A randomized clinical study of gefitinib combined with concurrent thoracic radiotherapy in the treatment of local-advanced non-small cell lung cancer with sensitive EGFR mutations / 中国基层医药

Objective To evaluate the efficacy and safety of gefitinib combined with concurrent thoracic radiotherapy in the treatment of local - advanced non - small cell lung cancer with sensitive EGFR mutations. Methods From June 2015 to December 2016,fifty-six eligible patients in Chongqing Three Gorges Central Hospital were randomly assigned into two groups by one to one ratio,with 28 cases in each group.A group received treatment of gefitinib combined with concurrent thoracic radiotherapy, and B group adopted concurrent chemoradiotherapy. The toxic effects were recorded and all patients were followed up as defined by the study protocol.Primary study endpoints included:severe toxic effects,objective response rate and disease control rate,progression free survival and overall survival.Results Twenty-six patients in A group completed the study,and the severe toxic effects were as followed:interstitial pneumonia(3/26),radiation esophagitis(4/26),myelosuppression,skin rashes and gastrointestinal disruption. Twenty- eight patients in B group completed the study, and the severe toxicity included: interstitial pneumonia (4/26),radiation esophagitis(3/26),myelosuppression,skin rashes and gastrointestinal disruption.No toxicity higher than gradeⅢdeveloped in both two groups,and there were no statistically significant differences in incidence rates of interstitial pneumonia and radiation esophagitis between the two groups ( all P >0. 05 ). Moreover, there were no statistically significant differences in ORR and DCR between the two groups( ORR:61.5% vs.39.3% ,P=0.102;DCR:84. 6% vs. 71. 4% , P =0. 505 ). A group showed the benefit over B group in PFS ( 12. 45 months vs. 10.35 months,P=0.036).However,OS didn＇t reach and needed further follow-up.Conclusion The modality of gefitinib combined with concurrent thoracic radiotherapy in the treatment of local -advanced non -small cell lung cancer with sensitive EGFR mutations is safe and effective,and it yet needs further follow-up.

Calycosin-7-O-β-d-glucopyranoside stimulates osteoblast differentiation through regulating the BMP/WNT signaling pathways

The isoflavone calycosin-7-O-β-d-glucopyranoside (CG) is a principal constituent of Astragalus membranaceus (AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin (Ocal) mRNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2 (BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family (WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.

Genomic Diversity and Evolution of Bacillus subtilis / 生物医学与环境科学（英文）

Bacillus subtilis is the focus of both academic and industrial research. Previous studies have reported a number of sequence variations in different B. subtilis strains. To uncover the genetic variation and evolutionary pressure in B. subtilis strains, we performed whole genome sequencing of two B. subtilis isolates, KM and CGMCC63528. Comparative genomic analyses of these two strains with other B. subtilis strains identified high sequence variations including large insertions, deletions and SNPs. Most SNPs in genes were synonymous and the average frequency of synonymous mutations was significantly higher than that of the non-synonymous mutations. Pan-genome analysis of B. subtilis strains showed that the core genome had lower dN/dS values than the accessory genome. Whole genome comparisons of these two isolates with other B. subtilis strains showed that strains in different subspecies have similar dN/dS values. Nucleotide diversity analysis showed that spizizenii subspecies have higher nucleotide diversity than subtilis subspecies. Our results indicate that genes in B. subtilis strains are under high purifying selection pressure. The evolutionary pressure in different subspecies of B. subtilis is complex.

In vitro evaluation of cytotoxicity and oxidative stress induced by multiwalled carbon nanotubes in murine RAW 264.7 macrophages and human A549 lung cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate in vitro cytotoxicity and oxidative stress response induced by multiwalled carbon nanotubes (MWCNTs).</p><p><b>METHODS</b>Cultured macrophages (murine RAW264.7 cells) and alveolar epithelium cells type II (human A549 lung cells) were exposed to the blank control, DNA salt control, and the MWCNTs suspensions at 2.5, 10, 25, and 100 μg/mL for 24 h. Each treatment was evaluated by cell viability, cytotoxicity and oxidative stress.</p><p><b>RESULTS</b>Overall, both cell lines had similar patterns in response to the cytotoxicity and oxidative stress of MWCNTs. DNA salt treatment showed no change compared to the blank control. In both cell lines, significant changes at the doses of 25 and 100 μg/mL treatments were found in cell viabilities, cytotoxicity, and oxidative stress indexes. The reactive oxygen species (ROS) generation was also found to be significantly higher at the dose of 10 μg/mL treatment, whereas no change was seen in most of the indexes. The ROS generation in both cell lines went up in minutes, reached the climax within an hour and faded down after several hours.</p><p><b>CONCLUSION</b>Exposure to MWCNTs resulted in a dose-dependent cytotoxicity in cultured RAW264.7 cells and A549 cells, that was closely correlated to the increased oxidative stress.</p>

Effects of 1-bromopropane on neurological and hematological changes of female exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the health effects of 1-bromopropane (1-BP) on female exposed workers.</p><p><b>METHODS</b>Four 1-BP manufacturing plants were investigated. Workers were interviewed with questionnaire and examined with neurobehavioral core test battery, nerve conduction velocity tests of nervus tibialis and nervus suralis, vibration sensation test, hematological and biochemical tests. Ambient 1-BP concentration was measured with detection tube, and time-weighed average levels of individual workers were estimated with passive samplers.</p><p><b>RESULTS</b>1-BP concentration in the plants ranged from 0 to 402.40 mg/m3 (Geomean 32.19 mg/m3). Time-weighted average exposure levels (TWA-8 h) ranged from 0.35 to 535.19 mg/m3 (Geomean 14.08 mg/m3). Compared with the control group, 1-BP exposed workers showed reduced motor nerve conduction velocity [(44.8 +/- 8.7) m/s] and sensory nerve conduction velocity [(45.5 +/- 4.9) m/s], prolonged distal latency [(7.5 +/- 2.1) ms], reduced toe vibration perception, and altered neurobehavior parameters(POMS vigor, tension, anxiety, confusion) significantly (P < 0.05). As to hematological and biochemical indicators, the exposed workers showed decreased white blood cell count [(5.6 +/- 2.17) x 10(3)/microl], red blood cell count [(3.9 +/- 0.4) x 10(6)/microl], hemoglobin [(121.1 +/- 14.5) g/L] and creatine kinase [(82.0 +/- 27.5) IU/L] (P < 0.05), and increased serum total protein (8.0 +/- 0.5 g/dl), lactate dehydrogenase [(335.2 +/- 356.6) IU/L], thyroid-stimulating hormone [(3.6 +/- 2.3) microIU/ml] and follicle-stimulating hormone levels (18.7 +/- 24.4 mIU/ml) (P < 0.05).</p><p><b>CONCLUSION</b>1-BP exposure may affect peripheral nerves and central nervous system, and lead to abnormal hematological and biomedical indicators.</p>

Exposure to 1-bromopropane causes dose-dependent neurological abnormalities in workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the dose-effect relationship between 1-bromopropane (1-BP) exposure and health effects in workers.</p><p><b>METHODS</b>Occupational field investigations were conducted in 1-BP factories. Ambient 1-BP concentrations were detected with detection tube, and the 8 h time-weighted average individual exposure levels (TWA-8 h) were measured by passive sampler. Workers underwent questionnaire survey, neurological examination, nerve conduction velocity examination, vibration sensation test. routine blood test as well as blood biochemical test. According to TWA values or TWA x duration values, workers were divided into three dose groups for dose-effect relationship analysis. USEPA BMDS 2.1 software was applied to calculate 1-BP benchmark dose (BMD) and its 95% lower limit (BMDL).</p><p><b>RESULTS</b>The TWA-8h concentrations ranged from 0.35 to 535.19 mg/m3 (geo-mean 14.08 mg/m3). Dose-dependent analysis showed that the motor nerve distal latency (linear regression coefficient was 0.066 6), vibration sensation of toes (linear regression coefficient were 0.157 2 and 0.193 9), creatine kinase (linear regression coefficient was -1.05) and thyroid stimulating hormone levels (linear regression coefficient was 0.1024) of 1-BP exposed workers changed in a dose-dependent manner (P < 0.05). BMD calculation based on DL as 1-BP toxic effect endpoint showed that TWA-8h of the BMD values and BMDL values were 50.55 mg/m3 and 30.78 mg/m3, respectively.</p><p><b>CONCLUSION</b>1-BP causes dose-dependent changes in tibial nerve DL, vibration sensation, CK and TSH levels.</p>

MRI diagnosis of multiple cerebral sclerosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the magnetic resonance imaging (MRI) feature of multiple cerebral sclerosis (MS) for better understanding and diagnosis of this disease.</p><p><b>METHODS</b>The MRI data of 32 patients with MS were reviewed. Conventional scanning with T1WI, T2WI, Flair sequence was performed, and 26 patients underwent Gd-DTPA enhanced scanning. The MS plaques were analyzed for their locations, sizes, shapes, MR signals and enhanced features, space-occupying signs, and the related corpus callosum changes and brain atrophy. Descriptive statistical method was used for all the data.</p><p><b>RESULTS</b>MRI identified MS lesions in the brain in 30 cases, with the sensitivity of 93.75%. All the MS patients had multiple lesions with predilection sites of the cortical/juxtacortical and periventricle areas, the centrum semiovale, and the corpus callosum. Most of the MS plaques were round or oval of different sizes. Bilateral lesions were almost symmetrical in distribution. Twenty patients had "rectangular demyelination" and 12 had "dirty white matter" signs, and 11 had both manifestations. The lesions were isointense, slightly hypointense or hypointense on T1WI, and hyperintense on T2WI and Flair sequences. Most of the MS plaques presented no enhancement, with occasional nodular or circular enhancement. No or slight space-occupying effect was found in the plaques. Of the 28 MS patients undergoing sagittal scanning of the corpus callosum, 17 presented with abnormal signals, with the sensitivity of 60.71% (17/28). Five patients had corpus callosum atrophy, and 10 had brain atrophy of different degrees.</p><p><b>CONCLUSION</b>These results suggest that the corpus callosum is often compromised by the MS lesions to present diffusive, nodular, radiating signal abnormalities and irregular ependymal thickening, which can be most obvious with sagittal FLAIR imaging.</p>

Hemodynamic study of primary hepatocellular carcinoma evolved from viral-induced cirrhosis using CT perfusion imaging / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the hemodynamic changes of primary hepatocellular carcinoma (HCC) evolved from hepatic cirrhosis using CT perfusion imaging.</p><p><b>METHODS</b>Thirty-two patients with primary hepatocellular carcinoma evolved from virus-induced fibrosis or cirrhosis underwent dynamic CT scanning of the target slices for 60 min. The perfusion parameters of the hepatic parenchyma and HCC including the blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), hepatic arterial fraction (HAF), IRF time of arrival (IRF TO) were obtained. Paired-sample t test was used to determine the differences in the perfusion parameters between the hepatic parenchyma and the primary HCC mass.</p><p><b>RESULTS</b>Compared with hepatic BF (117.13-/+31.05 ml/100 mg/min), BV (14.73-/+3.91 ml/100 mg), PS (31.93-/+5.91 ml/100 mg/min), HAF (25.02-/+8.19%), MTT (12.79-/+3.31 s), IRF TO (3.14-/+1.09 s), the primary HCC mass showed significant increments in the BF (239.69-/+96.07 ml/100 mg/min), BV (20.26-/+6.73 ml/100 mg), PS (37.50-/+9.50 ml/100 mg/min), HAF (68.97-/+15.22%) with decreased MTT (7.17-/+1.38 s) and IRF TO (2.42-/+0.94 s). Significant differences were found in all the perfusion parameters between the hepatic parenchyma and HCC (P<0.05).</p><p><b>CONCLUSION</b>Liver perfusion parameters can represent the hemodynamic changes in the HCC derived from hepatic cirrhosis.</p>