Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

This study aims to investigate the correlations of the appearance traits, total antioxidant capacity, and component content of Forsythiae Fructus processed by different methods, explore the effects of different processing methods on the abovementioned three aspects of Forsythiae Fructus, and screen out the internal and external indicators that have important effects on its quality. It determined the length, diameter, stem length, chroma value L~*, a~*, b~*, and other appearance indexes and antioxidant activity of Forsythiae Fructus processed by different methods. The content of forsythiaside A, rutin, forsythin, pinoresinol, and phillygenin was determined by ultra performance liquid chromatography(UPLC). Correlation analysis, principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and independent sample t-test analysis were performed on the appearance indexes and the component content. The correlation analysis showed that there were differences in the appearance traits and the component content. L~* and E~* had highly significant negative correlations with pinoresinol and phillygenin(P<0.01) and significant positive correlations with forsythiaside A(P<0.05). There were a highly significant negative correlation between a~* and forsythiaside A(P<0.01) and highly significant positive correlations of a~* with pinoresinol and phillygenin(P<0.01). There were a highly significant positive correlation between b~* and forsythiaside A(P<0.01) and highly significant negative correlations of b~* with pinoresinol and phillygenin(P<0.01). The total antioxidant capacity had highly significant negative correlations with pinoresinol and phillygenin(P<0.01). The PCA results showed that there were differences among Forsythiae Fructus samples processed by different methods. OPLS-DA marked five important indicators, which were forsythiaside A, stem length, E~*, L~*, and b~*. The results of independent sample t-test showed that the content of forsythiaside A, pinoresinol, and phillygenin, the total antioxidant capacity, and the appearance traits such as L~*, a~*, b~*, and E~* were significantly different between the Forsythiae Fructus samples processed by steaming and boiling(P<0.05). According to content determination and a related biological activity analysis, steaming is a good choice from the perspective of improving the stability of chemical constituents and antioxidant activity of Forsythiae Fructus. From the point of view of improving the stability of chemical constituents and anti-inflammatory and anti-cancer activities of Forsythiae Fructus, it is recommended to use boiling as the processing method. Based on the above analysis methods, the main indexes for the appearance traits of Forsythiae Fructus processed by different methods are powder chroma value(L~*, a~*, b~*, E~*), stem length, and total antioxidant capacity, and those for chemical constituents are the content of forsythiaside A, pinoresinol, and phillygenin. This study provides reference for seeking scientific processing methods of Forsythiae Fructus.
Forsythia/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Fruit/chemistry* ; Antioxidants/analysis* ; Chromatography, High Pressure Liquid ; Glycosides/analysis* ; Principal Component Analysis ; Furans ; Lignans

The ultra-high performance liquid chromatography( UPLC) characteristic fingerprints of Angelica dahurica and A. dahurica var. formosana were established. The compounds corresponding to common peaks were identified by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The results were combined with chemometrics and quantitative analysis of multi-components with a single-marker method(QAMS) to study the quality control of A. dahurica and A. dahurica var. formosana. The separation was performed on a Titank C_(18) column(2. 1 mm × 150 mm, 1. 8 μm)with a mobile phase of acetonitrile-0. 2% formic acid at a flow rate of 0. 3 m L·min~(-1). The column temperature was 35 ℃ and the injection volume was 1. 2 μL. Seven batches of A. dahurica and 11 batches of A. dahurica var. formosana were injected and analyzed. The UPLC characteristic fingerprints of A. dahurica and A. dahurica var. formosana were established according to the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine( version 2012), and 19 and 20 characteristic peaks were matched respectively. The common peaks were identified by reference substance comparison and UPLC-Q-TOF-MS/MS. Cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA)were performed to analyze the chemical pattern recognition of A. dahurica and A. dahurica var. formosana. The results of CA and PCA could distinguish Angelicae Dahuricae Radix from different producing areas, and the differential quality markers of A. dahurica and A. dahurica var. formosana were obtained by OPLS-DA. With imperatorin as the internal reference, the relative correction factors of oxypeucedanin hydrate, byakangelicin, bergapten, isopimpinellin, oxypeucedanin, and isoimperatorin were 1. 310, 1. 069, 0. 729, 0. 633, 0. 753, and 1. 010, respectively. There was no significant difference between the QAMS and external standard method(ESM)results of each component, indicating that the QAMS established with imperatorin as the internal reference was accurate and reliable. The characteristic fingerprints, chemometrics, and QAMS established in this study can quickly and efficiently control the quality of A. dahurica and A. dahurica var. formosana.
Quality Control ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Angelica/chemistry* ; Chemometrics/methods* ; Tandem Mass Spectrometry/methods* ; Principal Component Analysis

In recent years, the spread of clubroot disease caused by Plasmodiophora brassicae infection has seriously affected the yield and quality of Brassica juncea (L.) Czern.. The cascade of mitogen-activated protein kinases (MAPKs), a highly conserved signaling pathway, plays an important role in plant responses to both biotic and abiotic stress conditions. To mine the MAPK genes related to clubroot disease resistance in B. juncea, we conducted a genome-wide analysis on this vegetable, and we analyzed the phylogenetic evolution and gene structure of the MAPK gene family in mustard. The 66 BjuMAPK genes identified by screening the whole genome sequence of B. juncea were unevenly distributed on 17 chromosomes. At the genomic scale, tandem repeats led to an increase in the number of MAPK genes in B. juncea. It was found that members of the same subfamily had similar gene structures, and there were great differences among different subfamilies. These predicted cis-acting elements were related to plant hormones, stress resistance, and plant growth and development. The expression of BjuMAPK02, BjuMAPK15, BjuMAPK17, and BjuMAPK19 were down-regulated or up-regulated in response to P. brassicae infection. The above results lay a theoretical foundation for further studying the functions of BjuMAPK genes in B. juncea in response to the biotic stress caused by clubroot disease.
Mustard Plant/parasitology* ; Plasmodiophorida/pathogenicity* ; Plant Diseases/genetics* ; Mitogen-Activated Protein Kinases/metabolism* ; Phylogeny ; Disease Resistance/genetics* ; Gene Expression Regulation, Plant ; Genome, Plant ; Plant Proteins/genetics*

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

Objective To investigate the recovery of plasma metabolism in asymptomatic and mild patients of coronavirus disease 2019(COVID-19)one year after recovery.Methods A total of 174 participants were recruited from the communities in Wuhan,including 80 healthy volunteers and the COVID-19 patients who had recovered for one year.According to the disease severity,the recovered COVID-19 patients were grouped as asymptomatic patients(n=80)and mild patients(n=14).The liquid chromatography mass spectrometry platform was employed to study the metabolomic characteristics of the plasma from all the participants.Results The plasma metabolites in asymptomatic patients and mild patients remained abnormal compared with those in healthy volunteers.Among the differential metabolites in asymptomatic patients and mild patients,some metabolites showed a downward trend only in mild patients,such as phosphatidylethanolamine[20∶3(5Z,8Z,11Z)/P-18∶0],sphingomyelin(d18∶1/24∶0),and cholesteryl(15∶0).The metabolic pathway involving the differential metabolites in mild patients was mainly glycerophospholipid metabolism.Conclusions Even one year after recovery,the mild COVID-19 patients still exhibit metabolic abnormalities.Hence,these patients may experience an extended period of time for recovery.
Humans ; COVID-19/metabolism* ; Metabolomics ; SARS-CoV-2 ; Metabolome ; Female ; Male ; Adult ; Middle Aged

Objective Uranium compounds are critical materials in the nuclear industry, and their mining, processing, and use pose occupational exposure risks. Epidemiological studies have shown that uranium exposure can impair health, with acute uranium poisoning primarily causing structural and functional damage to the kidneys. Currently, the molecular mechanisms underlying uranium-induced kidney injury remain unclear, and traditional biological models used in toxicological research are inadequate for simulating the human microenvironment. This study employed a human kidney organoid model system to elucidate the nephrotoxic mechanisms of uranyl ions, providing a scientific basis for the prevention and control of uranium poisoning. Methods Kidney organoids were constructed using the human embryonic stem cell line H1 and exposed to solutions with different uranyl ion concentrations. Morphological observation, ATP detection, reactive oxygen species detection, apoptosis assay, and untargeted metabolomics analysis were performed. Mechanisms of toxicity were further explored through KEGG pathway enrichment analysis. Results Uranium exposure led to structural damage in the organoids, accompanied by a dose-dependent decrease in ATP levels, accumulation of reactive oxygen species, and increased apoptosis rate. After 24-hour exposure to 300 μmol/L uranium, significantly disturbed differential metabolites and five core metabolic pathways were identified. Conclusion Uranium induces oxidative stress, mitochondrial dysfunction (ATP reduction), and metabolic disorder (disruption of phospholipid/amino acid metabolism), which synergistically cause DNA damage, apoptosis, and/or necrosis. These findings provide new insights into the mechanisms of uranium-induced kidney injury and support the development of prevention and control strategies.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.