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Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.
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Neoplasias Pulmonares , Proteínas de Fusión Oncogénica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Femenino , China , Proteínas de Fusión Oncogénica/genética , Persona de Mediana Edad , Anciano , AdultoRESUMEN
Nonpolar suspensions of organically modified particles exhibit a strong temperature sensitivity owing to the high-temperature-induced desorption/decomposition and the low-temperature-induced disorder/order conformational transition of the modifiers. This strong temperature sensitivity limits their applications, such as lubricants and oil-based drilling fluids, which require the suspensions to operate over a wide temperature range (e.g., 0-200 °C). We hypothesize that the introduction of a flexible ethylene oxide (EO) chain into the modifiers can disrupt the low-temperature-induced ordered conformation to improve the stability of the nonpolar suspensions. In this article, nonpolar suspensions with temperature insensitivity in the range of 5-160 °C were obtained via the covalent modification of silica NPs and the introduction of EO chains into the modifier molecules. Here, octadecyl-grafted silica NPs (C18-SiO2) and polyoxyethylene alkyl ether-grafted silica NPs (AEOn-SiO2) were synthesized and subsequently dispersed in mineral oil. The rheological properties of each suspension at different temperatures were evaluated, and the thermal stability of AEOn-SiO2 in mineral oil was investigated along with the conformational changes of the grafted chains. In the temperature range of 5-160 °C, the apparent viscosity and gel strength of the C18-SiO2 suspension changed dramatically, whereas the AEOn-SiO2 suspensions exhibited constant rheological properties over this temperature range. This temperature insensitivity of AEOn-SiO2 suspensions is attributed to the excellent thermal stability of AEOn-SiO2 in mineral oil and the disordered conformation of the EO chains upon cooling. This study provides a novel approach to preparing temperature-insensitive nonpolar suspensions, which have potential applications in the petroleum and lubricant industries.
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Hydrothermal treatment (HT) can effectively dehydrate and reduce oily sludge (OS) volume, but the resulting hydrothermal oily sludge (HOS) presents greater challenges for washing than the initial oily sludge (IOS). This study examines the effects of HT on OS by analyzing changes in water, oil, and solid. Results indicate that HT considerably decreases the water content in OS while increasing resin and asphaltenes contents. In addition, condensation, side-chain scission, and oxidation reactions occur during the HT process, resulting in coking, agglomeration, and an increase in oxygen-containing groups. This increase, further confirmed by X-ray photoelectron spectroscopy (XPS), enhances the interaction between oil and solids. Calcite, the most prevalent solid-phase component, may form a calcium bridge with the oxygen-containing groups. Moreover, HT reduces the solid particle size, thereby increasing the oil-solid contact area. Interestingly, the process of deasphalting diminishes the interaction between oil and solids, facilitating sludge washing. After washing, the residual oil content in HOS is reduced to less than 0.34%. This study elucidates why HOS is challenging to separate from oil and solids and introduces a novel method that combines dodecylbenzene sulfonic acid (DBSA)-assisted heptane deasphalting with conventional washing techniques. This method shows promise for applications in OS affected by weathering processes.
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BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluatedâ¯≤â¯Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab nâ¯=â¯236; placebo nâ¯=â¯237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], pâ¯<â¯0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], pâ¯<â¯0.0001) and TASS (LSD -0.25 [-0.45, -0.05], pâ¯=â¯0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.
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Accurate diagnosis of chronic obstructive pulmonary disease (COPD) and exacerbations by metabolic biomarkers enables individualized treatment. Advanced metabolic detection platforms rely on designed materials. Here, we design mesoporous PdPt alloys to characterize metabolic fingerprints for diagnosing COPD and exacerbations. As a result, the optimized PdPt alloys enable the acquisition of metabolic fingerprints within seconds, requiring only 0.5 µL of native plasma by laser desorption/ionization mass spectrometry owing to the enhanced electric field, photothermal conversion, and photocurrent response. Machine learning decodes metabolic profiles acquired from 431 individuals, achieving a precise diagnosis of COPD with an area under the curve (AUC) of 0.904 and an accurate distinction between stable COPD and acute exacerbations of COPD (AECOPD) with an AUC of 0.951. Notably, eight metabolic biomarkers identified accurately discriminate AECOPD from stable COPD while providing valuable information on disease progress. Our platform will offer an advanced nanoplatform for the management of COPD, complementing standard clinical techniques.
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Background: Serum anion gap (AG) has been proven to be associated with prognosis in critically ill patients. However, few studies have investigated the association between AG and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Objective: We hypothesized that the initial AG level would predict the mortality risk in critically ill patients with COPD. Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. We extracted demographics, vital signs, laboratory tests, comorbidity, and scoring systems from the first 24 hours after patient ICU admission. Multivariable logistic regression analysis models were used to explore the association between serum AG levels and mortality. Interaction and stratified analyses were conducted including age, gender and comorbidity. Results: A total of 5531 critically ill patients with COPD were enrolled, composed of 53.6% male and 46.4% female with a median age of 73 years. The all-cause mortality of these patients during ICU hospitalization was 13.7%. The risk of all-cause mortality increased as the AG level increased in the univariate logistic regression analysis (OR=1.13, 95% CI: 1.11-1.15, p<0.01). After adjusting for all the covariates in multivariate logistic regression analysis, the odds ratio was 1.06 (95% CI: 1.04-1.09, p<0.01). Compared with the lowest AG group Q1 (≤11mmol/L), the adjusted OR value for AG and mortality in Q2 (12-13mmol/L) was 0.89 (95% CI: 0.63-1.25, p=0.502), Q3 (14-15mmol/L) was 0.95 (95% CI: 0.68-1.34, p=0.788), and Q4 (≥16mmol/L) was 1.49 (95% CI: 1.10-2.02, p=0.009) respectively. In addition, the results of the subgroup and stratified analyses were robust. Conclusion: AG is positively related to all-cause mortality in critically ill patients with COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Femenino , Masculino , Anciano , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Equilibrio Ácido-Base , Enfermedad Crítica , Estudios Retrospectivos , Unidades de Cuidados IntensivosRESUMEN
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Recent studies have elucidated the potential role of local tumor microbiota in the development and progression of lung adenocarcinoma (LUAD). However, whether intratumoral microbes are involved in the TIME that mediates the prognosis of LUAD remains unknown. Here, we obtained the matched tumor microbiome and host transcriptome and survival data of 478 patients with LUAD in The Cancer Genome Atlas (TCGA). Machine learning models based on immune cell marker genes can predict 1- to 5-year survival with relative accuracy. Patients were stratified into high- and low-survival-risk groups based on immune cell marker genes, with significant differences in intratumoral microbial communities. Specifically, patients in the high-risk group had significantly higher alpha diversity (p < 0.05) and were characterized by an enrichment of lung cancer-related genera such as Streptococcus. However, network analysis highlighted a more active pattern of dominant bacteria and immune cell crosstalk in TIME in the low-risk group compared to the high-risk group. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
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BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.
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Asma , COVID-19 , Enfermedad Coronaria , Diabetes Mellitus , Reflujo Gastroesofágico , Femenino , Humanos , Lactante , Masculino , SARS-CoV-2 , Estudios Transversales , Vacunas contra la COVID-19 , COVID-19/complicaciones , COVID-19/epidemiología , Tos/epidemiología , Factores de Riesgo , Tos Crónica , China/epidemiología , Asma/complicaciones , Asma/epidemiologíaRESUMEN
Ostwald ripening, the dominant mechanism of droplet size growth for an O/W nanoemulsion at high surfactant concentrations, depends on micelles in the water phase and high aqueous solubility of oil, especially for spontaneously formed nanoemulsions. In our study, O/W nanoemulsions were formed spontaneously by mixing a water phase with an oil phase containing fatty alcohol polyoxypropylene polyoxyethylene ether (APE). By monitoring periodically the droplet size of the nanoemulsions via dynamic light scattering, we demonstrated that the formed O/W nanoemulsions are stable against Ostwald ripening, i.e., droplet growth. In contrast, the nanoemulsion droplets grew with the addition of micelles, demonstrating the pivotal role of the presence of micelles in the water phase in the occurrence of Ostwald ripening. The influence of the initial phase of APE, the oil or water phase in which APE is present, on the micelle formation is discussed by the partition coefficient and interfacial adsorption of APE between the oil and water phase using a surface and interfacial tensiometer. In addition, the spontaneously formed O/W nanoemulsion, which is stable against Ostwald ripening, can be used as a nanocarrier for the delivery of water-insoluble pesticides. These results provide a novel approach for the preparation of stable nanoemulsions and contribute to elucidating the mechanism of instability of nanoemulsions.
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OBJECTIVES: BF.7 (BA.5.2.1.7) is a novel sublineage of Omicron BA.5, whose clinical characteristics are not yet established. METHODS: From 28 September 2022 to 3 October 2022, the first 421 patients with BF.7 were assessed in Hohhot China and the clinical data were extracted and analysed. The basic reproduction number (R0) was estimated using a statistical model calculation method. RESULTS: The R0 value was determined to be 13.79 (95% confidence interval: 12.44-15.24). The mean age was 33.43 ± 18.78 years. Asymptomatic, mild, moderate, severe, and critical patients accounted for 12.35% (52/421), 82.42% (347/421), 4.75% (20/421), 0.24% (1/421), and 0.24% (1/421) proportion, respectively. The main clinical symptoms were fever accounting for 41.09% (173/421), cough accounting for 41.09% (173/421), and throat dryness and soreness accounting for 30.88% (130/421). In the 3-dose vaccination subgroup, 31.22% (64) cases had a fever, which were significantly lower than 51.37% (96) cases of the 2-dose vaccination subgroup (p 0.000). The rates of abnormally increased C-reactive protein level in the 2-dose and 3-dose vaccination subgroups were 10.16% (19/187) and 4.88% (10/205), significantly lower than 66.67% (10/15) of the 1-dose vaccination subgroup (1-dose vs. 2-dose: p 0.000, 1-dose vs. 3-dose: p 0.000). Notably, the population with complete 3 doses of vaccination did not exhibit any severe or critical status. DISCUSSION: BF.7 exhibited a higher transmission than previously emerged SARS-CoV-2. The vaccine against COVID-19 was found to relieve fever, nausea, and vomiting as well as reduce the abnormal ratio of lymphocytes, eosinophils, neutrophils, and the C-reactive protein level.
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Proteína C-Reactiva , COVID-19 , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Vacunas contra la COVID-19 , Número Básico de Reproducción , China/epidemiología , FiebreRESUMEN
CO2-responsive microemulsion (ME) is considered a promising candidate for deep-cleaning and oil recovery from oil-contaminated soils. Understanding the responsive nature of different microstructures (i.e., oil-in-water (O/W), bicontinuous (B.C.) and water-in-oil (W/O)) is essential for unlocking the potential and mechanisms of CO2-responsive emulsions in complex multiphase systems and providing comprehensive guidance for remediation of oil-contaminated soils. Herein, the responsiveness of microstructures of ME to CO2 trigger was investigated using experimental designs and coarse-grained molecular dynamic simulations. MEs were formed for the first time by a weakly associated pseudo-Gemini surfactant of indigenous organic acids (naphthenic acids, NAs are a class of natural surface-active molecules in crude oil) and tetraethylenepentamine (TEPA) through fine tuning of co-solvent of dodecyl benzene sulfonic acid (DBSA) and butanol. The O/W ME exhibited an optimal CO2-responsive character due to easier proton migration in the continuous aqueous phase and more pronounced dependence of configuration on deprotonated NA ions. Conversely, the ME with W/O microstructure exhibited a weak to none responsive characteristic, most likely attributed to its high viscosity and strong oil-NA interactions. The O/W ME also showed superior cleaning efficiency and oil recovery from oil-contaminated soils. The results from this study provide insights for the design of CO2-responsive MEs with desired performance and guidance for choosing the favorable operating conditions in various industrial applications, such as oily solid waste treatment, enhanced oil recovery (EOR), and pipeline transportation. The insights from this work allow more efficient and tailored design of switchable MEs for manufacturing advanced responsive materials in various industrial sectors and formulation of household products.
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Dióxido de Carbono , Aceites , Aceites/química , Tensoactivos/química , Emulsiones/química , Agua/química , SueloRESUMEN
Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).
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Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions.
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BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.
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Antiasmáticos , Asma , Femenino , Masculino , Humanos , Tos , Estudios Prospectivos , Fenotipo , Antiasmáticos/uso terapéuticoRESUMEN
The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common. Here, we demonstrate a chemical-resistant triboelectric nanogenerator (CR-TENG) based on polysulfonamide (PSA) and polytetrafluoroethylene (PTFE) non-woven fabrics. The CR-TENG can stably harvest biological motion energy and perform intelligent safety protection monitoring in a strong corrosive environment. After treatment with strong acid and alkali solution for 7 days, the fabric morphology, diameter, tensile properties and output of CR-TENG are not affected, showing high reliability. CR-TENG integrated into protective equipment can detect the working status of protective equipment in real time, monitor whether it is damaged, and provide protection for wearers working in high-risk situations. In addition, the nonwoven-based CR-TENG has better wearing comfort and is promising for self-powered sensing in harsh environments.
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Pulmonary hypertension (PH) is a cardiopulmonary vascular disease that acutely endangers human health and can be fatal. It progresses rapidly and has a high mortality rate. Its pathophysiology is complicated and still not completely elucidated; therefore, achieving treatment breakthroughs are difficult. In this study, data from 58 normal controls and 135 patients with PH were extracted from the GSE24988, GSE113439, and GSE117261 datasets in the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and hub genes associated with PH. Eight PH-associated hub genes were identified. Furthermore, correlation analysis between immune cell infiltration and hub genes was performed, and the receiver operating characteristic (ROC) curves showed that TARDBP had the best diagnostic efficacy. Moreover, a rat hypoxic pulmonary hypertension (HPH) model was generated, and the expression of hub genes in the lungs and pulmonary arteries of HPH rats was verified using western blotting assays. Our results showed that mTOR, PSMD2, RBM8A, SMARCA4, TARDBP, and UBXN7 were highly expressed in the lungs. In addition, EFTUD2, mTOR, RBM8A, SMARCA4, TARDBP, and UBXN7 were significantly upregulated, whereas DDB1 was significantly downregulated in the pulmonary arteries of HPH rats compared with those of controls. In conclusion, we identified PH hub genes with diagnostic and predictive value by performing WGCNA on data from the GEO database. Furthermore, we provided novel insights of PH that might be utilized to evaluate potential biomarker genes and therapeutic targets.
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Hipertensión Pulmonar , Enfermedades Vasculares , Humanos , Animales , Ratas , Western Blotting , Bases de Datos Factuales , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción , Factores de Elongación de Péptidos , Ribonucleoproteína Nuclear Pequeña U5RESUMEN
Axonal regeneration has been the research focus in the field of clinical treatment for spinal cord injury (SCI). The growth and extension of neuronal axons is a dynamic biological process mediated by the cytoskeleton, and microtubule plays an important role in axonal growth. Moderate stabilization of microtubule promotes axonal growth and eliminates various intra- and extracellular mechanisms that impede axonal regeneration. After SCI, the damaged axons rapidly form a growth cone, wherein the stability of tubulin decreases, impairing axonal regeneration. Taxol with proven clinical safety is commonly used as a broad-spectrum antitumor drug. Importantly, Taxol can promote axonal extension by enhancing and stabilizing the microtubule assembly. In our study, we systematically investigated the differentiation of neural stem cells (NSCs) in vitro and functional recovery in injured rats in vivo following Taxol treatment. Low-dose Taxol promoted differentiation of NSCs to neurons and significantly extended the axons in vitro. In vivo, Taxol promoted the expression of ßIII-tubulin in the injured areas and motor function recovery after SCI. Low-dose Taxol is a promising clinical agent to promote axonal regeneration after SCI.
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Paclitaxel , Traumatismos de la Médula Espinal , Ratas , Animales , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Recuperación de la Función/fisiología , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/uso terapéutico , Neuronas/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Axones/metabolismo , Regeneración Nerviosa/fisiología , Médula Espinal/patologíaRESUMEN
BACKGROUND: Previous research shows that scar tissue formed in the injured area after spinal cord injury blocks nerve regeneration and functional recovery. However, those researchers tried to prevent the formation of scar after spinal cord injury to promote nerve regeneration, but it ran counter to their desire, indicating that the formation of scar might play a role in functional recovery after spinal cord injury. METHODS: To investigate roles of scar formation on functional repair after spinal cord injury, we selected several different key time points to resect the scar tissue formed after spinal cord injury based on the rat models of the T8-T9 transection injury of spinal cord. First, the recovery of motor function was evaluated by Basso Beattie Bresnahan score and electrophysiologic examination; second, the pathologic features of functional recovery were analyzed mainly by immunofluorescence ßâ ¢-tubulin staining; finally, the genes related to the recovery of motor function were predicted by high-throughput sequencing analysis. RESULTS: Immunofluorescence results showed that the resection of scar tissue promoted significantly the recovery of motor function and the expression of ßâ ¢-tubulin in the injured area in the second week after spinal cord injury. Furthermore, RNA-seq studies showed that Tubb3 and Tubb6 gene expression and other neural regeneration pathways were significantly different in the tissue before and after early resection. CONCLUSIONS: Excision of scar tissue in the second week promoted nerve regeneration after spinal cord injury. Tubb3 and Tubb6 genes might be the potential targets for spinal cord injury therapy in our study.
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Traumatismos de la Médula Espinal , Tubulina (Proteína) , Ratas , Animales , Ratas Sprague-Dawley , Cicatriz/patología , Médula Espinal/patología , Recuperación de la Función/fisiología , Regeneración Nerviosa/fisiologíaRESUMEN
Previous studies have suggested that dysbiosis of the gut microbiota is associated with the development of pulmonary hypertension (PH). In this study, we established a left pulmonary artery ligation (LPAL)-induced PH rat model due to high flow and hemodynamic stress and investigated the association between gut microbiota composition and host metabolome signatures (in both gut and lung tissues) by using multiomics and correlation analysis. The results showed that LPAL successfully induced PH, characterized by increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodelling. Moreover, gut pathological abnormalities were observed in association with dramatic alterations in the gut microbiome and metabolome as well as the lung metabolome. The increased bacterial genus Sporobacter and decreased genera Eubacterium, Eubacteriaceae, Deltaproteobacteria and Desulfovibrio featured the altered gut microbiome in LPAL-PH versus SHAM rats. Moreover, imbalanced abundance of protective metabolites (e.g., butyrate, propionate) and pathogenic metabolites (e.g., proinflammatory mediators) were seen in the gut metabolome of LPAL-PH versus SHAM rats. In addition, the altered gut microbiome strongly correlated with the altered metabolome patterns in both the gut and lung of LPAL-PH rats. In conclusion, this study revealed significant gut dysbiosis in LPAL-PH rats, characterized by altered gut microbiota composition, in association with specific changes in gut and lung metabolome profiles. These findings enriched our understanding of the unique signature of the gut microbiome and the close association of the "gut-lung axis" in LPAL-PH induced by long-term high flow, leading to novel therapeutic, diagnostic or management paradigms for this subtype of PH.
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Hipertensión Pulmonar , Microbiota , Animales , Ratas , Butiratos , Disbiosis/microbiología , Pulmón/metabolismo , Metaboloma , PropionatosRESUMEN
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 3B on p. 1092, the western blots shown for 'Bax' in the MCF-7 group and 'Cleaved Caspase-8' in the MDA-MB-231 group were strikingly similar, such that these may have been the identical data re-used in the same figure. The authors have subsequently reexamined their data, and realize that the Cleaved Caspase-8 blots were incorrectly used in Fig. 3B during the process of assembling this figure (i.e., the western blots were duplicated, and these were correctly shown as the data for Bax in the MCF-7 group). Furthermore, the authors have realized that the western blots selected for the Cleaved Caspase-3 experiment in the western blots shown in Fig. 5D on p. 1093 were not as clear as they could have been, and also requested that the data here be changed for those from one of the repeated experiments. Consequently, the revised versions of Figs. 3 and 5, containing the correct data for the Cleaved Caspase-8 blots in the MDA-MB-231 group in Fig. 3B and the replacement Cleaved Caspase-3 blots in Fig. 5C, are shown on the next page. These errors did not affect the major conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. The authors regret the error that went unnoticed during the compilation of the figures in question, and apologize to the readership for any confusion that this may have caused. [International Journal of Molecular Medicine 40: 1089-1095, 2017; DOI: 10.3892/ijmm.2017.3081].