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23 result(s) for "Guo, Meixuan"
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Mechanistic insights into Jianpi Qinghua Sanyu Yin treatment of raised erosive gastritis: ceRNA-mediated PI3K/AKT signaling pathways
Raised erosive gastritis (REG) is a chronic gastritis with a high risk of malignant transformation. Current treatments often result in high recurrence rates and complications. Jianpi Qinghua Sanyu Yin (JPQHSYY), a traditional Chinese medicine, shows promise in treating REG. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the potential mechanism of JPQHSYY's therapeutic effects on REG. RNA-seq was employed to systematically analyze mRNA, lncRNA, and miRNA profiles in gastric mucosal tissues from REG patients before and after JPQHSYY treatment. The pivotal lncRNA-miRNA and miRNA-mRNA networks were predicted from sequencing data and bioinformatic analysis, and the results were exported using Cytoscape software. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional exploration. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate RNA-seq analysis results. CCK8, cell cycle, apoptosis and western blot were performed to detect the effects of miR-122-5p in GES-1 cells . RNA-seq analysis revealed 576 differentially expressed lncRNAs (269 upregulated, 307 downregulated), 33 differentially expressed miRNAs (13 upregulated, 20 downregulated), and 1717 differentially expressed mRNAs (777 upregulated, 940 downregulated) in JPQHSYY-treated REG patients. GO and KEGG analyses highlighted key pathways, including the PI3K/AKT signaling pathway, involved in cell cycle and apoptosis regulation. The ceRNA network analysis suggested that JPQHSYY impacts the miRNA-lncRNA interactions. Validation experiments confirmed that JPQHSYY inhibits the PI3K/AKT pathway, reducing cell viability, colony formation, and promoting apoptosis in miR-122-5p transfected GES-1 cells. The therapeutic efficacy of JPQHSYY in treating REG might be mediated by the ceRNA-driven PI3K/AKT pathway signaling pathways, which is implicated in the proliferation of gastric mucosal epithelial cells. Furthermore, the investigation of miRNA-lncRNA networks could reveal more information on potential new mechanisms and targets for JPQHSYY in the management of REG.
Clara cell 16 KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition
Background House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16. Methods Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5 μg/g or 10 μg/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus. Results CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis. Conclusions Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.
Comparison of the measurement properties of the EQ-5D-5L and SF-6Dv2 among overweight and obesity populations in China
Objective To evaluate and compare the measurement properties of the EQ-5D-5L and SF-6Dv2 among Chinese overweight and obesity populations. Methods A representative sample of Chinese overweight and obesity populations was recruited stratified by age, gender, body mass index (BMI), and area of residence. Social-demographic characteristics and self-reported EQ-5D-5L and SF-6Dv2 responses were collected through the online survey. The agreement was assessed using intraclass correlation coefficients (ICC). Convergent validity and known-group validity were examined using Spearman’s rank correlation and effect sizes, respectively. The test-retest reliability was assessed using among a subgroup of the total sample. Sensitivity was compared using relative efficiency and receiver operating characteristic. Results A total of 1000 respondents (52.0% male, mean age 51.7 years, 67.7% overweight, 32.3% obesity) were included in this study. A higher ceiling effect was observed in EQ-5D-5L than in SF-6Dv2 (30.6% vs. 2.1%). The mean (SD) utility was 0.851 (0.195) for EQ-5D-5L and 0.734 (0.164) for SF-6Dv2, with the ICC of the total sample was 0.639 (p < 0.001). The Spearman’s rank correlation (range: 0.186–0.739) indicated an acceptable convergent validity between the dimensions of EQ-5D-5L and SF-6Dv2. The EQ-5D-5L showed basically equivalent discriminative capacities with the SF-6Dv2 (ES: 0.517–1.885 vs. 0.383–2.329). The ICC between the two tests were 0.939 for EQ-5D-5L and 0.972 for SF-6Dv2 among the subgroup (N = 150). The SF-6Dv2 had 3.7–170.1% higher efficiency than the EQ-5D-5L at detecting differences in self-reported health status, while the EQ-5D-5L was found to be 16.4% more efficient at distinguishing between respondents with diabetes and non-diabetes. Conclusions Both the EQ-5D-5L and SF-6Dv2 showed comparable reliability, validity, and sensitivity when used in Chinese overweight and obesity populations. The two measures may not be interchangeable given the systematic difference in utility values between the EQ-5D-5L and SF-6Dv2. More research is needed to compare the responsiveness.
Effectiveness of acceptance and commitment therapy for mental illness in cancer patients: A systematic review and meta‐analysis of randomised controlled trials
Background Disease awareness is an important aspect of psychological adjustment in cancer patients; however, there is limited evidence that acceptance and commitment therapy (ACT) is recommended for the treatment of mental illness in cancer patients. Purpose To assess the effectiveness of ACT for cancer patients with mental illness. Methods Ten databases were searched for publications up to July 25, 2020, using combinations of search terms related to mental health, cancer, and randomised controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the quality of the study. Results Seventeen RCTs (877 cancer patients) were mainly of low quality, compared with control group, ACT was associated with improved outcomes after treatment completion and at 1‐3 months and at 3‐6 months of follow‐up for depression (Standardised mean difference [SMD] = −0.93, 95% CI, −1.36 to −0.51, P < .001), anxiety (SMD = −1.22, 95% CI, −2.16 to −0.29, P = .01), quality of life (SMD = 0.85, 95% CI, 0.17 to 1.11, P = .01), psychological distress (SMD = −0.80, 95% CI, −1.24 to 0.35, P < .001), and stress (SMD = −0.54, 95% CI, −1.02 to −0.07, P = .03). After 6 months of follow‐up, depression, anxiety, quality of life, and stress were still significant. ACT was associated with psychological flexibility and was not associated with a reduction in fear at treatment completion. However, psychological flexibility (1‐3 months) decreased and fear (1‐6 months) decreased, and the longer‐term effect was still significant. Conclusion ACT can be an important component of future cancer care, as it may alleviate depression, anxiety, stress, and fear, and improve quality of life. However, further research is required to determine long‐term treatment effects. High‐quality RCTs are needed to more reliably estimate treatment effects.
The methodological quality of robotic surgical meta-analyses needed to be improved: a cross-sectional study
The aims of the article were to assess the methodological quality of robotic surgical meta-analyses (MAs) using A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) and to explore the factors of methodological quality. Robotic surgical MAs published between 2015 and 2018 were identified through a systematical search in PubMed, EMBASE, Cochrane library, and Web of Science databases. The methodological quality of eligible MAs was evaluated by AMSTAR-2. Data extraction and the methodological quality of MAs assessment were double checked by four trained reviewers. The intraclass correlation coefficient (ICC) was used to assess the consistency of quantitative measurements, and the ICC for overall score and score of critical domains were 0.952 and 0.912, respectively. Multivariate regression analysis was used to identify potential factors affecting methodological quality. A total of 123 MAs focused on 18 surgical locations were included. The findings showed that, regarding quality, only two (1.6%) of 123 MAs were high, two (1.6%) were moderate, two (1.6%) were low, and the remainder 117 (95.1%) were critical low. Multiple linear regression analysis revealed that publishing year and journal rank independently associated with methodological quality of MAs; origin region (P > 0.05), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P = 0.421), randomized controlled trial enrollment (P = 0.304), and funding support (P = 0.958) did not influence the quality of the MAs. Registration (item 2) and funding reported for individual studies (item 10) showed the poorest adherence in the MAs. Our study showed that the previously published robotic surgical MAs lack good scientific quality, especially in those published in Q2- to Q4-rated journals. Potential solutions to improve the quality of future robotic surgical MAs include preregistration and funding reported for individual studies.
Implementing liquid biopsy NGS in stage III/IV NSCLC: clinical utility assessment from a real-world Chinese cohort
Background Cell-free circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) has demonstrated the potential to guide the personalized treatment of non-small cell lung cancer (NSCLC). Furthermore, clinical treatment-response data guided by ctDNA remain scarce. This study systematically evaluates an NGS platform’s detection accuracy and clinical utility in a large Chinese NSCLC cohort, establishing therapeutic-response evidence. Methods We first established the cutoff and quality control parameters for the NGS test using clinical plasma samples from NSCLC patients, with ddPCR serving as the reference standard. The performance of the assay was then robustly validated in an independent cohort of 522 samples. Finally, we analyzed the driver and resistance mutations for their distribution, concordance with tissue samples, and therapeutic relevance. Results Through analysis of plasma samples using ROC and downsample methods, we established a 0.2% detection threshold and identified > 1400x mean effective depth as the critical QC metric; under these parameters, ddPCR validation of 17 specific sites in the 522-sample cohort demonstrated > 80% positive percentage agreement (PPA) and > 95% negative percentage agreement (NPA), confirming strong NGS-ddPCR concordance. The 21-gene panel detected mutations in 73.75% of patients, with 45.59% harboring NCCN-recommended targetable mutations. In the tissue-plasma concordance analysis, stage-specific performance was observed: Stage III showed 28.57% PPA (2/7) versus 99.20% NPA (124/125), while Stage IV demonstrated 99.20% PPA (124/125) and 99.46% NPA (183/184). Clinically relevant plasma-specific mutations were identified throughout, and pooled data demonstrated equivalent targeted therapy response rates between this ctDNA-based NGS and National Medical Products Administration (NMPA)-approved tissue-based assays. Conclusions This study highlights the feasibility of ctDNA-based NGS in clinical practice, offering valuable and clinically relevant mutational genomic profiling for stage III/IV NSCLC in Chinese patients. Trial registration This study is registered with Chinese Clinical Trial Registry, ChiCTR2000041034, on December 16, 2020.
More than appearance: the uncanny valley effect changes with a robot’s mental capacity
Robots are being used to socially interact with humans. To enhance the quality of human-robot interaction, engineers aim to build robots with both a humanlike appearance and high mental capacity, but there is a lack of empirical evidence regarding how these two characteristics jointly affect people’s emotional response to robots. The current two experiments (each N  = 80) presented robots with either a mechanical or humanlike appearance, with mental capacities operationalized as low or high, and with either self-oriented mentalization to mainly concentrate on the robot itself or other-oriented mentalization to read others’ minds. It was found that when the robots had a humanlike appearance, they were more dislikeable than when they had a mechanical appearance, replicating the uncanny valley effect for appearance. Importantly, given a humanlike appearance, robots with high mental ability elicited stronger dislike than those with low mental ability, showing an uncanny valley effect for mind, but this difference was absent for robots with a mechanical appearance. In addition, this effect was limited to robots with self-oriented mentalization ability and did not extend to robots with other-oriented mentalization ability. Hence, the exterior appearance and interior mental capacity of robots interact to influence people’s emotional reaction to them, and the uncanny valley as it pertains to the mind depends on the robot’s appearance in addition to its mental ability. This implies that social robots with humanlike appearances should be designed with obvious other-directed social abilities to make them more likeable.
Optic nerve-mediated modulation of temporally interfering electric fields for potential targeted retinal disease therapy: a computational modeling study
Traditional extraocular electrical stimulation typically produces diffuse electric fields across the retina, limiting the precision of targeted therapy. Temporally interfering (TI) electrical stimulation, an emerging approach, can generate convergent electric fields, providing advantages for targeted treatment of various eye conditions.IntroductionTraditional extraocular electrical stimulation typically produces diffuse electric fields across the retina, limiting the precision of targeted therapy. Temporally interfering (TI) electrical stimulation, an emerging approach, can generate convergent electric fields, providing advantages for targeted treatment of various eye conditions.Understanding how detailed structures of the retina, especially the optic nerve, affects electric fields can enhance the application of TI approach in retinal neurodegenerative and vascular diseases, an essential aspect that has been frequently neglected in previous researches.ObjectiveUnderstanding how detailed structures of the retina, especially the optic nerve, affects electric fields can enhance the application of TI approach in retinal neurodegenerative and vascular diseases, an essential aspect that has been frequently neglected in previous researches.We developed an anatomically accurate multi-layer human eye model, incorporating the optic nerve segment and setting it apart from current research endeavors. Based on this model, we conducted in silico investigations to predict the influence of the optic nerve on spatial characteristics of the temporally interfering electric field (TIEF) generated by diverse electrode configurations.MethodsWe developed an anatomically accurate multi-layer human eye model, incorporating the optic nerve segment and setting it apart from current research endeavors. Based on this model, we conducted in silico investigations to predict the influence of the optic nerve on spatial characteristics of the temporally interfering electric field (TIEF) generated by diverse electrode configurations.Optic nerve directly influenced spatial distributions and modulation rules of TIEFs. It caused convergent areas to shift nasally or temporally in relation to return electrode positions, and further increased the axial anisotropy within the convergent TIEF. Furthermore, alterations in electrode positions and adjustments to current ratios among channels induced diverse spatial patterns of TIEFs within the macular region, the area surrounding the optic nerve, as well as peripheral retina.ResultsOptic nerve directly influenced spatial distributions and modulation rules of TIEFs. It caused convergent areas to shift nasally or temporally in relation to return electrode positions, and further increased the axial anisotropy within the convergent TIEF. Furthermore, alterations in electrode positions and adjustments to current ratios among channels induced diverse spatial patterns of TIEFs within the macular region, the area surrounding the optic nerve, as well as peripheral retina.Our findings suggested that presence of the optic nerve necessitated the utilization of different modulating paradigms when employing TI strategy for targeted treatment of various retinal lesions. And also provided theoretical references for developing a novel retinal electrical stimulation therapeutic device based on TI technology.ConclusionOur findings suggested that presence of the optic nerve necessitated the utilization of different modulating paradigms when employing TI strategy for targeted treatment of various retinal lesions. And also provided theoretical references for developing a novel retinal electrical stimulation therapeutic device based on TI technology.
The upregulation of peripheral CD3-CD56+CD16+ natural killer cells correlates with Th1/Th2 imbalance in asthma patients during acute upper respiratory viral infections
Purpose The aim of this study is to clarify the changes of peripheral CD3 − CD56 + CD16 + NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs). Methods Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3 − CD56 + CD16 + NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay. Results The asthmatics had lower levels of peripheral CD3 − CD56 + CD16 + NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3 − CD56 + CD16 + NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3 − CD56 + CD16 + NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections. Conclusions Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3 − CD56 + CD16 + NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.
The Metabolism of Salidroside to Its Aglycone p-Tyrosol in Rats following the Administration of Salidroside
Salidroside is one of the major phenolic glycosides in Rhodiola, which has been reported to possess various biological activities. In the present study the in vivo deglycosylation metabolism of salidroside was investigated and its aglycone p-tyrosol but not the original salidroside was identified as the main form in rat tissues following the administration of salidroside. After the i.v. administration of salidroside at a dose of 50 mg/kg in rats, salidroside was quantified only in the liver, kidney and heart tissues. The highest level of p-tyrosol was detected in the heart, followed by the spleen, kidney, liver and lungs, in order. Salidroside was detected only in the liver, in contrast, p-tyrosol was detectable in most tissues except the brain, and the kidney tissues contained a significant amount of p-tyrosol compared to the other tissues after the i.g. administration of 100 mg/kg salidroside. The excretion behaviour revealed that the administrated salidroside mainly eliminated in the form of salidroside but not its aglycone metabolite p-tyrosol through urine. After i.v. and i.g. administration in rats, 64.00% and 23.80% of the total dose was excreted through urine in the form of salidroside, respectively. In addition, 0.19% and 2.25% of the dose was excreted in the form of p-tyrosol through urine after i.v. and i.g. administration, respectively. The faecal salidroside and p-tyrosol concentrations were 0.3% and 1.48% of the total dose after i.v. administration, respectively. After the i.g. administration of salidroside, trace salidroside and p-tyrosol were quantified in faeces within 72 h. In addition, the biliary excretion levels of salidroside after i.v. and i.g. administration were 2.86% and 0.02% of the dose, respectively. The obtained results show that salidroside was extensively metabolised to its aglycone p-tyrosol and distributed to various organs and the original salidroside was cleared rapidly through urine following the administration of salidroside.