BackgroundSleep disorders and primary headaches are both more prevalent among nursing staff than in the general population. However, there have been no reports about the comorbidity of poor sleep and primary headaches among nursing staff.MethodsStratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals in north China. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The diagnosis of primary headaches including migraine, tension-type headache (TTH), and chronic daily headache (CDH) was based on the International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3-beta).ResultsThe response rate was 93 %. Among 1023 nurses, the prevalence of poor sleep was 56.7 %. Of these, 315 nurses (34.13 %) had poor sleep comorbid with primary headaches. The prevalence of poor sleep in the groups with CDH (82.1 %), migraine (78.9 %), and TTH (59.0 %) was significantly higher than that in the group without headaches (47.3 %) (all P < 0.05). Multivariate logistic regression revealed that rotating shifts and suffering headache were independent risk factors for poor sleep. Also, the 1-year prevalence of the three types of primary headache was significantly increased in the poor sleep group (migraine: 21.2 % vs. 7.2 %; TTH: 27.9 % vs. 24.9 %; CDH: 4.1 % vs. 1.1 %; P < 0.05). Compared with normal sleepers, nurses with poor sleep were 1.72 times more likely to have severe headache (OR: 1.72, 95 % CI: 1.14–2.57).ConclusionComorbidity of poor sleep and primary headaches among nursing staff is common. Therefore, sleep quality should be carefully evaluated in nurses with primary headaches.

BackgroundThe hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole group and selectively under hypoxic conditions releases the DNA cross-linker bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of Chk1 inhibition on TH-302-mediated pharmacological activities.MethodsWe employed in vitro cell viability, DNA damage, cellular signaling assays and the in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on TH-302 antitumor activities.ResultsTH-302 cytotoxicity is greatly enhanced by Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH-302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15 phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we observed a potentiation of the TH-302 dependent tail moment. TH-302 induced γH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor. Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell lines proficient in, but not deficient in homology-directed DNA repair. We also show that combination treatment led to lowering of Rad51 expression levels as compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts, supporting the hypothesis that these in vitro results can translate to enhanced in vivo efficacy of the combination.ConclusionsTH-302-mediated in vitro and in vivo anti-tumor activities were greatly enhanced by the addition of Chk1 inhibitors. The preclinical data presented in this study support a new approach for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors with the hypoxia-activated prodrug TH-302.

BackgroundFor patients with locally advanced non-small-cell lung cancer (LA-NSCLC), the role of consolidation chemotherapy (CCT) following concurrent chemoradiotherapy (CRT) is partially defined. The aim of this study was to evaluate the efficacy and toxicity of CCT.MethodsThe characteristics of LA-NSCLC patients treated with curative concurrent CRT from 2001 to 2010 were retrospectively reviewed.ResultsAmong 203 patients, 113 (55.7 %) patients received CCT. The median number of delivered CCT was 3 and 89.4 % patients completed ≥2 cycles. The OS was significantly better for patients in the CCT group compared with that in the non-CCT group (median OS, 27 months vs. 16 months; 5-year OS, 30.4 % vs. 22.5 %; p = 0.012). The median PFS were 12 months in the CCT group and 9 months in the non-CCT group (p = 0.291). The survival advantages of CCT were significant for males (HR: 0.63; 95 % CI, 0.44 − 0.90), patients with age < 60 years (HR: 0.63; 95 % CI, 0.42 − 0.95), non-squamous histology (HR: 0.44; 95 % CI, 0.25 − 0.76), pretreatment KPS ≥ 80 (HR: 0.67; 95 % CI, 0.48 − 0.93), stage IIIb (HR: 0.64; 95 % CI, 0.43 − 0.95), stable disease (HR: 0.31; 95 % CI, 0.14 − 0.65) and radiotherapy dose ≥ 60 Gy (HR: 0.69; 95 % CI, 0.48 − 1.00). There was no significant difference between the CCT group and the non-CCT group regarding treatment-related toxicities.ConclusionsCCT might further prolong survival compared with CRT alone for LA-NSCLC without increasing treatment-related toxicities, especially for males, patients with age < 60 years, non-squamous histology, pretreatment KPS ≥ 80, stage IIIb, stable disease and radiotherapy dose ≥ 60 Gy. Large size prospective investigations that incorporate patient characteristics and treatment response are warranted to validate our findings.

BackgroundSoybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most fatal pests of soybean (Glycine max (L.) Merr.) worldwide and causes huge loss of soybean yield each year. Multiple sources of resistance are urgently needed for effective management of SCN via the development of resistant cultivars. The aim of the present study was to investigate the genetic architecture of resistance to SCN HG Type 0 (race 3) and HG Type 1.2.3.5.7 (race 4) in landraces and released elite soybean cultivars mostly from China.ResultsA total of 440 diverse soybean landraces and elite cultivars were screened for resistance to SCN HG Type 0 and HG Type 1.2.3.5.7. Exactly 131 new sources of SCN resistance were identified. Lines were genotyped by SNP markers detected by the Specific Locus Amplified Fragment Sequencing (SLAF-seq) approach. A total of 36,976 SNPs were identified with minor allele frequencies (MAF) > 4 % that were present in 97 % of all the genotypes. Genome-wide association mapping showed that a total of 19 association signals were significantly related to the resistance for the two HG Types. Of the 19 association signals, eight signals overlapped with reported QTL including Rhg1 and Rhg4 genes. Another eight were located in the linked regions encompassing known QTL. Three QTL were found that were not previously reported. The average value of female index (FI) of soybean accessions with resistant alleles was significantly lower than those with susceptible alleles for each peak SNP. Disease resistance proteins with leucine rich regions, cytochrome P450s, protein kinases, zinc finger domain proteins, RING domain proteins, MYB and WRKY transcription activation families were identified. Such proteins may participate in the resistant reaction to SCN and were frequently found in the tightly linked genomic regions of the peak SNPs.ConclusionsGWAS extended understanding of the genetic architecture of SCN resistance in multiple genetic backgrounds. Nineteen association signals were obtained for the resistance to the two Hg Types of SCN. The multiple beneficial alleles from resistant germplasm sources will be useful for the breeding of cultivars with improved resistance to SCN. Analysis of genes near association signals may facilitate the recognition of the causal gene(s) underlying SCN resistances.

BackgroundCurrently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH.MethodsA total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-μm and 100-μm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter.ResultsThe prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P < .0.01), the mean QoL (5.0 vs 3.0; P < 0.01), the mean Qmax (8.5 vs 14.5; P < 0.01), the mean PVR (125.0 vs 40.0; P < 0.01), and PV (118.0 vs 69.0, with a mean reduction of 41.5%; P < 0.01 ) at 24-month after PAE were significantly different with respect to baseline. The mean IIEF-5 was not statistically different from baseline. No major complications were noted.ConclusionsPAE is a safe and effective treatment method for patients with LUTS due to large volume BPH. PAE may play an important role in patients in whom medical therapy has failed, who are not candidates for open surgery or TURP or refuse any surgical treatment.