Bilateral Chronic Subdural Hematoma after Endoscopic Third Ventriculostomy in a Child: A Case Report and Review of the Literature

Hydrocephalus had been managed by ventriculoperitoneal shunt (VPS) or endoscopic third ventriculostomy (ETV) since several years. But these two different technics had some complications that must be managed promptly to avoid eventual fatal evolution. Chronic subdural hematomas after ETV is among these complications and is a very rarely situation observed in our department. This rare event associated with malaria in a child is considered to have a high mortality. Here we report a rare case of bilateral chronic subdural hematoma occurring in a 4-month-old boy after ETV and we discuss the likely pathogenesis and the difficulties of management.

Effect of down-regulation of voltage-gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain

Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting the Navl.7 gene was constructed,and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats.Lentiviral vector was injected.Rats in each model were divided into 4 groups:model group,PBS group,vehicle group and LV-Nav1.7 group.The expression levels of GFAP and OX42 in dorsal root ganglia(DRG) were measured.Results:After the animal model was built,the level of Navl.7,GFAP and OX42 was improved obviously with the time prolonged,which was statistically significant(P<0.05).The expression level of GFAP and OX42 in the DRG in the LV-Navl.7 group declined obviously compared to the model group,PBS group and vehicle group(P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7and inhibit the activation of astrocytes and microglia in DRG.The effort is also effective in morphine tolerance bone cancer pain model rats.

Malignant Transformation of Cerebellar Pleomorphic Xanthoastrocytoma: A Case Report

Pleomorphic xanthoastrocytoma (PXA) generally occurs in children and young adults and is classified as a low-grade astrocytic tumor with a potential favorable prognosis. But these data must be interpreted with much caution, because of some rapid progression or malignant transformation during the postoperative follow-up. We report herein a rare case of a cerebellar PXA manifested as a benign lesion at first time in a 39 year-old woman, but with malignant transformation two years later. In this paper, we discuss the clinical signs, radiological findings and the therapeutic data on the subject according to literature review.

Therapeutic Effect of Chinese Herbal Medicine for Strengthening Qi,Nourishing Yin,and Removing Stasis on Serum Osteopontin and Quality of Life of Patients with Primary Sjogren's Syndrome

Objective：To observe the therapeutic effect of Chinese herbal medicine for strengthening qi, nourishing yin,and removing stasis on serum osteopontin（OPN） and quality of life（QOL） in patients with primary Sjogren＇s syndrome（pSS） and to study the correlation between OPN level and the disease.Methods：Sixtyeight pSS patients were randomly assigned to two groups：the treatment group（35 cases） treated by Chinese herbal medicine for strengthening qi,nourishing yin,and removing stasis combined with hydroxychloroquine sulfate tablet（HCQ） and the control group（33 cases） treated by HCQ only.Both were treated for 3 months. Before and after treatment,immunoglobulin G（IgG） level,erythrocyte sedimentation rate（ESR）,and OPN level were measured.The QOL in patients was evaluated using the Short Form-36 Health Survey（SF-36） before and after treatment.Thirty healthy females were taken as the normal control.Results：Before treatment,levels of IgG,ESR,and OPN in patients were higher than those in the normal control.After 3 months of treatment, those in both treatment groups decreased but were lower in the treatment group than those in the control group （P0.05）.The scores of 8 dimensions of SF-36 were lower in the pSS patients than those in the normal control （P0.05） and higher in the treatment group than in the control group after treatment（P0.05）.Furthermore, there was a positive correlation between the levels of OPN and the levels of IgG and ESR,and a negative correlation between OPN levels and the overall score of SF-36（P0.05）.Conclusions：Chinese herbal medicine for strengthening qi,nourishing yin,and removing stasis could alleviate pSS disease and improve the QOL.In addition,the OPN level might be used as an evaluating index for pSS disease.

Proteomic Portrait of Human Lymphoma Reveals Protein Molecular Fingerprint of Disease Specific Subtypes and Progression

An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders.Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies,particularly for borderline cases.Therefore,we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups.In this study,109 fresh-frozen lymph node tissues from patients with various lymphatic disorders(with a focus on Non-Hodgkin’s Lymphoma)were analyzed by data-independent acquisition mass spectrometry.A quantitative proteomic landscape was comprehensively characterized,leading to the identification of featured protein profiles for each subgroup.Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed.Two representative signature proteins,phospholipid-binding proteins Annexin A6(ANXA6)and Phospholipase C Gamma 2(PLCG2),were successfully validated via immunohistochemistry.We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins,such as Sialic Acid Binding Ig Like Lectin 1(SIGLEC1)and GTPase of immunity-associated protein 5(GIMAP5).In summary,the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states,thus extending the existing human tissue proteome atlas.Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies,while also providing novel protein candidates to classify various lymphomas for more precise medical practice.

Efficacy and Safety of All-oral,12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naive Noncirrhotic HCV Genotype 1 Patients:Results from a Phase 2/3 Clinical Trial in China

Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.

An isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand

Glucocorticoid-induced tumor-necrosis factor receptor(GITR)and its ligand,GITRL,play significant roles in regulating immune responses.It is clear that human soluble GITRL(hsGITRL)transduces signal activity through multiple oligomerization states.To develop human soluble trimeric GITRL protein as a potential therapeutic target,we explored the link of the isoleucine-zipper(ILZ)motif to the N-terminus of the human soluble GITRL with two leucine sequences.hsGITRL,with the ILZ motif(ILZ-hsGITRL),was firstly expressed in Escherichia coli,which exhibited a predominant trimer when identified by Sephadex G-100 filtration and non-reducing SDS–polyacrylamide gel electrophoresis(SDS-PAGE).The significantly higher biological activity of the ILZ-hsGITRL compared with hsGITRL was confirmed by CD41 T proliferation,interferon-c(IFN-c)secretion and binding activity assay.To reveal and compare the underlying mechanisms,the level of extracellular signal-regulated kinase-1/2(ERK1/2)phosphorylation was examined,indicating that ILZ-hsGITRL induced more persistent and stronger ERK1/2 activation than hsGITRL.In conclusion,the incorporation of an ILZ motif could markedly improve the costimulation of hsGITRL.

Curcumin co-treatment ameliorates resistance to gefitinib in drug-resistant NCI-H1975 lung cancer cells

OBJECTIVE: To examine whether a combinative treatment with curcumin enhances the effects of the epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI) gefitinib on cell proliferation, clonogenic capacity and apoptosis in the drug-resistant lung cancer cell line NCI-H1975, and further investigate the molecular mechanisms involved.METHODS: NCI-H1975 cells were treated with curcumin and gefitinib alone or in combination, and cell proliferation, clonogenic capacity and apoptosis were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, clone forming experiments, and flow cytometry, respectively, while p38, extracellular regulated protein kinase(ERK)1/2, and protein kinase B(AKT)phosphorylation were examined using Western blotting.RESULTS: Compared with the effects of either agent alone, the combination of curcumin and gefitinib had a stronger suppressive effect on proliferation and the clonogenic capacity(P < 0.05), and showed an increased ability to promote apoptosis(P < 0.05) and reduce p38, ERK1/2, and AKT phosphorylation(P < 0.05).CONCLUSION: Co-treatment of curcumin and gefitinib significantly improves the ability of gefitinib to inhibit cell proliferation, suppress the clonogenic capacity and enhance apoptosis in NCI-H1975 cells,and these effects are possibly mediated via a decrease in phosphorylation of proteins in downstream pathways of the epidermal growth factor receptor.

Pure Total Flavonoids from Citrus paradisi Macfad InduceLeukemia Cell Apoptosis In Vitro

Objective： To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel（PTFC） on the proliferation and apoptosis of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. Methods： PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. Results： Treatment with PTFC inhibited leukemia cell proliferation in a dose-and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. Conclusion： PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.