Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

OBJECTIVES: To study the clinical effect of the L-shape technique combined with concentrated growth factor on the horizontal bone defects of maxillary anterior teeth. METHODS: Twenty-five implants from 25 patients who underwent single maxillary anterior tooth implantation with simultaneous bone grafting were selected as the study subjects. Based on the bone grafting techniques, the patients were divided into a test group (L-shaped technique with guided bone regeneration combined with concentrated growth factor, 11 cases) and a control group (traditional guided bone regeneration combined with concentrated growth factor, 14 cases). The early discomfort and wound healing conditions in the two groups at two weeks after surgery were compared. The horizontal bone thickness, vertical bone thickness, and grayscale values in the augmentation area were measured immediately postsurgery and six months after surgery. Implant stability, hard tissue resorption within six months, and grayscale values were compared between the two groups. RESULTS: Differences in early discomfort, wound healing, implant stability, and grayscale values between the two groups were not statistically significant (P>0.05). Vertical bone thickness in the test group was significantly better than that in the control group at six months after surgery (P<0.05). The variation in horizontal bone thickness in the test group was significantly higher than that in the control group (P<0.05). CONCLUSIONS The application of the L-shape technique with concentrated growth factor for horizontal bone defects in the anterior maxillary area yielded satisfactory short-term results in terms of bone augmentation, early discomfort, wound healing, and implant stability at six months after surgery.
Humans ; Maxilla/diagnostic imaging* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Wound Healing ; Bone Transplantation/methods* ; Dental Implantation, Endosseous/methods* ; Bone Regeneration ; Male ; Female ; Adult ; Dental Implants, Single-Tooth ; Middle Aged

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

BACKGROUND:Indolepropionic acid has been shown to reduce diabetes-induced central nervous system inflammation.However,there is a lack of research on whether to inhibit microglia M1 polarization for the treatment of spinal cord injury. OBJECTIVE:To investigate the mechanism of indolepropionic acid inhibition of microglial cell M1 polarization for the treatment of spinal cord injury through cell and animal experiments. METHODS:(1)In vitro experiments:BV2 cell viability was assessed using the CCK-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,BV2 cells were categorized into control group,administration group(50 μmol/L indolepropionic acid),lipopolysaccharide group(100 ng/mL lipopolysaccharide),and treatment group(100 ng/mL lipopolysaccharide + 50 μmol/L indolepropionic acid).Nitric oxide content was quantified using the Griess method.Real-time quantitative PCR and western blot assay were employed to measure mRNA and protein levels of pro-inflammatory factors.Cell immunofluorescence staining was conducted to assess inducible nitric oxide synthase expression.The Seahorse assay was employed to assess glycolytic stress levels in BV2 cells.(2)In vivo experiments:30 SD rats were randomly divided into three groups:sham surgery group,spinal cord injury group,and indolepropionic acid group.Motor function recovery in rats after spinal cord injury was assessed using BBB scoring and the inclined plane test.Immunofluorescence staining of spinal cord tissue was conducted to evaluate the expression of inducible nitric oxide synthase in microglial cells.ELISA was employed to measure protein expression levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in spinal cord tissue. RESULTS AND CONCLUSION:(1)In vitro experiments:Indolepropionic acid exhibited significant suppression of BV2 cell viability when its concentration exceeded 50 μmol/L.Indolepropionic acid achieved this by inhibiting the activation of the nuclear factor κB signaling pathway,thereby suppressing the mRNA and protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α),as well as the M1 polarization marker,inducible nitric oxide synthase,in BV2 cells.Additionally,indolepropionic acid notably reduced the glycolytic level in BV2 cells induced by lipopolysaccharides.(2)In vivo experiments:Following indolepropionic acid intervention in spinal cord injury rats,there was a noticeable increase in BBB scores and the inclined plane test angle.There was also a significant decrease in the number of M1-polarized microglial cells in spinal cord tissue,accompanied by a marked reduction in the protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α).(3)These results conclude that indolepropionic acid promotes functional recovery after spinal cord injury by improving the inflammatory microenvironment through inhibition of microglia M1 polarization.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

ObjectiveTo investigate the structural and functional characteristics of gut microbiota in common traditional Chinese medicine （TCM） syndromes of irritable bowel syndrome with diarrhea （IBS-D）. MethodsIBS-D patients who visited the Hospital of Chengdu University of Traditional Chinese Medicine， and healthy participants from the Physical Examination Centre of the same hospital were recruited from 1st January 2020 to 31st March 2021.The IBS-D patients were classified into syndrome of liver constraint and spleen deficiency， and syndrome of spleen deficiency and dampness exuberance； together with the recruited healthy participants， there were liver-constraint group， dampness-exuberance group， and healthy group. General information， including age， gender and body mass index （BMI）， were collected， and Irritable Bowel Syndrome Symptom Severity Scale （IBS-SSS） as well as Irritable Bowel Syndrome Quality of Life Scale （IBS-QOL） scores were additionally collected from IBS-D patients. Fresh fecal samples were also collected and tested by macro-genome sequencing technology for abundance statistical display， PCoA， Anosim， LEfSe bioinformatic analysis of the annotated gut microbiota structure and function. ResultsThere was no statistically significant difference in the general information of the participants in the three groups （P＞0.05）； the difference in the IBS-SSS and IBS-QOL scores between liver-constraint group and dampness-exuberance group were not statistically significant （P＞0.05）. The study included 28 cases each in liver-constraint group， dampness-exuberance group， and healthy group. The number of specific genes to patients in liver-constraint group was 269 135， with 216 156 in dampness-exuberance group and 249 759 in healthy group， accounting of total 1 784 036 in the three groups. There were differences in the relative abundance distribution of the top ten species of gut microbiota among the three groups， with smaller differences at the phylum， class and order levels， and larger differences at the family， genus and species levels. There were differences in the relative abundance of structure and function of the gut microbiota among the three groups. Species PCoA and Anosim analyses at the species level showed significant differences in the composition of the microbiota among the three groups. Further LEfSe analyses showed that patients in liver-constraint group were screened for 14 dominant strains， of which Clostridium sp. CAG 217， Lachnospira pectinoschiza， Anaerotruncus sp. CAG 528， Paeniclostridium sordellii， Eubecterium sp. CAG 76， Bacillus cereus were affected to a greater extent in abundance differences； dampness-exuberance group screened 24 species of dominant bacteria， of which Roseburia inulinivorans， Eubacterium sp. CAG 251， Roseburia hominis， Unclassified Eubacterium rectale， Roseburia intestinalis， and Megamonas funiformis were affected to a greater extent in abundance differences； no dominant functional genes were screened for patients in liver-constraint group， and dampness-exuberance group was screened for flagellum assembly （ko02040）， porphyrin metabolism （ ko00860）， salmonella infection （ko05132）， and benzoic acid degradation （ko00362）. The differentially dominant functional genes in liver-constraint group and dampness-exuberance group may mainly focus on metabolism （including biodegradation and metabolism of exogenous substances， energy metabolism， lipid metabolism， etc.）. ConclusionIBS-D with syndrome of liver constraint and spleen deficiency is characterized by the enrichment of 14 gut microbiota， such as Clostridium sp. CAG 217， while IBS-D with syndrome of spleen deficiency and dampness exuberance is characterized by the enrichment of 24 gut microbiota， such as Roseburia inulinivorans， and 4 functional enrichments， such as flagellum assembly. Clostridium sp. CAG 217 and Roseburia inulinivorans are expected to be biomarkers for IBS-D patients in the two syndromes， respectively.

Objective:To investigate the effect of mobile phone dependence on suppression control under the conditions of emotional loss and cognitive loss in college students.Methods:A total of 553 college students were recruited,and 108 in the mobile phone dependence group and 194 in the non-dependent group were screened with the Mobile Phone Addiction Tendency Scale(MPATS).Ninety-nine of them were selected to participate in experi-ment 1,and the effect of emotional loss on the inhibitory control,and 101 students were selected to participate in ex-periment 2 to investigate the effect of cognitive loss on the inhibitory control.The GO/NOGO paradigm was used to compare the correct rate and response of different mobile phones dependent on college students under different emo-tional and cognitive depletion conditions.Results:In experiment 1,the main effect of emotional loss was statistically significant[F(1,55)=6.16,178.91;Ps＜0.05],the inhibition control accuracy rates were lower and reaction tim-es were shorter in the high emotional loss group than in the low emotional loss group.In experiment 2,the main effect of the group was statistically significant[F(1,57)=17.90,19.06;Ps＜0.001],the accuracy rates of inhibi-tion control were lower and the inhibition control reaction times were longer in the mobile phone-dependent group than in the non-dependent group.The interaction between groups and cognitive loss types was statistically significant[F(1,57)=7.95,P＜0.01],and the inhibition control accuracy rates of the mobile phone-dependent group were lower under high cognitive loss.Conclusion:Emotional loss and cognitive loss could reduce the inhibition and con-trol ability of individuals,and the mobile phone dependence group is more likely to be affected in the case of cogni-tive loss.