Outcome Following the Treatment of Ventriculitis Caused by Multi/Extensive Drug Resistance Gram Negative Bacilli; Acinetobacter baumannii and Klebsiella pneumonia

Introduction: CNS ventriculitis is a serious complication following an intracranial insult that demands immediate treatment with broad-spectrum antibiotics in a critical care setting. Infections due to multi/extensive drug resistance (MDR/XDR) microorganisms are very challenging, which may demand an additional approach to the ongoing practice; intravenous and intraventricular administration of antibiotics.Aim: To study the efficacy and safety of thorough ventricular irrigation followed by daily intraventricular antibiotic administration in patients with MDR/XDR ventriculitis.Materials and Methods: A retrospective analysis was done on 19 inpatients with ventriculitis caused by Acinetobacter baumannii (AB) or Klebsiella pneumonia (KP), at Shanghai Tenth People's Hospital from January 2016 to October 2017. We reviewed our experience; the role of thorough ventricular irrigation with Colistin mixed normal saline, followed by intraventricular Colistin therapy. Treatment outcomes were evaluated based on the clinical symptoms, Cerebro-Spinal Fluid (CSF) culture, laboratory findings and complications.Results: A total of 19 patients were included (15 males and 4 females), with a mean age in years of 51, which ranged from 18–67. Fourteen patients had Acinetobacter baumannii (AB) and 5 had Klebsiella pneumoniae (KP). The average CSF sterilization period following ventricular irrigation and intraventricular Colistin was 6 days. Sixteen patients (84%) were cured, and 3 patients (15%) died during the course of the treatment.Conclusion: In addition to Intraventricular Colistin, thorough ventricular irrigation could increase the cure rate up to 84% in patients suffering from MDR/XDR CNS ventriculitis

Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival.</p> <p>Methods</p> <p>Tissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC <it>in vitro</it>.</p> <p>Results</p> <p>Skp2 expression correlated closely with the T category (<it>p</it> = 0.035) and the pathological tumor-node-metastasis (TNM) stage (<it>p</it> = 0.027). High expression of Skp2 was associated with poor overall survival in resectable ESCC (<it>p</it> = 0.01). The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. <it>In vitro</it> assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs.</p> <p>Conclusions</p> <p>Negative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.</p

Inhibiting Receptor of Advanced Glycation End Products Attenuates Pressure Overload-Induced Cardiac Dysfunction by Preventing Excessive Autophagy

The receptor for advanced glycation end products (RAGE) is involved in heart failure (HF) by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, the role of RAGE in pressure overload-induced HF is not well understood. We found that stimulation of RAGE triggered the death of neonatal rat ventricular myocytes (NRVMs), while cell death was alleviated by ATG5 knockdown. Using transverse aortic constriction (TAC) in mice as a model of pressure overload-induced HF, we demonstrated that RAGE knockout or RAGE blockade attenuated cardiac hypertrophy and fibrosis as well as cardiac dysfunction at 8 weeks after TAC. Importantly, RAGE knockout reversed upregulation of autophagy related proteins (LC3BII/I and Beclin 1) and reduced cardiomyocyte death, indicating that excessive autophagy after TAC was inhibited. Moreover, RAGE knockout or blockade reduced the upregulation of pp65-NFκB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of HF by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

Aqueous Extract of Clerodendranthus spicatus

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is commonly used to treat kidney diseases in traditional Chinese medicine for its prominent anti-inflammatory effect and nourishing function to kidneys. In this study, aqueous extract of CS was assessed for its protective effect on UV-induced skin damage of mice. The chemical compositions of CS aqueous extract were determined by HPLC-ESI-MS/MS, in which 10 components were identified. During the experimental period, CS (0.9, 1.8, and 3.6 g/mL) was externally applied to shaved dorsal skins of mice prior to UV irradiation, daily for ten weeks. The results presented that CS (3.6 g/mL) apparently improved photodamaged skin appearance such as erythema, edema, and coarseness. The abnormal epidermal thickening was significantly reduced, and the dermal structures became more complete. The underlying protective mechanisms were associated with improving antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), downregulating inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2, and PGE2) expressions, recovering collagen density, and reducing matrix metalloproteinases productions. Sun protection factor of CS (3.6 g/mL) was 16.21±0.03. Our findings for the first time demonstrated that CS had therapeutic effect on the photoaged skin. The results indicated that CS is a potential agent for photoprotective cosmetics

Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF- κ

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPS via inhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting

White Pepper and Piperine Have Different Effects on Pharmacokinetics of Puerarin in Rats

This study attempted to explore the effects of white pepper and its major component piperine on puerarin administered to rats. Pharmacokinetic parameters of puerarin in rats were determined by oral administration (400 mg/kg) or intravenous injection (40 mg/kg) of puerarin, pretreated with or without white pepper and piperine given orally. Compared to the control group given oral puerarin only, the combined use of piperine (10 or 20 mg/kg) increased the Cmax of puerarin by 1.30-fold or 1.64-fold and the AUC0–∞ by 133% or 157%, respectively. In contrast, coadministration of white pepper (125 or 250 mg/kg) decreased oral absorption of puerarin to 83% or 74%, respectively. On the other hand, pretreatment with piperine orally did not alter the intravenous pharmacokinetics of puerarin, while the AUC of puerarin after intravenous administration was increased by pretreatment with white pepper. The results indicate that pretreatment with piperine or pepper exerts different effects on pharmacokinetics of puerarin administrated via intragastric and intravenous routes. Therefore, it is suggested that the combined application of piperine or white pepper with puerarin should be carefully monitored for potential diet-drug interactions