Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis, prognosis and recurrence risk in patients with cervical epithelioma.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

Increasing DNA damage sensitivity through corylin-mediated inhibition of homologous recombination.

BACKGROUND: DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2CtIP has specific functions in initiating DNA end resection, as well as coordinating cell cycle checkpoints, and it also greatly interacts with the DDR at different levels. RESULTS: In this study, we demonstrated that corylin, a potential sensitizer, causes deficiencies in DNA repair and DNA damage checkpoints in yeast cells. More specifically, corylin increases DNA damage sensitivity through the Sae2-dependent pathway and impairs the activation of Mec1-Ddc2, Rad53-p and γ-H2A. In breast cancer cells, corylin increases apoptosis and reduces proliferation following Dox treatment by inhibiting CtIP. Xenograft assays showed that treatment with corylin combined with Dox significantly reduced tumor growth in vivo. CONCLUSIONS: Our findings herein delineate the mechanisms of action of corylin in regulating DNA repair and indicate that corylin has potential long-term clinical utility as a DDR inhibitor.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

The Effectiveness of 23-valent Pneumococcal Polysaccharide Vaccine on Elderly Colorectal Cancer Long-Term Survivors: A population-based exact-matched cohort study.

Colorectal cancer (CRC) long-term survivor is a rapid enlarging group. However, the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) on this group is unknown. This nationwide population-based study in Taiwan was designed to examine the effect of PPSV23 on incidence rate ratio (IRR) of pneumonia hospitalization, cumulative incidence, and overall survival rate for these long-term CRC survivors. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2000-2017. After individual exact matching to covariates with 1:1 ratio, there were a total of 1,355 vaccinated and 1,355 unvaccinated survivors. After adjusted by multivariate Poisson regression model, vaccinated group had a non-significantly lower pneumonia hospitalization risk than unvaccinated, with an adjusted IRR of 0.879 (p = .391). Besides, vaccinated group had both lower cumulative incidence rate and higher overall survival time than unvaccinated.

Interpretation of course conceptual structure and student self-efficacy: an integrated strategy of knowledge graphs with item response modeling.

BACKGROUND: There is a scarcity of studies that quantitatively assess the difficulty and importance of knowledge points (KPs) depending on students' self-efficacy for learning (SEL). This study aims to validate the practical application of psychological measurement tools in physical therapy education by analyzing student SEL and course conceptual structure. METHODS: From the "Therapeutic Exercise" course curriculum, we extracted 100 KPs and administered a difficulty rating questionnaire to 218 students post-final exam. The pipeline of the non-parametric Item Response Theory (IRT) and parametric IRT modeling was employed to estimate student SEL and describe the hierarchy of KPs in terms of item difficulty. Additionally, Gaussian Graphical Models with Non-Convex Penalties were deployed to create a Knowledge Graph (KG) and identify the main components. A visual analytics approach was then proposed to understand the correlation and difficulty level of KPs. RESULTS: We identified 50 KPs to create the Mokken scale, which exhibited high reliability (Cronbach's alpha = 0.9675) with no gender bias at the overall or at each item level (p > 0.05). The three-parameter logistic model (3PLM) demonstrated good fitness with questionnaire data, whose Root Mean Square Error Approximation was < 0.05. Also, item-model fitness unveiled good fitness, as indicated by each item with non-significant p-values for chi-square tests. The Wright map revealed item difficulty relative to SEL levels. SEL estimated by the 3PLM correlated significantly with the high-ability range of average Grade-Point Average (p < 0.05). The KG backbone structure consisted of 58 KPs, with 29 KPs overlapping with the Mokken scale. Visual analysis of the KG backbone structure revealed that the difficulty level of KPs in the IRT could not replace their position parameters in the KG. CONCLUSION: The IRT and KG methods utilized in this study offer distinct perspectives for visualizing hierarchical relationships and correlations among the KPs. Based on real-world teaching empirical data, this study helps to provide a research foundation for updating course contents and customizing learning objectives. TRIAL REGISTRATION: Not applicable.

Hidden social complexity behind vocal and acoustic communication in non-avian reptiles.

Social interactions are inevitable in the lives of most animals, since most essential behaviours require interaction with conspecifics, such as mating and competing for resources. Non-avian reptiles are typically viewed as solitary animals that predominantly use their vision and olfaction to communicate with conspecifics. Nevertheless, in recent years, evidence is mounting that some reptiles can produce sounds and have the potential for acoustic communication. Reptiles that can produce sound have an additional communicative channel (in addition to visual/olfactory channels), which could suggest they have a higher communicative complexity, the evolution of which is assumed to be driven by the need of social interactions. Thus, acoustic reptiles may provide an opportunity to unveil the true social complexity of reptiles that are usually thought of as solitary. This review aims to reveal the hidden social interactions behind the use of sounds in non-avian reptiles. Our review suggests that the potential of vocal and acoustic communication and the complexity of social interactions may be underestimated in non-avian reptiles, and that acoustic reptiles may provide a great opportunity to uncover the coevolution between sociality and communication in non-avian reptiles. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics'.

Exosomal miRNA Changes Associated with Restoration to Sinus Rhythm in Atrial Fibrillation Patients.

We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

Development and validation of health-oriented personal evaluation for the community-dwelling older person based on the International Classification of Functioning, Disability and Health.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) offers a standardized international terminology to operationalize function management across multiple domains, but the summary score of the ICF qualifier scale provides limited information on the comparison of personal abilities and functioning difficulties. OBJECTIVES: To enhance the interpretative power of the ICF-based Health-oriented Personal Evaluation for the community-dwelling older person (iHOPE-OP) scale through the implementation of the item response theory (IRT) modelling. METHODS: This cross-sectional, multi-centre study administrated 161 ICF categories (58 on body functions, 15 on body structures, 60 on activities or participation and 28 on environmental factors) to evaluate the functional level of 338 older citizens (female = 158, male = 180) residing in community or supportive living facilities. The validation process encompassed assessing the IRT model fitness and evaluating the psychometric properties of the IRT-derived iHOPE-OP scale. RESULTS: The age of participants ranged from 60 to 94.57, with the mean age of 70. The analysis of non-parametric and parametric models revealed that the three-parameter logistic IRT model, with a dichotomous scoring principle, exhibited the best fit. The 53-item iHOPE-OP scale demonstrated high reliability (Cronbach's α = 0.9729, Guttman's lambda-2 = 0.9749, Molenaar-Sijtsma Statistic = 0.9803, latent class reliability coefficient = 0.9882). There was a good validity between person abilities and the Barthel Index (p < .001, r = .83), as well as instrumental activities of daily living (p < .001, r = .84). CONCLUSIONS: IRT methods generate the reliable and valid iHOPE-OP scale with the most discriminable and minimal items to represent the older person's functional performance at a comprehensive level. The use of the Wright map can aid in presby-functioning management by visualizing item difficulties and person abilities. IMPLICATIONS FOR PRACTICE: Considering the intricate and heterogeneous health status of older persons, a single functional assessment tool might not fulfil the need to fully understand the multifaceted health status. For use in conjunction with the IRT and ICF framework, the reliable and valid iHOPE-OP scale was developed and can be applied to capture presby-functioning. The Wright map depicts the distribution of item difficulties and person abilities on the same scale that facilitates person-centred goal setting and tailors intervention.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

Trained quantity discrimination in invasive red-eared slider and a comparison with the native stripe-necked turtle.

Little is known about the behavioral and cognitive traits that best predict invasion success. Evidence is mounting that cognitive performance correlates with survival and fecundity, two pivotal factors for the successful establishment of invasive populations. We assessed the quantity discrimination ability of the globally invasive red-eared slider (Trachemys scripta elegans). We further compared it to that of the native stripe-necked turtle (Mauremys sinensis), which has been previously evaluated for its superior quantity discrimination ability. Specifically, our experimental designs aimed to quantify the learning ability as numerosity pairs increased in difficulty (termed fixed numerosity tests), and the immediate response when turtles were presented with varied challenges concurrently in the same tests (termed mixed numerosity tests). Our findings reaffirm the remarkable ability of freshwater turtles to discern numerical differences as close as 9 vs 10 (ratio = 0.9), which was comparable to the stripe-necked turtle's performance. However, the red-eared slider exhibited a moderate decrease in performance in high ratio tests, indicating a potentially enhanced cognitive capacity to adapt to novel challenges. Our experimental design is repeatable and is adaptable to a range of freshwater turtles. These findings emphasize the potential importance of cognitive research to the underlying mechanisms of successful species invasions.

Association of spironolactone use with risk of urinary tract cancer in the general population: A matched population-based cohort study.

PURPOSE: The correlation between spironolactone usage and cancer risk has sparked interest. The objective of this study is to examine the association between spironolactone use and the incidence of urinary tract cancer in the general population. METHODS: We conducted a matched population-based cohort study. The study population was obtained from the Taiwan National Health Insurance Research Database (TNHIRD) during the period from 2000 to 2016. The multivariate Cox proportional hazard model was performed to examine the impact of spironolactone use on the risk of urinary tract cancer. A total of 8,608 individuals exposed to spironolactone were exact matched by 1:1 ratio with unexposed controls on factors including age, gender, comorbidities, CCI scores and socioeconomic status. The incidences of urinary tract cancer, including prostate, renal and bladder cancer, were estimated in both spironolactone exposed and non-exposed cohorts. RESULTS: After adjusting for confounding variables, the multivariate Cox regression analysis showed no significant association between spironolactone exposure and urinary tract cancer incidence, including bladder (adjusted hazard ratio [aHR] = 1.19, 95% confidence interval [CI] = 0.72-1.96, p = 0.50), renal (aHR = 1.75, 95% CI = 0.99-3.07, p = 0.053), and prostate cancer (aHR = 0.67, 95% CI = 0.43-1.04, p = 0.07). When the population was stratified into low (cumulative dose < = 29,300 mg) and high (cumulative dose >29,300 mg) dose of spironolactone, only high dose of spironolactone use was significantly associated with a reduced risk of prostate cancer (aHR = 0.45, 95% CI = 0.23-0.89, p = 0.02), while being associated with an elevated risk of renal cancer (aHR = 2.09, 95% CI = 1.07-4.08, p = 0.03). However, no clear cumulative dose-response relationship was observed in theses associations. CONCLUSIONS: High cumulative dose of spironolactone may be potentially associated with a decreased incidence of prostate cancer and an increased incidence of renal cancer, while no significant association was observed with bladder cancer incidence. However, given the lack of support from the dose-response pattern, the available evidence is inconclusive to establish a definitive association between spironolactone use and urinary tract cancer.

RIPK1 inhibitor ameliorates pulmonary injury by modulating the function of neutrophils and vascular endothelial cells.

Acute lung injury (ALI) is an acute and progressive hypoxic respiratory failure that could progress to acute respiratory distress syndrome (ARDS) with a high mortality rate, thus immediate medical attention and supportive care are necessary. The pathophysiology of ALI is characterized by the disruption of the alveolar-capillary barrier and activation of neutrophils, leading to lung tissue damage. The receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising target for the treatment of multiple inflammatory diseases, but the role of RIPK1 in the ALI remains poorly understood. In this study, we aimed to figure out the pathological role of RIPK1 in ALI, especially in the pulmonary immune microenvironment involving neutrophils and endothelial cells. In vivo experiments showed that RIPK1 inhibitor protected against lipopolysaccharide (LPS)-induced lung injury in mouse models, with reduced neutrophils and monocytes infiltration in the lungs. Further studies demonstrated that, besides the inhibitory action on necroptosis, RIPK1 inhibitor directly suppressed reactive oxygen species (ROS) generation and inflammatory cytokines secretion from neutrophils. Furthermore, RIPK1 inhibition maintains the barrier function in TNF-α-primed vascular endothelial cells and prevents their activation induced by the supernatant from LPS-stimulated neutrophils. Mechanistically, the aforementioned effects of RIPK1 inhibitor are associated with the NF-κB signaling pathway, which is partially independent of necroptosis inhibition. These results provide new evidence that RIPK1 inhibitor directly regulates the function of neutrophils and endothelial cells, as well as interferes with the interactions between these two cell types, therefore contributing to a better understanding of RIPK1 in ALI and providing a potential avenue for future therapeutic interventions.

Naringin activates semaphorin 3A to ameliorate TGF-ß-induced endothelial-to-mesenchymal transition related to atrial fibrillation.

The loss of semaphorin 3A (Sema3A), which is related to endothelial-to-mesenchymal transition (EndMT) in atrial fibrosis, is implicated in the pathogenesis of atrial fibrillation (AF). To explore the mechanisms by which EndMT affects atrial fibrosis and assess the potential of a Sema3A activator (naringin) to prevent atrial fibrosis by targeting transforming growth factor-beta (TGF-ß)-induced EndMT, we used human atria, isolated human atrial endocardial endothelial cells (AEECs), and used transgenic mice expressing TGF-ß specifically in cardiac tissues (TGF-ß transgenic mice). We evaluated an EndMT marker (Twist), a proliferation marker (proliferating cell nuclear antigen; PCNA), and an endothelial cell (EC) marker (CD31) through triple immunohistochemistry and confirmed that both EndMT and EC proliferation contribute to atrial endocardial fibrosis during AF in TGF-ß transgenic mice and AF patient tissue sections. Additionally, we investigated the impact of naringin on EndMT and EC proliferation in AEECs and atrial fibroblasts. Naringin exhibited an antiproliferative effect, to which AEECs were more responsive. Subsequently, we downregulated Sema3A in AEECs using small interfering RNA to clarify a correlation between the reduction in Sema3A and the elevation of EndMT markers. Naringin treatment induced the expression of Sema3A and a concurrent decrease in EndMT markers. Furthermore, naringin administration ameliorated AF and endocardial fibrosis in TGF-ß transgenic mice by stimulating Sema3A expression, inhibiting EndMT markers, reducing atrial fibrosis, and lowering AF vulnerability. This suggests therapeutic potential for naringin in AF treatment.

Helicobacter pylori eradication with high-dose proton pump inhibitor-amoxicillin dual therapy: A systematic review and meta-analysis.

BACKGROUND: Resistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent. AIMS: This study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study. METHODS: Several open public databases, including Cochrane, EMBASE, PubMed, and MEDLINE, were searched. The results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapies were analysed. Notably, 14 out of the 16 included studies were conducted in Asian regions. RESULTS: The eradication rate of HDDT was lower but not significantly different from those of control therapies (odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.67-1.26) in the intent-to-treat (ITT) analysis. A similar trend was observed in the per-protocol (PP) analysis (OR = 0.88, 95% CI = 0.47-1.63). Notably, the adverse effect risk in HDDT was significantly lower than in other therapies (I2 = 67.75%, OR = 0.42, 95% CI = 0.33-0.54, P = 0.00004). When the eradication rate of the control group was lower than 81%, HDDT was significantly better than control therapies (OR = 2.44, 95% CI = 1.23-4.84). CONCLUSION: HDDT used four times a day for 14 days showed better efficacy and safety than the guideline treatments for H. pylori infection in areas with high antimicrobial resistance.

Intersubject representational similarity analysis uncovers the impact of state anxiety on brain activation patterns in the human extrastriate cortex.

The current study used functional magnetic resonance imaging (fMRI) and showed that state anxiety modulated extrastriate cortex activity in response to emotionally-charged visual images. State anxiety and neuroimaging data from 53 individuals were subjected to an intersubject representational similarity analysis (ISRSA), wherein the geometries between neural and behavioral data were compared. This analysis identified the extrastriate cortex (fusiform gyrus and area MT) to be the sole regions whose activity patterns covaried with state anxiety. Importantly, we show that this brain-behavior association is revealed when treating state anxiety data as a multidimensional response pattern, rather than a single composite score. This suggests that ISRSA using multivariate distances may be more sensitive in identifying the shared geometries between self-report questionnaires and brain imaging data. Overall, our findings demonstrate that a transient state of anxiety may influence how visual information - especially those relevant to the valence dimension - is processed in the extrastriate cortex.