[Application of hybrid surgery in the clipping of large complex paraclinoid aneurysms].

Nine patients with large complex paraclinoid aneurysms were treated by hybrid surgery in the Second Affiliated Hospital of Zhejiang University between January 2016 and July 2021. Intraoperative angiography was conducted for real-time evaluation of the aneurysm and its clipping efficacy. A total of 8 aneurysms were clipped under temporary proximal control with balloon occlusion. Suction decompression was simultaneously applied in 2 of these cases. After surgery, 2 patients developed symptomatic cerebral infarction, 3 patients developed transient oculomotor nerve palsy, but no patients had vision deterioration. Postoperative follow-up showed that small neck residue occurred in 1 case, but with the rest of aneurysms were completely occluded without parent artery stenosis. Hybrid surgery was proved to be advantageous in real-time assessment of aneurysm morphology and clipping efficacy. Combination of temporary proximal balloon occlusion and suction decompression technique can help in reducing the difficulty of aneurysm exposure and remodeling, thereby improving the outcome and decreasing the complications.

[A multicenter study on the prognostic factors of one year outcomes in patients with poor grade intracranial aneurysm after early treatment].

OBJECTIVES: To explore the one year outcome of subarachnoid hemorrhage (SAH) patients with poor grade intracranial aneurysm who underwent early treatment (within 72 hours), and to analyze the possible predictors of the prognosis. METHODS: This clinical study was a prospective, multicenter, observational registry of SAH patients with poor grade intracranial aneurysm. Data pertaining to 203 SAH patients with poor grade intracranial aneurysm between October 2010 and March 2013 from 10 medical centers. There were 100 male and 103 female patients. Neurological outcomes at 12 months after the surgery were measured using the Glasgow Outcome Scale (GOS). Genders, age, smoke, breath, herniation, aneurysm location, World Federation of Neurosurgical Societies (WFNS) grade, CT Fisher's grade, alcohol consumption, aneurysm diameter, surgical procedure and operation time were identified as possible prognostic factors, the association between possible prognostic factors and outcome were analyzed, using univariate and multivariate analysis. Univariate analysis included Wilcoxon rank sum test, Kruskal-Wallis H test and Nemenyi test, multivariate analysis included Logistic regression test. RESULTS: Among 203 patients, 94 patients were WFNS grade Ⅳ, and 109 patients were WFNS grade Ⅴ; 31 patients were CT Fisher's grade 1 to 2, 172 patients were CT Fisher's grade 3 to 5. Herniation (OR=2.535, 95%CI: 1.204 to 5.339, P=0.014), WFNS grade Ⅴ (OR=3.728, 95%CI: 1.972 to 7.043, P=0.000), CT Fisher's grade 3 to 5 (OR=5.641, 95%CI: 2.032 to 15.643, P=0.001), and anterior circulation location (OR=6.234, 95%CI: 1.996 to 19.472, P=0.002) were found to be independent prognostic factors of unfavorable prognosis. CONCLUSIONS: Early surgical treatment could improve the prognosis of SAH patients with poor-grade-aneurysm. The patients with herniation, WFNS grade Ⅴ, CT Fisher's grade 3 to 5, anterior circulation aneurysms suffered unfavorable prognosis.

Terbinafine inhibits KSR1 and suppresses Raf-MEK-ERK signaling in oral squamous cell carcinoma cells.

Terbinafine inhibits the proliferation of many types of cancer cells, but the underlying mechanism remains to be determined. By computer simulation, we found that kinase suppressor of Ras 1 (KSR1) is a possible target of terbinafine. Treatment of human oral squamous cell carcinoma (OSCC) KB cells with either terbinafine or siRNA to knockdown KSR1 reduced proliferation and induced apoptosis, which was accompanied by suppression of the Raf-MEK-ERK pathway. In vivo, KSR1 expression was significantly associated with the clinical staging of OSCC and the smoking habit of patients. Kaplan Meyer survival analysis demonstrated that the cumulative survival time of patients without KSR1 expression was significantly longer than those with KSR1 overexpression. Our data provide the basis for developing terbinafine to treat OSCC.

MiR-141 promotes cell proliferation and invasion in non-small cell lung cancer by targeting KLF9.

OBJECTIVE: Non-small cell lung cancer is the cancer with the highest mortality rate in the whole world. MicroRNA-141 (miR-141) has been reported to be an abnormal expression in multiple tumors including in non-small cell lung cancer. The aim of this study was to verify the potential roles of miR-141 in non-small cell lung cancer and evaluate the effects on cell proliferative and invasive abilities. PATIENTS AND METHODS: MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were conducted to calculate the tissues and cell lines' proliferative and invasive abilities. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blotting were utilized to evaluate the mRNA and protein levels of specific genes. RESULTS: MiR-141 was significantly upregulated, while krüppel-like factor 9 (KLF9) downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. MiR-141 and KLF9 mRNA levels had a negative correlation in NSCLC tissues. The overexpression of miR-141 promoted the proliferation and invasion of A549 cells, while caused contrast results when knockdown miR-141. In addition, KLF9 was a direct target gene of miR-141 and KLF9 partially reversed the roles of miR-141 in A549 cells. MiR-141 promoted the proliferation and invasion by binding to KLF9 in NSCLC. CONCLUSIONS: MiR-141 promoted the proliferation and invasion by targeting the KLF9 in non-small cell lung cancer, and the newly identified miR-141/KLF9 axis provides novel insight into the pathogenesis of non-small cell lung cancer.

Combinatorial transcriptional regulation: the interaction of transcription factors and cell signaling molecules with homeodomain proteins in Drosophila development.

Patterning and cell fate specification during development require complex interplay among multiple families of transcription factors to establish, maintain, and coordinate transcriptional cascades. During these processes, homeodomain proteins and cell signaling proteins cooperate to generate tissue-and stage-specific responses. This review of physical and genetic interactions in Drosophila melanogaster development highlights the cross-talk among these protein families. Protein-protein association can modulate regulation by both signal transduction-regulated transcription factors and homeodomain proteins, as observed in Drosophila and other organisms. Enhancers or genes regulated by multiple transcription factors provide opportunities for protein-protein binding to modulate transcription factor function. Combinatorial regulation of several enhancers by homeodomain proteins and cell signaling-regulated transcription factors is discussed; detailed maps of the genetic interactions that pattern the embryonic midgut and the larval wing imaginal disc are used to illustrate the multiplicity of potential protein-protein interactions. These interactions potentially provide direct mechanisms for communication between transcription factors as well as for generating the requisite functional specificity.

Inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by cocaine, norcocaine and cocaethylene in rat brain.

The interaction of cocaine, its metabolites norcocaine and benzoylecgonine, and cocaethylene, which is formed following a combined cocaine and ethanol exposure, with muscarinic receptor binding and phosphoinositide metabolism was investigated in brain from immature rats. Cocaine and norcocaine inhibited binding of [3H]telenzepine and carbachol-stimulated phosphoinositide metabolism in cerebral cortex, while benzoylecgonine was devoid of any inhibitory activity. Cocaethylene was the most potent inhibitor of both binding and phosphoinositide metabolism. The effect of cocaine was more pronounced at the muscarinic receptors, but a small inhibition of histamine--and serotonin--stimulated phosphoinositide metabolism was also observed.

Long-lasting microencephaly following exposure to cocaine during the brain growth spurt in the rat.

In utero exposure to cocaine has been shown to produce somatic and behavioral effects. As microencephaly is often present in children born from cocaine-addicted mothers, aim of the present study was to develop an animal model for cocaine-induced microencephaly. Rats were treated with cocaine (20, 30 or 50 mg/kg/day, s.c., each dose divided in two equal doses given 3 h apart) from postnatal day 4 through 10. None of the doses had any effect on growth, however, at 50 mg/kg, cocaine caused a significant decrease in brain weight, measured on day 12. The effect of cocaine was similar in male and female rats, and microencephaly was still present in 45-day-old animals. When the same dose of cocaine was given as a single daily injection, long-lasting microencephaly was also present, but it was accompanied by a decrease in body weight and significant toxicity. Ethanol (4 g/kg), used as a positive control, also caused microencephaly without affecting body weight, but, differently from cocaine, its effect was more pronounced in female animals. Blood and brain levels of cocaine and its metabolites norcocaine and benzoylecgonine were measured by HPLC during treatment (postnatal day 8). After administration of the 50 mg/kg dose, concentrations of cocaine were 1.92 micrograms/g in brain and 0.94 microgram/ml in blood. These levels are encountered in cases of cocaine overdoses and have been found in meconium of newborns from crack-addicted mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal development of muscarinic receptor-stimulated phosphoinositide metabolism in mouse cerebral cortex: sensitivity to ethanol.

An enhanced coupling of cholinergic muscarinic receptors to phosphoinositide metabolism had been previously observed in brain from immature rat. This study reports that the postnatal development of muscarinic receptor-stimulated phosphoinositide metabolism is also enhanced in cerebral cortex slices from immature Swiss-Webster and Balb-c mice, as compared to adults. Response to the agonist carbachol was lower on postnatal day 3, peaked between days 5 and 12 and then declined to adult levels. Density of muscarinic binding sites, measured with the M1 ligand [3H]telenzepine on postnatal day 7, was, on the other hand, only half of the adult value. Phosphoinositide hydrolysis stimulated by glutamate decreased with age, while that elicited by norepinephrine increased. These results are also similar to those previously reported in the rat. Ethanol has been found to inhibit muscarinic receptor-stimulated phosphoinositide metabolism in rat brain in an age-dependent manner. This was confirmed in mouse brain, where ethanol inhibited this response in cerebral cortex of immature but not adult animals. These results indicate that the enhanced muscarinic receptor-stimulated phosphoinositide metabolism, which coincides with the brain growth spurt, is similar in rats and mice. Mice may be a useful species in which to genetically manipulate muscarinic receptors to gain a better understanding of their potential role in brain development.

Interaction of ethanol with muscarinic receptor-stimulated phosphoinositide metabolism during the brain growth spurt in the rat: role of acetaldehyde.

The developing brain is extremely sensitive to the neurotoxicity of ethanol; however, the mechanism(s) of its developmental neurotoxicity are still elusive. In the developing rat brain, ethanol exerts an age-, brain region-, and receptor-specific inhibitory effect on muscarinic receptor-stimulated phosphoinositide metabolism, which may be linked to some of the neurotoxic effects of ethanol found in children with fetal alcohol syndrome. Since some studies have suggested that the ethanol metabolite acetaldehyde may mediate, at least in part, the developmental effects of ethanol, in the present study we have examined whether acetaldehyde would inhibit carbachol-stimulated phosphoinositide metabolism in brain slices from immature rats. We also tested propionaldehyde, the corresponding aldehyde of n-propanol, another alcohol shown to cause microencephaly and to affect phosphoinositide metabolism in the developing rat. Neither acetaldehyde nor propionaldehyde, at concentrations up to 1 mM, had any inhibitory effect on this system, while the two alcohols did, as previously reported. These results suggest that ethanol itself may be the primary agent responsible for its developmental neurotoxicity.

Biomarkers in environmental medicine: alterations of cell signalling as early indicators of neurotoxicity.

Many environmental and occupational chemicals are known to affect the central and/or peripheral nervous system, causing changes that may result in neurological and psychiatric disorders. Because of the limited accessibility of the mammalian nervous tissue, new strategies are being developed to identify biochemical parameters of neuronal cell function, which can be measured in easily obtained tissues, such as blood cells, as potential markers of the chemically-induced alterations occurring in the nervous system. This review includes a comparative analysis of the effects of mercurials on calcium signalling in the neuroadrenergic PC12 cells and rat splenic T lymphocytes in an attempt to characterize this second messenger system as a potential indicator of subclinical toxicity. The suitability of neurotransmitter receptors in blood cells, such as the sigma binding sites, as biological markers of psychiatric disorders is also discussed.

Effects of inorganic and organic mercury on intracellular calcium levels in rat T lymphocytes.

The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura-2 as fluorescent Ca2+ indicator, we found that both methyl-mercury (MeHg; 0.02-2 microM) and inorganic mercury (HgCl2; 0.01-1 microM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration-dependent manner. The effect of MeHg was rapid and the increase of Ca2+ level was sustained in time, while HgCl2 caused a slow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCl2 quench between control and mercury-treated cells. However, HgCl2 (1 microM) and MeHg (2 microM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca(2+)-free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCl2 had no effect. Heparin, an inhibitor of inositol 1,4,5-trisphosphate-induced Ca2+ mobilization partially blocked this rise of [Ca2+]i, while carbonyl cyanide m-chlorophenylhydraxone (CCCP), an inhibitor of mitochondrial function, had a lesser effect. When added together, heparin and CCCP almost completely block the response to MeHg. These results suggest that MeHg and HgCl2 exert their effects of [Ca2+]i in different ways: MeHg-induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCl2 causes only Ca2+ influx from the extracellular medium.