Clinical efficacy and safety of edaravone therapy in acute cerebral haemorrhage

Purpose: To evaluate the clinical efficacy and safety of edaravone in the treatment of acute cerebral haemorrhage (ACH).Methods: This study recruited 120 patients who developed ACH. The patients were divided into control and treatment groups with 60 patients per group. The control group underwent conventional treatment and the treatment group also received intravenous edaravone. The volumes of cerebral edema and cerebral hematoma, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels, and Chinese Stroke Scale (CSS) score before and after treatment were compared between the two groups.Results: The respective cerebral edema volumes of the control and treatment groups decreased from 20.99 ± 12.09 and 21.80 ± 12.01 mL on day 0 to 11.23 ± 6.34 and 12.11 ± 5.98 mL at day 7 and 4.69 ± 4.03 and 4.64 ± 3.9 mL on day 14 (P < 0.05). The respective cerebral hematoma volumes of the control and treatment groups decreased from 18.98 ± 12.04 and 18.97 ± 12.07 mL on day 0 to 12.34 ± 6.57 and 11.89 ± 4.01 mL at day 7 and 9.49 ± 3.95 and 9.52 ± 3.96 mL on day 14. Compared with pretreatment, hs-CRP and IL-6 levels and CSS score of the two groups decreased significantly following treatment (p < 0.05); the differences in the cerebral edema and hematoma volumes of the two groups on days 7 and 14 were not significant (p > 0.05). The hs-CRP and IL-6 levels and CSS scores of the treatment group decreased appreciably (p < 0.05), while the incidence of adverse reactions in the treatment and control groups was 16.67 and 13.33 %, respectively, but the difference was not significant (p > 0.05).Conclusion: Edaravone shows remarkable clinical efficacy and safety with no obvious adverse reactions in the treatment of ACH. Therefore, its use is recommended.Keywords: Cerebral haemorrhage, Edaravone, Cerebral edema, C-reactive protein, Interleukin-6, Chinese Stroke Scal

Prevalence of Stroke and Hypoperfusion in Patients With Isolated Vertigo and Vascular Risk Factors

Background and Purpose: The aim of this study was to determine the prevalence and associated factors of stroke and hypoperfusion among patients with isolated vertigo and vascular risk factors.Methods: We studied 157 patients with isolated vertigo who had undergone multimodal magnetic resonance imaging. Magnetic resonance angiography (MRA) was used to measure the diameters of vertebrobasilar arteries and to evaluate morphologic changes to vessels. Measurements obtained included length of the basilar artery and curvature index for the vertebral artery (VA). Perfusion-weighted imaging (PWI) was performed to determine relative cerebral blood flow, relative cerebral blood volume (rCBV), time to peak (TTP), and mean transit time for two mirror regions of interest (ROIs) in each map. Regional hypoperfusion of the cerebellum was considered significant when TTP and mean transit time (MTT) were present in ≥2 adjacent slices.Results: The prevalence of stroke in patients with isolated vertigo and vascular risk factors was 24.8% (n = 39). Visual assessment revealed cerebellar hypoperfusion in 57.6% (68/118) of non-stroke patients. Multivariate logistic regression indicated that diabetes mellitus (P = 0.049, OR = 2.758), VA stenosis or hypoplasia (P = 0.023, OR = 3.486), and relative TTP of cerebellum (P = 0.002, OR = 3.197) were independent risk factors for stroke and LVA curvature index (P = 0.026, OR = 2.049), VA stenosis and hypoplasia (P = 0.009, OR = 2.977) were independent risk factors for hypoperfusion.Conclusions: The prevalence of stroke and hypoperfusion is higher in patients with isolated vertigo and vascular risk factors, compared with matched controls. Potential risk factors include diabetes mellitus, VA stenosis or hypoplasia, and enlarged VA curvature index

A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson’s Disease

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson’s disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P<0.01), two studies for improving the swim-score values (P<0.01), six studies for improving the level of TH protein expression (P<0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P<0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n=10), antioxidant stress (n=3), and antiapoptosis (n=11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials

Treatment of Acute Leukemia with Unmanipulated HLA-Mismatched/Haploidentical Blood and Bone Marrow Transplantation

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulotyce-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P = .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P = .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest

The growth of northeastern Tibet and its relevance to large-scale continental geodynamics: A review of recent studies

Recent studies of the northeastern part of the Tibetan Plateau have called attention to two emerging views of how the Tibetan Plateau has grown. First, deformation in northern Tibet began essentially at the time of collision with India, not 10–20 Myr later as might be expected if the locus of activity migrated northward as India penetrated the rest of Eurasia. Thus, the north-south dimensions of the Tibetan Plateau were set mainly by differences in lithospheric strength, with strong lithosphere beneath India and the Tarim and Qaidam basins steadily encroaching on one another as the region between them, the present-day Tibetan Plateau, deformed, and its north-south dimension became narrower. Second, abundant evidence calls for acceleration of deformation, including the formation of new faults, in northeastern Tibet since ~15 Ma and a less precisely dated change in orientation of crustal shortening since ~20 Ma. This reorientation of crustal shortening and roughly concurrent outward growth of high terrain, which swings from NNE-SSW in northern Tibet to more NE-SW and even ENE-WSW in the easternmost part of northeastern Tibet, are likely to be, in part, a consequence of crustal thickening within the high Tibetan Plateau reaching a limit, and the locus of continued shortening then migrating to the northeastern and eastern flanks. These changes in rates and orientation also could result from removal of some or all mantle lithosphere and increased gravitational potential energy per unit area and from a weakening of crustal material so that it could flow in response to pressure gradients set by evolving differences in elevation

A Randomized Controlled Phase IIb Trial of Antigen-Antibody Immunogenic Complex Therapeutic Vaccine in Chronic Hepatitis B Patients

BACKGROUND: The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed. METHODS AND PRINCIPAL FINDINGS: Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8% (17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05). CONCLUSIONS: Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-00000022

Angiogenesis in Differentiated Placental Multipotent Mesenchymal Stromal Cells Is Dependent on Integrin α5β1

Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated from term placenta, but their angiogenic ability and the regulatory pathways involved are not known. hPMSCs were shown to express integrins αv, α4, α5, β1, β3, and β5 and could be induced to differentiate into cells expressing endothelial markers. Increases in cell surface integrins α5 and β1, but not α4, αvβ3, or αvβ5, accompanied endothelial differentiation. Vascular endothelial growth factor-A augmented the effect of fibronectin in enhancing adhesion and migration of differentiated hPMSC through integrin α5β1, but not αvβ3 or αvβ5. Formation of capillary-like structures in vitro from differentiated cells was inhibited by pre-treatment with function-blocking antibodies to integrins α5 and β1. When hPMSCs were seeded onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive cells were observed to engraft in the chick endothelium. CAMs transplanted with differentiated hPMSCs had a greater number of vessels containing human cells and more incorporated cells per vessel compared to CAMs transplanted with undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the differentiated cells. Function-blocking antibodies to integrins α5 and β1 inhibited angiogenesis in the CAM assay. These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin α5β1

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types