Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: distinct mechanisms, different efficacies to treatments.

With the development of antitumor therapies, different treatment methods including monotherapy and combined therapy have achieved clinical efficacy in advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients. Exon 19 deletion (ex19del) and exon 21 L858R mutation are common sensitive subtypes of EGFR mutation. However, potential distinct mechanisms are found from several dimensions including molecular structures, biological behaviors, concomitant mutations, resistance mechanisms and tumor mutation burdens. More evidence indicates the prognostic difference of EGFR subgroups. This review focused on the progress of potential distinct mechanisms and outcomes in clinical trials of advanced NSCLC patients with ex19del or exon 21 L858R mutation.

Survival prediction with score model based on clinical characteristics in advanced HCC patients receiving oxaliplatin-containing regimens.

A score model based on clinical characteristics in advanced hepatocellular carcinoma (HCC) patients treated with systemic chemotherapy of oxaliplatin-containing regimens was established to evaluate progression-free survival (PFS) and overall survival (OS). Thirty HCC patients eligible for radical resection were involved in the retrospective study, and these were divided into the good response group (complete response (CR)/partial response (PR) and the poor response group (stable disease (SD)/progression disease (PD). The median PFS and OS were compared in the two groups. PFS and OS combined with clinical characteristics were evaluated by univariate and multivariate analyses. The score model was defined with 1 score for each characteristic, and score model cut-off values were determined by the receiver operating characteristic curve (ROC) which describes treatment response. The median PFS was 10 and 2 months (p<0.001), and the median OS was 13 and 4 months (p=0.011) for the CR/PR and SD/PD groups, respectively. The score of 1 was the optimal cutoff value, with sensitivity ranging from 52.6 to 63.2% and specificity from 81.8 to 100% (AUC= 0.773, p=0.014). The median PFS for good and poor response groups was 9 months and 1month (p<0.001) and the median OS was 22 and 3months at p<0.001, respectively. Patients with scores above 1 had poor response, with median 3 months OS and 1 month PFS, and patients with scores of 0 and 1 established good response, with median 22 months OS and 9 months PFS, respectively.

Finite element analysis on tooth and periodontal stress under simulated occlusal loads.

The tooth stress elicited by occluding contact represents critical biomechanical information about dental health during chewing. Effects of occlusal contact on tooth stress remain obscure. In this study, a mandibular first molar finite element model was built from CT images. The effects of area size, location and direction of occlusal loading on both tooth and periodontal stresses were analysed. Results showed tooth and periodontal stress had drastically different patterns. Tooth stress value was much higher than periodontal stress value under the same task. Tooth stress concentration area and its value decreased from outside to inside. The Maximum Tooth Stress (MTS) always occurred at the loading site and a larger loading area elicited a smaller MTS value. The variation of MTS was larger when the fossa bottoms were inclined loaded than when the cusp tips were inclined loaded, larger when lingually loaded than when buccally loaded and larger when mesially loaded than when distally loaded. Distal loadings generally induced smaller Maximum Periodontal Stress (MPS) variations than the mesial loadings. These findings indicated exposure of the rational site(s) to occlusal contact should be helpful to achieve proper tooth and periodontal stress, thus to diminish loading associated structure problems.

Effects of low-dose radiation on adaptive response in colon cancer stem cells.

PURPOSE: Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Adaptive response is an important biological effect following low-dose radiation. Cancer stem cells (CSCs) have self-renewal and multidirectional differentiation potency which results in relapse and metastasis of cancer. In this study, we aimed to examine whether adaptive response could be induced in CSCs by LDR. METHODS: Parental cells of three colon cancer cell lines (HRT18, HT29, and HCT116) and CSCs of these three cell lines were irradiated with LDR (i.e., D1) and then high-dose radiation (HDR) of X-rays (i.e., D1 + D2) or only HDR (D2 alone), followed by examination of adaptive response. RESULTS: Adaptive response was not observed either in the three tumor parental cells lines or in three CSCs lines following LDR, due to the lack of resistance to subsequent D2-induced cell growth inhibition. CONCLUSION: These results suggested that LDR may not induce adaptive response in colon cancer cells or colon CSCs under in vitro conditions. Our study provided experimental and clinical foundations for the application of LDR in the treatment of colon cancers.

[Survival analysis of patients with pneumoconiosis from 1963 to 2014 in Yueyang].

OBJECTIVE: To know the incidence and survival rate of patients with pneumoconiosis in Yueyang and investigate the related factors of death hazard ratio. METHODS: A total; of 1404 patients with pneumoconiosis were diagnosed and reported from 1963.1-2014.12. Log Rank method and Cox regression model were used to make the survival analysis. RESULTS: The case fatality rate of pneumoconiosis was 24.57%,and rose with the increase of pneumoconiosis stage, the average course of disease was (14.7±8.7) years, the average age of death was (60.6±11.3) years, tuberculosis、Chronic cardiopulmonary disease and pneumonia were the top three cause of death for patients. The survival rates which included three stages of pneumoconiosis patients and the patients whether or not complicated with tuberculosis were significant statistical differences. Cox regression analysis revealed that the main impact. factors for the survival of patients with pneumoconiosis and the value of. the death hazard ratios (RR) of above seven factors were silicosis (2.28) 、the increase of pneumoconiosis stage (1.77) 、pneumoconiosis complicated with tuberculosis (1.29) 、the increase of stage promotion (1.20) 、the increase of age of the first contacting dust (1.08) 、the expansion of the scale of enterprise (0.55) and the later period of contacting dust (0.37). CONCLUSION: Prevention of pneumoconiosis should focus on silicosis in Yueyang, the prevention and treatment of pneumoconiosis complicated with tuberculosis is an important means for improving the survival of patients.

Local expression and role of BMP-2/4 in injured spinal cord.

We investigated local changes in BMP-2/4 expression in rat spinal cords 1 week following injury to study the damage effects of BMP-2/4 in spinal cord injury (SCI). Sprague Dawley rats (45, 4 months old) were randomized into three groups comprising 15 rats each: a SHAM group, an SCI without noggin group (SCIO), and an SCI with noggin group (SCID). The SCIO and SCID groups were subjected to spinal cord hemisection, and motor activity was assessed using the BBB score. Expression of BMP-2/4 in each injured spinal cord section was examined by hematoxylin and eosin staining, immunohistochemistry, and western blot. There were no significant differences in BBB scores among the three groups (P > 0.05). Following hemisection, the BBB score in the SHAM group was significantly higher than in the other two groups on the 1st day after modeling (P < 0.05), and the BBB scores in the SCIO and SCID groups were not significantly different (P > 0.05). Seven days after modeling, the BBB score in the SHAM group was significantly higher than in the other two groups (P < 0.05), and the BBB score in the SCID group was obviously higher than in the SCIO group (P < 0.05). The expression of BMP-2/4 was highest in the SCIO group and lowest in the SHAM group (P < 0.05). SCI can cause severe impairment of motor activity in rats. Seven days after SCI, the local expression of BMP-2/4 had obviously increased; noggin can effectively inhibit the expression of BMP-2/4 and reduce impairment.

Identification of key micro-organisms involved in Douchi fermentation by statistical analysis and their use in an experimental fermentation.

AIMS: To screen and identify safe micro-organisms used during Douchi fermentation, and verify the feasibility of producing high-quality Douchi using these identified micro-organisms. METHODS AND RESULTS: PCR-denaturing gradient gel electrophoresis (DGGE) and automatic amino-acid analyser were used to investigate the microbial diversity and free amino acids (FAAs) content of 10 commercial Douchi samples. The correlations between microbial communities and FAAs were analysed by statistical analysis. Ten strains with significant positive correlation were identified. Then an experiment on Douchi fermentation by identified strains was carried out, and the nutritional composition in Douchi was analysed. Results showed that FAAs and relative content of isoflavone aglycones in verification Douchi samples were generally higher than those in commercial Douchi samples. CONCLUSIONS: Our study indicated that fungi, yeasts, Bacillus and lactic acid bacteria were the key players in Douchi fermentation, and with identified probiotic micro-organisms participating in fermentation, a higher quality Douchi product was produced. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to analyse and confirm the key micro-organisms during Douchi fermentation by statistical analysis. This work proves fermentation micro-organisms to be the key influencing factor of Douchi quality, and demonstrates the feasibility of fermenting Douchi using identified starter micro-organisms.

Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia.

Erythroleukemia induced by Friend Murine Leukemia Virus (F-MuLV) serves as a powerful tool for the study of multistage carcinogenesis and hematological malignancies in mice. Fli-1, a proto-oncogene and member of the Ets family, is activated through viral integration in F-MuLV-induced erythroleukemia, and is the most critical event in the induction of this disease. Fli-1 aberrant regulation is also observed in human malignancies, including Ewing's sarcoma, which is often linked to expression of the EWS/Fli-1 fusion oncoprotein. Here we examined the effects of Fli-1 inhibition to further elucidate its role in these pathological occurrences. The constitutive suppression of Fli-1, through RNA interference (RNAi), inhibits growth and induces death in F-MuLV-induced erythroleukemia cells. Expression of a dominant negative protein Engrailed (En)/Fli-1 reduces proliferation of EWS/Fli-1-transformed NIH-3T3 cells, and both F-MuLV-induced and human erythroleukemia cells. F-MuLV-induced erythroleukemia cells also display increased apoptosis, associated with reduced expression of bcl-2, a known fli-1 target gene. Introduction of En/Fli-1 into an F-MuLV-infected erythroblastic cell line induces differentiation, as shown by increased alpha-globin expression. These results suggest, for the first time, an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in murine and human erythroleukemias.

Effects of trinitrotoluene on serum phosphorylase A activities and on calcium contents in men and rats.

Wistar rats were exposed to trinitrotoluene (TNT) for 6 weeks. After initiation of TNT exposure, serum phosphorylase A activities and calcium contents were assayed for every 2 weeks. Both of these 2 parameters increased in rats treated with 50 and 100 mg TNT/kg b.w. at 3 intervals. Serum phosphorylase A activities and calcium contents of TNT exposure worker increased too.

Effects of exposure to trinitrotoluene on male reproduction.

A cross-sectional study was performed in 2 plants located in Henan Province in 1990 for observing the reproductive and sexual functions of male workers exposed to trinitrotoluene (TNT). The TNT concentrations in the workplace air, except the packing site, were found to have exceeded MAC (1 mg/m3). TNT exposed male workers complained of more sexual disorders such as impotence, the loss of libido and sexual hypoesthesia than the control group. Compared with the control group, the volume of semen and percentage of motile spermatozoa were found to have significantly decreased, and the sperm malformation incidence increased significantly in TNT exposed workers. The serum testosterone content in TNT exposed male workers was significantly decreased too.