Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Wheat silage partially replacing oaten hay exhibited greater feed efficiency and fibre digestion despite low feed intake by feedlot lambs

This study aimed to investigate the feeding effect of wheat silage on growth performance,nutrient digestibility,rumen fermentation,and microbiota composition in feedlot lambs.Sixty-four male crossbred Chinese Han lambs(BW=27.8±0.67 kg,3 months of age)were randomly assigned to four ration groups with wheat silage replacing 0%(WS0),36%(WS36),64%(WS64),and 100%(WS100)of oaten hay on forage dry matter basis.The concentrate-to-forage ratio was 80:20 and the feeding trial lasted 52 d.Increasing wheat silage inclusion linearly decreased dry matter intake by 4%to 27%(P<0.01).However,increasing the wheat silage replacement of oaten hay by no more than 64%improved the feed efficiency by 14%as noted by the feed-to-gain ratio(P=0.04).Apparent digestibility of organic matter(P<0.01),neutral detergent fibre(P=0.04)and acid detergent fibre(P<0.01)quadratically increased.Ammonia nitrogen(P=0.01)decreased while microbial protein production(P<0.01)increased with the increase of wheat silage inclusion.Total volatile fatty acids concentration increased quadratically with the increase of wheat silage inclusion(P<0.01),and the highest occurred in WS64.The molar proportion of acetate(P<0.01)and acetate-to-propionate ratio(P=0.04)decreased while butyrate(P<0.01)and isovalerate(P=0.04)increased.Increasing wheat silage inclusion increased the Firmicutes-toBacteroidota ratio by 226%to 357%,resulting in Firmicutes instead of Bacteroidota being the most abundant phylum.The relative abundance of cellulolytic Ruminococcus numerically increased but that of amylolytic Prevotella(P<0.01)decreased as increasing wheat silage inclusion.Taken together,increasing wheat silage replacement of oaten hay by no more than 64%exhibited greater feed efficiency and fibre digestion despite low feed intake by feedlot lambs due to the change of Firmicutes-to-Bacteroidota ratio in the rumen.

Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows

Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperaturehumidity index（THI） is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines（leptin and adiponectin）, AMP-activated protein kinase（AMPK）, and heat shock signal molecules（heat shock transcription factor（HSF） and heat shock proteins（HSP）） in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment： eighteen lactating Holstein dairy cows were used. The treatments were： heat stress（HS, THI average=81.7, n=9） and cooling（CL, THI average=53.4, n=9）. Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment： HS treatment cows（n=9） from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90（P〈0.05）. Adiponectin is strongly associated with AMPK. The increases of adiponectin and AMPK may be one of the mechanisms to maintain homeostasis in heat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat stress in dairy cows in the future.

Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis

The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2(Her-2)-positive breast cancer(BC). We analyzed correlations between micro RNAs(mi RNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas(TCGA) database. The expression levels of mi R-455, mi R-143, and mi R-99 a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed mi R-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA(lnc RNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) by quantitative real-time polymerase chain reaction(q RT-PCR). The expression of mi R-455 was significantly and positively correlated to the prognosis and overall survival(OS) of the BC(P=0.028), according to TCGA information. The expression level of mi R-455 was positively correlated with OS and relapse-free survival(RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes(P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive(P<0.01) after being transfected with mi R-455 mimics. During the q RT-PCR, the expression level of MALAT1 declined significantly after transfection(P<0.01). Overexpressed mi R-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that mi R-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. mi R-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.

Unilateral hemilaminectomy for patients with intradural extramedullary tumors

A modified hemilaminectomy was introduced in an attempt to explore the operative techniques and the values of the limited approach to spinal cord tumors.Forty-five consecutive patients with intradural extramedullary lesions,who underwent modified hemilaminectomy,were studied retrospectively.The intraspinal tumors were removed via the limited bone window with a 3.3-cm mean length (range: 2.0–6.5 cm) and a 1.2-cm mean width (range: 0.6–1.5 cm),in which the inner parts of the medial and lateral laminae were mostly undercut for wider view.Spinal lesions were cervical in 21 cases,thoracic in 12 cases,lumbar in 10 cases,and multiple in 2 cases.Forty-three cases were completely excised via hemilaminectomy alone.Two subjects with dumbbell neurinoma underwent two-stage tumor removal via anterolateral cervical approach following hemilaminectomy.With respect to neurological status,the percentage of good Frankel scale (D+E grade) was markedly improved from 22.2% on admission to 93.3% at follow-up.At the median 26-month follow-up evaluation by magnetic resonance imaging (MRI),none of the subjects showed spinal deformity or instability.By preserving musculoligamentous attachments and posterior bony elements as much as possible,the modified approach is minimally invasive and may be routinely used to remove intradural and extramedullary tumors,especially in patients with meningiomas and neurinomas.

Gossypol detoxification in the rumen and Helicoverpa armigera larvae:A review

Gossypol,a phenolic compound found in the cotton plant,is widely distributed in cottonseed byproducts.Although ruminant animals are believed to be more tolerant of gossypol toxicity than monogastric animals due to rumen microbial fermentation,the actual mechanisms of detoxification remain unclear.In contrast,the metabolic detoxification of gossypol by Helicoverpa armigera(Lepidoptera:Noctuidae)larvae has achieved great advances.The present review discusses the clinical signs of go ssypol in ruminant animals,as well as summarizing advances in the study of gossypol detoxification in the rumen.It also examines the regulatory roles of several key enzymes in gossypol detoxification and transformation known in H.armigera.With the rapid development of modern molecular biotechnology and-omics technology strategies,evidence increasingly indicates that research into the biological degradation of gossypol in H.armigera larvae and some microbes,in terms of these key enzymes,could provide scientific insights that would underpin future work on microbial gossypol detoxification in the rumen,with the ultimate aim of further alleviating gossypol toxicity in ruminant animals.

The release and catabolism of ferulic acid in plant cell wall by rumen microbes:A review

Ferulic acid(FA)is one of the most abundant hydroxycinnamic acids in the plant world,especially in the cell wall of grain bran,in comparison with forage and crop residues.Previous studies noted that FA was mainly linked with arabinoxylans and lignin in plant cell walls in ester and ether covalent forms.After forages were ingested by ruminant animals or encountered rumen microbial fermentation in vitro,these cross-linkages form physical and chemical barriers to protect cell-wall carbohydrates from microbial attack and enzymatic hydrolysis.Additionally,increasing studies noted that FA presented some toxic effect on microbial growth in the rumen.In recent decades,many studies have addressed the relationships of ester and/or ether-linked FA with rumen nutrient digestibility,and there is still some controversy whether these linkages could be used as a predicator of forage digestibility in ruminants.The authors in this review summarized the possible relationships between ester and/or ether-linked FA and fiber digestion in ruminants.Rumen microbes,especially bacteria and fungi,were found capable of breaking down the ester linkages within plant cell walls by secreting feruloyl and p-coumaroyl esterase,resulting in the release of free FA and improvement of cell wall digestibility.The increasing evidence noted that these esterases secreted by rumen microbes presented synergistic effects with xylanase and cellulase to effectively hydrolyze forage cell walls.Some released FA were absorbed through the rumen wall directly and entered into blood circulation and presented antioxidant effects on host animals.The others were partially catabolized into volatile fatty acids by rumen microbes,and the possible catabolic pathways discussed.To better understand plant cell wall degradation in the rumen,the metabolic fate of FA along with lignin decomposition mechanisms are needed to be explored via future microbial isolation and incubation studies with aims to maximize dietary fiber intake and enhance fiber digestion in ruminant animals.