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OBJECTIVE: To investigate the effect of γ-secretase inhibitor DAPT in inflammation-induced brain white matter injury in neonatal mice. METHODS: Sixty C57BL/10J neonatal mice are randomly divided into control group, control+DAPT (10 mg•kg-1) group, inflammation (LPS) group, LPS+DAPT group (inflammation exposure after 10 mg•kg-1 DAPT treatment). All neonatal mice were killed and brain was removed to the following observation and detection:at P5, the mRNA expression variation of IL-1β, IL-8,TNF-α,Hes1 and NICD by Real-time PCR methods. Oligodendrocytes were identified by immunofluorescence staining. Myelin basic protein (MBP) protein expression was detected by Western blot assay. RESULTS: LPS group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expression of IL-1β, IL-8, TNF-α, Hes1 and NICD between LPS+DAPT group and LPS group (P<0.05), and the mRNA expression of IL-1β, IL-8,TNF-α,Hes1 and NICD in inflammation-treated were significantly increased than control group (P<0.05). The results showed more expression of MBP in LPS+DAPT group compared with LPS group (P<0.05). Compared with the blank control group, which was obviously decreased after 48 h of inflammation (P<0.05).CONCLUSION: Inflammation leads to abnormal of notch signal expression in neonatal mice, and which is shows inflammation involved in brain damage.Its mechanism is probably associated with the maturation of oligodendrocytes.
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Objective To investigate the mechanism of affinity down-regulation between Von Willebrand factor mutant G561S and its ligand. Methods Three molecular systems were constructed for WT-A1, G561S-A1, and R543Q-A1, respectively. G561S-A1 mutant was constructed by replacing the Gly561 with Ser561 in the wild-type A1 domain. The crystal structures of WT-A1 and R543Q-A1 were downloaded from Protein Data Base (PDB). Free molecular dynamics simulation was performed to observe the changes of conformation, alterations of flexibility, and the formation and evolution of hydrogen bond and/or salt bridge, among the three A1 domains (WT-A1, G561S-A1, and R543Q-A1). ResultsG561S mutation lowered the localized dynamic properties of α2 helix and increased the interactions between the N-terminal arm and body region in A1 domain, thus leading to the decreased binding affinity with its ligand GPIbα. However, the Gain-of-function mutation R543Q followed the pathway which was contrary to G561S. ConclusionsThe change of localized dynamic properties of α2 helix is a potential mechanism in the regulation of the binding affinity of A1, and this research finding is helpful in developing allosteric drugs against the activated A1 domain and relevant anti-thrombus drugs.
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Objective To provide a quantitative analysis tool by building a mathematical model of seasickness habituation to make adaptive training plans scientifically for anti-seasickness purpose. Methods Based on the regular pattern of seasickness habituation, an exponential model of motion sickness incidence (MSI) was established to extract such seasickness habituation parameters as anti-motion sickness incidence (AMSI) and anti-motion sickness rate (μ) through making the seasickness habituation data fitting into the corresponding training, and the effects of AMSI and μ on MSI was also simulated. Results The data from two marine adaptive trainings were well fitted with the MSI model, and the fitting results of AMSI and μ were 0.87 and 0.048 for intermittent training, or 0.81 and 0.34 for continuous training. Effects of seasickness habituation training would be enhanced by increasing the value of AMSI and μ. Conclusions The present model of MSI is suitable for evaluating the effect of training on anti-seasickness and making the optimal strategy for such seasickness habituation training.
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Objective To develop a novel computer method for identifying the critical amino acid residues in the receptor-ligand interactions. Methods GPIbα/vWF-A1 crystal structure was taken from Protein Data Bank (PDB code 1SQ0). Free molecular dynamics simulations were performed to observe the formation and evolution of hydrogen bonding and salt bridge on the binding sites of GPIbα and vWF-A1 by VMD. A residue interaction index, which was scored with the survival ratios of salt bridges and/or hydrogen bonds involved in interaction of a residue to other(s), was used as a criterion of the residue’s role in interaction between the receptor and ligand. Results In the interface, 21 residues in GPIbα and 21 residues in vWF-A1 were significantly identified to participate in the interaction between GPIbα and vWF-A1; 20 of these 42 key residues were verified by previous mutagenesis experiments. Conclusions This novel approach is useful for computationally identifying the key residues involved in GPIbα-vWF interaction, and has potential in developing new strategy for the traditional mutagenesis experiments and the antithrombotic mAbs drug design.
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Objective: To evaluate the efficacy and safety of nimodipine for cerebral vasospasm (CVS) in patients with aneurysmal subarachnoid hemorrhage. Methods: The database of searched Pubmed, OVID, EMBase, Cochrane library, Stroke Trials Register (U. S. Clinical Trials Registry) , and the National Science and Technology Library up to November 2010 were reviewed. The prospective, randomized, controlled clinical trials about preventive application of nimodipine in patients with aneurysmal subarachnoid hemorrhage controlled clinical trials was collected. Meta-analysis was performed for the studies met the inclusion criteria. Results: Circled digit oneEight studies met the inclusion criteria. A total of 1499 patients completed the trials and observations of the different indicators respectively. In all the patients, the complete recovery rate increased 64% in the nimodipine group compared to the placebo group (P = 0.0002, OR = 1.64, 95% CI 1.26-2.13; the number of patients needed to treat [NNT] = -1.048). The patients with complete recovery or moderate disability increased 79% (P = 0.0007, OR = 1.79, 95% CI 1.28-2.51; NNT = -5.889); the rates of death, severe disability or vegetative survival decreased 38% (P = 0.0003, OR = 0.62, 95% CI 0.48-0.80; NNT = 1.529); the mortality of the patients with CVS decreased 74% (P = 0.008, OR = 0.26, 95% CI 0.09-0.71; NNT = 2.29%); the incidence of symptomatic CVS decreased 46% (P < 0.00001, OR = 0.54, 95% CI 0.42-0.69; NNT = 1.952); the incidence of delayed neurological deficits in all patients decreased 38% (P < 0.0001, OR = 0.62, 95% CI 0.50-0.78; NNT = 1.078); the incidence of symptomatic cerebral infarction decreased 46% (P < 0.00001, OR = 0.54, 95% CI 0.42-0.69; NNT = 1.079); the incidence of cerebral infarction confirmed by CT was 58% of the placebo group (P < 0.001, OR = 0.58, 95% CI 0.42-0.81; NNT = 3.314); the incidence of cerebral infarction in patients with CVS was 35% of the placebo group (P = 0.003, OR = 0.35, 95% CI 0.17-0.69; NNT = 3.688), and the incidence of cerebral infarction in all the patients was only 52% of the placebo group (P < 0.00001, OR = 0.52, 95% CI 0.41-0.66; NNT = 1.196); and there were no significant differences for the incidences of rehemorrhage and adverse reaction between the nimodipine group and the placebo group (rehemorrhage: P = 0.15, OR = 0.75, 95% CI 0.50-1.11; adverse reaction; P = 0.59, OR = 1.13, 95% CI 0.71 -1.81). Conclusion: Nimodipine may significantly improve the clinical outcome in patients with aneurysmal subarachnoid hemorrhage, and decrease the incidence of symptomatic CVS, delayed neurological deficits and cerebral infarction, while the incidence of rehemorrhage and adverse reaction were almost the same with the placebo group.
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Objective To describe the survival state and to investigate the risk factors of death on patients with subarachnoid hemorrhage (SAH). Methods Age, past history, number of encephalic region suffering SAH, laboratory examination indexes, therapeutic measures, complications and prognosis of 174 patients with SAH were followed-up and investigated. The survival states and risk factors of death of the patients with SAH were identified by both Kaplan-Meicr survival analysis and Cox proportional risk model. Results There were 10 patients (5.75%) losing follow-up investigation and 164 patients with SAH completed the follow-up investigation. 66 patients died and the longest follow-up invcstigation time was 5.64 years. The survival rates of 28 days, 1 year and 3-5 years were 70.60%,63.40% and 57.20% respectively. The treatment of nimotop, aneurysm occlusion treatment and aneurysm embolotherapy could decrease the death of SAH. At the same time, advanced age, the long time smoking, hyponatremia, the rising of leucocyte in acute stage, repeated hemorrhage and cerebral angio spasm were the independent risk factors to the death of patients. Conclusion Prognosis of patients with advanced age, the rising of leucocyte in acute stage, gastrointestinal blooding, hyponatremia, repeated hemorrhage and cerebral angio spasm were unfavorable. When giving patients with aneurysm, the aneurysm occlusion and embolotherapy and nimotop treatment, the death risk could be reduced.
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<p><b>OBJECTIVE</b>To investigate the value of contrast-enhanced ultrasound in the differential diagnosis of solid focal lesions of pancreas (s-FLPs).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 56 s-FLPs examined with contrast agent combined with low mechanical indicators contrast-enhanced ultrasound.</p><p><b>RESULTS</b>The surrounding pancreas parenchyma enhancement time, lesion enhancement time, and peak enhancement time between different groups of s-FLPs had no significant differences (P > 0.05), while the beginning to peak enhancement time showed significant difference (P < 0.05). When using the enhancement speed as a diagnostic indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 90.5%, 71.4%, and 85.7% for pancreatic carcinoma and 75.0%, 91.7%, and 89.3% for tumor-like pancreatitis. When using the enhancement pattern as a diagnosis indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 85.7%, 78.6%, and 83.9% for pancreatic carcinoma and 75.0%, 100%, and 94.6% for tumor-like pancreatitis. When different indicators were combined, enhancement pattern and enhancement speed showed the best diagnostic results; however, the Youden index was not improved.</p><p><b>CONCLUSIONS</b>Different s-FLPs show different enhancement findings on contrast-enhanced ultrasound. The enhancement pattern and enhancement speed are the most useful diagnostic indicators.</p>
Subject(s)
Humans , Diagnosis, Differential , Pancreas , Diagnostic Imaging , Pancreatic Neoplasms , Diagnostic Imaging , Pancreatitis , Diagnostic Imaging , Retrospective Studies , UltrasonographyABSTRACT
@#ObjectiveTo observe the effect of equilibrium therapy of decontamination living creature of blood dilution (ETBD) on acute cerebral infarction.Methods124 inpatients were divided randomly into the treatment group and control group with 62 cases in each group. The patients of the treatment group were treated with routine medicine and ETBD. The patients of the control group were treated only with routine medicine. The blood-lipid and blood viscosity were tested and nerve function evaluation was performed before and on the 15th day after the treatment in two groups.ResultsAfter treatment, the levels of blood-lipid, blood viscosity and nerve functions of all patients in two groups were better than that before the treatment, but the effect of the treatment group was better than that of the control group ( P<0.05), and no obvious adverse reaction was found.ConclusionETBD is a safe, effect, simply and convenient therapeutic method for acute cerebral infarction and it is suitable for primarily medical units.
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<p><b>OBJECTIVE</b>To evaluate the clinical performance of an innovative contrast-enhanced ultrasound (CEUS) technique in characterization of focal liver lesions (FLL).</p><p><b>METHODS</b>CEUS was performed in 505 patients with FLLs. A sulfur hexafluoride-filled microbubble ultrasound contrast agent and a continuous real-time imaging technique of contrast pulse sequencing were used. The observation items included initial nodule enhancement time, enhancement level and pattern, and dynamic evolution of enhancement along with the CEUS phases.</p><p><b>RESULTS</b>There were similar findings for both malignant and benign FLLs in initial enhancement time and enhancement level on CEUS. The dynamic evolution of enhancement along with enhancement phase was the most significant parameter for characterization of FLLs. Most malignant lesions showed enhancement at arterial phase and hypo-enhancing at late phase, whereas the benign lesions presented enhancement at arterial phase and persistent hyper- or iso-enhancing until late phase. Using these characteristics as a diagnostic criteria, the sensitivity, specificity, positive predicative value, negative predicative value and accuracy of CEUS in identifying malignant FLLs were 95.7% (313/327), 86.0% (153/178), 92.6% (313/338), 91.6% (153/167) and 92.3% (466/505), respectively.</p><p><b>CONCLUSIONS</b>Characterization of FLLs by using the innovative CEUS technique is recommendable due to its safety, facility and high accuracy.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Diagnosis, Differential , Liver Diseases , Diagnostic Imaging , Sulfur Hexafluoride , Ultrasonography , MethodsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical values of ultrasound-guided percutaneous composite thermal ablation technique in the treatment of medium and large hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>By the composite technique of multiple-needle insertion and multi-point energy application, ultrasound-guided percutaneous radiofrequency ablation (RFA) or microwave ablation (MWA) were employed to treat 68 patients of HCC with tumor nodule > or = 3.1 cm in diameter. There was a total number of 73 tumor nodules, with a mean diameter of (4.5 +/- 1.7) cm (3.1-13.0 cm). Sixty-three patients had single tumor nodule, and the remaining 5 had 2 nodules. With a follow-up time of 1.9 - 67.6 months [(16.0 +/- 14.8) months], the local and long-term efficacy was analyzed.</p><p><b>RESULTS</b>Hepatic subcapsular hematoma were found in 1 patient. And skin burning in 1 patient 1. Complete ablation rate was 78.1% (57/73), local tumor progression was presented in 24.6% tumor nodules (14/57) and distant recurrence developed in 56.7% patients (38/67). The 1-, 3-, 5-years survival rate was 62.3%, 29.6% and 21.6%, respectively, with a median survival time of 18.6 months, (95% confidence interval: 10.9 months, 26.3 months). There were no remarkable differences in complete ablation rate, local tumor progression, distant recurrence rate and survival rate between RFA and MWA.</p><p><b>CONCLUSIONS</b>By the composite ablation technique, ultrasound-guided percutaneous thermal ablation was effective in treating medium and large unresectable HCC. And the advantage is minimal invasiveness. RFA and MWA had no marked differences in terms of therapeutic efficacy.</p>