Additional HONO and OH Generation from Photoexcited Phenyl Organic Nitrates in the Photoreaction of Aromatics and NOx.

HONO acts as a major OH source, playing a vital role in secondary pollutant formation to deteriorate regional air quality. Strong unknown sources of daytime HONO have been widely reported, which significantly limit our understanding of radical cycling and atmospheric oxidation capacity. Here, we identify a potential daytime HONO and OH source originating from photoexcited phenyl organic nitrates formed during the photoreaction of aromatics and NOx. Significant HONO (1.56-4.52 ppb) and OH production is observed during the photoreaction of different kinds of aromatics with NOx (18.1-242.3 ppb). We propose an additional mechanism involving photoexcited phenyl organic nitrates (RONO2) reacting with water vapor to account for the higher levels of measured HONO and OH than the model prediction. The proposed HONO formation mechanism was evidenced directly by photolysis experiments using typical RONO2 under UV irradiation conditions, during which HONO formation was enhanced by relative humidity. The 0-D box model incorporated in this mechanism accurately reproduced the evolution of HONO and aromatic. The proposed mechanism contributes 5.9-36.6% of HONO formation as the NOx concentration increased in the photoreaction of aromatics and NOx. Our study implies that photoexcited phenyl organic nitrates are an important source of atmospheric HONO and OH that contributes significantly to atmospheric oxidation capacity.

Synergistic Effects of SO2 and NH3 Coexistence on SOA Formation from Gasoline Evaporative Emissions.

Vehicular evaporative emissions make an increasing contribution to anthropogenic sources of volatile organic compounds (VOCs), thus contributing to secondary organic aerosol (SOA) formation. However, few studies have been conducted on SOA formation from vehicle evaporative VOCs under complex pollution conditions with the coexistence of NOx, SO2, and NH3. In this study, the synergistic effects of SO2 and NH3 on SOA formation from gasoline evaporative VOCs with NOx were examined using a 30 m3 smog chamber with the aid of a series of mass spectrometers. Compared with the systems involving SO2 or NH3 alone, SO2 and NH3 coexistence had a greater promotion effect on SOA formation, which was larger than the cumulative effect of the two promotions alone. Meanwhile, contrasting effects of SO2 on the oxidation state (OSc) of SOA in the presence or absence of NH3 were observed, and SO2 could further increase the OSc with the coexistence of NH3. The latter was attributed to the synergistic effects of SO2 and NH3 coexistence on SOA formation, wherein N-S-O adducts can be formed from the reaction of SO2 with N-heterocycles generated in the presence of NH3. Our study contributes to the understanding of SOA formation from vehicle evaporative VOCs under highly complex pollution conditions and its atmospheric implications.

Combined Smog Chamber/Oxidation Flow Reactor Study on Aging of Secondary Organic Aerosol from Photooxidation of Aromatic Hydrocarbons.

Secondary organic aerosol (SOA) is a significant component of atmospheric fine particulate matter (PM2.5), and their physicochemical properties can be significantly changed in the aging process. In this study, we used a combination consisting of a smog chamber (SC) and oxidation flow reactor (OFR) to investigate the continuous aging process of gas-phase organic intermediates and SOA formed from the photooxidation of toluene, a typical aromatic hydrocarbon. Our results showed that as the OH exposure increased from 2.6 × 1011 to 6.3 × 1011 molecules cm-3 s (equivalent aging time of 2.01-4.85 days), the SOA mass concentration (2.9 ± 0.05-28.7 ± 0.6 µg cm-3) and corrected SOA yield (0.073-0.26) were significantly enhanced. As the aging process proceeds, organic acids and multiple oxygen-containing oxidation products are continuously produced from the photochemical aging process of gas-phase organic intermediates (mainly semi-volatile and intermediate volatility species, S/IVOCs). The multigeneration oxidation products then partition to the aerosol phase, while functionalization of SOA rather than fragmentation dominated in the photochemical aging process, resulting in much higher SOA yield after aging compared to that in the SC. Our study indicates that SOA yields as a function of OH exposure should be considered in air quality models to improve SOA simulation, and thus accurately assess the impact on SOA properties and regional air quality.

Smog Chamber Study on the Role of NOx in SOA and O3 Formation from Aromatic Hydrocarbons.

China is facing dual pressures to reduce both PM2.5 and O3 pollution, the crucial precursors of which are NOx and VOCs. In our study, the role of NOx in both secondary organic aerosol (SOA, the important constituent of PM2.5) and O3 formation was examined in our 30 m3 indoor smog chamber. As revealed in the present study, the NOx level can obviously affect the OH concentration and volatility distribution of gas-phase oxidation products and thus O3 and SOA formation. Reducing the NOx concentration to the NOx-sensitive regime can inhibit O3 formation (by 42%), resulting in the reduction of oxidation capacity, which suppresses the SOA formation (by 45%) by inhibiting the formation of O- and N-containing gas-phase oxidation products with low volatility. The contribution of these oxidation products to the formation of SOA was also estimated, and the results could substantially support the trend of SOA yield with NOx at different VOC levels. The atmospheric implications of NOx in the coordinated control of PM2.5 and O3 are also discussed.

A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial-mesenchymal transition.

BACKGROUND: Integrin, beta-like 1 (ITGBL1) is involved in a variety of human malignancies. However, the information on the involvement of ITGBL1 in gastric carcinoma (GC) is limited. Hence, this study aimed further to explore the functions and mechanisms of ITGBL1 in GC. METHODS: First, multiple bioinformatics databases, including Oncomine, Tumor Immune Estimation Resource, UALCAN, and Kaplan-Meier Plotter, were used to predict the expression level and prognostic value of ITGBL1, as well as its association with immune infiltration and epithelial-mesenchymal transition (EMT) in GC. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to detect the expression of ITGBL1 in both GC tissues and cells. Then, targeted silencing of ITGBL1 in GC cells was further used to examine the biological functions of ITGBL1. RESULTS: These databases revealed that ITGBL1 was overexpressed and affected the overall survival in GC. Besides, the expression of ITGBL1 positively correlated with immune-infiltrating cells and EMT-related markers. Subsequently, molecular biology experiments verified these predictions. In GC tissues and cells, ITGBL1 was notably overexpressed. Loss-of-function studies showed that the knockdown of ITGBL1 significantly suppressed migration and invasion but promoted apoptosis in MGC803 GC cells. Furthermore, the inhibition of ITGBL1 resulted in remarkably increased protein expression levels of cadherin 1, while the expression of Vimentin, Snail, and transforming growth factor-ß1 was downregulated, indicating the initiation and progression of GC caused by ITGBL1 partly via inducing EMT. CONCLUSIONS: To sum up, the findings indicated that ITGBL1 acted as a valuable oncogenic factor in GC.

Precursors and Pathways Leading to Enhanced Secondary Organic Aerosol Formation during Severe Haze Episodes.

Molecular analyses help to investigate the key precursors and chemical processes of secondary organic aerosol (SOA) formation. We obtained the sources and molecular compositions of organic aerosol in PM2.5 in winter in Beijing by online and offline mass spectrometer measurements. Photochemical and aqueous processing were both involved in producing SOA during the haze events. Aromatics, isoprene, long-chain alkanes or alkenes, and carbonyls such as glyoxal and methylglyoxal were all important precursors. The enhanced SOA formation during the severe haze event was predominantly contributed by aqueous processing that was promoted by elevated amounts of aerosol water for which multifunctional organic nitrates contributed the most followed by organic compounds having four oxygen atoms in their formulae. The latter included dicarboxylic acids and various oxidation products from isoprene and aromatics as well as products or oligomers from methylglyoxal aqueous uptake. Nitrated phenols, organosulfates, and methanesulfonic acid were also important SOA products but their contributions to the elevated SOA mass during the severe haze event were minor. Our results highlight the importance of reducing nitrogen oxides and nitrate for future SOA control. Additionally, the formation of highly oxygenated long-chain molecules with a low degree of unsaturation in polluted urban environments requires further research.

Parameterization of heterogeneous reaction of SO2 to sulfate on dust with coexistence of NH3 and NO2 under different humidity conditions.

Sulfate plays an important role in atmospheric haze in China, which has received considerable attention in recent years. Various types of parameterization methods and heterogeneous oxidation rates of SO2 have been used in previous studies. However, properly representing heterogeneous sulfate formation in air quality models remains a big challenge. In this study, we quantified the heterogeneous oxidation reaction using experimental results that approximate the haze conditions in China. Firstly, a series of experiments were conducted to investigate the heterogeneous uptake of SO2 with different relative humidity (RH) levels and the presence of NH3 and NO2 on natural dust surfaces. Then the uptake coefficients for heterogeneous oxidation of SO2 to sulfate at different RH under NH3 and NO2coexistence were parameterized based on the experimental results and implemented in the Community Multiscale Air Quality modeling system (CMAQ). Simulation results suggested that this new parameterization improved model performance by 6.6% in the simulation of wintertime sulfate concentrations for Beijing. The simulated maximum growth rate of SO4 2- during a heavy pollution period increased from 0.97 µg m-3 h-1 to 10.11 µg m-3 h-1. The heterogeneous oxidation of SO2 in the presence of NH3 contributed up to 23% of the sulfate concentration during heavy pollution periods.

Effects of ultrasonic treatment on dithiothreitol (DTT) assay measurements for carbon materials.

The dithiothreitol (DTT) assay is the most commonly used method to quantify the oxidative potential of fine particles. However, the reported DTT decay rates of carbon black (CB) materials vary greatly among different researchers. This might have resulted from either the intrinsic toxicity of CB or the unsuitability of the DTT assay protocol for CB particles. In the current study, the protocol of the DTT assay for CB materials has been carefully evaluated. It was found that the dispersion degree of CB particles in water has a great influence on the DTT decay rate of CB materials. For CB particles (special black 4A (SB4A) and Printex U) and single-walled carbon nanotube tube (SWCNT), the DTT decay rate after sonication for 10 min became 4.2, 4.6 and 1.7 times higher than that without sonication. The rate continued to grow as a function of ultrasound time up to 30 min of sonication. Although the concentration of soluble transition metals and surface oxygen-containing species such as carbonyls increased slightly with sonication, they had no significant effects on the measured DTT activity, while the increase in the dispersion degree of aggregates was found to play a vital role in the observed enhancement of the DTT decay rates for different CB materials. Based on our results, 30 min of sonication is recommended for sample dispersion when measuring the DTT decay rate of CB materials.

Differences of the oxidation process and secondary organic aerosol formation at low and high precursor concentrations.

Current atmospheric quality models usually underestimate the level of ambient secondary organic aerosol (SOA), one of the possible reasons is that the precursors at different concentrations may undergo different oxidation processes and further affect SOA formation. Therefore, there is a need to perform more chamber studies to disclose the influence. In this work, SOA formation over a wide range of initial precursor concentrations (tens of ppb to hundreds of ppb levels) was investigated in a 30 m3 indoor smog chamber, and mainly through the analysis of multiple generations of VOCs detected from HR-ToF-PTRMS to expound the difference in the oxidation process between low and high precursor concentrations. Compared to high initial concentrations, gas-phase intermediates formed at low concentrations had a higher intensity by about one order of magnitude, and the low-volatility compounds also had a higher formation potential due to the competition between semi-volatile intermediates and precursors with oxidants. In addition, the formed SOA was more oxidized with higher f44 value (0.14 ±â€¯0.02) and more relevant to real atmosphere than that formed at high concentrations. This work should help to deeply understand SOA formation and improve the performance of air quality models for SOA simulation.

Bioinformatics insight into glycosyltransferase gene expression in gastric cancer: POFUT1 is a potential biomarker.

Aberrant glycosylation plays an important role in the progression of gastric cancer. Although many enzymes are involved in glycoconjugate synthesis, little information is known about glycosyltransferase (GT)'s alteration in gastric cancer. To give an insight into the differential expression of GTs as obtained from the TCGA database, bioinformatics analysis of 415 gastric cancer samples and 35 normal samples was performed. Using a 0.6-fold change threshold to compare GT expression in normal and cancer tissues, it was noted that 36 GTs were upregulated including POFUT1 and 30 GTs were downregulated in cancer tissues (P < 0.01). Enriched pathway analysis indicated that POFUT1 was correlated positively with cell cycle and cell carcinoma process but correlated negatively with cell adhesion and apoptosis (P < 0.05). Furthermore, immunohistochemistry analysis verified that 33 out of 51 tumor tissues had detectable POFUT1 expression. POFUT1-positive samples were associated with aggressive tumor phenotypes like higher T and N classification (P = 0.026, 0.042) as well as poor differentiation (P = 0.031). No correlation was observed between POFUT1 expression and age, gender, stage, and Lauren classification. These results suggested that POFUT1 is increased and may serve as a potential biomarker in gastric cancer.

Ozonolysis of Trimethylamine Exchanged with Typical Ammonium Salts in the Particle Phase.

Alkylamines contribute to both new particle formation and brown carbon. The toxicity of particle-phase amines is of great concern in the atmospheric chemistry community. Degradation of particulate amines may lead to secondary products in the particle phase, which are associated with changes in the adverse health impacts of aerosols. In this study, O3 oxidation of particulate trimethylamine (TMA) formed via heterogeneous uptake of TMA by (NH4)2SO4, NH4HSO4, NH4NO3 and NH4Cl, was investigated with in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and proton transfer reaction mass spectrometry (PTR-MS). HCOOH, HCHO, CH3N═CH2, (CH3)2NCHO, CH3NO2, CH3N(OH)CHO, CH3NHOH and H2O were identified as products on all the substrates based upon IR (one-dimensional IR and two-dimensional correlation infrared spectroscopy), quantum chemical calculation and PTR-MS results. A reaction mechanism was proposed to explain the observed products. This work demonstrates that oxidation might be a degradation pathway of particulate amines in the atmosphere. This will aid in understanding the fate of particulate amines formed by nucleation and heterogeneous uptake and their potential health impacts during atmospheric aging.

A Novel Multi-Effect Photosensitizer for Tumor Destruction via Multimodal Imaging Guided Synergistic Cancer Phototherapy.

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.

Heterogeneous reactions significantly contribute to the atmospheric formation of nitrated aromatic compounds during the haze episode in urban Beijing.

Nitrated aromatic compounds (NACs) are key components of air pollution; however, due to the presence of complex mixtures of primary and secondary species, especially in urban environments, their atmospheric formation is poorly understood. Here we conducted a field campaign during a winter haze episode in urban Beijing, China to monitor gaseous and particulate NACs at 2-h time resolution. Through a standard-independent non-targeted approach, a total of 238 NACs were screened, of which 127 species were assigned chemical formula and 25 structures were confirmed. Four main classes were identified: nitrated aromatic hydrocarbons, nitrophenols, oxygenated nitrated aromatic compounds, and nitrated heterocyclic aromatic compounds. Hierarchical clustering analysis revealed disparate temporal variances of diurnal or nocturnal elevation, among which different nitration formations were captured, i.e., daytime photochemical oxidation and nighttime heterogeneous reactions. Isomeric information, particularly the substitution position of the nitro group on biphenyl, further demonstrated a potential heterogeneous mechanism of electrophilic nitration by NO2+. Assisted by source apportionment, we found that nighttime heterogeneous reactions significantly contributed to NAC formation, e.g., 31.3 % and 60.8 %, respectively, to 2-nitrofluoranthene and 2-nitropyrene, which were previously considered as classical daytime gas-phase products. This study provides comprehensive information on urban NAC species and highlights the importance of unheeded heterogeneous reactions in the atmosphere.

Major source categories of PM2.5 oxidative potential in wintertime Beijing and surroundings based on online dithiothreitol-based field measurements.

Fine particulate matter (PM2.5) causes millions of premature deaths each year worldwide. Oxidative potential (OP) has been proposed as a better metric for aerosol health effects than PM2.5 mass concentration alone. In this study, we report for the first time online measurements of PM2.5 OP in wintertime Beijing and surroundings based on a dithiothreitol (DTT) assay. These measurements were combined with co-located PM chemical composition measurements to identify the main source categories of aerosol OP. In addition, we highlight the influence of two distinct pollution events on aerosol OP (spring festival celebrations including fireworks and a severe regional dust storm). Source apportionment coupled with multilinear regression revealed that primary PM and oxygenated organic aerosol (OOA) were both important sources of OP, accounting for 41 ± 12 % and 39 ± 10 % of the OPvDTT (OP normalized by the sampled air volume), respectively. The small remainder was attributed to fireworks and dust, mainly resulting from the two distinct pollution events. During the 3.5-day spring festival period, OPvDTT spiked to 4.9 nmol min-1 m-3 with slightly more contribution from OOA (42 ± 11 %) and less from primary PM (31 ± 15 %). During the dust storm, hourly-averaged PM2.5 peaked at a very high value of 548 µg m-3 due to the dominant presence of dust-laden particles (88 % of total PM2.5). In contrast, only mildly elevated OPvDTT values (up to 1.5 nmol min-1 m-3) were observed during this dust event. This observation indicates that variations in OPvDTT cannot be fully explained using PM2.5 alone; one must also consider the chemical composition of PM2.5 when studying aerosol health effects. Our study highlights the need for continued pollution control strategies to reduce primary PM emissions, and more in-depth investigations into the source origins of OOA, to minimize the health risks associated with PM exposure in Beijing.

Clinical characteristics of second primary malignancies among first primary malignancy survivors: A single-center study, 2005-2020.

The cancer survivor population is growing due to advances in detection and treatment. For improved long-term patient management, it is critical to examine the clinical characteristics and outcomes of second primary malignancies (SPMs). An SPM is defined as a second distinct pathological diagnosis, with the same or different origin as the first primary malignancy (FPM). In the present retrospective study, categorical clinical variables were compared between subgroups and the impact on overall survival was evaluated. A total of 1,188 patients with an FPM were included, of which 102 experienced an SPM (8.59%). When compared with the patients who did not develop an SPM, patients with an SPM were significantly older at first diagnosis, had a higher pathological stage and higher rates of biliary tract disease and thyroid disease. In addition, patients with an SPM were more likely to have received postoperative chemotherapy (28.43 vs. 12.16%, P<0.0001) and to be long-term consumers of cigarettes and alcohol (25.00 vs. 8.95%, P<0.05). In addition, an increase in the number of regimens received but not in the number of courses of chemotherapy was associated with a reduction in the time interval to SPM development. Non-small cell lung cancer (NSCLC) was the most common type of FPM (18.27%). In patients with NSCLC the occurrence of SPMs was relatively low (5.07%) and the SPM-associated mortality rate was 2.30%. Breast cancer was the second common type of FPM (12.09%). Patients with breast cancer had a relatively high likelihood of developing an SPM (9.30%), for which family history of malignancy and postoperative chemotherapy were identified as potential risk factors. Patients with stomach cancer were the most vulnerable to SPM (17.95%) and patients with digestive tract cancer had the longest time interval between the FPM and SPM development. In addition, thyroid adenoma was identified as a potential risk factor for SCLC. The findings of the present study may provide valuable guidance for the short- and long-term monitoring of FPM survivors.

Effect of bone morphogenetic protein-2 on proliferation and apoptosis of gastric cancer cells.

OBJECTIVE: To investigate the effects of bone morphogenetic protein-2 (BMP-2) on the proliferation, differentiation and apoptosis of normal human gastric mucosal cells and gastric cancer cells. METHODS: Poorly differentiated gastric cancer BGC823 cells, moderately differentiated gastric cancer cells and normal human gastric mucosal epithelial GES-1 cells were independently treated with recombinant human BMP-2 or its inhibitor Noggin. MTT assay was performed to detect the proliferation, flow cytometry done to measure the cell cycle and apoptosis and immunohistochemistry carried out to determine the expression of cyclin-dependent kinase 4 (CDK4). RESULTS: BMP-2 exerted inhibitory effect on the growth of all types of cells and the inhibition become more evident with the increase of BMP-2 dose. After treatment with 200 ng/ml BMP-2, cancer cells arrested in G1 phase and those in S phase reduced. Gastric cancer cells had higher CDK4 expression than GES-1 cells. BMP-2 decreased CDK-4 expression in cancer cells but had no influence in GES-1 cells. Noggin conferred promotive effect on the growth of 3 types of cells. In 2 types of cancer cells, treatment with 2000 ng/ml Noggin significantly increased the proportion of cells in S phase but reduced that in G1 phase. However, Noggin did not affect the cell cycle of GES-1 cells. The CDK4 expression was markedly increased in 2 types of cancer cells but that of GES-1 remained unchanged after treatment with 2000 ng/ml Noggin. CONCLUSIONS: BMP-2 may inhibit the proliferation of both normal and malignant gastric epithelial cells, down-regulate CDK4 expression in gastric cancer cells and arrest gastric cancer cells in G1-phase in cell cycle. Through antagonizing BMP-2, Noggin, may accelerate the proliferation of gastric cancer cells. Thus, the abnormality of BMP signaling pathway may play an important role in the pathogenesis of gastric cancer.

N-nitration of secondary aliphatic amines in the particle phase.

Amines are frequently detected in atmospheric particles and are internally mixed with other particle-phase components. However, research on the further reactions of amine with reactive species after entering the particle phase is still limited. This study investigated the nitration reaction process of particulate dimethylamine (DMA), formed via a substitution reaction between DMA and (NH4)2SO4, with NOx. In situ attenuated total reflectance-infrared Fourier transform spectroscopy (in situ ATR-FTIR) and proton transfer reaction mass spectroscopy (PTR-MS), as well as DFT methods at the B3LYP level using the 6-311++G (d, p) basis set, were mainly used to confirm the formation of nitramine and nitrosamine in the nitration/nitrosation process of DMA. A hydrogen-bonding intermediate ([(CH3)2N⋯HONO]) is initially formed when particulate DMA reacts with NO2 followed by aminyl radical formation, and then nitr- and nitros-amine form through addition reactions with NO2 and NO, respectively. The dimer of NO2 (i.e., N2O4) and the product of NO and NO2 (i.e., N2O3) can also react with DMA to attack the lone pair electrons on the central N atom of DMA to finally form nitr- and nitros-amine. This study helps reveal the nitration reaction mechanism of organic amines in the particle phase. It also aids in understanding the process of nitrogen cycling in the atmosphere.

An Immune Signature Robustly Predicts Clinical Deterioration for Hepatitis C Virus-Related Early-Stage Cirrhosis Patients.

Hepatitis C virus (HCV)-related cirrhosis leads to a heavy global burden of disease. Clinical risk stratification in HCV-related compensated cirrhosis remains a major challenge. Here, we aim to develop a signature comprised of immune-related genes to identify patients at high risk of progression and systematically analyze immune infiltration in HCV-related early-stage cirrhosis patients. Bioinformatics analysis was applied to identify immune-related genes and construct a prognostic signature in microarray data set. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted with the "clusterProfiler" R package. Besides, the single sample gene set enrichment analysis (ssGSEA) was used to quantify immune-related risk term abundance. The nomogram and calibrate were set up via the integration of the risk score and clinicopathological characteristics to assess the effectiveness of the prognostic signature. Finally, three genes were identified and were adopted to build an immune-related prognostic signature for HCV-related cirrhosis patients. The signature was proved to be an independent risk element for HCV-related cirrhosis patients. In addition, according to the time-dependent receiver operating characteristic (ROC) curves, nomogram, and calibration plot, the prognostic model could precisely forecast the survival rate at the first, fifth, and tenth year. Notably, functional enrichment analyses indicated that cytokine activity, chemokine activity, leukocyte migration and chemotaxis, chemokine signaling pathway and viral protein interaction with cytokine and cytokine receptor were involved in HCV-related cirrhosis progression. Moreover, ssGSEA analyses revealed fierce immune-inflammatory response mechanisms in HCV progress. Generally, our work developed a robust prognostic signature that can accurately predict the overall survival, Child-Pugh class progression, hepatic decompensation, and hepatocellular carcinoma (HCC) for HCV-related early-stage cirrhosis patients. Functional enrichment and further immune infiltration analyses systematically elucidated potential immune response mechanisms.

A Somatic Mutation-Derived LncRNA Signature of Genomic Instability Predicts Prognosis for Patients With Liver Cancer.

Background: Genomic instability is considered as one of the hallmarks of hepatocellular carcinoma (HCC) and poses a significant challenge to the clinical treatment. The emerging evidence has revealed the roles of long non-coding RNAs (lncRNAs) in the maintenance of genomic instability. This study is aimed to develop a genomic instability-related lncRNA signature for determining HCC prognosis and the suitability of patients for immunotherapy. Methods: In this study, data related to transcriptome profiling, clinical features, and the somatic mutations of patients with HCC were downloaded from The Cancer Genomic Atlas (TCGA). Bioinformatics analysis was performed to identify and construct a somatic mutation-derived genomic instability-associated lncRNA signature (GILncSig). Single-sample gene set enrichment analysis (ssGSEA) was applied to estimate the levels of immune cell infiltration. A nomogram was constructed, and calibration was performed to assess the effectiveness of the model. Results: In the study, seven genomic instability-related lncRNAs were identified and used to define a prognostic signature. Patients with HCC were stratified into high- and low-risk groups with significant differences in the survival (median survival time = 1.489, 1.748 year; p = 0.006) based on the optimal cutoff value (risk score = 1.010) of the risk score in the training group. In addition, GILncSig was demonstrated to be an independent risk factor for the patients with HCC when compared to the clinical parameters (p < 0.001). According to the receiver operating characteristic (ROC) curve, nomogram, and calibration plot, the signature could predict the survival rate for the patients with HCC in the 1st, 3rd, and 5th years. Furthermore, ssGSEA revealed the potential of the signature in guiding decisions for administering clinical treatment. Conclusions: In this study, we developed a novel prognostic model based on the somatic mutation-derived lncRNAs and validated it using an internal dataset. The independence of the GILncSig was estimated using univariate and follow-up multivariate analyses. Immunologic analysis was used to evaluate the complex factors involved in the HCC progression.

Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature.

In this report, we gave the first case of successful treatment for laryngeal NMC, which is exceedingly rare with dismal prognosis. intensity-modulated radiation therapy accompanied by traditional Chinese medicine was administrated for the young woman, instead of radical resection, and she got continuous remission for more than 2 years, with no recurrence detected.