Background
The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral ...infiltrating immune/inflammatory cells (IICs) in patients after surgery.
Methods
Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort.
Results
CD15+ neutrophils, CD20+ B cells and CD206+ tumour‐associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence‐predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3·63, 95 per cent c.i. 2·18 to 6·04; P < 0·001) and recurrence‐free (HR 2·93, 1·81 to 4·75; P < 0·001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound‐guided fine‐needle aspiration.
Conclusion
PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy.
Surgical relevance
The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4.
This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.
Immunosuppressive phenotype has poor prognosis
Background
The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G‐NECs) or mixed ...adenoneuroendocrine carcinomas (G‐MANECs).
Methods
The study included patients with G‐NECs or G‐MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan–Meier method.
Results
In total, 804 patients with resectable G‐NECs or G‐MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no‐chemotherapy group. Among patients with G‐NECs, survival in the fluorouracil (5‐FU)‐based chemotherapy group and the non‐5‐FU‐based chemotherapy group was similar to that in the no‐chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G‐NECs. Among patients with G‐MANECs, OS in the non‐5‐FU‐based chemotherapy group was worse than that in the no‐chemotherapy group. Patients with G‐MANECs did not have better OS when platinum‐based chemotherapy was
used.
Conclusion
There was no survival benefit in patients who received adjuvant chemotherapy for G‐NECs or G‐MANECs.
Antecedentes
El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G‐NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G‐MANECs).
Métodos
Se incluyeron pacientes con G‐NECs y G‐MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan‐Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento.
Resultados
En total, se incluyeron en el estudio 804 pacientes con G‐NECs y G‐MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G‐NECs, la supervivencia en los grupos con quimioterapia basada en 5‐FU (fluorouracilo) y de quimioterapia sin 5‐FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G‐NECs. En pacientes con G‐MANECs, la OS del grupo con quimioterapia sin 5‐FU fue peor que la del grupo sin quimioterapia. Los pacientes con G‐MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos.
Conclusión
La administración de quimioterapia adyuvante en pacientes con G‐NECs y G‐MANECs no mejoró la supervivencia.
This multicentre study enrolled 804 patients with resectable gastric neuroendocrine carcinomas and gastric mixed adenoneuroendocrine carcinomas. In propensity score matching analysis, there were no associations between the use of adjuvant chemotherapy and improved overall survival. Similar results were obtained in stratified analysis according to different chemotherapy regimens.
No benefit
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
A simple, efficient scheme was developed to obtain near-gigaelectronvolt electron beams with energy spreads of few per-mille level in a single-stage laser wakefield accelerator. Longitudinal plasma ...density was tailored to control relativistic laser-beam evolution, resulting in injection, dechirping, and a quasi-phase-stable acceleration. With this scheme, electron beams with peak energies of 780–840 MeV, rms energy spreads of 2.4‰–4.1‰, charges of 8.5–23.6 pC, and rms divergences of 0.1–0.4 mrad were experimentally obtained. Quasi-three-dimensional particle-in-cell simulations agreed well with the experimental results. The dechirping strength was estimated to reach up to 11 TeV/mm/m, which is higher than previously obtained results. Such high-quality electron beams will boost the development of compact intense coherent radiation sources and x-ray free-electron lasers.
We investigate polarization-dependent ultrafast photocurrents in the Weyl semimetal TaAs using terahertz (THz) emission spectroscopy. Our results reveal that highly directional, transient ...photocurrents are generated along the noncentrosymmetric c axis regardless of incident light polarization, while helicity-dependent photocurrents are excited within the ab plane. This is consistent with earlier static photocurrent experiments, and demonstrates on the basis of both the physical constraints imposed by symmetry and the temporal dynamics intrinsic to current generation and decay that optically induced photocurrents in TaAs are inherent to the underlying crystal symmetry of the transition metal monopnictide family of Weyl semimetals.
Caveolin-1 exhibits a stage-dependent, functional fluctuation during pancreatic cancer development, but the underlying mechanisms remain unclear. Here, we report that cavin-1, a structural protein of ...caveolae, modulates the oncogenic function of caveolin-1 and cooperates with caveolin-1 to enhance pancreatic cancer aggressiveness. Cavin-1 expression is associated with caveolin-1 in pancreatic cancer tissue samples and cell lines, and predicts the metastatic potential of pancreatic cancer. Interactome analyses further revealed the physical interaction of cavin-1 and caveolin-1 and their colocalization in pancreatic cancer cells. Cavin-1 stabilizes caveolin-1 expression or activity by inhibiting its internalization and subsequent lysosomal degradation. More in-depth functional experiments showed that caveolin-1-enhanced aggressiveness of pancreatic cancer cells is dependent on the presence of cavin-1. In contrast, cavin-1 depletion inhibited the invasion and metastasis of pancreatic cancer cells, which could not be restored by caveolin-1-rescue construct. Tissue microarray analyses in two independent clinic cohorts also supported the augment of cavin-1 on the prognostic potency of caveolin-1, and showed that combination of cavin-1 with caveolin-1 predicted worse survival in pancreatic cancer patients. Of note, the phenotypes because of cavin-1 could not be achieved by other cavins such as cavin-2, and the tumor-promoting role of cavin-1 in pancreatic cancer was found to be largely dependent on caveolin-1 expression, which highlights the critical role of cavin-1/caveoin-1 in pancreatic cancer progression, and suggests that the interruption of cavin-1/caveolin-1 interaction is a promising therapeutic strategy for pancreatic cancer.
The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This ...work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2
/
years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.
Abstract
The Kagome superconductors AV
3
Sb
5
(A = K, Rb, Cs) have received enormous attention due to their nontrivial topological electronic structure, anomalous physical properties and ...superconductivity. Unconventional charge density wave (CDW) has been detected in AV
3
Sb
5
. High-precision electronic structure determination is essential to understand its origin. Here we unveil electronic nature of the CDW phase in our high-resolution angle-resolved photoemission measurements on KV
3
Sb
5
. We have observed CDW-induced Fermi surface reconstruction and the associated band folding. The CDW-induced band splitting and the associated gap opening have been revealed at the boundary of the pristine and reconstructed Brillouin zones. The Fermi surface- and momentum-dependent CDW gap is measured and the strongly anisotropic CDW gap is observed for all the V-derived Fermi surface. In particular, we have observed signatures of the electron-phonon coupling in KV
3
Sb
5
. These results provide key insights in understanding the nature of the CDW state and its interplay with superconductivity in AV
3
Sb
5
superconductors.
The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A ...hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
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