Lung imaging characteristics in a patient infected with Elizabethkingia miricola following cerebral hemorrhage surgery: A case report.

BACKGROUND: Elizabethkingia miricola is a non-fermenting gram-negative bacterium, which was first isolated from the condensate of the Russian peace space station in 2003. Most studies on this bacterium have been carried out in the laboratory, and clinical case studies are rare. To date, a total of 6 clinical cases have been reported worldwide. CASE SUMMARY: We present the first case of postoperative pulmonary infection in a patient with intracerebral hemorrhage due to Elizabethkingia miricola. The imaging characteristics of pulmonary infection were identified and the formulation and selection of the clinical treatment plan for this patient are discussed. CONCLUSION: Elizabethkingia miricola infection is rare. When pulmonary infection occurs, computed tomography imaging may show diffuse distribution of a ground glass density shadow in both lungs, the air containing bronchial sign in local areas, thickening of bronchial vascular bundle, and pleural effusion.

The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and ß-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma.

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and ß-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ß-elemene liposome and cabazitaxel-ß-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ß-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and ß-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ß-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ß-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that ß-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

Efficacy and Safety of Microvascular Decompression and Gamma Knife Surgery Treatments for Patients with Primary Trigeminal Neuralgia: A Prospective Study.

PURPOSE: To compare efficacy and safety of microvascular decompression (MVD) and Gamma Knife surgery (GKS) treatments for trigeminal neuralgia. METHOD: Patients with primary trigeminal neuralgia were randomly divided into 2 groups to undergo either MVD or GKS. All patients were followed for 2 years to evaluate efficacy, recurrence rates, and complications of treatment. RESULTS: Of 441 enrolled patients, 220 were in the MVD group, and 221 were in the GKS group. There were no deaths in either group. At the 2-year follow-up, 183 patients (83%) in the MVD group reported complete pain relief, 5 (2%) had obvious pain relief, and 20 (9%) had no relief. In the GKS group, 55 patients (25%) reported complete pain relief, 106 (48%) had obvious pain relief, and 37 (17%) had no relief. There was no significant difference in the recurrence rate (0.45% vs. 0.9%) between the 2 groups. The most common complications in the MVD group were chemical meningitis (6%), cerebrospinal fluid leakage (4%), and facial palsy (4%). Loss of corneal reflex (6%) and facial numbness (5%) were the most common complications in the GKS group. CONCLUSIONS: Both MVD and GKS are effective surgical treatments for trigeminal neuralgia. The rate of complete pain relief in the MVD group was significantly superior to the rate of complete pain relief in the GKS group. There was no significant difference in recurrence rates between the groups; however, there were more severe complications in the MVD group than in the GKS group.

Neuroprotective effects of p53/microRNA­22 regulate inflammation and apoptosis in subarachnoid hemorrhage.

The present study aimed to investigate whether the neuroprotective effects of p53/microRNA­22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA­22 expression was upregulated. In addition, downregulation of microRNA­22 in HEB cells increased the mRNA expression levels of interleukin (IL)­6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B­cell lymphoma 2­associated X protein (Bax) and caspase­3 activity. Treatment with the p53 inhibitor, pifithrin­α, suppressed p53 protein expression, increased IL­6 mRNA expression, decreased microRNA­22 expression, Bax protein expression and caspase­3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA­22 expression and increased IL­6 mRNA expression, inhibited Bax protein expression and caspase­3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA­22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.

c-Ski inhibits autophagy of vascular smooth muscle cells induced by oxLDL and PDGF.

Autophagy is increasingly being recognized as a critical determinant of vascular smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski inhibits VSMC proliferation stimulated by transforming growth factor ß (TGF-ß), but it is not clear whether c-Ski has the similar protective role against other vascular injury factors and whether regulation of autophagy is involved in its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs were treated with 40 µg/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml platelet-derived growth factor (PDGF), both of which were autophagy inducers and closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy. This action of c-Ski resulted in inhibiting the cell proliferation, the decrease of contractile phenotype marker α-SMA expression while the increase of synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF. Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL or PDGF on A10 cell growth and phenotype transition. And further investigation found that inhibition of AKT phosphorylation to downregulate proliferating cell nuclear antigen (PCNA) expression, was involved in the regulation of autophagy and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs. Collectively, c-Ski may play an important role in inhibiting autophagy to protect VSMCs against some harsh stress including oxLDL and PDGF.

Anemia on admission increases the risk of mortality at 6 months and 1 year in hemorrhagic stroke patients in China.

BACKGROUND: The relationship between anemia and intracerebral hemorrhage is not clear. We investigated the associations between anemia at the onset and mortality or dependency in patients with intracerebral hemorrhage (ICH) registered at the China National Stroke Registry (CNSR). METHODS: The CNSR recruited consecutive patients with diagnoses of ICH in 2007-2008. Their vascular risk factors, clinical presentations, and outcomes were recorded. The mortality and dependency at 1, 3, and 6 months and at 1 year were compared between ICH patients with and without anemia. A favorable outcome was defined as a modified Rankin Scale (mRS) score of 2 or less and a poor outcome as an mRS score of 3 or more. Multivariable logistic regression was performed to analyze the association between anemia and the 2 outcomes after adjusting for age, gender, body mass index, history of smoking and heavy drinking, National Institutes of Health Stroke Scale score on admission, random glucose value on admission, and hematoma volume. RESULTS: Anemia was identified in 484 (19%) ICH patients. Compared with ICH patients without anemia, patients with anemia had no difference in mortality rate at discharge and at 1 month. The rate of mortality at 3 months, 6 months, 1 year, and dependency at 1 year were significantly higher for those patients with anemia than those without (P<.05, P<.001, P<.001, and P<.05, respectively). After adjusting for potential confounders, anemia was an independent risk factor for death at 6 months and 1 year (adjusted odds ratio [OR]=1.338, 95% confidence interval 1.01-1.78, and adjusted OR=1.326, 95% confidence interval 1.00-1.75) in ICH patients. CONCLUSIONS: Anemia independently predicted mortality at 6 months and 1 year after the initial episode of intercerebral hemorrhage.

A feedback loop in PPARγ-adenosine A2A receptor signaling inhibits inflammation and attenuates lung damages in a mouse model of LPS-induced acute lung injury.

Although peroxisome proliferator-activated receptor-γ (PPARγ) and adenosine A2A receptor (A2AR) are reported to be anti-inflammatory factors in acute lung injury (ALI), their internal link and synergic or antagonistic effect after activation are poorly understood. Here, we found that PPARγ and A2AR could upregulate the mRNA and protein expressions of each other in lung tissues of LPS-induced mouse ALI model and murine macrophages. Further investigation demonstrated that PPARγ upregulated A2AR expression by directly binding to a DR10 response element (-218 to -197) within A2AR gene promoter region. Instead of directly interacting with PPARγ, A2AR stimulated PPARγ expression via protein kinase A (PKA)-cAMP response element binding protein (CREB) signaling by provoking the binding of CREB to a cAMP responsive element (CRE)-like site in PPARγ gene promoter region. In addition, combination of PPARγ and A2AR agonists was found to exert obviously better effect on suppressing neutrophil infiltration and inflammatory cytokine expressions, attenuating lung edema, pathological changes and improving lung function of blood gas exchange than their single application. These findings reveal a novel functional positive feedback loop between PPARγ and A2AR signaling to potentialize their effect on inhibiting inflammation and attenuating lung damages in ALI. It suggests that targeting this PPARγ-A2AR signaling rather than PPARγ or A2AR alone may be a more attractive and efficient potential therapeutic strategy for ALI.

Sinomenine protects against lipopolysaccharide-induced acute lung injury in mice via adenosine A(2A) receptor signaling.

Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO2/FIO2 (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1ß expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A(2A) receptor (A(2A)R) expression, and the protective effect of SIN was abolished in A(2A)R knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A(2A)R by SIN and showed that A(2A)R-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A(2A)R-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI.

MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRα.

BACKGROUND: MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor α (LXRα), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells. METHODS: HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXRα and its target genes involved in lipogenesis, binding site for miR-613 in 3'-untranslated region (3'-UTR) of LXRα mRNA and lipid droplet accumulation in the cells. RESULTS: MiR-613 dramatically suppressed the expression of LXRα and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3'-UTR of LXRα mRNA. Moreover, miR-613 significantly repressed LXRα-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXRα without 3'-UTR markedly attenuated the miR-613-mediated downregulation of LXRα's target genes and LXRα-induced lipid droplet accumulation. CONCLUSIONS: MiR-613 suppresses lipogenesis by directly targeting LXRα in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.

Minimally-invasive treatment of communicating hydrocephalus using a percutaneous lumboperitoneal shunt.

OBJECTIVE: To investigate the clinical value of a minimally-invasive treatment of communicating hydrocephalus using a percutaneous lumboperitoneal (LP) shunt. METHOD: The clinical and long-term follow-up data of 256 patients suffering from communicating hydrocephalus and undergoing percutaneous LP shunt during 1998 to 2008 were retrospectively analyzed. RESULTS: After the follow-up, which lasted 6 months to 10 years, 219 cases of communicating hydrocephalus recovered well (ventricular size returned to normal and symptoms completely disappeared), 25 cases were brought under control (ventricle size reduced by 50% and symptoms partially abated), and 12 cases showed no obvious changes. Fifteen obese subjects needed modifications of the shunt due to the obstruction of the abdominal end following wrapping, and one subject underwent extubation as the subject was unable to tolerate stimulation of the cauda equina. The effectiveness of shunting was 91.40% and the probability of shunt-tube obstruction, which occurs predominantly in the abdominal end, was only 5.85%, far lower than that of ventriculoperitoneal (VP) shunt. Three subjects had a history of infection following VP shunting. CONCLUSION: LP shunting is minimally invasive and effective in treating communicating hydrocephalus, with fewer complications.

[PPARγ up-regulates TGFß/smad signal pathway repressor c-Ski].

TGFß/smad pathway is recognized as an important signal pathway to promote the pathogenesis of atherosclerosis (AS). Peroxisome proliferator-activated receptor γ (PPARγ) activation is considered to be important in modulating AS. Herein, we investigated the regulation of PPARγ on c-Ski, the repressor of TGFß/smad pathway, in rat AS model and cultured vascular smooth muscle cells (VSMCs). c-Ski mRNA and protein expression were detected by real-time PCR and Western blot, respectively, in vivo and in vitro with treatment of PPARγ agonist rosiglitazone and antagonist GW9662. The proliferation and collagen secretion of VSMCs after c-Ski transfection were investigated. The underlying mechanism was further investigated by online program NUBIScan and luciferase reporter gene analysis. Results showed that both mRNA and protein expressions of c-Ski in the AS lesions was down-regulated in vivo, while in cultured VSMCs, c-Ski transfection significantly suppressed the proliferation and collagen secretion of rat VSMCs. Rosiglitazone significantly up-regulated mRNA and protein levels of c-Ski in VSMCs, which could be blocked by GW9662. Online NUBIScan analysis suggested possible PPARγ binding sites in the promoter region of c-Ski. In addition, luciferase activity of c-Ski reporter gene was also increased obviously in the presence of rosiglitazone. These results indicate that c-Ski is one of the newly found target genes of PPARγ and thus involved in the anti-AS effect of PPARγ.

Chronic or high dose acute caffeine treatment protects mice against oleic acid-induced acute lung injury via an adenosine A2A receptor-independent mechanism.

The antagonism or genetic deletion of adenosine A(2A) receptors has been shown to exacerbate tissue damage in acute lung injury. Caffeine, a widely consumed behavioral drug, acts as a non-selective antagonist of A(2A) receptor and also has additional pharmacological effects. Thus, the protective vs. deleterious effects of caffeine in acute lung injury should be evaluated. In a murine oleic acid-induced model of acute lung injury, we found that chronic caffeine treatment by drinking water (0.1g/l or 0.25g/l for 2 weeks before acute lung injury) or acute caffeine treatment at high dose (i.p. 50mg/kg, injection, 30min before acute lung injury) significantly attenuated the lung edema, hemorrhage, neutrophil recruitment as well as the inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) expressions in both of the wild type (WT) and A(2A) receptor knockout (KO) mice. This profile was accompanied by increased cAMP levels and up-regulation of A2B receptor mRNAs in the lungs. In contrast, acute caffeine treatment at low dose (i.p. 5mg/kg or 15mg/kg, injection, 30min before acute lung injury) enhanced the inflammation and lung damage in WT mice with decreasing cAMP but not in A(2A) receptor KO mice. These results indicate that caffeine either enhances lung damage by antagonizing A(2A) receptor or exerts protection against lung damage via A(2A) receptor-independent mechanisms, depending on the timing of exposure (chronic vs. acute) and dose of administration (low vs. high). These findings provide new insight of caffeine in acute lung injury and highlight the potential benefit and strategy of caffeine intake or administration for preventing acute lung injury.

Detection of human herpes virus 6B in patients with mesial temporal lobe epilepsy in West China and the possible association with elevated NF-κB expression.

BACKGROUND: There has been a long-standing suspicion that an association exists between mesial temporal lobe epilepsy (MTLE) and the herpes virus. Evidence for HHV-6B involvement has been reported. However, no investigation has been performed in China. METHODS: We used nested PCR and immunohistochemistry to detect viral DNA of human herpes virus (HHV)-6B, HHV-6A, herpes simplex virus (HSV)-1 and HSV-2 in resected brain tissues from patients with MTLE and control. A principal transcription factor, NF-κB, that is associated with the inflammatory response was also investigated by real-time PCR, western blotting and immunohistochemistry. RESULTS: HHV-6B DNA was detected in hippocampal samples from 9 out of 32 (28.1%) patients with MTLE and in 1 of 12 (8.3%) control samples. Immunoreactivity for HHV-6B was consistently present in MTLE patients positive for HHV-6 detected by PCR. Significant staining for HHV-6B antigen was distributed mainly around or in the nucleus of cells that morphologically resembled astrocytes and microglia. HHV-6B positivity was related to febrile convulsion history of patients with MTLE. The expression of NF-κB was up-regulated and distributed in the nucleus of glial cells in MTLE patients positive for HHV-6B. CONCLUSION: This study was first to find HHV-6B in MTLE patients from West China and demonstrate a possible association between HHV-6B positivity and activation of NF-κB. The detailed role of HHV-6B and its association with NF-κB in the development of chronic MTLE requires further investigation.

The epidemiology and clinical management of craniocerebral injury caused by the Sichuan earthquake.

BACKGROUND: Earthquake is one of the most devastating natural disasters that threaten human lives. Worldwide more than 3 million deaths have been caused by earthquakes in recent 20 years. AIM: To analyze clinical features of head injuries after Sichuan earthquake. MATERIALS AND METHODS: From May 12 to June 12, 2008, Departments of Neurosurgery in major Hospitals in Sichuan Province admitted 1368 patients with head injuries caused by the Sichuan earthquake; the epidemiology, mechanism, severity, complications, treatments and outcome of head injury were retrospectively analyzed. RESULTS: Of the 1,368 patients, 755 were men and 613 women. Collapsing building was the most important cause of head injury. Most of the patients, 85% had mild to moderate head injury. The type of injury was open scalp injury in 65% of patients. About 47% of the head-injured patients were admitted within 72 h after earthquake. Skeletal bone fracture was the most common associated injury (9%). Only 98 patients received surgery. Glasgow Outcome Scale on discharge or transfer was: 5 in 1,121 (82%) patients, 4 in 173 (13%) patients, and 3 or less in 74 (5%) patients. Overall 33 (2%) patients died. CONCLUSIONS: The characteristics of Sichuan earthquake-related head injury are quite distinct. Early standardized treatment is important to have better outcomes.

Aberrant glutamate receptor 5 expression in temporal lobe epilepsy lesions.

Glutamate receptor 5 (GluR5) plays a role as an excitatory regulator of synaptic transmission and plasticity; however, its exact role in the pathological mechanism underlying epilepsy is not fully known. We investigated GluR5 expression in resected brain tissues from humans with temporal lobe epilepsy (TLE) and from a macaque model of Coriaria lactone-induced TLE. GluR5 was upregulated in the hippocampus, but not in the temporal neocortex, of patients with TLE compared to the control group. In contrast, GluR5 expression in the hippocampus of macaques treated with Coriaria lactone was not upregulated compared to the control. In addition, mossy fiber sprouting in the hippocampus of TLE patients was correlated with GluR5 upregulation, whereas mossy fiber sprouting was not observed in the macaque model lacking GluR5 upregulation, suggesting that GluR5 function is mainly associated with mossy fiber sprouting.