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Background and objective Noninvasive prognostic tools for colorectal cancer (CRC) are urgently needed. This study was designed to investigate the prognostic value of preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels retrospectively in CRC patients. Methods Preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels were analyzed retrospectively in 250 patients with CRC. The prognostic significance of these indexes was determined by univariate and multivariate Cox hazard models. Results CRC patients with higher levels of ApoA-I and HDL-C and lower levels of CRP had significantly longer overall survival (OS, log rank test, p

Topographical factor is one of the most important factors in understanding the formation mechanism of shallow mass movements on gully slopes on the Loess Plateau, China. However, the sensitivity of shallow mass movements on gully slopes to topography is poorly understood. Here, a series of rainfall simulation experiments was performed to quantitatively explore the influences of slope height (1.0 and 1.5 m) and gradient (60° and 70°) on shallow mass movements on the natural loess slopes on the Loess Plateau. Our research observed shallow mass movement processes on undisturbed slopes by using a Topography Meter and collected data that well reflected the nature of the processes. The conducted study has advantageous over traditional methods that are usually used in laboratory tests of backfilled soil. Results showed that the amount of shallow mass movement increased with increased slope height and gradient. The shallow mass movement rates (i.e., gravity erosion rates) increased by approximately 3–8 times with increased slope height from 1.0 m to 1.5 m, and increased by 148%–525% with increased slope gradient from 60° to 70°. The sensitivity coefficient of slope gradients for shallow mass movements was 2.1 times larger than that of slope heights for the shallow mass movements. Slope heights had the greatest effect on earthflow relative to slide and avalanche, whereas slope gradients had the greatest effect on slide. Our results provided insights into natural hazard susceptibility assessment and control erosion processes.

Despite therapeutic advances, the effective treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a major clinical challenge. Evasion of apoptosis through upregulating antiapoptotic B-cell lymphoma-2 (BCL-2) family members and p53 inactivation, and abnormal activation of B-cell receptor signaling pathway are two important pathogenic factors for DLBCL. In this study, our aim is to explore a rational combination of BCL-2 inhibitor plus Brutons tyrosine kinase (BTK) blockade or p53 activation for treating DLBCL with the above characteristics. We demonstrated that a novel BCL-2 selective inhibitor APG-2575 effectively suppressed DLBCL with BCL-2 high expression via activating the mitochondrial apoptosis pathway. BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression. For p53 wild-type DLBCL with high expression of BCL-2, APG-2575 showed strong synergic effect with mouse double minute 2 (MDM2)p53 inhibitor APG-115 that can achieve potent antitumor effect and markedly prolong survival in animal models. Collectively, our data provide an effective and precise therapeutic strategy through rational combination of BCL-2 and BTK or MDM2p53 inhibitors for DLBCL, which deserves further clinical investigation.

Gravity erosion is a widespread geologic hazard in the rural area of the Loess Plateau, China. Recently, an avalanche struck Tuban Town in northwest China. The small-size collapse, which led to seven fatalities, demonstrated the fragile defense capability in the area. Adverse destabilization from human activities, i.e., no protection practice after slope cutting, is the major cause of the incident; unrecorded slight geological activity could make an avalanche imminent. We look forward to alleviating such disasters in the near future with effective, low-cost measures.

Hydrodistillation of the fresh leaves of E.grandis×E.urophylla hybrids and pure species E.grandis, E.urophylla, E.pellita, E.camaldulensis, E. dunni, and E.saligna collected from the trees grown in Guangxi Huangmian Forest (China), afforded essential oils in yields varying from 0.24±0.15% to 5.36±0.28%, according to the species. Analysis by GC (FID) and GC/MS allowed the identification of 67 compounds, representing 82.55% to 91.03% of the total oil composition. The dominant compounds were 1,8-cineole in E.saligna, E.urophylla, E.grandis×E.urophylla, E.grandis, E.pellita and E. dunni (67.48, 57.12, 48.21, 23.64, 20.34, 20.22%), p-Cymene in E.camaldulensis,E. dunni and E.grandis(21.32, 14.74, 13.38%), α-pinene in E.grandis and E.grandis×E.urophylla (21.77, 15.55%), α-terpinene in E. dunni and E.grandis (17.96, 9.35%), α-terpineol in E.pellita and E.saligna (19.24,11.54%), respectively. Hierarchical Cluster Analysis separated the characterized essential oils into two groups, each constituting a chemotype. E.grandis×E.urophylla and E.urophylla were classified in the same group, while E.grandis in the other.

Background: Despite advances in the treatment of non-Hodgkin's lymphoma (NHL), refractory NHL remains a major clinical challenge. The B-cell lymphoma protein-2 (BCL-2) family is frequently overexpressed in NHL, which is associated with poor prognosis by promoting cell growth and resistance to antitumorigenic agents. In this study, by using different BCL-2 family protein inhibitors, we aim to further classify the survival dependency of NHL for anti-apoptotic BCL-2 family members and explore novel approaches to rationally develop combination therapies by completely blocking the activity of the Bcl-2 family proteins. Methods: Cell viability was determined by CCK-8 assay. Apoptotic activity was confirmed by Annexin V-propidium iodide (PI) apoptosis detection, Western blot analysis and mitochondrial membrane potentials detection analysis. In vivo, NHL xenograft models were established to analyze the antitumor effect of the BCL-2 family protein inhibitors. Results: We evaluated the inhibitory effect of of Bcl-2 targeted inhibitors and synergy in combination with other molecular targeted agents in NHL. While those NHL cell lines with only high levels of BCL-2 protein are sensitive to Bcl-2 selective inhibitor, the dual Bcl-2/Bcl-xL inhibitor APG-1252 and its active metabolite APG-1252-M1 potently induced mitochondria-dependent apoptosis in NHL cell lines that possess high expression of both BCL-2 and BCL-XL proteins. After the treatment of APG-1252-M1, apoptosis including caspase-3 activation, PARP cleavage, and mitochondrial membrane potentials change was observed rapidly within four hours. We further demonstrated that APG-1252-M1 showed synergistic effects with Bruton's tyrosine kinase (BTK) inhibitor ibrutinib in those sensitive cell lines by modulating STAT3 signaling pathways. However, cell lines harboring high expression of anti-apoptotic protein MCL-1 were resistant to APG-1252-M1. Furthermore, we observed that APG-1252-M1 exhibited strong synergistic effect with dual PI3K/mTOR inhibitors NVP-BEZ235 in those resistant cell lines with high levels of Mcl-2 protein. Conclusions: Taken together, our data provide an effective and precise therapeutic strategy for NHL through determining NHL addiction to anti-apoptotic BCL-2 family proteins, and then target-guided application of BCL-2 family inhibitors as a monotherapy or in combination with other molecular targeted agents to completely block the Bcl-2 family proteins, thus to restore the apoptotic cell death. Citation Format: Qiu-Yun Luo, Han-Jie Yi, Xiang-Lei Yan, Miaozhen Qiu, Bao-Xia Li, Lin Zhang, Wen-Tao Pan, Lu-Ping Yuan, Zhen-Yi Liu, Douglas D. Fang, Yifan Zhai, Jian Sun, Da-Jun Yang. Targeting the anti-apoptotic BCL-2 family protein provides an effective and precise therapeutic strategy for NHL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 301.