Exopolysaccharide from Lacticaseibacillus paracasei alleviates gastritis in Helicobacter pylori-infected mice by regulating gastric microbiota.

Introduction: Many probiotics have the ability to produce extracellular polysaccharides (EPS). EPS derived from these probiotics has been confirmed to regulate the host intestinal microecological balance and alleviate the symptoms of diseases caused by gastrointestinal microecological imbalance. Results: Lactic acid bacteria (LAB) strain with good exopolysaccharide (EPS) producing ability, namely, Lacticaseibacillus paracasei ZFM54 (L. paracasei ZFM54) was screened. The fermentation conditions of L. paracasei ZFM54 for EPS production were optimized. The EPS54 was characterized by chemical component and monosaccharide composition determination, UV, FT-IR and NMR spectra analysis. Cango red, SEM, AFM and XRD analysis were conducted to characterize the structure of EPS54. The EPS54 effectively reduced the colonization of Helicobacter pylori to AGS cells and recovered the cell morphology. EPS54 could also effectively alleviate the gastritis in the H. pylori-infected mice by down-regulating the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-8, IL-1ß and TNF-α and up-regulating the mRNA expression of inflammatory cytokine IL-10 in gastric cells. EPS54 was also found to be able to positively regulate the structure of gastric microbiota. Conclusion: The EPS 54 from L. paracasei ZFM54 can alleviate gastritis in H. pylori-infected mice by modulating the gastric microbiota.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

The impact of varying trolley case usage modes and weights on body posture.

OBJECTIVE: To study the body posture characteristics when walking with trolley case, and to explore the effects of different usage methods and weights of trolley case on body posture characteristics. METHODS: Fifteen subjects pushed and pulled(Condition 1 and 2) the case with three load weights of 10 %, 20 % and 30 % of their own body weight with 0 % no load as baseline for both conditions. The basic gait parameters, kinematic and kinetic data were collected using the VICON infrared motion capture system and a 3D force platform. Two repeated measures factor (condition×weight) analysis of variance was used for statistical analysis of the gait temporal and spatial parameters, as well as trunk angle, kinetic ground reaction force, shoulder joint force, and trunk moment. RESULTS: Significant condition*weight interactions were detected in DLST (Double Limb Stance Time) (F=5.341，P = 0.006), GRF (Ground Reaction Force) in frontal plane (F=10.507, p < 0.001) and vertical plane (F=3.751, p = 0.021), shoulder joint force in sagittal plane (F=21.129, p < 0.001), and flexion-extension angle of the trunk in the sagittal plane (F=4.888, p < 0.010). Significant main effects were detected in walking speed (F=35.842, p < 0.001), right support time (F=12.156, p < 0.001), left swing time (F=8.506, p < 0.001), left support time (F=1.122, p < 0.001), right step length (F=33.900, p < 0.001), and left step length (F=14.960, p < 0.001) under different weights. A significant main effect was detected in sagittal GRF (F=11.77, p < 0.001), trunk rotation angle (F=4.124, p = 0.016), amplitude of COM (F=2.993, p = 0.046), under different weights. CONCLUSION: When the weight of the case exceeds 20 % of the body weight, from the perspective of energy efficiency, the push method is more advantageous than the pull method. When walking with luggage, people tend to maintain the stability of their trunk posture by adjusting the force on their arms more often.

Two-Dimensional Amorphous Titanium Dioxide/Silver (TiO2/Ag) Nanosheets as a Surface-Enhanced Raman Spectroscopy Substrate for Highly Sensitive Detection.

For the purpose of investigating the chemical enhancement of amorphous semiconductors as well as increasing the sensitivity of the surface-enhanced Raman spectroscopy (SERS) substrate, titanium dioxide (TiO2) precursors were calcined at different temperatures to generate crystallized TiO2 (c-TiO2) and amorphous TiO2 (a-TiO2) nanosheets, respectively. Afterward, a two-dimensional (2D) a-TiO2/Ag nanosheet SERS substrate was successfully fabricated using electrostatic interaction between a-TiO2 and Ag nanoparticles. In order to demonstrate a greater SERS sensitivity on a-TiO2/Ag compared to either c-TiO2 or Ag nanoparticles alone, the SERS probe molecules rhodamine 6G (R6G) and malachite green (MG) were utilized. Based on the results of SERS detections for probe molecules and contaminants, it demonstrates that a-TiO2/Ag nanosheets produce highly sensitive and repeatable Raman signals. The detectable concentration limits for R6G and MG were found to be 10-11 M and 10-10 M, respectively. And it has been determined that the system exhibits an enhancement factor (EF) of up to 1 × 108. The limit of detection for 4-mercaptobenzoic acid and alizarin red can both reach 1 × 10-8. Furthermore, a finite-difference time-domain simulation is performed in order to evaluate the magnetic field strength generated by Ag nanoparticles. As a result of the simulation, it is evident that the actual EF is smaller than the calculated one, leading support to the view that a-TiO2 nanosheets have a beneficial effect on the chemical enhancement of SERS.

Self-Assembled Three-Dimensional Polyamide/Silver Nanoparticle Pore Array as a Highly Sensitive and Reproducible SERS Substrate for Pesticide Detection in Water.

In this study, silver nanoparticles (AgNPs) are self-assembled onto the polyamide (PA) pore array through hydrogen bonding, resulting in and optimizing the PA/Ag 3D pore array substrates. The best surface-enhanced Raman scattering (SERS) substrate is obtained with a pore depth of 500 nm in the PA array, 30 nm AgNPs, at a pH of 5.0, and a 24 h assembly time. The SERS performance of the substrates is assessed using rhodamine 6G (R6G) as a probe molecule. The detection limit of the R6G molecule reaches 10-13 M, and the relative standard deviation is under 20%, indicating good enhancement ability and reproducibility. Furthermore, label-free detection of pesticide contaminant diquat with a detection limit of 2.69 × 10-9 M is achieved using the optimized 3D substrate, which meets environmental monitoring requirements for drinking water. The findings demonstrate that this 3D SERS substrate has promising potential for use and development in the fields of contaminant detection and chemical sensing.

Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host.

Helicobacter pylori (H. pylori) is a highly successful human pathogen that colonizes stomach in around 50% of the global population. The colonization of bacterium induces an inflammatory response and a substantial rise in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), mostly derived from host neutrophils and gastric epithelial cells, which play a crucial role in combating bacterial infections. However, H. pylori has developed various strategies to quench the deleterious effects of ROS, including the production of antioxidant enzymes, antioxidant proteins as well as blocking the generation of oxidants. The host's inability to eliminate H. pylori infection results in persistent ROS production. Notably, excessive ROS can disrupt the intracellular signal transduction and biological processes of the host, incurring chronic inflammation and cellular damage, such as DNA damage, lipid peroxidation, and protein oxidation. Markedly, the sustained inflammatory response and oxidative stress during H. pylori infection are major risk factor for gastric carcinogenesis. In this context, we summarize the literature on H. pylori infection-induced ROS production, the strategies used by H. pylori to counteract the host response, and subsequent host damage and gastric carcinogenesis.

Hydrophilic magnetic Ti3C2Tx-based nanocomposite as an efficient boron adsorbent: Synthesis, characterization, and application.

It is widely recognized that wastewater containing boron is an environmental issue. Therefore, the development of adsorbents with excellent adsorption capacity, stability, and recyclability is essential in water treatment applications. A Fe3O4/PDA/Ti3C2Tx/PEI/DHHA nanocomposite has been prepared that can be used to separate and recover boric acid by adjusting the pH of the solution, based on the affinity theory of boric acid and cis-diol. Through series characterization, it was determined that the adsorbent possessed good magnetic properties, high hydrophilicity and high loading capacities. In this study, 4-formylphenylboronic acid (FPBA) was selected as the model compound. The nanocomposite exhibited an adsorption equilibrium time of 10 h and an adsorption capacity of 98.99 mg/g at pH = 8.5 and 25 °C. The Langmuir isothermal model and the quasi-secondary kinetic model are both appropriate for describing the adsorption process. Thermodynamic results suggest that adsorption is a spontaneous chemisorption process. Furthermore, the nanocomposite retains good regeneration performance after five adsorption-desorption cycles.

Achieving Stable and Switchable Ultralong Room-Temperature Phosphorescence from Polymer-Based Luminescent Materials with Three-Dimensional Covalent Networks for Light-Manipulated Anticounterfeiting.

Developing polymer-based organic afterglow materials with switchable ultralong organic phosphorescence (UOP) that are insensitive to moisture remains challenging. Herein, two organic luminogens, BBCC and BBCS, were synthesized by attaching 7H-benzo[c]carbazole (BBC) to benzophenone and diphenyl sulfone. These two emitters were employed as guest molecules and doped into epoxy polymers (EPs), which were constructed by in situ polymerization to achieve polymer materials BBCC-EP and BBCS-EP. It was found that BBCC-EP and BBCS-EP films exhibited significant photoactivated UOP properties. After light irradiation, they could produce a conspicuous organic afterglow with phosphorescence quantum yields and lifetimes up to 5.35% and 1.91 s, respectively. Meanwhile, BBCS-EP also presented photochromic characteristics. Upon thermal annealing, the UOP could be turned off, and the polymer films recovered to their pristine state, showing switchable organic afterglow. In addition, BBCC-EP and BBCS-EP displayed excellent water resistance and still produced obvious UOP after soaking in water for 4 weeks. Inspired by the unique photoactivated UOP and photochromic properties, BBCC and BBCS in the mixtures of diglycidyl ether of bisphenol A (DGEBA) and 1,3-propanediamine were employed as security inks for light-controlled multilevel anticounterfeiting. This work may provide helpful guidance for developing photostimuli-responsive polymer-based organic afterglow materials, especially those with stable UOP under ambient conditions.

Importance of residue 248 in Escherichia coli RNase P RNA mediated cleavage.

tRNA genes are transcribed as precursors and RNase P generates the matured 5' end of tRNAs. It has been suggested that residue - 1 (the residue immediately 5' of the scissile bond) in the pre-tRNA interacts with the well-conserved bacterial RNase P RNA (RPR) residue A248 (Escherichia coli numbering). The way A248 interacts with residue - 1 is not clear. To gain insight into the role of A248, we analyzed cleavage as a function of A248 substitutions and N-1 nucleobase identity by using pre-tRNA and three model substrates. Our findings are consistent with a model where the structural topology of the active site varies and depends on the identity of the nucleobases at, and in proximity to, the cleavage site and their potential to interact. This leads to positioning of Mg2+ that activates the water that acts as the nucleophile resulting in efficient and correct cleavage. We propose that in addition to be involved in anchoring the substrate the role of A248 is to exclude bulk water from access to the amino acid acceptor stem, thereby preventing non-specific hydrolysis of the pre-tRNA. Finally, base stacking is discussed as a way to protect functionally important base-pairing interactions from non-specific hydrolysis, thereby ensuring high fidelity during RNA processing and the decoding of mRNA.

Lactiplantibacillus plantarum ZJ316 Reduces Helicobacter pylori Adhesion and Inflammation by Inhibiting the Expression of Adhesin and Urease Genes.

SCOPE: The present study aims to investigate the anti-Helicobacter pylori (H. pylori) effects of Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) both in vitro and in vivo. METHODS AND RESULTS: This study finds that L. plantarum ZJ316 effectively suppresses H. pylori adhesion in inhibition (Pre-ZJ316), competition (Co-ZJ316), and displacement (Post-ZJ316) assays, and Pre-ZJ316 displaying the most potent inhibitory effect with an impressive inhibition ratio of 70.14%. Upon anti-adhesion, L. plantarum ZJ316 significantly downregulates the expression of H. pylori virulence genes, including ureA, ureB, flaA, and sabA, with inhibition ratios of 46.83%, 24.02%, 21.42%, and 62.38% at 2 h, respectively. In addition, L. plantarum ZJ316 is observed to reduce the level of interleukin 8 (IL-8) and improve cell viability in infected AGS cells. Furthermore, in vivo studies show that supplementation with L. plantarum ZJ316 effectively hinders H. pylori colonization and significantly suppresses the infiltration of immune cells and IL-8 production with H. pylori infection, protecting host from inflammatory damage. CONCLUSION: L. plantarum ZJ316 exhibits excellent adhesion inhibition on H. pylori, and may be used as a probiotic candidate in the prevention or adjuvant therapy of gastric disease caused by H. pylori.

Identification of different types of tumors based on photoacoustic spectral analysis: preclinical feasibility studies on skin tumors.

Significance: Collagen and lipid are important components of tumor microenvironments (TME) and participates in tumor development and invasion. It has been reported that collagen and lipid can be used as a hallmark to diagnosis and differentiate tumors. Aim: We aim to introduce photoacoustic spectral analysis (PASA) method that can provide both the content and structure distribution of endogenous chromophores in biological tissues to characterize the tumor-related features for identifying different types of tumors. Approach: Ex vivo human tissues with suspected squamous cell carcinoma (SCC), suspected basal cell carcinoma (BCC), and normal tissue were used in this study. The relative lipid and collagen contents in the TME were assessed based on the PASA parameters and compared with histology. Support vector machine (SVM), one of the simplest machine learning tools, was applied for automatic skin cancer type detection. Results: The PASA results showed that the lipid and collagen levels of the tumors were significantly lower than those of the normal tissue, and there was a statistical difference between SCC and BCC (p<0.05), consistent with the histopathological results. The SVM-based categorization achieved diagnostic accuracies of 91.7% (normal), 93.3% (SCC), and 91.7% (BCC). Conclusions: We verified the potential use of collagen and lipid in the TME as biomarkers of tumor diversity and achieved accurate tumor classification based on the collagen and lipid content using PASA. The proposed method provides a new way to diagnose tumors.

Phenyl lactic acid alleviates Helicobacter pylori infection in C57BL/6 mice.

Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. In the present study, we found that phenyl lactic acid (PLA) derived from Lactobacillus plantarum ZJ316 (L. plantarum ZJ316) can directly inhibit the growth and urease activity of H. pylori in vitro with a minimum inhibitory concentration (MIC) of 2.5 mg mL-1. Moreover, PLA also caused a dramatic morphological transformation from a spiral to a coccoid form in H. pylori. In this work, we also analyzed the beneficial effects of PLA in mice. The results showed that PLA administration ameliorated H. pylori-induced gastric mucosal damage and significantly decreased lymphocyte infiltration and inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and interferon-γ (IFN-γ) by 59.93%, 63.95%, and 48.05%, respectively, but elevated the interleukin-10 (IL-10) and glutathione (GSH) levels. Furthermore, PLA administration improved microbiota diversity with increased Bacteroidetes abundance and decreased Proteobacteria abundance by 46.39% and 24.05%, respectively. PLA also significantly reduced the abundance of H. pylori but increased the relative abundances of potential beneficial bacteria, such as Faecalibacterium, Bifidobacterium, and Lactobacillus. These results demonstrated that PLA can ameliorate H. pylori-induced inflammation and support beneficial gut bacteria, providing a new perspective against H. pylori infection.

Targeting proteostasis of the HEV replicase to combat infection in preclinical models.

BACKGROUND & AIMS: Appropriate treatment options are lacking for hepatitis E virus (HEV)-infected pregnant women and immunocompromised individuals. Thus, we aimed to identify efficient anti-HEV drugs through high-throughput screening, validate them in vitro and in vivo (in a preclinical animal study), and elucidate their underlying antiviral mechanism of action. METHODS: Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interactions and performed a preclinical study of the corresponding antivirals, which target proteostasis of the HEV replicase. RESULTS: We found 17 inhibitors that target HEV-HSP90 interactions by unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered rapid ubiquitin/proteasome-mediated degradation of ORF1, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage. CONCLUSIONS: In this study, we uncover a proteostatic pathway that is critical for host-HEV interactions and we provide a foundation from which to translate this new understanding of the HEV life cycle into clinically promising antivirals. IMPACT AND IMPLICATIONS: Appropriate treatment options for hepatitis E virus (HEV)-infected pregnant women and immunocompromised patients are lacking; hence, there is an urgent need for safe and effective HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly limit HEV infection by targeting the viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and were found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and pave the way for antiviral development.

Effectiveness of "Stop the Bleed" Courses: A Systematic Review and Meta-analysis.

OBJECTIVE: Our object was to comprehensively analyze the existing body of evidence to evaluate the Stop the Bleed (STB) course effectiveness and satisfaction and find the direction of improvement for the future. STUDY DESIGN: A literature search with the term "Stop the Bleed" in the electronic databases PubMed, Web of Science, EMBASE, Cochrane Library was performed, retrieving records from January 1, 2013 to April 13, 2022 based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. In addition, all selected papers' references were examined for qualified studies that were missed during the first search. Original publications were included that reported on (1) clinical studies of the STB course implementation; and (2) studies comparing students' hemostasis ability and attitude (comfort, confidence, and willingness) before and after the STB course. The literature search and data extraction were done independently by 2 writers. To establish consensus, disagreements will be handled with the help of a third reviewer. For data synthesis, the most inclusive data from studies with repeated data were abstracted. Changes in hemostasis questionnaire scoring and operation evaluation after the STB course were the main outcomes. RESULTS: This systematic review and meta-analysis includes 36 trials with a total of 11,561 trainees. Thirty-one of them were undertaken in the USA, while the other 5, accounting for 13.9%, were conducted in other regions. Among various evaluation methods, 3 trials with 927 trainees indicated that scores of correct uses of tourniquet significantly increased after the STB course (mean difference of post versus pre groups, 44.28; 95% CI 41.24-47.32; p < 0.001). Significant difference was also observed in the willingness to apply a hemostatic dressing in a real-world situation (risk ratio for post versus pre groups, 1.28; 95% CI 1.08-1.52; p = 0.004) (7 studies and 2360 participants). The results indicate that hemostasis knowledge and skills after the STB course had improved, but statistics indicated that STB courses implemented in the USA were more effective than other regions. CONCLUSIONS AND RELEVANCE: Meta-analysis showed that comparison before and after the STB course were significantly different. However, the outcome measures in each study were different and could not, therefore, be compiled in all cases. The effectiveness and worth of implementation of STB in different countries should be continuously evaluated in the future.

Targeting TBK1 attenuates ocular inflammation in uveitis by antagonizing NF-κB signaling.

Uveitis with complex pathogenesis is a kind of eye emergency involving refractory and blinding inflammation. Dysregulation of TANK binding kinase 1 (TBK1), which plays an important role in innate immunity, often leads to inflammatory diseases in various organs. However, the role of TBK1 in uveitis remains elusive. In this study, we identified that the mRNA expression level of TBK1 and its phosphorylation level were significantly increased in peripheral blood mononuclear cells (PBMCs) of patients with uveitis. Consistent with this, the expression of Tbk1 was elevated in the ocular tissues of uveitis rats and primary peritoneal macrophages while its phosphorylation levels, which present activation forms, were upregulated as well, accompanied by an increase in the level of nuclear factor-κB (NF-κB) and proinflammatory cytokines. In addition, inhibition of TBK1 may effectively reduce the inflammatory response of uveitis rats by blocking NF-κB entry into the nucleus and impeding the initiation of NLRP3 inflammasome- and caspase-1-mediated pyroptosis pathways.

Color-Tunable Dual-Mode Organic Afterglow from Classical Aggregation-Caused Quenching Compounds for White-Light-Manipulated Anti-Counterfeiting.

Color-tunable dual-mode organic afterglow excited by ultraviolet (UV) and white light was achieved from classical aggregation-caused quenching compounds for the first time. Specifically, two luminescent systems, which could produce significant organic afterglow composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence under ambient conditions, were constructed by doping fluorescein sodium and calcein sodium into aluminum sulfate. Their lifetimes surpassed 600 ms, and the dopant concentrations were as low as 5×10-6  wt %. Moreover, the persistent luminescence colors of the materials could be tuned from blue to green and then to yellow by simply varying the concentrations of guest compounds or the temperature in the range of 260-340 K. Inspired by these exciting results, the afterglow materials were used for UV- and white-light-manipulated anti-counterfeiting and preparation of elastomers with different colors of persistent luminescence.

Current status and influencing factors of health literacy among older adults in combined medical and nursing care institutions: a cross-sectional study.

Introduction: Health literacy is linked to the health status of older adults and is a critical component in achieving active aging. This study to characterize the current health literacy status among older adults in combined medical and nursing care institutions, as well as the factors that influenced this status. Methods: This cross-sectional study used a convenience sampling method to select 740 older adults who were in 16 combined medical and nursing care institutions in Chengdu, China, from July 2022 to June 2023, using the Health Literacy Management Scale, the Social Support Rating Scale, and the Short Form-36 Health Survey. Results: The results showed a health literacy score of 75.25 ± 12.33, the percentage of older adults with basic health literacy was 6.33%, a social support score of 37.37 ± 6.10, and a health-related quality of life score of 55.34 ± 15.48. Factors influencing health literacy included age, educational level, previous occupation, family size, monthly per capita household income, and health-related quality of life. Discussion: Health literacy is an essential factor in improving the health status of older adults. Relevant departments should therefore improve health education and health promotion interventions for older adults in combined medical and nursing care institutions to improve health literacy.

Advances in targeted therapy for gastric cancer based on tumor driver genes. / é¶å‘è‚¿ç˜¤é©±åŠ¨åŸºå› çš„èƒƒç™Œæ²»ç–—ç ”ç©¶è¿›å±•.

As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances, drugs targeting gastric cancer driver genes have been applied in clinical practice. Among them, trastuzumab, as the first targeted drug for gastric cancer, effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2 (HER2). Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients. Ramucirumab, on the other hand, inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2 (VEGFR2) and has been used as second-line therapy for advanced gastric cancer patients. In addition, bemarituzumab targets overexpressed fibroblast growth factor receptor 2 (FGFR2), while zolbetuximab targets overexpressed claudin 18.2 (CLDN18.2), significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials. This article reviews the roles of tumor driver genes in the progression of gastric cancer, and the treatment strategies for gastric cancer primarily based on targeting HER2, VEGF, FGFR2, CLDN18.2 and MET. This provides a reference for clinical application of targeted therapy for gastric cancer.

Lumbar Spinal Epidural Capillary Hemangioma: A Case Report and Literature Review.

BACKGROUND Capillary hemangiomas are often seen on the skin of young individuals and are rarely found in the spine. These vascular lesions can arise from any spinal compartment, although they are more commonly found in the intradural extramedullary (IDEM) than the epidural location. We present a unique case of a woman with a histologically proven spinal epidural capillary hemangioma (SECH). The imaging and histopathological characteristics, as well as the treatment strategy of this vascular lesion, are highlighted along with a comprehensive review of the literature. CASE REPORT A 38-year-old woman presented with progressively worsening low back pain that radiated to both legs. Neurological examination revealed a weakness of the left leg without sensory loss. Magnetic resonance imaging (MRI) demonstrated an epidural tumor at L1-L2 level, making an obtuse angle with the cerebrospinal fluid (CSF) on sagittal T2-weighted images. The patient underwent a complete tumor resection without complications or recurrence. The histology revealed a capillary hemangioma. CONCLUSIONS SECH is exceedingly rare, with only 22 cases in the reported literature. Females are more commonly affected than males, and the thoracic spine is more commonly involved than the lumbar spine. SECH often mimics other epidural and IDEM lesions, leading to misdiagnosis. MRI is useful to differentiate SECH from lesions in the various spinal compartments; additionally, MRI is essential for preoperative planning and patient surveillance. Preoperative embolization is an option given the high vascularity of SECH. Surgery is the mainstay treatment, with a good prognosis, in most cases without recurrence.

Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches.

Fibrosis is a persistent inflammatory response that causes scarring and tissue sclerosis by stimulating myofibroblasts to create significant quantities of extracellular matrix protein deposits in the tissue. Oxidative stress has also been linked to the development of fibrosis in several studies. The nuclear erythroid 2-related factor 2 (NRF2) transcription factor controls the expression of several detoxification and antioxidant genes. By binding to antioxidant response elements, NRF2 is activated by oxidative or electrophilic stress and promotes its target genes, resulting in a protective effect on cells. NRF2 is essential for cell survival under oxidative stress conditions. This review describes Kelch-like epichlorohydrin-associated protein 1 (KEAP1)/NRF2 signaling mechanisms and presents recent research advances regarding NRF2 and its involvement in primary fibrotic lesions such as pulmonary fibrosis, hepatic fibrosis, myocardial fibrosis, and renal fibrosis. The related antioxidant substances and drugs are described, along with the mechanisms by which KEAP1/NRF2 regulation positively affects the therapeutic response. Finally, the therapeutic prospects and potential value of NRF2 in fibrosis are summarized. Further studies on NRF2 may provide novel therapeutic approaches for fibrosis.