Highlights • Guanabenz extended the lifespan of SOD1 G93A mice. • Guanabenz delayed the disease onset of SOD1 G93A mice. • Guanabenz improved motor performance in SOD1 G93A mice. • Guanabenz ...attenuated motor neuron loss in SOD1 G93A mice. • Guanabenz attenuated ER stress and mitochondrial stress.
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
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of ...more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)
and 12 HPV
HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV
TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.
Highlights • The Notch pathway was activated in in vitro and in vivo models of ALS. • Suppression of Notch activation reduced the neuronal apoptotic signaling. • Lithium and VPA suppressed Notch ...activation associated with SOD1 mutation. • Lithium–VPA co-treatment had a synergistic effect in the Notch pathway inhibition.
Compared with other nanofiber fabrication processes, electrospinning is versatile and superior in production and construction of ordered or more complex nanofibrous assemblies. Besides traditional ...two-dimensional (2D) nanofibrous structures, electrospinning is powerful in fabrication of three-dimensional (3D) fibrous macrostructures, especially for tissue engineering applications. This article summarizes and reviews recent advances in various promising and cutting-edge electrospinning techniques, including multilayering electrospinning, post-processing after electrospinning, liquid-assisted collection, template-assisted collection, porogen-added electrospinning, and self-assembly. And their formation mechanisms, features, and the challenges of electrospinning have also been discussed. Furthermore, these 3D nanofibrous macrostructures have been demonstrated to have potential applications in tissue engineering, energy harvesting and storage, and filtration.
It has so far remained a major challenge to quantitatively predict the boson peak, a THz vibrational anomaly universal for glasses, from features in the amorphous structure. Using molecular dynamics ...simulations of a model Cu_{50}Zr_{50} glass, we decompose the boson peak to contributions from atoms residing in different types of Voronoi polyhedra. We then introduce a microscopic structural parameter to depict the "orientational order," using the vector pointing from the center atom to the farthest vertex of its Voronoi coordination polyhedron. This order parameter represents the most probable direction of transverse vibration at low frequencies. Its magnitude scales linearly with the boson peak intensity, and its spatial distribution accounts for the quasilocalized modes. This correlation is shown to be universal for different types of glasses.
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CMK, CTK, FMFMET, NUK, UL
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.
We examined the global incidence and mortality rates of liver cancer, and evaluated the association between incidence/mortality and socioeconomic development (Human Development Index HDI and Gross ...Domestic Product GDP) using linear regression analysis. The average annual percent change (AAPC) of the trends was evaluated from join-point regression analysis. The global incidence of liver cancer varied widely by nine-fold, and was negatively correlated with HDI (men: r = -0.232, p = 0.003; women: r = -0.369, p < 0.001) and GDP per capita (men: r = -0.164, p = 0.036; women: r = -0.212, p = 0.007). Its mortality showed a similarly negative correlation with both indices. The greatest incidence rise in men was observed in Poland (AAPC = 17.5, 95% C.I. = 5.6, 30.9) and Brazil (AAPC = 13.2, 95% C.I. = 5.9, 21.0), whereas Germany (AAPC = 6.6, 95% C.I = 2.0, 11.5) and Norway (AAPC = 6.5, 95% C.I. = 3.2, 10.0) had the greatest increase in women. The mortality rates paralleled the incidence rates in most countries. For mortality, Malta (AAPC = 11.5, 95% C.I. = 3.9, 19.8), Australia (AAPC = 6.8, 95% C.I. = 2.2, 11.5) and Norway (APCC = 5.6, 95% C.I. = 2.8, 8.5) reported the biggest increase among men; whilst Australia (AAPC = 13.4, 95% C.I. = 7.8, 19.4) and Singapore (AAPC = 7.7, 95% C.I. = 4.1, 11.5) showed the most prominent rise among women. These epidemiological data identified countries with potentially increasing trends of liver cancer for preventive actions.
The aim of this study was to screen antitumour and antimicrobial activities of endophytic actinomycetes isolated from pharmaceutical plants in rainforest in Yunnan province, China. Antitumour ...activity was studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and antimicrobial activity was determined by agar well diffusion method. The high bioactive endophytic isolates were identified and further investigated for the presence of polyketide synthases (PKS-I, PKS-II) and nonribosomal peptide synthetases (NRPS) sequences by specific amplification. The molecular identification confirmed that the 41 isolates showed significant activities were members of the genus Streptomyces. Among them, 31·7% of endophytic streptomycete cultures were cytotoxic against A549 cells, 29·3% against HL-60 cells, 85·4% against BEL-7404 cells, 90·2% against P388D1 cells, 65·9% were active against Escherichia coli, 24·4% against Staphylococcus aureus, 31·7% against Staphylococcus epidermidis, 12·2% against Candida albicans and no strain displayed antagonistic activity against Klebsiella pneumoniae. High frequencies of positive PCR amplification were obtained for PKS-I (34·1%), PKS-II (63·4%) and NRPS (61·0%) biosynthetic systems. Many endophytic streptomycetes isolated from pharmaceutical plants in rainforest possess remarkable and diverse antitumour and antimicrobial bioactivities. These endophytic streptomycetes are precious resources obtained from rainforests, and they could be a promising source for bioactive agents.
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