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Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a fungal disease that significantly devastates wheat production worldwide. This disease is most effectively restrained by developing and deploying wheat cultivars with highly durable resistance. One adult plant resistance (APR) gene, Yr48, was validated and introgressed from germplasm PI 610750 into three Chinese elite wheat cultivars: Chuanmai 42 (CM42), Lunxuan 987 (LX987), and Bainongaikang 58 (BNAK58), using marker-assisted selection. The three Chinese elite cultivars, as the recipient parents, were used to cross with the donor parent PI 610750. Eighty-seven introgression lines (ILs) were gained from all three cross populations in the F5 generation through phenotypic selection. To validate the ILs possessing Yr48 in the 87 selected lines, linked SSR markers were used to detect its presence or absence in different genetic backgrounds. The 87 ILs from the three crosses were also evaluated for agronomic traits following stringent phenotypic criteria. Field evaluation and genotypic results identified 33 ILs with improved stripe rust resistance. Phenotypic investigation of 33 promising ILs showed that nine lines had better desirable agronomic traits. These ILs had more high-level resistance to stripe rust (infection type range 2–4, disease severity of 5–35%) as well as increased thousand-grain weight (4.5–31.1%), productive till number (25–75%), spike length (9.1–42.5%), grain number (7–51.6%), and appropriate plant height in infested environments compared to the recipient parents. Based on the improved stripe rust resistance and agronomic performance, the selected lines can be further evaluated and promoted as candidate varieties. This study serves as a demonstration of utilizing conventional breeding and molecular marker-assisted selection to improve elite wheat cultivars.

Background Brain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China. Methods First, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan–Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort. Results BS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs. Conclusions The new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice.

To assess the effect of saxagliptin monotherapy on blood glucose and islet β-cell function in obese patients with newly diagnosed pre-diabetes and abnormal fat metabolism.A 24-week, randomized controlled trial was conducted involving 25 obese subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (mean age 45years) to receive lifestyle intervention only (control group) or combined with saxagliptin 2.5mg or 5mg daily (S2.5 or S5 group), metformin 1500mg daily (Met group). Anthropometrics, body fat and biochemical parameters were measured before and after 4, 12 and 24weeks intervention.S5 group and Met group showed a significant decrease in fasting plasma glucose (FPG) and HbA1c compared with the control group (all P0.05) after 24-week intervention. However, the decrease in 2h postprandial plasma glucose levels (2hPPG) in S5 group were greater compared with control group (P0.01). Insulin resistance (HOMA-IR) was reduced in S5 group, Met group and control group (P0.05), and the β-cell function (HOMA-β) was improved in all groups (P0.05). However, the changes in obesity-related indicators including waist circumference, hip circumference, weight, BMI, body fat, percentage of body fat and waist-to-hip fat ratio were greate in Met group (all P0.05) compared with other groups (P0.05).Saxagliptin monotherapy may prevent or delay the progression of IGT or IFG to type 2 diabetes mellitus in obese patients with newly diagnosed pre-diabetes. ClinicalTrials.gov: NCT01960205.

Objective: To demonstrate the underlying pathogenesis of osteoporosis occurring in patients with lipodystrophy. Methods: MEDLINE was searched using the following key terms: lipodystrophy, osteoporosis, and reduced bone mineral density. Manual searching identified additional studies from the bibliographies of reports and reviews obtained in the MEDLINE search. Results: Lipodystrophy is a very rare disease characterized by pathologic alterations in the distribution of adipose tissues in association with a diverse range of metabolic derangements such as hypertriglyceridemia, insulin resistance, diabetes, and abnormal bone formation. Reduced bone mineral density has been assessed extensively in human immunodeficiency virus-infected patients with lipodystrophy, but far less is known in other lipodystrophy types. This is the first review to discuss the mechanisms of osteoporosis occurrence in various types of lipodystrophy. We herein focus on the cross-regulation of fat and bone and propose that marrow fat accumulation and reduced serum leptin and adiponectin levels may play important roles in the pathophysiologic process of osteoporosis in patients with lipodystrophy. Conclusion: Osteoporosis is an emerging threat to patients with lipodystrophy. When evaluating the clinical course of a patient with lipodystrophy, osteoporosis should also be considered. Abbreviations: BMD = bone mineral density; CGL = congenital generalized lipodystrophy; HIV = human immunodeficiency virus; MAT = marrow adipose tissue; OB-R = leptin receptor

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor. The MDSCs were then characterized for phenotype, gene expression and function. Administration with ATO in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. Treatment with ATO in these murine tumor models significantly inhibited tumor growth and splenomegaly, decreased the percentages of MDSCs in the spleen, promoted their differentiation, reduced tumor necrosis factor-α and interleukin-10 levels and weakened the immune inhibition activity of MDSCs on T cells. In addition, we observed the underlying mechanism involved in the regulation of MDSCs by ATO, which included a panel of cytokines and signaling pathways. The findings showed the immunoregulatory effects of ATO by inducing apoptosis, promoting differentiation and inhibiting the function of MDSCs, suggesting that ATO has potential clinical benefit as it selectively attenuates MDSC-induced immunosuppression.

Background: Currently, the treatment of symptomatic brain metastases from lung adenocarcinoma has remained difficult. Bevacizumab combined with chemotherapy is one of the standard treatments of lung adenocarcinoma. This study was designed to investigate the efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma that are not suitable for local treatments, and to explore the predictive value of baseline serum vascular endothelial growth factor (VEGF) for the treatment. Methods: We retrospectively reviewed 14 consecutive patients, between Jan 2015 and Jul 2017, with brain metastases from lung adenocarcinoma who received bevacizumab and chemotherapy to determine efficacy and toxicity. Kaplan-Meier method was used to estimate survival curves, and univariate and multivariate analyses were performed by Cox proportional hazard model. The primary endpoints were objective response rate (ORR) and intracranial ORR (iORR). The secondary endpoints were progression-free survival (PFS), intracranial PFS (iPFS), overall survival (OS) and disease control rate (DCR). Results: The efficacy of 12 patient was evaluated. Overall ORR was 25% (3/12) and the iORR of brain lesions was 33.3% (4/12). DCR was 75% (9/12). The median OS was 18.3 months, the median PFS was 6.7 months, and the median iPFS was 12 months. After 2 cycles of bevacizumab, 10 patients showed improved symptoms of central nervous system (CNS), and the symptom control rate was 83.3% (10/12). Head MRI showed that edema in the brain was greatly reduced in 6 patients, resulting in the lessened usage of dexamethasone. iPFS was significantly shorter in high VEGF group (3.6 vs . 8.0 m, P=0.02), and multivariate analysis showed a significant correlation between iPFS and serum baseline VEGF level (P=0.023). The most commonly adverse events of bevacizumab included leukopenia [5 (35.7%)], fatigue [3 (21.4%)], thrombocytopenia [3 (21.4%)], anemia [2 (14.3%)], which were mostly degree I and II. Conclusions: This study showed bevacizumab combined with chemotherapy could effectively control intracranial lesions, relieve symptoms, and improve the quality of life and survival of patients with brain metastases from lung adenocarcinoma. Serum baseline VEGF may be a predictor of efficacy of bevacizumab plus chemotherapy in the treatment of brain metastases from lung adenocarcinoma.

There is a great demand for blood and stem cells in clinic. It is difficult to achieve high throughput and to increase the cooling rate at the same time during vitrification. In this paper, a micro-droplet spray system with a container collection device was fabricated, and HepG2 cells were sprayed by this system for high-throughput vitrification. First, the container collection device and a cryo-paper were used to receive micro-droplets in the spray vitrification system. The results showed that the cell survival rate and 24h adhesion rate in container collection vitrification group were significantly higher than those in cryo-paper collection group. Second, HepG2 cells were sprayed and vitrified at increased cell density, and it was found that the results of micro-droplet spray vitrification did not change significantly. Finally, micro-droplet spray vitrification is compared with slow freezing. Cell processing capacity in the vitrification group increased, meanwhile, the cell survival rate and 24h adhesion rate in the vitrification group were significantly higher than those in slow freezing group. The results indicated that the micro-droplet spray vitrification system with container collection device designed in this paper can achieve high-throughput cell vitrification, which is of great significance for mass preservation of small cells.血液、干细胞等在临床上的需求量很大，其玻璃化保存面临着要提高降温速率就难以实现高通量这一矛盾问题。本文设计并制作了带容器式收集装置的微滴喷射玻璃化系统，开展了对人肝癌细胞（HepG2) 进行高通量玻璃化保存的研究。首先，比较容器式收集与薄片式接收两种方式对微滴喷射玻璃化保存效果的差异，结果表明容器式收集玻璃化组细胞的存活率和 24 h 贴壁率明显高于薄片式接收玻璃化组。其次，增加微滴喷射的 HepG2 细胞密度，发现细胞密度成倍增加时，微滴喷射玻璃化保存效果没有显著变化。最后，将微滴喷射容器式收集玻璃化与慢速冷冻法作比较，容器式收集玻璃化组的细胞处理量增大，且细胞存活率和 24 h 贴壁率明显高于慢速冷冻组。研究结果表明，本文设计的带容器式收集装置的微滴喷射玻璃化系统不仅能实现细胞的玻璃化保存，而且具有高通量的特点，这对小体积细胞的大体量保存具有重要意义。.

Network slicing has emerged as a key technology to support the coexistence of multi-service in the the 5G/B5G networks. However, due to the resource scarcity and the diversity of slice requests, how to allocate resources efficiently to maximize the long-term reward of the infrastructure network is a challenging issue. In this paper, we model the resource allocation problem as a semi-Markov decision process (SMDP), which is defined by state space, action space, reward and transition probability distribution. The reward function jointly considers the total income, the cost of available resource and the utilization of the total resource for the infrastructure network. Not focusing on one step decisions reward, we apply the Bellman equation to obtain long-term reward by accumulating. Then we exploit value iteration algorithm to determine the resource allocation scheme according to a certain state in such a way that the long-term reward can be maximized. Extensive simulation results show that the proposed SMDP can achieve a superior performance compared with the existing heuristic methods.

The presence of specific mutations in the EGFR gene informs the clinical pathway of therapy for patients with lung adenocarcinoma (LAC), including those with central nervous system (CNS) metastases. Plasma circulating cell-free DNA (cfDNA) has been demonstrated to carry the mutational information of LACs, which serves as a biomarker to guide treatment. However, whether the cerebrospinal fluid (CSF) enriches circulating tumor DNA (ctDNA) released from CNS metastatic lesions of LAC, and whether the CSF ctDNA can be used to characterize these lesions remains unknown. To explore the EGFR status in CNS metastases of LAC patients, and to guide the treatment of intra- and extracranial tumors in these patients. The EGFR mutational status in the cfDNA from paired CSF and plasma samples from LAC patients with CNS metastases, including 20 brain metastases (BM) and 15 leptomeningeal metastases (LM), was assessed by droplet digital polymerase chain reaction (ddPCR). The clinical outcomes of the EGFR status-based intervention were investigated. EGFR mutations were detected in 23/35 LAC patients (65.7%). EGFR mutations in the plasma or CSF were detected in 6/11 (54.5%) and 5/10 (50%) BM patients, and in 4/11 (36.4%) and 9/12(75%) LM patients, respectively. The prevalence of the T790M mutation was significantly higher in plasma (9/23) than in CSF (3/23) samples. The sensitivity and specificity of the ddPCR-based EGFR mutation test in CSF or plasma samples versus the primary tumor samples were 56% and 89% versus 46% and 100%, respectively. Twelve patients received a first-generation EGFR TKI (tyrosine kinase inhibitor) after the detection of sensitive EGFR mutations in their CSF or plasma, and five patients were switched from a first-generation EGFR TKI to osimertinib after the detection of the T790M mutation. The EGFR T790M mutation in plasma cfDNA is a sensitive marker for EGFR TKI resistance when CNS metastases progressed. CSF ctDNA increases the diagnostic validity for EGFR genotyping of lung cancer brain metastasis. ddPCR in CSF and plasma samples could provide less invasive and close monitoring of the EGFR status of LAC patients with CNS metastases.

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Oocyte cryopreservation is an important technology in assisted reproduction and fertility preservation. However, the developmental potential of cryopreserved oocyte remains poor. Osmotic stress injury (OSI) during cryoprotectants (CPAs) loading and unloading steps has critical impact on successful cryopreservation. In order to minimize OSI to oocytes, a microfluidic device was designed and fabricated to achieve continuous CPA concentration change. MII porcine oocytes were loaded and unloaded CPAs with step-wise and microfluidic methods, oocyte volume changes were recorded and compared, loading and unloading duration of microfluidic methods were optimized. The survival and developmental rate of treated oocytes in step-wise and microfluidic linear methods were also evaluated. The results showed that oocyte volume changes with microfluidic method were obviously less than step-wise method, and the survival, cleavage and blastocyst rate of oocytes were 95.3%, 64.4%, and 19.4%, respectively, which were significantly higher than the traditional step-wise method (79.4%, 43.6%, and 9.7%) (p 0.05). In conclusion, microfluidic device can effectively reduce the osmotic damage to oocytes and improve the survival rate and developmental rate of oocytes, which may provide a new path for oocyte cryopreservation.

Background The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples from lung adenocarcinoma (LAC) patients with leptomeningeal metastases (LM). Methods Paired CSF cell free DNA (cfDNA), CSF cells, plasma and formalin-fixed and paraffin-embedded (FFPE) samples of primary tumors were collected from 29 LAC patients with LM to detect the mutations by different NGS pipelines. Results DNA libraries were generated successfully for 79 various samples in total for NGS sequencing, of which mutations were detected in 7 plasma samples (24.14%), 12 CSF cfDNA samples (66.67%), and 10 CSF cells (76.9%) samples. For the 26 patients with detected mutations, 8/26(30.77%) had mutations in plasma, which was significantly lower than that those from CSF cfDNA (12/15, 80.00%), CSF cells (10/11, 90.91%) and FFPE samples (13/17, 76.47%). When the input DNA of CSF cells was less than 20 ng, the cHOPE pipeline of NGS identified the most mutations for epidermal growth factor receptor (EGFR). Conclusions NGS-based detection of mutations in cfDNA or cells from CSF provided more information than from plasma samples from LAC patients with LM. In addition, the cHOPE pipeline performed better than the other three NGS pipelines when input DNA from CSF cells was low. Electronic supplementary material The online version of this article (10.1186/s12885-019-5348-3) contains supplementary material, which is available to authorized users.

The development of nanothermites with adjustable reactivity has always been the research hotspot in the field of energetic materials, and its key issue is to control the interfacial contact extent and diffusion length between fuel and oxidizer. Here, the 3DOM CuO/Al, 3DOM CuO/Al-NPs and CuO-NPs/Al-NPs nanothermites, which show a gradual decrease in contact extents between reactants, were firstly prepared simultaneously using magnetron sputtering, P4VP self-assembly and ultrasonic mixing, respectively. The DSC thermograms show that the heat release of the 3DOM CuO/Al (sputtering 200 nm Al) can reach 2541.4 J/g, much larger than either value of the prepared 3DOM CuO/Al-NPs and CuO-NPs/Al-NPs. The activation energies of these CuO/Al systems also exhibit the similar results as the heat releases. However, the 3DOM CuO/Al-NPs can lead to the highest combustion pressure (24.6 MPa), the shortest pressure rise time (0.067 ms), and the fastest pressurization rate (647.98 GPa/s), followed orderly in corresponding values by the CuO-NPs/Al-NPs and 3DOM CuO/Al. All data indicate that the contact extent between CuO and Al plays a great effect on the overall reactivity, and their differences in structure and volume are responsible for the diverse combustion pressure performance. Furthermore, the presence of reaction voids between components can promote the O diffusion to enhance the continuous mass and heat transfer for an efficacious reaction. Hence, it is believed that similar methods can be used to improve the contact extent and diffusion length between fuels and oxidants so as to achieve an adjustment in reactivity for various nanothermites.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G-MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G-MDSCs were determined and the differential expression of microRNAs between G-MDSCs from tumor-bearing mice and tumor-free mice was examined. The number of G-MDSCs in spleens of Lewis lung carcinoma (LLC)-bearing mice was ~6-fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P1.3-fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA-468 (miR-486), miR-192, miR-128, miR-125a, miR-149, miR-27a, miR-125b, miR-350 and miR-328, were also analyzed by RT-qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor-induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G-MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC-induced granulocytic MDSCs and the target genes that mediate their functions.

Epidemiological evidence suggests that thyrotropin (TSH) levels are closely correlated with the severity of hypercholesterolemia. Reverse cholesterol transfer (RCT) plays an important role in regulating bloodcholesterol. However, the molecular mechanism of hypercholesterolemia in subclinical hypothyroidism (SCH) has not been fully clarified. The SCH mouse model, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a significant increase in plasma cholesterol compared with controls. Interestingly, Tshr KO mice, with normal thyroid hormone levels after thyroid hormone supplementation, showed lower plasma cholesterol levels compared with their wild-type littermates. ATP binding cassette subfamily A member 1(ABCA1) is a member of the ABC superfamily, which induces transfer of intracellular cholesterol to extracellular apolipoprotein. TSH upregulated hepatic ABCA1 to promote the efflux of intercellular cumulative cholesterol, resulting in increased plasma cholesterol. These data might partially explain the pathogenesis of hypercholesterolemia in SCH.

YrSM139-1B maybe a new gene for effective resistance to stripe rust and useful flanking markers for marker-assisted selection were developed. Stripe rust, caused by Puccinia striiformis f. sp. tritici, is an important foliar disease of wheat. Two dominant stripe rust resistant genes YrSM139-1B and YrSM139-2D were pyramided in bread wheat cultivar Shaanmai 139; one from wild emmer and the other from Thinopyrum intermedium. Three near-isogenic F7:8 line pairs (contrasting RILs), N122-1013R/S, N122-185R/S, and N122-1812R/S, independently derived from different F2 plants and differing at the YrSM139-1B locus were generated from the cross Shaanmai 139 × Hu 901-19 through marker-assisted selection. A large F2:3 population from cross N122-1013R × N122-1013S tested for stripe rust response and subjected to analysis with markers in the 1BS10-0.5 bin region using SSR expressed sequence tags (EST) and site-specific sequence markers developed from the 90 K Illumina iSelect SNP array. Five EST–STS markers and four allele-specific PCR markers were mapped to the YrSM139-1B region. The 30.5 cM genetic map for YrSM139-1B consisted of nine markers, two of which were closer to YrSM139-1B than Xgwm273, which was used in producing the contrasting RIL pairs. Race response data and allelism tests showed that YrSM139-1B is different from Yr10, Yr15, and Yr24/26/CH42.

Aims Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear. Main methods To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting. Key findings The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid β oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak. Significance Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.

Background Steroid 21‐hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype–phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. Methods Mutation analysis of CYP21A2 gene, 21‐hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype–phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. Results Among the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt‐wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459‐P464del) were detected and induced a significantly reduced 21‐hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%). Conclusion Four novel mutations were identified and a high consistency of genotype–phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease.

Growing evidence indicates that phosphoserine phosphatase (PSPH) is up-regulated and correlates with prognosis in multiple types of cancer. However, little is known about the roles of PSPH in NSCLC. Thus, the aim of the present study was to demonstrate the expression of PSPH in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of PSPH in migration and invasion were determined using trans-well and wound-healing assays. Cell proliferation capacity was performed by cell counting kit-8 (CCK-8), colony formation assays and cell cycle analysis. We demonstrated that PSPH was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of PSPH was associated with clinical stage, metastasis and gender in NSCLC. Decreased expression of PSPH inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that PSPH might regulate NSCLC progress through MAPK signaling pathways. Lastly, immunohistochemistry (IHC) revealed that the PSPH expression level was positively correlated with the clinical stage in NSCLC patients. These results suggest that PSPH may act as a putative oncogene and a potential therapeutic target in NSCLC.

Brain metastasis (BM) is the primary contributor to mortality in non-small cell lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing studies suggest the potential for personalizing therapeutic approaches, the genetic profiles and underlying mechanisms of BM progression remain poorly understood. Here, we investigated the genetic profiles of brain metastases from NSCLC in six patients with primary tumors and corresponding BM samples via whole exome sequencing and targeted panel sequencing. We have demonstrated considerable genetic heterogeneity between primary lung cancer and corresponding brain metastases specimens. High-frequency mutations were found in NOTCH2,NOTCH2NL,FANCD2,EGFR, and TP53. Additionally, EGFR and TP53 consistently exhibited high frequencies of mutation between primary tumors and corresponding brain metastases. The implication is that most of the genetic alterations may be acquired or lost during malignant progression, and the stable EGFR and TP53 mutational status between paired primary tumors and metastatic sites confirms that most mutations detected on analysis of the primary tumor or metastases are sufficient for clinical decision-making, and suggest there is no need to re-biopsy recurrent tumors or metastases for most NSCLC patients.

In order to reduce osmotic damage and chemical toxicity of cryoprotectants (CPA) to oocytes during unloading process, the microfluidic chip was used to remove CPA from porcine MⅡ oocytes in this study. Firstly, the effects of unloading time, composition and concentration of diluting solutions of microfluidic method on survival rate and developmental capacity of oocytes were studied, then microfluidic method was compared with traditional one-step and two-step CPA unloading protocols. The results showed that when the total time is 8 minutes, the survival rate and morula rate of oocytes treated with microfluidic method could achieve 95.99% ± 4.64% and 74.17% ± 1.18%, respectively, which were not significantly different from fresh control group (98.53% ± 2.94%; 78.22% ± 1.34%). In addition, 1 mol/L sucrose diluting solutions were more beneficial than other solutions, and it was also showed that microfluidic method achieved better survival, cleavage rate of oocytes than traditional methods. Microfluidic CPA removal protocol can reduce the damage to oocytes during unloading process, and may further improve the cryopreservation effect of oocytes.为了减小低温保护剂去除过程对卵母细胞造成的渗透损伤和毒性损伤，本文利用微流控芯片对猪二次减数分裂中期（MⅡ-stage）卵母细胞低温保护剂的去除方案进行了优化研究。首先分析了微流控去除方法中去除时间、去除液成分及浓度对卵母细胞存活率及体外发育情况的影响，然后将微流控去除方法与传统的一步法、两步法进行了比较。研究结果表明，微流控法中去除总时间为 8 min 时，卵母细胞存活率（95.99% ± 4.64%）及桑椹胚率（74.17% ± 1.18%）与新鲜细胞（98.53% ± 2.94%；78.22% ± 1.34%）相比，差异无统计学意义；1 mol/L 蔗糖去除液最有利于卵母细胞低温保护剂去除后的存活及体外发育；微流控法去除低温保护剂后，卵母细胞的存活率、体外发育情况等，均好于传统去除方法。本文研究结果提示，以微流控法去除低温保护剂可减小对卵母细胞的损伤，从而可能进一步提高卵母细胞的低温保存效果。.

Microfluidic chips can be used to realize continuous cryoprotectants(CPA)loading/unloading for oocytes,reducing osmotic damage and chemical toxicity of CPA.In this study,five different Y-shape microfluidic chips were fabricated to realize the continuous CPA loading/unloading.The effects of flow rate,entrance angle,aspect ratio and turning radius of microchannels on the mixing efficiency of microfluidic chips were analyzed quantitatively.The experimental results showed that with the decrease of flow rates,the increase of aspect ratios and the decrease of turning raradius of microchannel,the mixing length decreased and the mixing velocity was promoted,while the entrance angle had little effect on the mixing efficiency.However,the operating conditions and structural parameters of the chips in practical application should be determined based on an overall consideration of CPA loading/unloading time and machining accuracy.These results would provide a reference to the application of microfluidic chip in CPA mixing.

The Internet of Things, which is called the IOT for short, is the third wave of the information industry. Some simple superposition of the existing technology of privacy protection cannot meet the new demand for privacy protection of the Internet of Things in the third wave of the information industry. A timely overview of the development of the Internet of Things security and privacy technology, from numerous existing research results, will serve as a cornerstone of future research. Despite some literatures have given us a detailed summary of the relevant issues of the Internet of Things according to its perception or network, previous studies fail to discuss the terms of the overall framework of the Internet of Things or simply apply the security and privacy protection of the internet to the Internet of Things, which will inevitably affect the directions of future research more or less. This paper first analyzes the system structure and features of the Internet of Things, and then focuses on the security and privacy protection technology of the perceived environment by presenting a systematic overview of the current privacy protection technology concerning the Internet of Things, with a view to laying a foundation for future research.

Background: Steroid 21-hydroxylase deficiency (21OHD) is the most common enzymatic defect. Genotype-phenotype associations were concluded in different ethnic group. However, such correlations have not been well established in Chinese. This study aimed to analyze this correlation in a Chinese 21OHD cohort and the function of four novel mutations of CYP21A2 gene. Methods: A Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. Symptoms and laboratory findings of all the members were collected. Mutation analysis of CYP21A2 gene, 21-hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype and phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. Findings: Among the total cohort, 47 patients (65.3%) were diagnosed as SW phenotype, 11 (15.3%) were SV type and 14 (19.4%) were NC type. Interestingly, the value of FSH and LH for the prediction of the severe SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q and p.L459-P464del) were detected. All these four mutations were predicted to destroy 21-hydroxylase three-dimensional structure and induced a significantly reduced CYP21 activity of less than 5% compared with the wild type. Interpretation: A high consistency of genotype-phenotype association was found in SW CAH and a less matched correlation in SV and NC CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease. Funding: This work was supported by grants from the National Natural Science Foundation (No. 81370891 and No. 81670720), Special Funds for Taishan Scholar Project (No. tsqn20161071). Declaration of Interests: The author reports no conflicts of interest in this work. Ethical Approval Statement: This study was approved by the Ethics Committee of the Shandong Provincial Hospital. Written informed consent was obtained from all patients or their guardians.

Ultrasound has been often used to assist nucleation process in liquid samples, while solid samples were barely taken into account. In this study, direct-contact ultrasound was used to realize the sonocrystallization for solid sample and the influence of ultrasound-assisted nucleation on freeze-drying process was investigated. First, a microscopic observation was performed to exam the effectiveness of direct-contact ultrasound on inducing nucleation for carrot slice at different supercooling degrees. Second, an ultrasonic vibrating plate was used to integrate the contact ultrasound into freeze-drying process and its influence on ice crystals size and sublimation rate was evaluated. The results showed that direct-contact ultrasound is applicable to stimulate nucleation in carrot slice at lower supercooling degree and obtain bigger ice crystals. Compared to the control sample, the sublimation time of the samples under sonocrystallization was significantly reduced, by 21.80%. Therefore, direct-contact...

Summary Objective Gitelman syndrome (GS) is one of the most common causes of inherited hypokalaemia. As it was caused by 2 mutations in the SLC12A3 gene, GS is a highly heterogeneous disease. Here, we aimed to investigate the clinical and genetic characteristics of two Chinese pedigrees and summarize the advance in GS genetics, diagnosis and management. Subjects and methods Two three-generation families with GS were identified and screened for mutations in the SLC12A3 gene. Genotype–phenotype correlations were analysed. Results The two probands (A and B) were characterized by hypokalaemia, hypomagnesaemia and hypocalciuria without hypertension. Complete DNA sequencing of the SLC12A3 gene revealed two novel compound heterozygous mutations (c.179C>T and c.234delG; c.486-490delTACGGinsA and c.1925G>A), which are predicted to drastically affect normal protein structure. The female members of the pedigrees showed mild-to-no phenotype, although they carried the same mutations as the probands. Moreover, proband B presented with more severe symptoms than did proband A, which might be related to a lower serum magnesium level. During the 1-year follow-up, both probands showed satisfactory symptom improvement following the use of potassium and magnesium supplements. Conclusion Our findings strongly suggested that the two novel mutations in the SLC12A3 gene are the causative agents of GS, which may provide further insights into the function of this gene and help clinicians better understand this disorder.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus (T2DM), dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors were widely used to treat T2DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor (GLP-1R) is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride (TG) content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and mRNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Objective: Medullary breast carcinoma is a rare breast carcinoma with good prognosis. Although it has been established that axillary lymph node metastasis is a poor prognostic factor, little is known about the relationship between axillary lymph node metastasis and clinicopathological characteristics of medullary breast carcinoma patients. The aim of this study was to identify factors that predict occurrence of axillary lymph node metastasis in medullary breast carcinoma patients. Methods: We performed a retrospective study of axillary lymph node status and the relevant clinicopathological characteristics in 49 triple-negative medullary breast carcinoma patients with axillary lymph node dissection between November 2004 and July 2011. Results: A total of 49 patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph node metastasis that was confirmed pathologically. Axillary lymph node metastasis was not associated with age, menopausal status, primary tumor size or its location, the degree of inflammation within the tumor or mitotic count. However, we found a statistically significant association between axillary lymph node metastasis and Ki67 labeling index in primary tumors (P < 0.001). Conclusions: There is a positive association between Ki67 labeling index in the primary tumor and axillary lymph node metastasis in triple-negative medullary breast carcinoma patients.

The monocytic MDSC (M‐MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M‐MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M‐MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor‐induced M‐MDSCs (TM‐MDSCs) and their counterparts from tumor‐free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT‐qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR‐486 was overexpressed in TM‐MDSCs. Cebpa was predicted to be one of the target genes of miR‐486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR‐486 in TM‐MDSCs, and we found that overexpression of miR‐486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT‐qPCR. Overexpression of miR‐486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR‐486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR‐486 and Cebpa might be involved in the expansion of TM‐MDSCs in tumor‐bearing mice.

First, this paper researches the micro-blog information push, which leads to the concept of user’s friends, expounds the reason and meaning of friends recommendation algorithm, and introduces its current research situation, the paper has made the detailed introduction and analysis of existing algorithms and made a comprehensive comparison of the advantages and disadvantages of them. Then we make a recommendation of the micro-blog friend recommendation algorithms, which has two broad categories and three types: the recommendation algorithm based on content, the topology recommendation algorithm based on social relations and the filtering recommendation algorithm. Through the analysis of existing micro-blog friends recommendation algorithm, we represent the process of the algorithm and emphatically elaborated the implementation process, and finally we work out the Reasonable weighting of the three recommendation algorithm, get a sequence of recommended as a result, improved the algorithms, and reached a more comprehensive recommendation method. The improved algorithm could be a more effective way of potentially friends recommended for users.

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P

Oxidative stress is associated with obesity and may be accompanied by liver insulin resistance and mitochondrial dysfunction. Decreased mitochondrial respiratory chain enzymatic activities and decreased insulin metabolic signaling may promote these maladaptive changes. In this context, exenatide has been reported to reduce hepatic lipid deposition, improve insulin sensitivity and improve mitochondrial dysfunction. We hypothesized that exenatide would attenuate mitochondrial dysfunction by reducing hepatic lipid deposition, blunting oxidant stress and promoting insulin metabolic signaling in a high fat diet-induced model of obesity and insulin resistance. Sixteen-week-old male C57BL/6 diet-induced obese (DIO) mices and age-matched standard diet (STD) mices were treated with exenatide (10 μg/kg twice a day) for 28 days. Compared with untreated STD mice, untreated DIO mice exhibited deposited excessive lipid in liver and produced the oxidative stress in conjunction with insulin resistance, abnormal hepatic cells and mitochondrial histoarchitecture, mitochondrial dysfunction and reduced organism metabolism. Exenatide reduced hepatic steatosis, decreased oxidative stress, and improved insulin resistance in DIO mice, in concert with improvements in the insulin metabolic signaling, mitochondrial respiratory chain enzymatic activation, adenine nucleotide production, organism metabolism and weight gain. Results support the hypothesis that exenatide reduces hepatic cells and mitochondrial structural anomaly and improves insulin resistance in concert with improvements in insulin sensitivity and mitochondrial function activation, concomitantly with reductions in oxidative stress.

Cholesterol synthesis is regulated by the transcription factor sterol regulatory element binding protein 2 (SREBP-2) and its target gene 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is the rate-limiting enzyme in cholesterol synthesis. Cyclic adenosine monophosphate-responsive element (CRE) binding protein-regulated transcription coactivator (CRTC) 2 is the master regulator of glucose metabolism. However, the effect of CRTC2 on cholesterol and its potential molecular mechanism remain unclear. Here, we demonstrated that CRTC2 expression and liver cholesterol content were increased in patients with high serum cholesterol levels who underwent resection of liver hemangiomas, as well as in mice fed a 4% cholesterol diet. Mice with adenovirus-mediated CRTC2 overexpression also showed elevated lipid levels in both serum and liver tissues. Intriguingly, hepatic de novo cholesterol synthesis was markedly increased under these conditions. In contrast, CRTC2 ablation in mice fed a 4% cholesterol diet (18 weeks) showed decreased lipid levels in serum and liver tissues compared with those in littermate wild-type mice. The expression of lipogenic genes (SREBP-2 and HMGCR) was consistent with hepatic CRTC2 levels. In vivo imaging showed enhanced adenovirus-mediated HMGCR-luciferase activity in adenovirus-mediated CRTC2 mouse livers; however, the activity was attenuated after mutation of CRE or sterol regulatory element sequences in the HMGCR reporter construct. The effect of CRTC2 on HMGCR in mouse livers was alleviated upon SREBP-2 knockdown. CRTC2 modulated SREBP-2 transcription by CRE binding protein, which recognizes the half-site CRE sequence in the SREBP-2 promoter. CRTC2 reduced the nuclear protein expression of forkhead box O1 and subsequently increased SREBP-2 transcription by binding insulin response element 1, rather than insulin response element 2, in the SREBP-2 promoter. Conclusion CRTC2 regulates the transcription of SREBP-2 by interfering with the recognition of insulin response element 1 in the SREBP-2 promoter by forkhead box O1, thus inducing SREBP-2/HMGCR signaling and subsequently facilitating hepatic cholesterol synthesis. (Hepatology 2017;66:481-497).

DDoS attacks are mostly adopted by attackers in the network. This attack is malicious on the network protocol, resulting in the object not working properly. At present, the Packet Marking is the main method to trace back the attackers under DDoS attacks, especially the Probabilistic Packet Marking (PPM) of Packet Marking. Therefore, the two main types of Probabilistic Packet Marking are studied in this paper: Advanced Packet Marking and Authenticated Packet Marking (APM) and Adjusted Probabilistic Packet Marking (APPM).

When users transfer the ownership of RFID tags, sometimes they may have the need to cut off the connection between tags and the original owner, while sometimes they may hope to keep the control. This paper proposes an Optional Ownership Transfer (OOT) mode according to this problem that users can choose from whether to keep the control of original owner or not, and designs the corresponding protocol. After private key exchange, the original reader sends all pertinent information of a tag to the new reader safely, together with its query for whether to keep/lose the right of control to the new reader and the tag. Then the new reader decides to permit or not and sends the response to the tag. Finally, the tag decides whether to delete the serial number of the original reader in delegated reader-numbers queue and adds that of the new reader in. Thus, we achieve the selectivity in ownership transfer and ensure new owner’s control over the tag as well.

The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis. An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg’s funnel plot and Egger’s test using Stata/SE version 10.1 software. Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88–1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90–1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90–1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00–1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97–1.14, p = 0.20). Grade 3–4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35–0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30–0.45, p

Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

Traditional health care system in the family-oriented application of monitoring system has some disadvantage, which is relatively small, and function relatively single operability is more complex, real-time performance is poor, the price is relatively expensive. In recent years, with the progress of integrated circuit technology and wireless communication technology, wireless body area network (WBAN) systems have got fast development. The application system base on BAN technology also has received more and more people’s attention. This paper presents a general framework BAN-based health care system, mainly introduces the design of the sensor from the perception layer and network protocol.

Thunderstorms pose great threat to human survival. As traditional statistics and fore-casts have great limitations, this paper applies credit scoring model into thunderstorm warning system. We select related data of the electric field as variables before and during the thunder-storms. And by actual monitoring system of thunderstorm data preprocessing, sampling, binning and so on, by using the method of logistic regression and neural network to deal with, the model based on the combination of location and data of electric field is an effective way of thunderstorm warning. From the angle of the method, the model based on the theory of credit scoring can be faster and more accurate. It can make the probability of forecasting thunderstorm more quantization.

Brain metastasis as the first symptom of lung cancer is a unique clinical entity. We conducted a retrospective study to investigate the clinical characteristics and survival of patients with lung cancer whose first symptom was brain metastases in an Asian population.A retrospective study of 186 such patients who had been admitted to one institution in China between January 1, 2003 and December 30, 2008 was performed. The following data were collected and analyzed: manifesting signs and symptoms, imaging studies, extracerebral metastases, initial diagnosis, treatment, and patient survival.This sample population exhibited high rates of misdiagnosis upon initial presentation (46.8 %). Fifty-seven (30.6 %) patients presented with silent extracerebral metastases. Pathologies among this cohort varied, and adenocarcinomas were most commonly observed. Most patients received surgical resection, and some patients had additional whole-brain radiotherapy or stereotactic radiosurgery. The median survival time for the entire cohort was 15 months (95 % confidence interval, 12.9-17.1 months). Survival rates for 1, 2, and 5 years were 58.2, 34.2, and 6.5 %, respectively. The median survival time was 15, 14, 19, and 7 months for the gross total resection, incomplete resection, surgery + whole-brain radiotherapy, and surgery + stereotactic radiosurgery groups, respectively.Brain metastasis as the first symptom of lung cancer is a distinct clinical entity. Although overall survival was poor, combined treatments based on surgery for selected patients were reasonable with the exception of a minority who experienced long-term survival.

It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58-0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93-2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39-2.22; P = 0.000; RR, 0.77; 95% CI, 0.64-0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC.

A meta-analysis of randomized controlled trials was performed to compare the efficacy, quality of life (QOL), symptom improvement and toxicities of gefitinib with docetaxel in previously treated advanced non-small-cell lung cancer.The PubMed database, the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for overall response rate, QOL and symptom improvement, and odds ratios (ORs) for main toxicities were pooled using STATA package.Four multicenter, randomized controlled trials involving 2257 patients with previously treated advanced NSCLC were ultimately analyzed. The pooled HRs showed no significant difference in OS and PFS between the two groups (HR = 1.02, 95% CI = 0.92-1.12, p = 0.70; HR = 0.97, 95% CI = 0.88-1.07, p = 0.57, respectively). Gefitinib significantly improved overall response rate (RR = 1.58, 95% CI = 1.02-2.45, p = 0.04) and QOL (RR = 1.55, 95% CI = 1.27-1.88, p = 0.00 by Functional Assessment of Cancer Therapy-Lung and RR = 1.86, 95% CI = 1.43-2.42, p = 0.00 by Trial Outcome Index, respectively). Gefitinib had fewer grade 3 or 4 neutropenia and fatigue (OR = 0.02, 95% CI = 0.01-0.03, p = 0.00; and OR = 0.47, 95% CI = 0.32-0.70, p = 0.00, respectively), but more grade 3 or 4 rash (OR = 2.87, 95% CI = 1.24-6.63, p = 0.01) than docetaxel. The grade 3 or 4 nausea, vomiting and diarrhea and symptom improvement were comparable between the two drugs.In conclusion, although similar OS and PFS, gefitinib showed an advantage over docetaxel in terms of objective response rate, QOL and tolerability. Therefore, gefitinib is an important and valid treatment option for previously treated advanced non-small-cell lung cancer patients.

To investigate the clinical characteristics of patients with brain metastases as the initial manifestation of their systemic cancer in a Chinese population, a retrospective study of 254 such patients admitted to Huashan Hospital, Fudan University, Shanghai, China between January 1, 2003 and December 30, 2008 was performed. Data were collected to determine the features of this group (i.e., manifesting signs and symptoms, imaging studies, extracerebral metastases, primary tumor sites, initial diagnosis, and survival data). Common symptoms included headache and motor impairment. The distribution of brain metastases paralleled blood flow, and the majority of brain metastases were located in the cerebral hemispheres. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) for confirming presence of brain lesions. This distinct clinical entity exhibited high rates of misdiagnosis at initial presentation. Pathology varied, and adenocarcinomas were most commonly observed. Underlying primary tumors were identified in 84.2% of patients, most often located in lung (71.7%), followed by digestive tract. Chest CT had high yield. Sixty-two patients presented with silent extracerebral metastases at initial presentation. Median survival time was 15 months (95% confidence interval, 12.2-17.8 months). Survival rates for 1, 2, and 5 years were 59.2%, 23.2%, and 15.1%, respectively. Contrast-enhanced MRI had high yield for detection of brain metastases. Adenocarcinoma was the most common histologic type. Given the high frequency of primary lung tumors and the sensitivity of chest CT, chest CT should be a part of the initial screen of primary site with brain metastases as the initial manifestation. Metastatic dissemination of malignancy to the brain as the initial manifestation is generally associated with dismal prognosis, with the exception of a minority who experience long survival.