A meta-analysis of the effects of transnasal high-flow oxygen therapy in gastrointestinal endoscopy.

Purpose: This study aimed to systematically evaluate the clinical effects of using transnasal high-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) in patients undergoing gastrointestinal endoscopy. Methods: A comprehensive literature search was conducted from 2004 to April 2024 to collect relevant studies on the application of HFNC in patients undergoing gastrointestinal endoscopy. Multiple Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, and Cochrane Library, were searched systematically for randomized controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. RevMan 5.4 software was utilized for conducting the network meta-analysis. Results: A total of 12 RCTs involving 3,726 patients were included. Meta-analysis results showed that HFNC reduced the incidence of hypoxemia and improved the minimum oxygen saturation (SpO2) compared with COT [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.29-0.53], [mean difference (MD) = 4.07, 95% CI: 3.14-5.01], and the difference was statistically significant. However, the baseline SpO2 levels and incidence of hypercapnia were not statistically significantly different between the HFNC and COT groups [MD = -0.21, 95% CI: -0.49-0.07]; [OR = 1.43, 95% CI: 0.95-2.15]. In terms of procedure time, the difference between HFNC and COT was not statistically significant, and subgroup analyses were performed for the different types of studies, with standard deviation in the gastroscopy group (MD = 0.09, 95% CI: -0.07-0.24) and the endoscopic retrograde cholangiopancreatography group (MD = 0.36, 95% CI: -0.50-1.23). The results demonstrated a significant reduction in the adoption of airway interventions in the HFNC group compared to the COT group (OR = 0.16, 95% CI: 0.05-0.53), with a statistically significant difference; this result was consistent with those of the included studies. Conclusion: The application of HFNC improves the incidence of hypoxemia, enhances oxygenation, and reduces airway interventions during gastrointestinal endoscopy. However, HFNC does not significantly affect baseline SpO2, hypercapnia, or procedure time. The limitations of this study must be acknowledged, and further high-quality studies should be conducted to validate these findings.

Linderae Radix extract attenuates ulcerative colitis by inhibiting the JAK/STAT signaling pathway.

BACKGROUND: Linderae Radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., is a traditional Chinese herbal medicine that has been used for thousands of years for promoting Qi circulation, soothing the liver, and treating diarrhea and dysentery. Previous studies have found that ethanol extract of LR plays an anti-ulcerative colitis (UC) role by regulating Th17/ Treg balance. Water extract is the classic clinical application form of LR, but the effect of water extract of LR (LRWE) on UC and its underlying mechanism is still unclear. PURPOSE: Purpose: UC is a gastrointestinal disease characterized by intestinal inflammation, mucosal injury, and fibrosis, and it is one of the high-risk factors for colon cancer. However, there is still a lack of remedies with satisfactory effects. This study aimed to investigate the efficacy and the potential mechanism of LRWE against UC. METHODS: LRWE samples were prepared using a reflux extraction method. Colitis in mice was induced by administering 2.5 % DSS water solution to evaluate the therapeutic effect of LRWE by assessing disease activity score, colon length, and fecal morphology. H&E staining, TEM, Masson staining, and AB-PAS staining were applied to observe histopathological changes in the colon tissues. Differentially expressed genes in colon tissues were analyzed by transcriptomics. Cell apoptosis was detected by TUNEL staining. The expression of inflammatory factors such as IL-6 and IL-1ß, as well as the expression of p-STAT1, p-JAK2, p-STAT3, Bax, and Bcl-2, were detected by immunofluorescence and immunohistochemistry. The expression of occludin, Bcl-2, Bax, and JAK/STAT signaling pathway-related vital proteins were quantified by Western blot (WB). RESULTS: LRWE alleviated body weight loss, colon shortening, DAI scores, pathological changes, and ultrastructural features of colon tissue in mice with colitis. It also inhibited the increase of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1ß) and increased IL-10 levels. Additionally, it protected the intestinal barrier by upregulating the expression of Occludin and Mucin-2. Mechanistically, LRWE could inhibit the activation of JAK-STAT signaling pathway by reducing the protein expression of p-JAK2, p-STAT3, p-STAT1, Bcl2, and Bax, thus reducing the inflammatory responses and inhibiting cell apoptosis. CONCLUSION: LRWE has a protective effect on DSS-induced UC. This effect is related to the inhibition of the JAK-STAT signaling pathway, the improvement of intestinal inflammation, and the reduction of intestinal epithelial cell apoptosis.

Latent profile analysis and related factors for fear of cancer recurrence among Chinese breast cancer patients in rehabilitation.

PURPOSE: Fear of cancer recurrence (FCR) is a psychological problem often faced by breast cancer patients in the rehabilitation period. The aim of this study was to identify FCR subgroups of Chinese breast cancer patients in rehabilitation and to analysis the factors affecting each subgroup. The effects of the subgroups on quality of life (QoL) were also explored. METHODS: Cross-sectional data were collected from 300 breast cancer patients in a rehabilitation setting. The researchers invited the subjects to complete questionnaires on FCR, fatigue, anxiety depression, perception of illness and QoL. The researchers conducted a latent profile analysis. The factors influencing the subgroups of FCR were identified using ANOVA and multinomial logistic regression analyses. Linear regression analyses were used to explore the effect of subgroups on QoL. RESULTS: There were three subgroups of FCR: profile 1 'Low FCR Group' (42.3%), profile 2 'Moderate FCR Group' (45.6%), and profile 3 'High FCR Group' (12.1%). Cancer stage II was a protective factor for FCR patients (OR = 0.107, P < 0.01) and was more likely to be categorized among the low FCR group. Anxiety depression was a risk factor for FCR patients and was more likely to be categorized in the medium FCR group (OR = 1.764, P < 0.001) and in the high FCR group (OR = 2.911, P < 0.001). In addition, patients subjected to a high perception of illness were more likely to be considered in the medium FCR group (OR = 1.041, P < 0.05), a risk factor affecting patients with FCR. Linear regression analysis showed that subgroups with higher FCR had a stronger negative predictive effect on their QoL (all P < 0.001). CONCLUSIONS: The FCR was identified as three subgroups among breast cancer patients in rehabilitation, which suggests that healthcare professionals should give full consideration to the impact of cancer stage, anxiety and depression, and illness perceptions on the FCR subgroups in order to improve their QoL.

Global incidence trends of early-onset colorectal cancer and related exposures in early-life: an ecological analysis based on the GBD 2019.

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

The impact of electrical stimulation at the back-shu acupoint with an extrinsic diaphragmatic pacing mode on respiratory function and extubation success rate in tracheostomized stroke patients: An observational study.

To observe of the effect of electrical stimulation at the back-shu acupoint with extrinsic diaphragmatic pacing (EDP) mode on respiratory function and extubation success rate in tracheostomized stroke patients. A total of 200 patients who underwent tracheostomy after a stroke from January 2022 to February 2023 were included in this study. They were divided into 2 groups based on whether electroacupuncture was used: the EDP + electroacupuncture group and the EDP group. We assessed the differences in cough reflex scores and clinical lung infection scores between the 2 groups, and measured levels of blood gas analysis indicators, diaphragmatic function, lung function, maximum inspiratory pressure, and maximum expiratory pressure in both groups. The total effective rate in the EDP + electroacupuncture group was 91.00% (91/100), which was higher than the EDP group's 80.00% (80/100) (P < .05). After treatment, both groups showed a decrease in clinical lung infection scores and cough reflex scores compared to before treatment, with the EDP + electroacupuncture group having lower scores than the EDP group (P < .05). After treatment, the pH value, arterial oxygen pressure, and oxygenation index all increased compared to before treatment, with the EDP + electroacupuncture group showing higher values than the EDP group (P < .05). After treatment, both groups showed a decrease in arterial carbon dioxide pressure compared to before treatment, with the EDP + electroacupuncture group having lower PaCO2 levels than the EDP group (P < .05). After treatment, both groups showed an increase in forced vital capacity as a percentage of predicted value (FVC%), diaphragm thickness, diaphragm mobility, maximum inspiratory pressure, maximum expiratory pressure, forced expiratory volume in the first second as a percentage of predicted value (FEV1%), and diaphragm contraction speed compared to before treatment. Additionally, the EDP + electroacupuncture group had higher values in these parameters compared to the EDP group (P < .05). The EDP + electroacupuncture group had a shorter average extubation time and a higher extubation success rate compared to the EDP group (P < .05). The combination of EDP mode and electroacupuncture at the back-shu acupoint appears to be effective in improving lung function and diaphragmatic function in tracheostomized stroke patients. It also leads to a shorter extubation time and higher extubation success rates.

Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Threshold effects between caffeine intake and urine flow rate: a population-based cross-sectional study.

PURPOSE: The potential benefits of caffeine intake are currently receiving much attention and exploration. Urine flow rate (UFR) is an objective index to comprehensively reflect bladder function. The aim of this study was to investigate the association between caffeine intake and UFR using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: 14,142 participants were enrolled in this study. Weighted multivariate adjusted regression models were used to explore the relationship between caffeine intake and UFR. The dose-response relationships were explored using a restricted cubic spline (RCS) and a threshold effect analysis was conducted based on the inflection points identified by the two-segment linear regression model. In addition, subgroup analysis and sensitivity analysis were applied. RESULTS: The findings suggested that the intake of caffeine was correlated with improved UFR [Model 3: 0.091 (0.057, 0.126), P value < 0.001]. In addition, the RCS supported a nonlinear relationship between them. The analysis of threshold effect further revealed a specific level of caffeine intake (34.51 mg/day) that exhibited a significant enhancement in UFR. Finally, through re-analyzing the data set obtained after multiple imputation (MI), we obtained similar results. CONCLUSION: This study found a nonlinear beneficial relationship between caffeine intake and UFR, and revealed the recommended intake of caffeine. The values varied by gender, race, education, and smoking status.

Biocontrol potential of plant growth-promoting rhizobacteria against plant disease and insect pest.

Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are very suitable for application in the cultivation of tea plants (Camellia sinensis) and tobacco, but it is rarely reported so far. In this study, production of a consortium of three strains of PGPR were applied to tobacco and tea plants. The results demonstrated that plants treated with PGPR exhibited enhanced resistance against the bacterial pathogen Pseudomonas syringae (PstDC3000). The significant effect in improving the plant's ability to resist pathogen invasion was verified through measurements of oxygen activity, bacterial colony counts, and expression levels of resistance-related genes (NPR1, PR1, JAZ1, POD etc.). Moreover, the application of PGPR in the tea plantation showed significantly reduced population occurrences of tea green leafhoppers (Empoasca onukii Matsuda), tea thrips (Thysanoptera:Thripidae), Aleurocanthus spiniferus (Quaintanca) and alleviated anthracnose disease in tea seedlings. Therefore, PGPR biofertilizers may serve as a viable biological control method to improve tobacco and tea plant yield and quality. Our findings revealed part of the mechanism by which PGPR helped improve plant biostresses resistance, enabling better application in agricultural production.

Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

A Deep Dynamic Causal Learning Model to Study Changes in Dynamic Effective Connectivity during Brain Development.

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

Coumestrol facilitates apoptosis in colorectal cancer cells by interacting with ZIP8 protein via the ferroptosis pathway.

Objective: So far, there have been no reports of coumestrol inhibiting colorectal cancer (CRC) through the ferroptosis pathway. This study is to investigate the mechanism of the traditional Chinese medicine monomer coumestrol in the treatment of CRC. Methods: Data on CRC transcriptome sequencing was obtained from the GEO database and TCGA database. Bioinformatics analyses were conducted to screen for CRC prognostic-related key genes and their potential binding monomers in traditional Chinese medicine. The inhibitory effect of coumestrol on CRC cell lines (COLO 205 & HCT 116) was determined using the CCK-8 assay, and cell apoptosis was assessed by flow cytometry. The content of ferrous ions was measured using the Ferrous Ion Content Assay Kit. The expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2 before and after small interference RNA (siRNA) was examined through real-time PCR and Western blotting. Results: SLC39A8 was found to be associated with CRC clinical progression staging, and its encoded protein ZIP8 may bind to coumestrol. KEGG enrichment analysis suggested that ZIP8 plays a role in iron transmembrane transport and may affect the expression of ferroptosis pathway-related genes NCOA4, VDAC2, and NOX2. Coumestrol was found to induce apoptosis in CRC cell lines by upregulating the expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2. However, coumestrol was unable to upregulate the expression of ferroptosis pathway-related genes in CRC cell lines after SLC39A8 interference. Conclusion: Coumestrol facilitates apoptosis in CRC cells by interacting with ZIP8 protein via the ferroptosis pathway.

The effectiveness of transnasal high flow nasal cannula in bronchoscopy under sedation: a systematic review and meta-analysis.

Background: The objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy. Methods: A comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria. Results: A total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18-0.41, p < 0.00001; MD = 6.09, 95% CI: 3.73-8.45, p < 0.00001). Furthermore, HFNC showed statistically significant differences when compared to non-invasive ventilation in terms of hypoxemia incidence (RR = 3.52, 95% CI: 1.13-10.97, p = 0.03) and minimum oxygen saturation (MD = -1.97, 95% CI: -2.97--0.98, p < 0.0001). In addition, HFNC resulted in significantly shorter surgical time and higher PaO2 at the end of the procedure compared to conventional oxygen therapy (MD = 1.53, 95% CI: 0.66-2.40, p = 0.0006; MD = 15.52, 95% CI: 10.12-20.92, p < 0.00001). However, there were no statistically significant differences observed in PaCO2, EtCO2, and MAP at the end of the procedure (MD = 1.23, 95% CI: -0.74-3.20, p = 0.22; MD = -0.35, 95% CI: -3.77-3.06, p = 0.84; MD = -0.54, 95% CI: -2.44-1.36, p = 0.58). Conclusion: When HFNC or NIV is utilized during the examination and treatment of bronchoscopy patients, both oxygenation modalities enhance oxygenation function and reduce the incidence of hypoxemia compared to conventional oxygen therapy. HFNC can be regarded as a viable alternative to NIV for specific high-risk patients undergoing bronchoscopy. It decreases the duration of bronchoscopy and improves the PaO2 levels at the end of the procedure, but does not significantly impact the PaCO2, EtCO2, and mean arterial pressure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier 1414374462@qq.com.

Linear-array Endoscopic Ultrasound and Narrow-Banding Imaging Measure the Invasion Depth of Nonpedunculated Rectal Lesions with Comparable Accuracy based on a Randomized Controlled Trial.

BACKGROUND AND AIMS: Linear-array endoscopic ultrasound (EUS) and narrow-banding imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs. METHODS: This study is a single-center, randomized, tandem trial. Eligible patients with NPRLs were randomly assigned to A group (Assessment with EUS followed by NBI) or B group (Assessment with NBI followed by EUS). The invasion depth of each lesion was independently measured by each procedure and categorized as mucosal to slight submucosal (M-SMs, invasion depth <1000 µm) or deep submucosal (SMd, invasion depth ≥1000 µm) invasion, with postoperative pathology as standard measurement. The primary outcome was diagnostic accuracy, and secondary outcomes included sensitivity, specificity, and procedure time. RESULTS: 86 patients with NPRLs were enrolled and 79 patients were finally analyzed, including 39 cases in the A group and 40 cases in the B group. Comparable diagnostic accuracies were observed between EUS and NBI (96.2% vs. 93.7%, P = 0.625). EUS identified lesions with deep submucosal invasion with 81.8% sensitivity, while that of NBI was 63.6% (P = 0.500). The specificity of both EUS and NBI was 98.5%. The procedure time was also similar between EUS and NBI (5.90 ± 3.44 vs. 6.4 ± 3.94 minutes, P = 0.450). Furthermore, the combined use of EUS and NBI did not improve diagnostic accuracy compared to EUS or NBI alone (94.9% vs 96.2% vs 93.7%, P = 0.333). CONCLUSIONS: Linear EUS and NBI measure the invasion depth of NPRLs with comparable accuracy. The combination of the two methods does not improve the diagnostic accuracy. Single NBI should be preferred, considering its simplicity and convenience in clinical practice.

Nrf2 deficiency exacerbated pulmonary pyroptosis in maternal hypoxia-induced intrauterine growth restriction offspring mice.

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5 % O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

SND1 regulates organic anion transporter 2 protein expression and sensitivity of hepatocellular carcinoma cells to 5-fluorouracil.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. Inadequate efficacy of 5-fluorouracil (5-FU) on HCC could be related to low expression of human organic anion transporter 2 (OAT2). However, the knowledge of down-regulation of OAT2 in HCC remains limited. We explored the underlying mechanism focusing on protein expression regulation and attempted to design a strategy to sensitize HCC cells to 5-FU. In this study, we revealed that 1 bp to 300 bp region of OAT2 mRNA 3' untranslated region (UTR) reduced its protein expression and uptake activity in Li-7 and PLC/PRF/5 cells. Mechanistically, it was demonstrated that staphylococcal nuclease and Tudor domain containing 1 (SND1) bound at 1 bp to 300 bp region of OAT2 mRNA 3' UTR, leading to a decrease in OAT2 protein expression. Enrichment analysis results indicated reduction of OAT2 might be mediated by translational inhibition. Furthermore, the knockdown of SND1 up-regulated OAT2 protein expression and uptake activity. Based on it, decreasing SND1 expression enhanced 5-FU-caused G1/S phase arrest in Li-7 and PLC/PRF/5 cells, resulting in suppression of cell proliferation. Besides, the knockdown of SND1 augmented the inhibitory effect of 5-FU on PLC/PRF/5 xenograft tumor growth in vivo by increasing OAT2 protein expression and accumulation of 5-FU in the tumor. Collectively, a combination of inhibition of SND1 with 5-FU might be a potential strategy to sensitize HCC cells to 5-FU from the perspective of restoring OAT2 protein level. Significance Statement We investigated the regulatory mechanism of OAT2 protein expression in HCC cells and designed a strategy to sensitize them to 5-FU (OAT2 substrate) via restoring OAT2 protein level. It found that SND1, an RNA binding protein, regulated OAT2 protein expression by interacting with OAT2 mRNA 3' UTR 1-300bp region. Through decreasing SND1, the anti-tumor effect of 5-FU on HCC was enhanced in vitro and in vivo, indicating that SND1 could be a potential target for sensitizing HCC cells to 5-FU.

Cone-beam CT evaluation of post-extraction alveolar bone changes at the maxillary incisor sites in an East Asian population: A cross-sectional study.

Objective: Understanding the characteristics of alveolar bone resorption in an East Asian population after maxillary incisor extraction and providing a reference for implant treatment plans. Study design: Cone-beam computerized tomography (CBCT) data of 125 East Asian patients with unilateral extraction of maxillary incisors for 3 months were collected. The alveolar bone width and height in the extraction sites were measured and compared with the corresponding contralateral sites. Results: The differences in alveolar bone width between the extraction site and contralateral site were as follows: 4.11 mm, 2.68 mm, and 2.09 mm (3 mm, 5 mm, 7 mm apical from CEJ of the contralateral tooth). Data are expressed as the median. The horizontal resorption ratio of alveolar bone was 49.94 %, 31.5 %, and 24.46 %. The difference in alveolar bone height was 0.78 mm. The vertical resorption ratio was 7.78 %. The resorption did not differ significantly between sexes and was not significantly affected by tooth positions. Conclusions: In the studied East Asian population, significant horizontal and vertical alveolar bone resorption occurs after natural healing of maxillary incisor extraction for 3 months. The closer to the alveolar ridge crest, the more significant the horizontal resorption, resulting in an "inverted triangle" shape residual alveolar bone.

In emergency situations, tracheal intubation replaces fiberoptic bronchoscopy to extract foreign bodies from the airway, a case report.

Introduction: Foreign bodies in the airways can cause significant morbidity and mortality. If emergency personnel are unable to clear an airway obstruction frequently results in cardiac arrest. Patient concerns: A 78-year-old man developed a persistent cough and dyspnoea after consuming alcohol. Fiberoptic bronchoscopy was performed, revealing complete blockage of the main airways on both sides by fish. Diagnosis: Endotracheal foreign body. Interventions: The foreign body was removed with an endotracheal tube under the guidance of a fiberoptic bronchoscope. Outcomes: The airway foreign body had been successfully removed and the man recovered uneventfully. Conclusion: When repeated attempts to extract airway foreign bodies under the guidance of bronchoscopy have failed, endotracheal intubation can be considered as a viable alternative in emergency situations.

CBD2: A functional biomarker database for colorectal cancer.

The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

Impacts of Fuel Stage Ratio on the Morphological and Nanostructural Characteristics of Soot Emissions from a Twin Annular Premixing Swirler Combustor.

Soot particles emitted from aircraft engines constitute a major anthropogenic source of pollution in the vicinity of airports and at cruising altitudes. This emission poses a significant threat to human health and may alter the global climate. Understanding the characteristics of soot particles, particularly those generated from Twin Annular Premixing Swirler (TAPS) combustors, a mainstream combustor in civil aviation engines, is crucial for aviation environmental protection. In this study, a comprehensive characterization of soot particles emitted from TAPS combustors was conducted using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy. The morphology and nanostructure of soot particles were examined across three distinct fuel stage ratios (FSR), at 10%, 15%, and 20%. The SEM analysis of soot particle morphology revealed that coated particles constitute over 90% of the total particle sample, with coating content increasing proportionally to the fuel stage ratio. The results obtained from HRTEM indicated that average primary particle sizes increase with the fuel stage ratio. The results of HRTEM and Raman spectroscopy suggest that the nanostructure of soot particles becomes more ordered and graphitized with an increasing fuel stage ratio, resulting in lower oxidation activity. Specifically, soot fringe length increased with the fuel stage ratio, while soot fringe tortuosity and separation distance decreased. In addition, there is a prevalent occurrence of defects in the graphitic lattice structure of soot particles, suggesting a high degree of elemental carbon disorder.