ABSTRACT
BACKGROUND: The fabrication technique of capillary column is the key to the development and application of capillary liquid chromatography (cLC) to improve separation efficiency for analytes. The capillary monolithic column possessed three-dimensionally connected porous or channel structures. Unique porous structure endows excellent permeability and high performance in diverse fields, especially in separation. Thereinto, organic monolithic columns have attracted widespread attention due to their advantages of simple preparation and excellent biocompatibility. However, their separation selectivity needs to be further developed and regulated to apply the separation of more diverse samples. RESULTS: A novel polymeric monolithic column was prepared via thermally initiated in situ copolymerization of 2-methyladamantan-2-yl acrylate (MADA) with ditrimethylolpropane tetraacrylate (DTTA) in fused silica. The prepared poly(MADA-co-DTTA) monolith showed adjustable permeability, developed porous structure and high thermal stability. Consequently, it exhibited excellent separation capability of small molecules (alkylbenzenes and polycyclic aromatic hydrocarbons). Especially, when acetonitrile/water (60/40, v/v) was used as the mobile phase, the theoretical plate numbers reached 84,000 plates m-1 for butylbenzene at a linear velocity of 0.5 mm s-1. Most importantly, the hydrophobicity of the poly(MADA-co-DTTA) monolithic column was regulated via host-guest interaction between adamantyl group and cucurbit [7]uril (CB[7]). Additionally, the poly(MADA-co-DTTA) monolith was further adopted for the analysis of the tryptic digest of proteins from HeLa by cLC-MS/MS. The 33,783 unique peptides and 5,299 proteins were identified on the monolith, which exhibited great separation ability for complex samples. SIGNIFICANCE AND NOVELTY: Due to abundant pore structure and good chemical properties, the poly(MADA-co-DTTA) monolithic column exhibited high performance for the separations of small molecules and biological sample. Meanwhile, owing to the existence of adamantyl-group, CB[7] was immobilized on the poly(MADA-co-DTTA) monolithic column to fabricate poly(MADA-co-DTTA)-CB[7] by host-guest interaction. It is possible to adjust the surface chemistry of the monolithic materials to accommodate more complex analytes.
ABSTRACT
Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two ß-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the ß-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the ß-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.
Subject(s)
Citrullination , Peptides , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Peptides/chemistryABSTRACT
Peptidyl arginine deiminase 4 (PAD4) plays a critical role in many autoimmune diseases including rheumatoid arthritis. Herein, a trypsin assisted highly immunoassay method was established to determine PAD4 activity and screen potent inhibitors from herbal plants extracts and purified natural products. The method was applied to determine endogenous PAD4 activity in both cell and tissue lysates, as well as the inhibitory effects of 20 herbal plants and 50 purified natural products. The Cinnamomi ramulus extract showed strongest inhibitory potency with IC50 value lower than 5 µg/mL. Meanwhile, pyrroloquinoline quinone (PQQ), widely used as a dietary supplement, was discovered as a promising PAD4 inhibitor with an IC50 value lower than 4 µM. The inhibition kinetic analysis, drug affinity response target stability (DARTS) and molecular docking were performed to confirm the interaction between PQQ and PAD4. This method has great potential for researchers to monitor activities and discover potential inhibitors of PAD4.
ABSTRACT
Peptidyl arginine deiminase 4 (PAD4) is a promising target for the treatment of metabolic diseases associated with autoimmune and central nervous system disease. By now there are limited numbers of PAD4 inhibitors, and no one is ready for clinical use. This study aims to find efficient and specific PAD4 inhibitors from traditional herbal medicines and to investigate their inhibitory mechanisms. The inhibitory effects of forty-eight extracts from sixteen traditional herbal medicines which are widely used in traditional herbal medicines were investigated. Salvia miltiorrhiza was found to have the most potent PAD4 inhibitory activity. After that, a practical bioactivity-guided fractionation coupling with a chemical profiling strategy was used to identify the fractions from Salvia miltiorrhiza with strong PAD4 inhibition activity, and the major constituents in these bioactive fractions were characterized by LC-MS/MS. Seven compounds were found to have inhibition on PAD4 with IC50 values ranging from 33.52 µM to 667 µM, in which salvianolic acid A showed the most potent inhibitory activity, with an IC50 value of 33.52 µM. Inhibition kinetic analyses indicated that salvianolic acid A effectively inhibited PAD4 in a mixed inhibitory manner, and computer simulation analyses demonstrated that salvianolic acid A binds to PAD4 mainly using hydrogen bonding. Overall, our results suggest that salvianolic acid A from Salvia miltiorrhiza is a potent inhibitor of PAD4, and that salvianolic acid A can be used as a promising lead compound for the development of more potent PAD4 inhibitors.
Subject(s)
Molecular Docking Simulation , Protein-Arginine Deiminase Type 4 , Salvia miltiorrhiza , Protein-Arginine Deiminase Type 4/antagonists & inhibitors , Salvia miltiorrhiza/chemistry , Molecular Structure , Plants, Medicinal/chemistry , Humans , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
OBJECTIVES: To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of pathologically confirmed HPSCC patients who had definitive radiation between January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO-based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). MAIN OUTCOME MEASURES AND RESULTS: RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. CONCLUSION: In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT.
Subject(s)
Hypopharyngeal Neoplasms , Humans , Male , Lymphocyte Count , Retrospective Studies , Female , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/pathology , Middle Aged , Aged , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/pathology , Treatment Outcome , Predictive Value of Tests , Adult , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , ROC CurveABSTRACT
Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.
Subject(s)
Biological Products , Drugs, Chinese Herbal , Enzyme Inhibitors , Protein-Arginine Deiminase Type 4 , Chromatography, High Pressure Liquid , Citrulline , Protein-Arginine Deiminase Type 4/antagonists & inhibitors , Reproducibility of Results , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/pharmacology , Drugs, Chinese Herbal/chemistryABSTRACT
Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.
Subject(s)
Armillaria , Polysaccharides , Armillaria/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purificationABSTRACT
Efficient and stable electrode materials are urgently required for wastewater treatment in the electrocatalytic degradation of toxic and refractory organic pollutants. Ti3+ self-doping black TiO2 nanotube arrays (Ti/B-TiO2-NTs) as an interlayer were used for preparing a novel PbO2 electrode via an electrochemical reduction technology, and a sodium dodecyl sulfate (SDS)-modified PbO2 catalytic layer was successfully achieved via an electrochemical deposition technology. The physicochemical characterization tests showed that the Ti/B-TiO2-NTs/PbO2-SDS electrodes have a denser surface and finer grain size with the introduction of Ti3+ in the interlayer of Ti/TiO2-NTs and the addition of SDS in the active layer of PbO2. The electrochemical characterization results showed that the Ti3+ self-doping black Ti/TiO2-NTs/PbO2-SDS electrode had higher oxygen evolution potential (2.11 V vs. SCE), higher electrode stability, smaller charge-transfer resistance (6.74 Ω cm-2), and higher hydroxyl radical production activity, leading to it possessing better electrocatalytic properties. The above results indicated that the physicochemical and electrochemical characterization of the PbO2 electrode were all enhanced significantly with the introduction of Ti3+ and SDS. Furthermore, the Ti/B-TiO2-NTs/PbO2-SDS electrodes displayed the best performance on the degradation of methylene blue (MB) in simulated wastewater via bulk electrolysis. The removal efficiency of MB and the chemical oxygen demand (COD) could reach about 99.7% and 80.6% under the optimal conditions after 120 min, respectively. The pseudo-first-order kinetic constant of the Ti/B-TiO2-NTs/PbO2-SDS electrode was 0.03956 min-1, which was approximately 3.18 times faster than that of the Ti/TiO2-NTs/PbO2 electrode (0.01254 min-1). In addition, the Ti/B-TiO2-NTs/PbO2-SDS electrodes showed excellent stability and reusability. The degradation mechanism of MB was explored via the experimental identification of intermediates. In summary, the Ti3+ self-doping black Ti/TiO2-NTs/PbO2-SDS electrode is a promising electrode in treating wastewater.
ABSTRACT
Fibrin clot structure and function are major determinants of venous and arterial thromboembolic diseases, as well as the key determinants of the efficiency of clot lysis. Studies have revealed that fungi fibrinolytic compound 1 (FGFC1) is a novel marine pyranisoindolone natural product with fibrinolytic activity. Here, we explore the impacts of FGFC1 on clot structure, lysis, and plasminogen activation in vitro using turbidimetric, enzyme-linked immunosorbent assay, confocal and electron microscopy, urokinase, or plasmin chromogenic substrate. Clots formed in the presence of FGFC1 expressed reduced fibrin polymerization rate and maximum turbidity; however, they did not influence the lag phase of fibrin polymerization. In the absence of scu-PA (single-chain urokinase plasminogen activator), microscopy revealed that FGFC1 increased the number of protofibrils within fibrin fiber and the pore diameter between protofibrils, inducing clots to form a region of thinner and looser networks separated by large pores. The effects of FGFC1 on scu-PA-mediated plasma clot structure were similar to those in the absence of scu-PA. In addition, FGFC1 promoted the lysis of clots and increased the D-dimer concentration in lysate. FGFC1 increased the generation rate of p-nitroaniline in plasma. These results show that FGFC1 has fibrinolytic activity in plasma, leading to interference with the release of fibrinopeptide B to affect lateral aggregation of protofibrils and increase clot susceptibility to fibrinolysis by altering its structure.
ABSTRACT
Cr(VI) pollution has seriously affected the survival of biological organisms and humans, so reducing the harm of Cr(VI) pollution is a significant scientific goal. Natural starch exhibits a low adsorption capacity for Cr(VI); thus, physical or chemical modification is needed to improve the adsorption and regeneration performance of starch. In this study, a novel starch-based porous carbon (SPC) was prepared to remove Cr(VI) from water by using soluble starch as a raw material. The characterization results show that the SPC shows a ratio surface area of 1325.39 m2/g. Kinetics suggest that the adsorption of Cr(VI) on SPC is dominated by chemisorption. The isotherm data demonstrated that the adsorption of Cr(VI) by SPC adhered to the Freundlich model. SPC exhibits a multimolecular layer adsorption structure, and the highest amount of adsorbed Cr(VI) in SPC was 777.89 mg/g (25 °C). Ion competition experiments show that SPC exhibits significant selectivity for Cr(VI) adsorption. In addition, the adsorption cycle experiment shows that SPC maintains a 63 % removal rate after 7 cycles. In this study, starch was transformed into high-quality adsorbent materials by hydrothermal and activation strategies, offering a new innovation for the optimization of starch-based adsorbents.
Subject(s)
Carbon , Water Pollutants, Chemical , Humans , Water , Porosity , Water Pollutants, Chemical/chemistry , Chromium/chemistry , Adsorption , Kinetics , Hydrogen-Ion ConcentrationABSTRACT
In this study, an adsorbent with mesoporous structure and PO/PO bonds is prepared by hydrothermal and phosphoric acid activation from industrial alkali lignin for the adsorption of oxytetracycline (OTC). The adsorption capacity is 598 mg/g, which is three times higher than that of the adsorbent with microporous structure. The rich mesoporous structure of the adsorbent provides adsorption channels and filling sites, and π-π attraction, cation-π interaction, hydrogen bonds, and electrostatic attraction provide adsorption forces at the adsorption sites. The removal rate of OTC exceeds 98 % over a wide range of pH values (3-10). It has high selectivity for competing cations in water, with higher than 86.7 % removal rate of OTC from medical wastewater. After 7 consecutive adsorption-desorption cycles, the removal rate of OTC remains as high as 91 %. This efficient removal rate and excellent reusability indicate the strong potential of the adsorbent for industrial applications. This study prepares a highly efficient, environmentally friendly antibiotic adsorbent that can not only efficiently remove antibiotics from water but also recycle industrial alkali lignin waste.
Subject(s)
Oxytetracycline , Water Pollutants, Chemical , Oxytetracycline/chemistry , Lignin , Carbon , Adsorption , Anti-Bacterial Agents/chemistry , Water , Water Pollutants, Chemical/chemistry , KineticsABSTRACT
This study compares postoperative enophthalmos between fresh and delayed unilateral orbital fractures after orbital reconstruction with titanium mesh using computer-assisted navigation. The sample was composed of 45 patients with post-traumatic unilateral enophthalmos who were divided into the fresh fracture group and the delayed fracture group. They underwent orbital reconstruction with standard preformed orbital implants and computer-assisted navigation system. The following parameters were measured with computed tomography images: the degree of enophthalmos, orbital volume, and fracture defect area. Patients were reviewed preoperatively (T0), 1 week postoperatively (T1), and 6 months postoperatively (T2). Computed tomography measurements showed that in both groups, the degree of enophthalmos decreased after surgery but increased significantly from T1 to T2 ( P <0.05). ΔE (difference in the degree of enophthalmos between T1 and T2) was similar in patients with fresh and delayed fractures. There was a significant difference in the degree of ΔE between patients with single-wall orbital fractures and those with two-wall orbital fractures. The findings indicate that postoperative enophthalmos is common in both the groups and is closely related to the degree of preoperative enophthalmos. Furthermore, the recurrence of enophthalmos is similar between the 2 groups, but it is higher in patients with orbital fractures involving 2 walls.
Subject(s)
Dental Implants , Enophthalmos , Eye Injuries , Orbital Fractures , Humans , Enophthalmos/surgery , Orbital Fractures/surgery , Titanium , Surgical Mesh , ComputersABSTRACT
In this study, honeycomb lignin-based biochar (HLB) was prepared by hydrothermal activation using industrial lignin as raw material to remove norfloxacin from water. Batch adsorption test results showed that HLB has a strong ability to remove norfloxacin at a wide pH. The maximum adsorption capacity was 529.85 mg/g at 298 K, which is 1.52-fold to 201.46-fold higher than that of other reported materials. HLB showed good selectivity and recycling ability for the adsorption of norfloxacin, the removal rate of NOR reached 99.5% in the presence of competitive ions and maintained at least 98% removal rate after 12 adsorption cycles. The removal rate of norfloxacin in different water reached more than 99% within 8 mins. Pore filling, electrostatic interaction, π-π interaction, and hydrogen bond contributed significantly to the removal of norfloxacin. Among them, the highly aromatized structure of HLB and the abundant oxygen-containing functional groups (OH, CO, etc.) promoted π-π interaction.
Subject(s)
Norfloxacin , Water Pollutants, Chemical , Norfloxacin/chemistry , Lignin , Adsorption , Water Pollutants, Chemical/chemistry , Charcoal/chemistry , Water , KineticsABSTRACT
INTRODUCTION: Due to its excellent sensitivity, nano-flow liquid chromatography tandem mass spectrometry (LC-MS/MS) is the mainstay in proteome research; however, this comes at the expense of limited throughput and robustness. In contrast, micro-flow LC-MS/MS enables high-throughput, robustness, quantitative reproducibility, and precision while retaining a moderate degree of sensitivity. Such features make it an attractive technology for a wide range of proteomic applications. In particular, large-scale projects involving the analysis of hundreds to thousands of samples. AREAS COVERED: This review summarizes the history of chromatographic separation in discovery proteomics with a focus on micro-flow LC-MS/MS, discusses the current state-of-the-art, highlights advances in column development and instrumentation, and provides guidance on which LC flow best supports different types of proteomic applications. EXPERT OPINION: Micro-flow LC-MS/MS will replace nano-flow LC-MS/MS in many proteomic applications, particularly when sample quantities are not limited and sample cohorts are large. Examples include clinical analyses of body fluids, tissues, drug discovery and chemical biology investigations, plus systems biology projects across all kingdoms of life. When combined with rapid and sensitive MS, intelligent data acquisition, and informatics approaches, it will soon become possible to analyze large cohorts of more than 10,000 samples in a comprehensive and fully quantitative fashion.
Subject(s)
Proteome , Proteomics , Humans , Chromatography, Liquid/methods , Proteomics/methods , Proteome/analysis , Tandem Mass Spectrometry/methods , Reproducibility of ResultsABSTRACT
BACKGROUND: Second primary malignancy (SPM) represents the leading long-term cause of death among patients with index head and neck squamous cell carcinoma (HNSCC). We aimed to quantify the association between postoperative radiotherapy (PORT) and the risk of SPM development for index HNSCC among adolescent and young patients, who are particularly vulnerable to radiation-associated impacts due to their increased tissue susceptibilities and longer life expectancies. METHODS: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of 5 year survivors of index young-onset HNSCC from 1975 to 2011. The outcome of interest was SPM, a new, metachronous malignancy after the index HNSCC. Standardized incidence ratios (SIRs) and excess absolute risks (EARs) were used to quantify the PORT-associated risks externally, and relative risks (RRs) were estimated by the multivariate Poisson regression analysis to quantify the PORT-associated risks internally. RESULTS: Of the included 2771 5 year survivors with index young-onset HNSCCs, the receipt of PORT (37.6%) was associated with higher risk of SPMs (RR, 1.23; 95% CI 1.07 to 1.43). PORT-associated risks were elevated for the majority of sites, including head and neck (RR, 1.19; 95% CI 0.95 to 1.50) and lung (RR, 1.67; 95% CI 1.18 to 2.34). With regarding to the subsites of head and neck, RRs were above unity in oral cavity squamous cell carcinoma (SCC) (RR, 1.68; 95% CI 1.39 to 2.03) and laryngeal SCC (RR, 1.02; 95% CI 0.73 to 1.43). A relatively greater RR was observed for patients younger than 35 years (RR, 1.44, 95% CI 0.37 to 5.57) and those diagnosed with localized diseases (RR, 1.16, 95% CI 0.9 to 1.5). PORT-associated risks were increased remarkably after 15 years of follow-up (RR, 1.24; 95% CI 0.97 to 1.58). CONCLUSIONS: An association was discovered between PORT treatment and increased long-term risk of SPM among patients with index young-onset HNSCC. The findings suggest long-term follow-up surveillance for these patients, particularly those with oral cavity SCC or laryngeal SCC.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Neoplasms, Second Primary , Adolescent , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/pathology , Risk Factors , SEER Program , Squamous Cell Carcinoma of Head and NeckABSTRACT
BACKGROUND: The oncologic outcomes between transoral laser microsurgery (TLM) and open partial laryngectomy (OPL) using comprehensive analysis in one clinical center is rare. The purpose of this study was to evaluate the oncologic outcomes of TLM in patients with early stage glottic carcinoma, and to compare the results with OPL. SUBJECTS AND METHODS: Records of 425 glottic carcinoma patients with T1 - T2 stage treated with TLM, vertical partial laryngectomy (VPL), and cricohyoidoepiglottopexy (CHEP) from 2005 to 2010 were retrospectively analyzed. The overall survival (OS), disease-specific survival (DSS), and laryngeal function preservation (LFP) of these three treatments were assessed. RESULTS: One hundred and twenty-two patients were treated with TLM. Regarding OPL, 167 patients underwent VPL, and 136 patients underwent CHEP. The mean age was 59.7 years, with men accounting for 97.2 % of all cases. The OS, DSS, and LFP rates of patients with anterior commissure (AC) involvement undergoing TLM were worse than those of patients without AC involvement, but these differences were not statistically significant. The 5-year OS, DSS, and LFP of patients undergoing TLM were 88.4 %, 89.9 %, and 83.5 %, respectively, and the oncologic outcomes of patients undergoing TLM, VPL, and CHEP were not statistically different. CONCLUSION: Glottic carcinoma patients with early stage treated with TLM experience satisfactory oncologic outcomes. No compelling difference in oncologic outcomes among three treatments of TLM, VPL and CHEP, as well as VPL and CHEP can be alternatives to patients who are not suitable for receiving TLM.
Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , Laser Therapy , Male , Humans , Middle Aged , Laryngectomy/methods , Glottis/surgery , Glottis/pathology , Microsurgery/methods , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Treatment Outcome , Laryngeal Neoplasms/pathology , Laser Therapy/methods , Lasers , Neoplasm StagingABSTRACT
Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 µM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.
Subject(s)
Thrombosis , Urokinase-Type Plasminogen Activator , Fibrin , Fluorescein-5-isothiocyanate , Humans , Isoindoles , PyransABSTRACT
Reducing the harm of heavy metals to the environment has been a major scientific challenge. In this study, D-(+)-xylose was used to prepare an adsorbent with rich O groups and three-dimensional porous structures for Cr(VI) adsorption. What's more, the adsorption sites of many oxygen groups in the material were combined with the three-dimensionally connected porous structures, which made the adsorption sites fully in contact with Cr(VI). At the concentration of 300 mg/L, the removal rate of Cr(VI) was 94.50%, 6.4 times that of the non-porous treatment and 9.6 times that of the non-porous and O group treatment. The adsorbent showed a high adsorption capacity (910.10 mg/g) for Cr(VI), and the adsorption model proved that the adsorbent was a multi-molecular layer adsorbent. In addition, the adsorption was controlled by chemical reaction and diffusion, which was also attributed to the three-dimensional porous structure and abundant oxygen groups of the material. XPS and FTIR indicated that four O groups participated in the adsorption reaction (-OH, C-O-C, CO, and C-O), and C-O-C and C-O were the main reaction sites. After treating wastewater from electroplating plants with X-PC, the discharged water met international and domestic discharge standards (Cr(VI) removal rate> 99.90%). This work provides a new idea for the application of sugars in the environment and the design of porous adsorbents.
Subject(s)
Wastewater , Water Pollutants, Chemical , Adsorption , Chromium/chemistry , Hydrogen-Ion Concentration , Kinetics , Oxygen , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , XyloseABSTRACT
A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer's disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.
ABSTRACT
OBJECTIVE: To assess the correlation of borderline fetal ventriculomegaly with genomic copy number variations (CNVs) and outcome of pregnancy. METHODS: For 84 singleton pregnancies diagnosed with VM, chromosomal microarray analysis (CMA) was carried out to detect the CNVs of the fetal genome. Outcome of the pregnancy and neonatal development were analyzed. The pregnant women were divided into mild group (10-12 mm), moderate group (12-15 mm) and severe group (>= 15 mm) based on the severity of fetal ventriculomegaly. The detection rate of pathogenic CNVs and pregnancy outcome were compared. Multivariate logistic regression was carried out to analyze the predictors for pregnancy outcome. RESULTS: Respectively, 24, 28 and 32 fetuses were assigned into the mild, moderate and severe groups. CMA has detected 15 cases of chromosomal abnormalities, including 11 pathogenic CNVs and 4 abnormal karyotypes. Abnormal pregnancy outcomes were found in 20 fetuses, including 12 with hydrocephalus and 8 with chromosomal microdeletion syndromes. A significant difference was found in the detection rate of fetal pathogenic CNVs and abnormal pregnancy outcome among the three groups (P<0.05). Multivariate logistic regression analysis showed that the largest change of lateral ventricle width (OR = 1.868, 95%CI = 1.120-3.116) and the extent of lateral ventricle widening (OR = 1.571, 95%CI = 1.120-2.206) were the key factors affecting the outcome of pregnancy (P<0.05). CONCLUSION: Borderline fetal VM is associated with the risk of pathogenic CNVs and adverse pregnancy outcome. A comprehensive examination is required after prenatal ultrasound diagnosis, which is conducive to prenatal consultation and prognostic evaluation of the fetus.