•Serum metabolomics was useful to identify biomarkers predicting efficacy of SLIT.•Serum lactic acid, ornithine, linolenic acid, etc, could predict the efficacy of SLIT.•Metabolism pathways ...dysfunction might underlie the mechanism of SLIT in AR patients.
Allergen-specific immunotherapy (ASIT) is currently the only therapy for allergic rhinitis (AR) that can induce immune tolerance to allergens. However, the course of ASIT is long and there is no objective biomarker to predict treatment efficacy. The present study aimed to explore potential biomarkers predictive of efficacy of AIT based on serum metabolomics profiles.
This prospective study recruited 72 consecutive eligible patients who were assigned to receive sublingual immunotherapy (SLIT). Serum samples were collected prior to SLIT and utilized to obtain metabolomics profiling by applying ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Treatment response was determined 3 years after SLIT, and patients were divided into effective group and ineffective group. Orthogonal partial least square-discriminate analysis (OPLS-DA) was performed to evaluate the metabolite differences between two groups.
Sixty-eight patients completed the whole SLIT, 39 patients were categorized into effective group and 29 patients were classified into ineffective group. A total of 539 metabolites were obtained, and 197 of which were identified as known substances. Using these 197 known metabolites, the OPLS-DA results showed that effective group and ineffective group exhibited distinctive metabolite signatures and metabolic pathways. Six metabolites including lactic acid, ornithine, linolenic acid, creatinine, arachidonic acid and sphingosine were identified to exhibit good performance in predicting the efficacy of SLIT, and these metabolite changes mainly involved glycolysis and pyruvate metabolism, arginine and proline metabolism and fatty acid metabolism pathways.
By metabolomics analysis, we identified several serum biomarkers that can reliably and accurately predict the efficacy of SLIT in AR patients. The discriminative metabolites and related metabolic pathways contributed to better understand the mechanisms of SLIT in AR patients.
•The overall survival rate of the endoscopic resection group was comparable with the open resection group.•The disease-free survival rate of the endoscopic resection group was higher than the open ...resection group.•The surgery approaches, the adjuvant therapy, the histopathology, and the T-stage have independent effects on the survival outcomes.
To compare the efficacy of endoscopic and open resection of sinonasal malignancies.
The search was performed using PubMed (1950–2020), Embase (1974–2020), the Cochrane library, and the website clinicaltrials.gov. The hazard ratio, HR, 95% confidence interval, CI, of the rates of overall survival and disease-free survival and the demographic characteristics of the included studies were extracted and analyzed. Pooled analysis was conducted with the studies’ individual patient data, using log-rank test, Kaplan–Meier survival, and Cox regression analysis.
Of 1939 articles retrieved, 23 articles were included. Overall, 1373 cases were incorporated into the final analysis, 653 (47.56%) of which underwent the surgery through an endoscopic approach, whereas 720 (52.44%) cases utilized the open approach. The overall survival was comparable between endoscopic and open resection (HR = 0.84 95% CI: 0.65–1.07, p = 0.16; random effects analysis). Pooled analysis with Cox regression revealed signifcant differences in overall survival (HR = 0.568 95%CI:0.380-0.849, p = 0.006) and disease-free survival (HR = 0.628 95%CI:0.424-0.929, p = 0.02) between endoscopic and open approaches.
The aggregated evidence suggests the survival outcome of endoscopic resection is comparable or greater than that of open resection of sinonasal malignancies.
Abstract
Due to the unique outermost orbitals of Sn, hole carriers in tin monoxide (SnO) possess small effective mass and high mobility among oxide semiconductors, making it a promising p-channel ...material for thin film field-effect transistors (TFTs). However, the Sn vacancy induced field-effect mobility deterioration and threshold voltage (
V
th
) shift in experiments greatly limit its application in complementary metal-oxide-semiconductor (CMOS) transistors. In this study, the internal mechanism of vacancy defect compensation by aluminum (Al) doping in SnO
x
film is studied combining experiments with the density functional theory (DFT). The doping is achieved by an argon (Ar) plasma treatment of Al
2
O
3
deposited onto the SnO
x
film, in which the Al
2
O
3
provides both the surface passivation and Al doping source. Experimental results show a wide
V
th
modulation range (6.08 to −19.77 V) and notable mobility enhancement (11.56 cm
2
V
−1
s
−1
) in the SnO
x
TFTs after the Al doping by Ar plasma. DFT results reveal that the most possible positions of Al in SnO and SnO
2
segments are the compensation to Sn vacancy and interstitial. The compensation will create an n-type doping effect and improve the hole carrier transport by reducing the hole effective mass (
m
h
*), which is responsible for the device performance variation, while the interstitial in the SnO
2
segment can hardly affect the valence transport of the film. The defect compensation is suitable for the electronic property modulation of SnO towards the high-performance CMOS application.
Background
This meta-analysis aimed to compare the efficacy of intensity-modulated radiotherapy (IMRT) and endoscopic surgery (ES) for high T-stage recurrent nasopharyngeal carcinoma (NPC).
Methods
...Relevant studies were retrieved in six databases from 02/28,2011 to 02/28,2021. The 2-year, 3-year, 5-year overall survival (OS) rates and 2-year disease-free survival (DFS) rates were calculated to compare the survival outcomes of the two treatments of IMRT and ES. Combined odds ratios (ORs) and 95% confidence interval (C Is) were measured as effect size on the association between high T-stage and 5-year OS rates.
Results
A total of 23 publications involving 2,578 patients with recurrent NPC were included in this study. Of these, 1611 patients with recurrent rT3-4 NPC were treated with ES and IMRT in 358 and 1,253 patients, respectively. The combined 2-year OS and 5-year OS rates for the two treatments were summarized separately, and the 2-year OS and 5-year OS rate for ES were 64% and 52%, respectively. The 2-year OS and 5-year OS rate for IMRT were 65% and 31%, respectively. The combined 2-year DFS rates of IMRT and ES were 60% and 50%, respectively. Combined ORs and 95% confidence intervals for 5-year survival suggest that ES may improve survival in recurrent NPC with rT3-4. In terms of complications, ES in the treatment of high T-stage recurrent NPC is potentially associated with fewer complications.
Conclusions
The results of our study suggest that ES for rT3-4 may be a better treatment than IMRT, but the conclusion still needs to be sought by designing more studies.
Subcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for ...monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.
We prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.
Sixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.
Our discover-validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.
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•Fe7S8 anchoring S-doped porous GE was successfully synthesized.•Rhodanine converted Fe3O4 to Fe7S8 and constructed porous S-doped GE.•Multi-band electromagnetic absorptions were ...realized, with effective bandwidth achieved up to 12.07 GHz.
At present, research bottleneck on electromagnetic absorption materials lied in achieving strong absorption with broadband and multi-band responses. In this paper, Fe7S8 anchoring S-doped porous graphene was synthesized for multi-band electromagnetic absorptions. Rhodanine played the role of ‘two birds in one stone’, converting Fe3O4 to Fe7S8 and constructing porous S-doped carbon. The hybrids exhibited multi-band electromagnetic absorptions at 10.52, 12.56 and 15.03 GHz, with effective bandwidth achieved up to 12.07 GHz. This paper showcases reference path for the design of multi-band electromagnetic absorption materials.
Nonvolatile optoelectronic memories based on organic–inorganic hybrid perovskites have appeared as powerful candidates for next-generation soft electronics. Here, ambipolar SnO transistor-based ...nonvolatile memories with multibit memory behavior (11 storage states, 120 nC state–1) and ultralong retention time (>105 s) are demonstrated for which an Al2O3/two-dimensional Ruddlesden–Popper perovskite (2D PVK) heterostructure dielectric architecture is employed. The unique storage features are attributed to suppressed gate leakage by Al2O3 layer and hopping-like ionic transport in 2D PVK with varying activation energy under different light intensities. The photoinduced field-effect mechanism enables top-gated transistor operation under illumination, which would not be achieved under dark. As a result, the device exhibits remarkable photoresponsive characteristics, including ultrahigh specific detectivity (2.7 × 1015 Jones) and broadband spectrum distinction capacity (375–1064 nm). This study offers valuable insight on the PVK-based dielectric engineering for information storage and paves the way toward multilevel broadband-response optoelectronic memories.
Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer ...treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsive to single therapies. Combination therapy has the potential to improve current treatment of refractory and drug-resistant tumors. Among the methods used in combination therapy, DDR is one of the most popular methods. Recent studies have shown that combined application of DDR-related drugs and immunotherapies significantly improve the therapeutic outcomes of malignant tumors, especially solid tumors.
Acral melanoma (AM) is an extremely aggressive subtype of melanoma that is prevalent in eastern Asia. AM exhibits high intertumoral and intratumoral heterogeneities with poor prognosis. To associate ...the genomic heterogeneities with phenotypic traits and efficacy of treatments, a method is needed to recover genomic information from limited samples with high specificity and sensitivity from early stage AM specimens. We performed laser capture microdissection to isolate single micro-tumor nests, containing only dozens of cells, from stained tissue slices and then applied multiple annealing and looping-based amplification cycles, a highly efficient whole-genome amplification method originally developed for single cells, to amplify the whole genome of each tumor nest for sequencing. We were able to accurately profile the landscape of copy number alterations and single nucleotide variations of every single micro-tumor nest and to quantitatively characterize the heterogeneities at different levels, between tumor and nevi, among patients, among different phenotypes within a same tumor, and among adjacent tumor cell clusters with identical phenotypic appearance. We have found that genomic heterogeneity exists extensively and that branched evolution happens in the early stage of AM development. We are able to build the phylogenetic tree among these phenotypically addressable cell clusters.
Recurrent nasopharyngeal carcinoma (NPC), which occurs in 10–20% of patients with primary NPC after the initial treatment modality of intensity-modulated radiation therapy (IMRT), is one of the major ...causes of death among NPC patients. Patients with recurrent disease without distant metastases still have a chance to be saved, but re-treatment often carries more serious toxicities or higher risks. For this group of patients, both otolaryngologists and oncologists are committed to developing more appropriate treatment regimens that can prolong patient survival and improve survival therapy. Currently, there are no international guidelines for the treatment of patients with recurrent NPC. In this article, we summarize past publications on clinical research and mechanistic studies related to recurrent NPC, combined with the experience and lessons learned by our institutional multidisciplinary team in the treatment of recurrent NPC. We propose an objective protocol for the treatment of recurrent NPC.
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