Conventional stents versus stents loaded with (125)iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial.

BACKGROUND: The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS: In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS: Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION: In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.

A novel reference coordinate system to locate the inferomedial point of the transverse-sigmoid sinus junction.

BACKGROUND: A coordinate system was previously developed to identify landmarks on the skull surface to help locate the transverse-sigmoid sinus junction in order to reduce surgical morbidity in retrosigmoid craniotomy; however, in practice we found that this system has important flaws. OBJECTIVE: To develop and evaluate a novel reference coordinate system to precisely locate the inferomedial point of the transverse-sigmoid sinus junction (IMTS) and evaluate the effect of gender and skull side (left or right). METHODS: Forty-two adult skulls (84 sides) were obtained for analyses. The X-axis was defined by point A (where the upper edge of the zygomatic arch joins with the frontal process of the zygomatic bone) and point B (where the upper edge of the zygomatic arch blends posterosuperiorly into the supramastoid crest). The Y-axis was defined by the line perpendicular to the X-axis and extending across the tip of the mastoid. The x and y coordinates of IMTS (IMTS-x and IMTS-y) were measured in this coordinate system. RESULTS: There were 20 male skulls and 22 female skulls. The mean IMTS-x measurements were significantly higher on the right side compared with the left side in both males and females. For the left skull side, the mean IMTS-y measurements were significantly lower in females compared with males. CONCLUSION: This novel reference coordinate system may be a reliable and practical method for identifying the IMTS during retrosigmoid craniotomy. There are significant differences in location of the axes with regard to gender and skull side.

Role of glycogen synthase kinase 3ß in protective effect of propofol against hepatic ischemia-reperfusion injury.

BACKGROUND: It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3ß (GSK-3ß) is known to play an important role in the oxidative stress-induced apoptosis. In this study, we investigated the role of GSK-3ß and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury. MATERIALS AND METHODS: The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential. RESULTS: Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Importantly, propofol suppressed the mitochondrial GSK-3ß by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse. CONCLUSIONS: Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3ß.

Effects of a new magnesium-rich artificial cerebrospinal fluid on contractile 5-hydroxytryptamine and endothelin receptors in rat cerebral arteries.

Objectives Cerebral vasospasm after subarachnoid haemorrhage (SAH) is associated with cerebrovascular contractile receptor upregulation resulted from haemolysis in the subarachnoid space. This study developed a new magnesium-rich artificial cerebrospinal fluid (MACSF) formula and investigated its effects on receptor-mediated contraction in rat basilar arteries. Methods Clear and haemorrhagic cerebrospinal fluid (CSF) were collected from patients with hydrocephalus or SAH. MACSF was freshly prepared using clinical intravenous injections. Rat basilar arteries were segmented and incubated with clear CSF, haemorrhagic CSF or MACSF. The contractile responses were studied by myograph. The messenger ribonucleic acid (mRNA) and protein expression of 5-hydroxytryptamine 1B (5-HT1B), endothelin subtype B (ETB) and endothelin subtype A (ETA) receptors were evaluated by real-time polymerase chain reaction (PCR) and Western blot analyses. Results Haemorrhagic CSF exposure shifted the contractile curves induced by 5-hydroxytryptamine (5-HT), sarafotoxins 6c (S6c) and endothelin-1 (ET-1) leftward with increased maximal contraction values. Furthermore, mRNA and protein expression were markedly elevated for 5-HT1B, ETB and ETA receptors on arteries exposed to haemorrhagic CSF. However, the contractile responses to 5-HT, S6c or ET-1 and expression of 5-HT1B, ETB and ETA receptors in rat cerebral arteries exposed to MACSF remained unaffected compared to those exposed to clear CSF. Besides, unlike normal saline which can inactive in-vitro vessels, MACSF can maintain their physiological activity. Conclusion Haemorrhagic CSF induces upregulation of 5-HT1B, ETB and ETA receptors in rat cerebral arteries. However, MACSF can maintain in-vitro rat basilar arteries in good physiological activity and normal expression of contractile 5-HT and ET receptors.

Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction.

Glioma remains the leading cause of brain tumor-related death worldwide, and radiation is a standard adjuvant therapy with proven efficacy. Salvianolic acid B (SalB), a bioactive compound isolated from Radix Salviae, has been shown to exert anti-cancer effects in many cancer cell lines, including glioma. This study aimed to investigate whether SalB could affect response to radiation in human glioma cells. We found that SalB decreased cell viability of U87 cells in a-dose-dependent manner. A subthreshold dose of SalB at 0.5 µM, which had no effect on cell viability and apoptosis, significantly increased radiation sensitivity of U87 cells in a dose- and time-dependent manner, but had no effect on sensitivity to temozolomide (TMZ). Similar results were also observed in human glioma U373 cells. In addition, SalB aggravated the radiation-induced apoptosis and mitochondrial dysfunction, as measured by mitochondrial Ca2+ buffering capacity and mitochondrial swelling. SalB treatment markedly promoted mitochondrial fission and differently regulated the expression of fission proteins. Furthermore, downregulation of the fission protein Fis-1 using siRNA was found to partially reversed the SalB-induced effects on cell viability, apoptosis and mitochondrial fission in U87 cells. In conclusion, our results suggest that a subthreshold dose of SalB renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction, and radiotherapy combined with SalB might be a novel treatment for glioma patients.

[Effect of drainage of the cerebrospinal fluid at the acute period of aneurysmal subarachnoid hemorrhage on the formation of hydrocephalus].

OBJECTIVE: To discuss the effect of drainage of the cerebrospinal fluid (CSF) at acute period after aneurysmal subarachnoid hemorrhage (SAH) on the formation of hydrocephalus. METHODS: Eighty-four patients with aneurysmal SAH were randomly divided into two groups according to therapeutic regimen. Forty-two cases in specific treatment group were given intravascular embolism at the acute period of hemorrhage after a ruptured aneurysm, then CSF was drained immediately. Forty-two cases were in conventional expectant treatment group. Clinical data and incidence of hydrocephalus of specific treatment group and conventional expectant treatment group were analyzed. RESULTS: Clinical data did not show any differences between two groups, so they could be compared (all P>0.05). The incidence rate of acute hydrocephalus in specific treatment group was 7.14% (3/42 cases), that of subacute hydrocephalus was 4.76% (2/42 cases), and that of chronic hydrocephalus was 16.67% (7/42 cases). The total incidence rate was 28.57%. In conventional expectant treatment group, the incidence rate of acute hydrocephalus was 23.81% (10/42 cases), incidence of subacute hydrocephalus was 9.52% (4/42 cases), and that of chronic hydrocephalus was 35.71% (15/42 cases), and total incidence rate was 69.05%. There was significant difference between specific treatment group and conventional expectant treatment group in incidence of acute and chronic hydrocephalus (acute chi (2)=4.46, chronic chi (2)=3.94, both P<0.05), and there was no difference in subacute hydrocephalus between two groups (chi (2)=0.72, P>0.05), but significant difference was found in total incidence rate between two groups (chi (2)=13.77, P<0.01). CONCLUSION: Embolization of the intracranial aneurysm with interventional treatment at the acute hemorrhage stage (within 7 days) for the aneurysmal SAH, followed by immediate drainage of CSF can prevent hydrocephalus or alleviate hydrocephalus, and the treatment plays a significant role in the formation and development of hydrocephalus.

CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells.

Nutrient absorption mediated by nutrient transporters expressed in the intestinal epithelium supplies substrates to support intestinal processes, including epithelial cell proliferation. We evaluated the role of Caudal type homeobox 2 (CDX2), an intestine-specific transcription factor, in the proliferation of pig intestinal epithelial cells (IPEC-1) and searched for novel intestinal nutrient transporter genes activated by CDX2. Our cloned pig CDX2 cDNA contains a "homeobox" DNA binding motif, suggesting it is a transcriptional activator. CDX2 overexpression in IPEC-1 cells increased cell proliferation, the percentage of cells in S/G2 phase, and the abundance of transcripts of the cell cycle-related genes Cyclin A2; Cyclin B; Cyclin D2; proliferating cell nuclear antigen; and cell cycle cyclin-dependent kinases 1, 2 and 4, as well as the predicted CDX2 target genes SLC1A1, SLC5A1 and SLC7A7. In addition, luciferase reporter and chromatin immunoprecipitation assays revealed that CDX2 binds directly to the SLC7A7 promoter. This is the first report of CDX2 function in pig intestinal epithelial cells and identifies SLC7A7 as a novel CDX2 target gene. Our findings show that nutrient transporters are activated during CDX2-induced proliferation of normal intestinal epithelial cells.

Effect of ERBB2 expression on invasiveness of glioma TJ905 cells.

OBJECTIVE: To investigate the influence and possible mechanism of ERBB2 expression on the invasiveness of glioma cells. METHODS: Glioma TJ905 cells were separated and cultured. ERBB2 shRNA and overexpressing vectors were constructed, which were then transfected. The ERBB2 expression was up-regulated or down-regulated. Changes of invasiveness of TJ905 cells were detected by Transwell assay, and the expressions of matrix metalloprotease (MMP)-2 and MMP-9 were measured by Western blot. RESULTS: ERBB2 shRNA transfection vector could effectively inhibit expression of ERBB2; while ERBB2 overexpressing vector transfection could significantly improve the expression of ERBB2 in TJ905 cells. Transwell assay showed that when ERBB2 expression was down-regulated, the invasiveness of TJ905 cells was notably decreased; when ERBB2 expression was up-regulated, the invasiveness of TJ905 cells was markedly increased. Meanwhile, Western blot indicated that down-regulating ERBB2 inhibited the expression of MMP-2 and MMP-9, while up-regulating ERBB2 enhanced their expressions. CONCLUSIONS: ERBB2 expression is closely related to the invasiveness of glioma TJ905 cells.

Aspiration thrombectomy of acute complete carotid bulb occlusion.

Two patients with acute complete carotid bulb occlusion were treated using intra-arterial aspiration thrombectomy a mean of 3 hours after stroke onset. A slightly angulated 8-F guiding catheter designed for general interventional use was employed to aspirate the thrombus in the carotid artery. Manual aspiration through a 50-mL syringe resulted in effective removal of the thrombus followed by good patency of the internal carotid artery. Aspiration thrombectomy is a simple, feasible and effective rescue procedure for patients with acute complete carotid bulb occlusion.