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AbstractObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres in China between 3 January 2016 and 17 July 2023.ParticipantsFemale patients aged 18-70 years with early triple negative breast cancer after definitive surgery.InterventionsAfter risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168).Main outcome measuresThe primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety.ResultsAmong the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred.ConclusionsThe multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity.Trial registrationClinicalTrials.gov NCT02641847.

Spodoptera litura (F.), one of the most devastating pests in many Asian countries, is normally controlled by relying on chemical insecticides. To encourage an integrated pest management approach, we determined the economic injury level (EIL) for S. litura on peanut, Arachis hypogaea L., by larval infestation with late instars at different crop growth stages. The cumulative consumption rate of the fifth- and sixth-instars was used as the relative unit for the “Spodoptera injury equivalent” (SIE). The yield of marketable pods significantly decreased from 6.19 to 1.63 g.plant–1 as larval infestation intensity increased throughout the entire cropping season. When supplemented with timely applications of the insecticide, indoxacarb, an oxadiazine insecticide, the EIL values obtained in the larval infestation trial ranged from 3.26 to 13.47 SIE per 20 plants depending on the timing of initial infestation. The economic threshold (ET) for late instars, i.e., multiplying the EIL by 0.75, could not be utilized as a control timing index for the outbreak of injurious larvae population because of the time-lag. When the occurrence of natural mortality in the egg to pupal stage was considered, the ETs were adjusted to reflect the average survivorship. ETs of 27.3, 55.9, 51.3, and 112.6 eggs.m–2 were recommended at the early vegetative growth, blooming/pegging, pod-setting, and pod-filling stages, respectively, for initiating control measures. By simulating the pest population with the program, Timing-MSChart, we integrated the stage-specific EILs and ETs with the life-table data of S. litura on peanut and then proposed a demography-based control timing.

Background and aims Windblown sand movements, i.e., wind denudation and sand burial, pose a strong selective pressure on dune vegetation. Dune plants commonly receive repeated wind denudation or sand burial. Therefore, simultaneously examining the role of sand movement intensity and frequency in shaping dune vegetation is critical for dune biodiversity conservation and ecological restoration. However, studies of this nature are rare. Methods We studied the integrated effects of sand movement intensity and frequency on the seedling performance of a dominant semi-shrub, Artemisia ordosica , in the Mu Us sandland. We subjected A. ordosica seedlings to a total intensity of 10 cm wind denudation or sand burial treatments conducted once, twice or four times. Key results We found, given that the total intensity of sand movement remains the same, increasing frequency and decreasing intensity per time largely improved seedling survival. Furthermore, increasing frequency and decreasing intensity per time significantly alleviated the negative effects of wind denudation, although such alleviation effect was not detected for sand burial. Seedlings of A. ordosica increased specific leaf area, root length, and biomass allocation to root to adapt to wind denudation, while they developed adventitious roots to adapt to sand burial. Conclusions Our results demonstrate that a single heavy sand movement is more detrimental than multiple light ones to the performance of A. ordosica seedlings. Our findings suggest that windproof measures to prevent severe sand movements is necessary to allow the establishment of A. ordosica during the dune restoration process.

Background The prognoses of young breast cancer patients are poor. The purpose of this study is to evaluate the different characteristics and prognoses among different subtypes of young breast cancer patients. Methods The study included 1360 patients <40 years-old (y) and 3110 patients 40-50y with operable breast cancer in Shanghai Cancer Center, Fudan University. The characteristics, overall survival (OS) and disease-free survival (DFS) were compared. Results The median follow-up was 54.1 months. More grade III tumors and more lymph-vascular invasions (P < 0.01) were presented in <40y group when compared with 40-50y group. More patients <40y presented with Luminal B (25.3% vs. 17.5%, P < 0.01) and triple negative (16.7% vs. 13.4%, P < 0.05) breast cancer while fewer had Luminal A tumor (48.5% vs. 59.2%, P < 0.01). Younger patients with tumors of both Luminal A and Luminal B types were at increased risk for worse DFS (P = 0.03, HR = 1.69, 95% CI = 1.05-2.72; P < 0.01, HR = 3.61, 95% CI = 2.50-5.22) when compared with the older patients. Patients <40y with Luminal B tumor had a two point five fold higher risk of death compared with older counterparts (P < 0.01, HR = 2.54, 95% CI = 1.35-4.79), however, a worse overall survival rate was not observed in the younger women with Luminal A breast cancer (P > 0.05). In multivariate analysis, Luminal B subtype was also a strong predictor of disease relapse (HR = 1.09, 95% CI = 1.01 to 1.19, P < 0.01) in younger patients with Luminal subtype tumors. Conclusion Characteristics of breast cancer suggested a more aggressive biology in Chinese patients with breast cancer diagnosed at young age. Luminal B subtype may have a negative effect on the prognosis of young patients in China which should be validated further.

The prognostic factors of young breast cancer patients (BCPs) are still controversial. This study is aimed at evaluating the prognosis of young BCPs by characteristics and treatment response. We analysed the data on 2,593 operable BCPs age ≤50 years who were treated in the Cancer Hospital of Fudan University, Shanghai, China between 1990 and 2004. The overall survival and recurrence/metastasis-free survival were compared. In the study, 782 patients (30.2%) were ≤40 years, and 1,811 (69.8%) were 41-50 years old at their primary diagnosis. BCPs ≤40 years presented more unfavourable features than the 41-50 years BCPs (P < 0.05). They were more likely to experience death (P < 0.001) and recurrence/metastasis events (P < 0.001) even when they underwent the same adjuvant therapy in parallel with their counterparts (P < 0.05). In a multivariate analysis, age was an independent predictive factor for RFS (HR = 0.26, 95% CI = 0.44-0.89, P = 0.009) but not for OS (P > 0.05). Higher TNM stage and chemotherapy, but not HER2/neu over-expression, were predictive factors for young Chinese BCPs. The characteristics of breast cancer are more aggressive in young Chinese BCPs. Their prognostic factors are obviously different from those of the elder group. Current therapy was not as effective for them.

Dear Editor, Males-absent-on-the-first （MOF, also called MYST1 or KAT8） is a histone acetyltransferase （HAT） belonging to the MOZ, Ybf2/Sas3, Sas2 and Tip60 （MYST） family. MOF has been shown to possess a specific HAT activity towards Lysl6 of histone H4 （H4K16） [1]. Homozygous knockout of MOF in mice results in loss of H4K16 acetylation and embryonic lethality,

The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus （S-OIV H1N1） that infected almost every country in the world. Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury. In this report, we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease. The clinical efficacy of the antiviral oseltamivir （Tamiflu） administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model. Moreover, elevated levels of IL-17, Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing. IL-17 deficiency or treatment with monoclonal antibodies against IL- 17-ameliorated acute lung injury induced by the S-OIV HIN1 virus in mice. These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.

Background： 15-Deoxy-^△^12、14-prostaglandin J2 （15d-PGJ2）, one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-1oaded poly（D,L-lactide-co-glycolide） nanocapsules （15d-PGJ2-NC） on inflammatory responses and bone regeneration in local bone defect. Methods： The study was conducted on 96 Wistar rats from June 2014 to March 2016. Saline, unloaded nanoparticles, free 15d-PGJ2 or 15d-PGJ2-NC, were delivered through a collagen vehicle inside surgically created transcortical defects in rat femurs, lnterleukin-6 （IL-6）, interleukin-1 beta （IL-I~）, and tumor necrosis factor-alpha （TNF-o0 levels in the surrounding soft tissue were analyzed by Western blot and in the defect by quantitative real-time polymerase chain reaction over 14 days. Simultaneously, bone morphogenetic protein-6 （BMP-6） and platelet-derived growth factor-B （PDGF-B） messenger RNA （mRNA） in the defect were examined. New bone formation and EphrinB2 and osteoprotegerin （OPG） protein expression in the cortical defect were observed by Masson＇s Trichrome staining and immunohistochemistry over 28 days. Data were analyzed by one-way analysis of variance. Least-significant difference and Dunnett＇s T3 methods were used with a bilateral P 〈 0.05. Results： Application of 15d-PGJfNC （100μg/ml） in the local bone defect significantly decreased 1L-6, IL-Iβ, and TNF-α mRNA and protein, compared with saline-treated controls （P 〈 0.05）. 15d-PGJfNC upregulated BMP-6 and PDGF-B mRNA （P 〈 0.05）. New bone formation was observed in the cortical defect in 15d-PGJ2-NC-treated animals from 7th day onward （P 〈 0.001）. Expression of EphrinB2 and OPG presented early on day 3 and persisted through day 28 in 15d-PGJfNC group （P 〈 0.05）. Conclusion： Stable 15d-PGJz-NC complexes were prepared that could attenuate IL-6, IL-1 β, and TNF-α expression, while increasing new bone formation and growth factors related to bone regeneration.

s Background The aim of this sub-study is to explore the incidence of skin rash among advanced breast cancer(ABC) patients in a phase II trial treated with weekly nab-paclitaxel and cisplatin combination. Methods Nab-paclitaxel(125 mg/m 2 ) was administered on days 1, 8, 15, followed by cisplatin(75 mg/m 2 ) on day 1 every 28 day cycle until disease progression, intolerable toxicities or the maximum of 6 cycles. Patients who received at least one injection of the study drug were included in this analysis of the incidence of skin rash among Chinese patients. Toxicity was graded using the CTCAE4.0 criteria. Statistical analysis was carried out by using SPSS 16.0 (SPSS Inc, Chicago, IL). Results Seventy three patients were enrolled and eligible for analysis. A total of 384 cycles were administered at the time of this analysis. Rash was presented in 27 patients (37.0%). The most common sites involved were face (14/27), neck (14/27), limbs (18/27) and frictional parts of the trunk (10/27). Macular and papular rash with pruritus commonly occurred 2 (95% CI: 1–7) days after the first day of chemotherapy. Only one patient developed Grade 3 skin toxicity with generalized erythroderma and disfigurement of the face requiring dose reduction. The rash gradually regressed 2 (95% CI: 1–10) days after antihistamines used, but pigmentation remained in 13/27 cases. The incidence rate of skin rash was significantly higher than what has been described for western patients (approximate 4%, P < 0.0001). Conclusion A higher rate of maculo-papular rash occurred in Chinese breast cancer patients treated with weekly nab-paclitaxel compared to western patients. The albumin component of nab-paclitaxel might be the cause of the skin disorder. Trial registration NCT01149798