide-type p53 expression plasmid, respectively. Mcl-1 protein was remarkably enhanced in HCC tissues as compared with adjacent non-tumor liver tissues. In addition, Mcl-1 was prominently expressed in HepG2 and Hep3B cells, weakly in SMMC7721 cells, and not in L02 cells. P53 protein was also overexpressed in HCC tissues and there was a significant correlation between the expression of p53 and Mcl-1. Silencing Mcl-1 by RNAi or LY294002 downregulated Mcl-1 expression and led to decreased cell viability and increased apoptosis. Combination of MMC and Mcl-1 RNAi or LY294002 exhibited a significant chemosensitizing effect. The expression of p53 was not influenced by Mcl-1 siRNA in HepG2 cells or transfection with the Mcl-1 expression plasmid in L02 cells. Furthermore, the expression of Mcl-1 in Hep3B cells was also not significantly changed after transfection with the wild-type p53 expression plasmid. It is concluded that Mcl-1 is overexpressed in HCC tissues. The mechanisms by which silencing Mcl-1 sensitizes hepatoma cells towards chemotherapy may be not attributed to the upregulated expression of p53 but the dysfunction of p53 through Mcl-1/p53 interaction. Mcl-1 may be a potential target of gene therapy for HCC.

Hemobilia After Laparoscopic Cholecystectomy: Imaging Features and Management of an Unusual Complication.

PURPOSE: To assess the imaging features and the management of hemobilia after laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: A total of 12 patients who were treated for hemobilia after LC were included in the study. Selective arteriography was performed to find the bleeding artery. Coils or microcoils were deployed superselectively to occlude the bleeding branch. The clinical course, imaging findings, the embolic effect, complications, and follow-up were evaluated. RESULTS: Risk factors for hemobilia included a variant ductal anatomy, a variant cystic artery, and intraoperative adhesion. Abdominal computed tomography (CT) could provide the diagnostic signs as follows: a hematocele in the abdominal cavity, the gallbladder fossa, and the bile duct, biliary dilation, pseudoaneurysm of the right hepatic artery, and contrast extravasations on contrast-enhanced CT. No rebleeding occurred after the transcatheter arterial embolization in all patients without immediate procedural complications. CONCLUSIONS: Gallbladder triangle anatomic variation and intraoperative adhesion were the risk factors for hemobilia after LC. Abdominal CT is a useful examination for the diagnosis. Transcatheter arterial embolization is the therapeutic option of choice.

Analysis of clinical features of painless aortic dissection.

The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement.

Estrogen regulates the expression of Ndrg2 in astrocytes.

N-myc downstream-regulated gene 2 (Ndrg2) is a newly identified molecule that is mainly expressed in astrocytes within the central nervous system (CNS) and is involved in the proliferation and activation of astrocytes. 17ß-estradiol (E2) is one of the most important circulating hormones, and in the CNS, astrocytes are a target and potential mediator of the action of E2. Our most recent study found that DPN, an estrogen receptor (ER) ß-specific agonist, activated the Ndrg2 promoter and elevated endogenous NDRG2 protein expression in MCF7, HSG and T-47D cells. However, whether E2 regulates Ndrg2 expression in astrocytes remains unknown. Here, we conducted both in vivo and in vitro experiments and found that ERß co-localized with NDRG2 in astrocytes. Furthermore, in primary cultured astrocytes, we demonstrated that E2 up-regulated Ndrg2 mRNA and protein expression in a dose- and time-dependent manner and that the ERß agonist DPN but not the ERα agonist PPT up-regulated Ndrg2 expression. In vivo, we found that in the hippocampus of adult ovariectomized (OVX) female mice, Ndrg2 mRNA and protein expression were significantly decreased compared with those in normal adult female mice. After the OVX mice received continuous subcutaneous injections of 50µg/kg E2, 100µg/kg E2 or the ERß agonist DPN for 10 days, the Ndrg2 expression significantly increased compared with that of the OVX mice. Our results indicate that E2 may affect astrocytes by regulating Ndrg2 expression.

Detection of residual tumor following radiofrequency ablation of liver metastases using 18F-FDG PET/PET-CT: a systematic review and meta-analysis.

Radiofrequency ablation (RFA), an effective, locally directed therapy for unresectable liver metastases, can improve the survival of patients. As a functional imaging approach, (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) or PET-computed tomography (PET-CT) may play a crucial role in the follow-up after RFA. Our objective was to evaluate the diagnostic accuracy of (18)F-FDG PET or PET-CT for the detection of residual tumor following RFA of liver metastases. Studies reporting the diagnostic value of (18)F-FDG PET or PET-CT for patients with residual tumor after RFA of liver metastases were identified. The methodological quality of these studies was systematically evaluated, and the overall sensitivity and specificity of these data sets are reported. Seven studies involving 155 patients were examined. When (18)F-FDG PET or PET-CT was performed within 2 days of RFA, the overall sensitivity and specificity were 79% [95% confidence interval (CI): 70-87%] and 84% (95% CI: 75-91%), respectively. When (18)F-FDG PET or PET-CT was performed 1 week after treatment, the pooled sensitivity and specificity were 48% (95% CI: 18-79%) and 94% (95% CI: 70-100%), respectively. Finally, when (18)F-FDG PET or PET-CT was performed 3 months after treatment, the pooled sensitivity and specificity were 52% (95% CI: 22-81%) and 94% (95% CI: 70-100%), respectively. Both (18)F-FDG PET and PET-CT are effective in detecting residual tumor following RFA of liver metastases. The ideal time to perform these imaging studies is within 2 days of RFA treatment.

A truncated Danio rerio PKZ isoform functionally interacts with eIF2α and inhibits protein synthesis.

A protein kinase containing Z-DNA binding domains (PKZ), which resembles protein kinase R (PKR) in domain organization, was recently discovered to be a member of the eIF2α kinase family in fish. PKR has roles in antiviral immunity through inhibiting protein synthesis and activating NF-κB; therefore, it is thought that PKZ may have a similar role in fish antiviral immunity. In the present study, the roles of two Danio rerio PKZ isoforms (DrPKZ-A and DrPKZ-B) in eIF2α phosphorylation and protein synthesis regulation were explored. DrPKZ-A and DrPKZ-B possess N-terminal Z-DNA binding domains and a conserved eIF2α kinase domain; however, they have domains of differing lengths inserted between kinase subdomains IV and V. DrPKZ-A has an insert domain of 73 amino acids (aa), whereas DrPKZ-B has an insert sequence of only 10 aa, suggesting that DrPKZ-B could be a dysfunctional isoform or could interact with different substrates. Our results show that both DrPKZ-A and DrPKZ-B functionally interact with eIF2α and inhibit protein synthesis, although DrPKZ-B possesses attenuated kinase activity. Our results also show that deletion of the insert in either isoform results in the complete abrogation of kinase activity, suggesting that the insert is critical for PKZ kinase activity. Kinase activity appears to be independent of insert length but may depend on the presence of specific amino acids within the insert domain. Furthermore, the effects of the N-terminal regulatory domain on kinase activity were analyzed. Deletion of the N-terminus results in reduced kinase activity of these isoforms relative to the wild-type forms, indicating that the isolated kinase domain is sufficient for eIF2α phosphorylation and that DrPKZ-A and DrPKZ-B may be regulated in a similar manner. Overall, our results show that DrPKZ-B is a functional kinase in zebrafish and contribute to our understanding of the function of PKZ in fish.

Entry of tiger frog virus (an Iridovirus) into HepG2 cells via a pH-dependent, atypical, caveola-mediated endocytosis pathway.

Tiger frog virus (TFV), in the genus Ranavirus of the family Iridoviridae, causes high mortality of cultured tiger frog tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH(4)Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.