Proposed modifications and incorporation of plasma Epstein-Barr virus DNA improve the TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma.

BACKGROUND: The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS: In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS: The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA >2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. CONCLUSIONS: The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.

Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.

Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment.

[Topographic distribution patterns of forest gap within an evergreen broad-leaved forest in Tiantong region of Zhejiang Province, Eastern China].

To explore the effects of multi-dimensional topographic factors on forest gap distribution, the forest gaps in a 20 hm2 dynamic monitoring plot of an evergreen broad-leaved forest in Tiantong region of Zhejiang were taken as the objects to study the distribution patterns of the gap fraction, gap density, and gap area under the effects of altitude, slope degree, slope shape, slope aspect, and slope position by using a geographic information system (GIS) software. In the plot, the gap fraction was 13.1% , gap density was 9.5 ind.hm-2, and average gap area was 137.82 m2. Because of the greater intensity of typhoon disturbance at high altitudes, the gap fraction and gap density at the high altitude (> or =500 m) sections were significantly larger than those at the medium and low altitude (<500 m) sections. The heavy precipitation produced by typhoon could easily cause small scale landslide, and thus, lead to the gap fraction and gap density being larger in valley area than in side-slope and ridge. It was suggested that typhoon and its produced heavy precipitation could be the main causes of the significant differences in the forest gaps along the gradients of altitude and slope position.

[Spatial heterogeneity of soil properties and its relationships with terrain factors in broad-leaved forest in Tiantong of Zhejiang Province, East China].

By using geostatistical methods, this paper studied the spatial heterogeneity and distribution patterns of soil pH, total carbon, total nitrogen, and total phosphorus in an evergreen broad-leaved forest in Tiantong of Zhejiang Province, and the effects of terrain factors (elevation, convexity, and slope) on the soil properties were quantified based on RDA ordination and partial regression analysis. The coefficient of variation for the soil pH, total carbon, total nitrogen, and total phosphorus was 5.18%, 42.98%, 36.55%, and 46.27%, respectively, and the spatial dependence of the soil properties was at a scale of 81.6-54.5 m. The soil pH, total carbon, and total nitrogen had moderate spatial autocorrelation, while the soil total phosphorus had a strong spatial autocorrelation. The soil pH, total carbon, and total nitrogen showed scattered spatial distribution, while the soil total phosphorus presented banded type. Among the terrain factors, convexity had the strongest effects on the soil pH and total phosphorus, both of which had negative correlation with convexity, and the convexity could explain 21.24% and 14.62% of the spatial variability of soil pH and total phosphorus, respectively. Elevation had the most powerful effects on the soil total carbon and total nitrogen, both of which had positive correlation with elevation, and the elevation could explain 10.54% and 10.60% of the spatial variability of soil total carbon and total nitrogen, respectively. There existed differences in the effects of different terrain factors on the spatial variability of the soil properties, which was related to the effects of terrain factors on the distribution of acidic rainfall in the region and on the local soil moisture content and air temperature.

[Association of HLA-A, B and DRB1 alleles with leukemia in Han population in Hunan Province].

OBJECTIVE: To investigate the association of HLA-A, B, and DRB1 alleles with leukemia in the Han population in Hunan Province. METHODS: HLA-A, B, and DRB1 alleles were genotyped in 105 patients with chronic myelocytic leukemia, 25 with acute lymphocytic leukaemia, and 48 with acute nonlymphocytic leukemia using polymerase chain reaction with sequence-specific primer (PCR-SSP). The hemopoietic stem cells from 3,664 unrelated normal individuals of Han nationality in Hunan were used as the control group. RESULTS: The phenotypic frequencies of HLA-B58, DR12, and DR14 were significantly higher in patients with chronic myelocytic leukemia than in the control group, with relative risk of 6.1287, 1.6519, and 1.6479, respectively. In patients with acute lymphocytic leukaemia, the phenotypic frequency of HLA-B58 was significantly higher than that in the control group, with the relative risk of 7.4055. In patients with acute nonlymphocytic leukemia, the frequencies of HLA-B58 and DR8 phenotypes were significantly higher but HLA-A24 frequency was significantly lower than those of the control group, with the relative risk of 13.9789, 2.2839, and 0.4012, respectively. CONCLUSION: HLA-B58, DR12, DR14 alleles appear to contribute to the genetic susceptibility of patients with chronic myelocytic leukemia. HLA-B58 allele can be associated with the genetic susceptibility for patients with acute lymphocytic leukaemia. In patients with acute nonlymphocytic leukemia, HLA-B58 and DR8 are probably the susceptible alleles whereas HLA-A24 allele may play a protective role.