First-Line Unrelated Double-Unit Umbilical Cord Blood Transplantation for Acquired Severe Aplastic Anemia.

We analyzed the outcomes of 14 patients with severe aplastic anemia (SAA) who received first-line double-unit cord blood transplantation (dUCBT). Patients' median age was 24.5 years (range, 10-44 years). The median numbers of infused nucleated and CD34+ cells were 5.48 × 107/kg (range, 3.33-7.96 × 107/kg) and 2.30 × 105/kg (range, 0.86-3.97 × 105/kg), respectively. One patient died 5 days after transplantation. Three of the 13 patients acquired autologous myeloid recovery. Neutrophil engraftment was observed in 10 patients (76.29%), and the median time of neutrophil recovery was 19 days (range, 15-40 days). Platelet engraftment was observed in 7 cases (53.8%), and 3 patients experienced platelet graft failure. The median time of platelet recovery was 32 days (range, 22-80 days). The cumulative incidence of grade II-IV acute graft-vs-host disease (GVHD) was 38.5%. One patient demonstrated mild chronic GVHD. After a median follow-up of 61 months (range, 18-102 months), 6 patients were alive. The predicted 5-year overall survival and GVHD-free, failure-free survival rates were 42.9% ± 13.2% and 14.3% ± 9.4%, respectively. The first-line dUCBT for SAA is still primarily evaluated through multicenter prospective clinical trials by an optimal conditioning regimen, cell dose, and other graft and transplantation-related factors.

[Plant community and soil nutrient of alpine meadow in different degradation stages on the Tibetan Plateau, China.] / é’è—é«˜åŽŸé«˜å±±åµ©è‰é«˜å¯’è‰ç”¸ä¸åŒé€€åŒ–é˜¶æ®µæ¤ç‰©ç¾¤è½ä¸ŽåœŸå£¤å »åˆ†.

We examined soil physical and chemical properties and plant community characteristics of four Kobresia alpine meadows at different degradation stages in Damxung County, Lhasa City, Tibet Autonomous Region, China, with the method of spatial sequence instead of time succession. The results showed that soil organic carbon, total nitrogen, available phosphorus, available potassium, ammonium, nitrate, and water content showed a decreasing trend as the degree of soil degradation increased, while pH showed an increasing trend. Plant community height, richness, diversity index and evenness index of the moderately degraded meadow were the highest. Community coverage and total biomass were the largest in undegraded meadow and the smallest in the severely degraded meadow. As the degree of meadow degradation intensifies, the biomass and proportion of Cyperaceae decreased, the biomass and proportion of legumes and weeds increased, and the biomass and proportion of Gramineae first increased and then decreased. The aboveground biomass of meadow was significantly positively correlated with soil organic carbon content, total nitrogen content, total phosphorus content, and soil water content, and significantly negatively correlated with soil pH. With the vegetation degradation in meadow, soil degradation had worsened, which ultimately manifested as a significant decline in grassland productivity.

[Functional magnetic resonance imaging in patients with long-term unilateral hearing loss].

OBJECTIVE: To evaluate the potential functional reorganization by functional magnetic resonance imaging (MRI) to measure the brain activation in responses to stimulation to healthy ears in patients with long-term unilateral hearing loss (UHL). METHODS: From June 1998 to December 2009, 23 patients with serious UHL (15 left, 8 right) were recruited along with 15 matched normal hearing subjects. Laterality index (LI) for activated voxel in primary auditory cortex (PAC) was calculated. And the activations outside auditory cortex were also evaluated. RESULTS: The data were discarded in 3 patients with left-ear UHL and 1 normal subject because of head motion. All control subjects showed contralateral dominant activation of PAC in group analysis. However, the group data of UHL patients showed that the activation was more symmetrical and the contralateral dominance diminished versus the control group. As compared with normal subjects outside PAC, heightened activation in left prefrontal cortex, bilateral inferior parietal lobule and left occipital/precuneus was found in UHL patients while reduced activation in left superior temporal gyrus was also found. CONCLUSIONS: The diminished contralateral dominance in PAC and heightened activation in non-auditory region suggest the reduction of interhemispheral inhibition and general increase in brain excitation in long-term UHL patients potentially occur as a result of functional reorganization adaptive to UHL. However, the reduced activation in superior temporal gyrus may be correlated with the deterioration of speech perception in these patients.

Identification of triazolopyridazinones as potent p38α inhibitors.

Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38α mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the identification of three compounds, 3g, 3j and 3m that are highly potent inhibitors of LPS-induced MAPKAP kinase 2 (MK2) phosphorylation in 50% human whole blood (hWB), and possess desirable in vivo pharmacokinetic and kinase selectivity profiles.

Discovery and evaluation of 7-alkyl-1,5-bis-aryl-pyrazolopyridinones as highly potent, selective, and orally efficacious inhibitors of p38alpha mitogen-activated protein kinase.

The p38alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED(50) < or = 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.