Medicine Database Research Articles

Silibinin, a PLC-β3 inhibitor, inhibits mast cell activation and alleviates OVA-induced asthma.

The immunoglobulin E (IgE) receptor FcεRI (Fc epsilon RI) plays a crucial role in allergic reactions. Recent studies have indicated that the interaction between FcεRIβ and the downstream protein phospholipase C beta 3 (PLCβ3) leads to the production of inflammatory cytokines. The aim of this study was to develop small molecules that inhibit the protein-protein interactions between FcεRIβ and PLCβ3 to treat allergic inflammation. Additionally, PLCβ3 has emerged as a potential target protein for treating allergic inflammation. In this study, we employed a virtual screening technique to search the Taiwan Traditional Chinese Medicine Database, followed by a second screening using absorption, distribution, metabolism, excretion, and toxicity (ADMET). Among the compounds screened, silibinin exhibited the best performance, forming strong hydrogen bond interactions with residues of PLCβ3, with a binding free energy of -119.277 kcal/mol. Therefore, silibinin effectively blocked the interaction between FcεRIβ and PLCβ3. Silibinin reduced the production of allergic inflammatory cytokines, including cytokine-induced neutrophil chemoattractant 2a (CINC-2a), interleukin-2 (IL-2), cytokine-induced neutrophil chemoattractant 1 (CINC-1), interleukin 1α (IL-1α), macrophage inflammatory protein 3 alpha (MIP3α), interferon γ (IFN-γ), activin A, granulocyte macrophage colony stimulating factor (GM-CSF), intercellular adhesion molecule-1 (ICAM-1), interleukin 4 (IL-4), interleukin 13 (IL-13), Fas ligand (FasL) and tumor necrosis factor alpha (TNF-α), without inducing cytotoxicity. Furthermore, in studies of IgE-mediated allergic responses, silibinin also decreased the expression of surface IgE receptors (FcεRIs). Moreover, silibinin effectively alleviated allergen-induced asthma responses and reduced the infiltration of inflammatory immune cells into the lungs of an OVA-induced allergic airway inflammation mouse model. Taken together, these results demonstrate the potential antiallergic mechanism of silibinin both in vitro and in vivo, making it a promising candidate for the development of asthma therapeutics.

Mechanistic insights into pachymic acid’s action on triple-negative breast Cancer through TOP2A targeting

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation. We acquired Microarray data of TNBC from the Gene Expression Omnibus (GEO). The related targets of PA were predicted and screened using the following 6 databases: Swiss Target Prediction, HERB (Herbal Medicine Database), ETCM (Encyclopedia of Traditional Chinese Medicine), BATMAN (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine), HIT (Herb Ingredients’ Targets Database), and PharmMapper. The STRING interaction network analysis tool was used to create Protein-Protein Interaction (PPI) networks. Enrichment analysis included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We conducted a pan-cancer analysis, tumor immune microenvironment analysis, and molecular docking. We performed cell experimental, included cytotoxicity assay, apoptosis analysis, proliferation assay, and migration and invasion assays. PA has potential for treating TNBC with the target of TOP2A, and platinum drug resistance possibly serving as the KEGG pathway through which PA exerts its therapeutic effects. PA is involved in processes such as nuclear division, chromosome segregation, mitotic nuclear division, condensed chromosome formation, and protein C-terminus binding. PA probably exert its therapeutic effects through the tumor immune microenvironment, involving elements such as Dendritic cells activated, Eosinophils, Macrophages M0, Macrophages M1, and T cells CD4 memory activated. The therapeutic effects of PA may vary across different subtypes of TNBC such as TNBC-BL1, TNBC-Metaplastic, and TNBC-BL2. This study provides compelling evidence that PA holds significant promise as a therapeutic agent for TNBC, primarily through its action on TOP2A and its influence on the TNBC.

Cognitive frailty in maintenance hemodialysis: a scoping review.

To conduct a scoping review of the related research on cognitive frailty (CF) in maintenance hemodialysis (MHD) patients, so as to provide a basis for early diagnosis, treatment and intervention of CF in MHD patients. Utilizing a scoping review approach, we searched PubMed, Embase, The Cochrane Library, Web of Science, CINAHL, the China Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu (VIP) for literature on CF in MHD patients up to October 20, 2024. Two researchers conducted independent screening and data extraction of the literature's fundamental characteristics. The study is registered in OSF ( https://doi.org/10.17605/OSF.IO/H6Q89 ). The review included 21 articles, revealing a concerningly high prevalence of CF in MHD patients, ranging from 4.6 to 56.4%. Six diagnostic combinations were identified, with the combination of Frailty Phenotype (FP), Montreal Cognitive Assessment (MOCA), and Clinical Dementia Rating (CDR) scales being the most prevalent. Influencing factors were categorized into demographic and lifestyle, physical condition, disease-related and psychosocial aspects. Interventions included exercise, cognitive therapy combined with exercise, social support and predictive nursing, yet there remains a scarcity of intervention studies. The prevalence of CF in MHD patients is high; however, understanding of CF in MHD patients is insufficient. There are many types of assessment tools, but there is a lack of unified standards and specificity; the influencing factors are complex and diverse; and prevention and intervention studies are scarce.

Network Pharmacology Unveils Multi-Systemic Intervention of Panax notoginseng in Osteoporosis via Key Genes and Signaling Pathways.

Panax notoginseng (Burk.) F. H. Chen (PN) is a traditional Chinese medicine that has been applied to prevent and treat osteoporosis. The mechanism of PN for osteoporosis remained a mystery. The objective was to reveal the therapeutic effect and illuminate the possible mechanism of PN for osteoporosis. The Traditional Chinese Medicine Database and Analysis Platform was searched to screen the potent ingredients of the PN and to analyze the potential therapeutic targets for osteoporosis. We excavated four disease databases to collect osteoporosis-related genes. After integrating the gene expression profile of osteoporosis and the chemical-protein data of PN, a protein-protein interaction network was constructed to demonstrate the interactions among the gene products. GO function, KEGG pathway, and docking analyses were executed. Network pharmacology obtained 31 active ingredients and 134 targets for the treatment of osteoporosis. The key components were beta-elemene, quercetin, methyl palmitate, oleic acid, and hexanal. The results of GO and KEGG analyses showed that Panax notoginseng was beneficial for osteoporosis by influencing the main pathways including AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, p53 signaling pathway, NF-kappa B signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway, and Wnt signaling pathway, modulating inflammation, metabolism, cell proliferation, cell survival, growth and angiogenesis. Panax notoginseng intervened in osteoporosis through multi-components, multi-targets, and multi-pathways. This study illustrates the mechanism of Panax notoginseng for osteoporosis, providing broader insights for novel research and developments of the Panax species for osteoporosis.

Molecular Profiling of Biliary Tract Cancers in African American and Caucasian Patients.

Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancers. BTCs have a number of genomic alterations, including isocitrate dehydrogenase 1 (IDH1) mutations, fibroblast growth factor receptor 2 (FGFR2) rearrangements, and ERBB2 amplifications. Therapies targeting these alterations have shown clinical benefit in patients with BTCs in the United States. However, molecular differences between races in BTCs are largely unknown. In particular, the genomic profiles of African American (AA) patients with BTCs have been infrequently reported. We sought to identify key genomic differences between AA and Caucasian patients with BTCs in the United States in the Foundation Medicine and American Association for Cancer Research (AACR) GENIE databases. BTC patients from AA and Caucasian patients from the Foundation Medicine and AACR GENIE databases were retrospectively reviewed. BTCs were divided into ICC, ECC, and GBCs in the Foundation Medicine database. BTCs were divided into cholangiocarcinomas and GBCs in the AACR GENIE database. The mean age of AA patients with BTCs was lower compared with Caucasians. TP53 and FGFR2 alterations were significantly more frequent in AA patients compared with Caucasian patients with BTCs. IDH1 mutations in Caucasian patients with BTCs were double that of AA patients. The results of this study suggest that significant genomic differences exist between races and warrant further investigation.

Genome-wide CRISPR-based screen identifies E2F transcription factor 1 as a regulator and therapeutic target of aristolochic acid-induced nephrotoxicity.

Aristolochic Acid I (AAI) is widely present in traditional Chinese medicines derived from the Aristolochia genus and is known to cause significant damage to renal tubular epithelial cells. Genome-wide screening has proven to be a powerful tool in identifying critical genes associated with the toxicity of exogenous substances. To identify undiscovered key genes involved in AAI-induced renal toxicity, a genome-wide CRISPR library screen was conducted in the human kidney-2 (HK-2) cell line. Among the altered sgRNAs, a significant enrichment of those targeting the E2F transcription factor 1 (E2F1) gene was observed in surviving HK-2 cells in the AAI-treated group. Interestingly, the role of E2F1 had not been previously explored in studies of AAI nephrotoxicity. Further investigations revealed that E2F1 promotes apoptosis by activating the p53 signaling pathway and upregulating pro-apoptotic genes, such as BAK and BAX. Additionally, using the high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB), cannabidiol (CBD) was identified as an inhibitor of E2F1 by suppressing the activity of NF-κB pathway. In vitro and in vivo models confirmed that CBD inhibits AAI-induced upregulation of E2F1, thereby suppressing p53-mediated apoptosis. In conclusion, this study highlights the crucial role of E2F1 in AAI-induced renal cell apoptosis and identifies CBD as a novel therapeutic candidate for mitigating AAI nephrotoxicity.

Analysis of Major Chemical Constituents in Jiuwei Decoction Based On Capillary Electrophoresis Coupled With Quadrupole Time‐of‐Flight Mass Spectrometry

ABSTRACTAn analytical method for identifying the chemical constituents in the Chinese herbal combination Jiuwei decoction was established using capillary electrophoresis coupled with quadrupole time‐of‐flight mass spectrometry. Nine herbs were extracted with a 60:40 (v/v) ethanol/water solution to prepare the Jiuwei decoction. Electrophoretic separation was carried out using a 50 µm i.d., 125 cm bare fused silica capillary at a constant temperature of 25°C for sample injection. The chemical composition was analyzed and identified in both positive and negative ion modes. In the positive separation mode, a separation voltage of 30 kV was applied, with a 1% aqueous formic acid solution serving as the background electrolyte (BGE), along with a 50:50 (v/v) methanol/water solution containing 0.1% formic acid as the sheath liquid. In the negative separation mode, a separation voltage of −30 kV was employed, utilizing a 50 mM ammonium acetate solution (pH 9.0) as the BGE, combined with a 50:50 (v/v) methanol/water solution containing 5 mM ammonium acetate as the sheath liquid. The MassHunter Qualitative Analysis software (version 10.0) was utilized to identify 52 compounds based on accurate mass, isotope abundance, isotopic patterns, and fragmentation information. The data were compared with the Agilent Personal Compound Database and Library of traditional Chinese medicine (TCM), as well as multiple online databases (TCMSP, ChemSpider, PubChem, PubMed, and Web of Science) and relevant literature. The fragmentation pathways of representative compounds were also characterized. This study identified the chemical composition of Jiuwei decoction, providing a molecular basis for further exploration of its pharmacological effects and presenting a robust methodology for the compositional analysis of complex TCM mixtures.

Association and predictive ability between significant perioperative cardiovascular adverse events and stress glucose rise in patients undergoing non-cardiac surgery

BackgroundThe predictive importance of the stress hyperglycemia ratio (SHR), which is composed of admission blood glucose (ABG) and glycated hemoglobin (HbA1c), has not been fully established in noncardiac surgery. This study aims to evaluate the association and predictive capability the SHR for major perioperative adverse cardiovascular events (MACEs) in noncardiac surgery patients.MethodsIndividuals who underwent noncardiac surgical procedures between 2011 and 2020, including both diabetic and non-diabetic patients, were identified in the perioperative medicine database (INSPIRE 1.1) and classified into tertiles based on their SHR. The connection between the SHR and the risk of MACEs was studied using Cox proportional hazards regression analysis, then restricted cubic spline (RCS) was employed to assess the association’s form. Additionally, the SHR’s incremental predictive utility for MACEs was assessed by the C-statistic, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI), thereby quantifying the enhancement in predictive accuracy brought by incorporating the SHR into existing risk models. Feature importance and predictive models were generated utilizing the Boruta algorithm and machine learning approaches.ResultsA total of 5609 patients were enrolled. With an upwards shift in SHR vertices, the rate of perioperative MACEs and cardiac death event steadily rose. The RCS analysis for perioperative MACEs and cardiac death event both indicated J-shaped associations. Inflection points occurred at SHR = 0.81 for MACEs and SHR = 0.97 for cardiac death. The model’s fit improved significantly, with a continuous NRI of 0.067 (95% CI: 0.025–0.137, P < 0.001) and an IDI of 0.305 (95% CI: 0.155–0.430, P < 0.001). When SHR was added as a categorical variable (> 0.81), the C-statistic increased to 0.785 (95% CI: 0.756–0.814) with a ΔC-statistic of 0.035 (P = 0.009), a continuous NRI of 0.007 (95% CI: 0.000-0.021, P = 0.016), and an IDI of 0.076 (95% CI -0.024-0.142, P = 0.092). In the Boruta algorithm, variables identified as important features in the green area were incorporated into the machine learning models development.ConclusionsThe SHR was related with an increased risk of perioperative MACEs in patients following noncardiac surgery, highlighting its potential as a useful and reliable predictive tool for assessing the risk of perioperative MACEs.Graphical

Network pharmacology and anticancer mechanism study of Dendrobium nobile dendrobine in the treatment of colorectal cancer

ObjectiveThis study aims to explore the potential targets and anticancer mechanisms of dendrobine from Dendrobium nobile in the treatment of colorectal cancer through network pharmacology, and to experimentally validate its specific effects.MethodsInitially, potential targets of dendrobine were identified using the ITCM Traditional Chinese Medicine database, while colorectal cancer-related genes were obtained from the NCBI Gene database, with the intersection of these datasets taken for further analysis. Functional enrichment analysis was conducted using the Metascape database, and a protein–protein interaction (PPI) network was constructed. Additionally, cell culture, cell proliferation assays, and wound healing assays were performed. The Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways were analyzed using PCR and Western blot experiments.ResultsThe PPI network constructed from 152 intersecting genes revealed that these genes play crucial roles in processes such as cell proliferation, apoptosis, and signal transduction. Cell-based assays demonstrated that dendrobine significantly inhibits the proliferation and migration of colorectal cancer cells. Furthermore, PCR and Western blot results indicated that dendrobine suppresses colorectal cancer cell proliferation and migration by modulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways.ConclusionDendrobine exhibits significant anticancer potential against colorectal cancer by regulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways, providing a theoretical foundation and experimental evidence for its therapeutic application in colorectal cancer.

Adverse Obstetric Outcomes in Pregnancies With Major Fetal Congenital Heart Defects

Understanding the risk profile of obstetric complications in pregnancies with fetal major congenital heart defects (MCHDs) is crucial for obstetric counseling and care. To investigate the risk of placenta-related adverse obstetric outcomes in pregnancies complicated by fetal MCHDs. This cohort study retrieved data from June 1, 2008, to June 1, 2018, from the Danish Fetal Medicine Database, which includes comprehensive data on more than 95% of all pregnancies in Denmark since the database was instituted in 2008. All singleton pregnancies that resulted in a live-born child after 24 weeks' gestation without chromosomal aberrations were included. A systematic search of the literature was performed in PubMed, Embase, and the Cochrane Library from inception to June 1, 2024, to compile existing knowledge and data on adverse obstetric outcomes among MCHD subtypes. Fetal MCHDs including 1 of 11 subtypes. The primary outcome was a composite adverse obstetric outcome defined as preeclampsia, preterm birth, fetal growth restriction, or placental abruption. Secondary outcomes consisted of each adverse obstetric event. Adjusted odds ratios (AORs) were computed using generalized estimating equations adjusted for maternal body mass index, age, smoking, and year of delivery. Meta-analyses were conducted using random-effects models to pool effect sizes for each MCHD subtype and adverse obstetric outcome. A total of 534 170 pregnancies were included in the Danish cohort, including 745 with isolated fetal MCHDs (median [IQR] maternal age, 29.0 [26.0-33.0] years) and 533 425 without MCHDs (median [IQR] maternal age, 30.0 [26.0-33.0] years). Pregnancies with fetal MCHDs exhibited a higher rate of adverse obstetric outcomes at 22.8% compared with 9.0% in pregnancies without fetal MCHDs (AOR, 2.96; 95% CI, 2.49-3.53). Preeclampsia (AOR, 1.83; 95% CI, 1.33-2.51), preterm birth at less than 37 weeks (AOR, 3.84; 95% CI, 3.15-4.71), and fetal growth restriction (AOR, 3.25; 95% CI, 2.42-4.38) occurred significantly more frequently in pregnancies with MCHDs. Except for fetal transposition of the great arteries (AOR, 1.19; 95% CI, 0.66-2.15), all MCHD subtypes carried a greater risk of adverse obstetric outcomes. The meta-analysis included 10 additional studies that supported these results. These findings suggest that nearly 1 in 4 women expecting a child with an MCHD, except transposition of the great arteries, may be at high risk of adverse obstetric outcomes.

Leveraging Drug-Gene Interaction Information for Personalized Hypertension Drug Molecule Discovery

Aims: To examine whether novel lead hypertension molecules can be used in the personalized treatment of hypertension. Background: Hypertension is a modifiable condition that affects over 1 billion adults worldwide. Maintaining a healthy blood pressure is vital for overall health, especially given that hypertension is a primary risk factor for developing cardiovascular conditions. However, some individuals have resistant hypertension, which may be due to variations in genetic expression, making standard hypertension treatments ineffective. Objective: The integration of genetic data into the personalized optimization of novel hypertension drugs is demonstrated. Method: This research created coding criteria for drug-gene recommendations based on the genomic profiles of ten pseudo-patients. The genomic data of these patients was created using chromosome and hypertension-implicated gene sequences from the NCBI National Library of Medicine database. Results: This study uses the proposed drug recommendation criteria to recommend novel hypertension lead molecules to each patient based on their gene expression profiles. Conclusion: This study’s patient-centric drug prescription approach integrates patient gene expression data with drug-gene interaction data and recommends novel hypertension drugs most suitable for each patient. Variations in patient gene expression explain the diverse treatment responses inherent across hypertensive patients, thus necessitating a personalized approach to their drug prescription. Future studies can investigate the challenges of ethical, technological, and technical expertise that may affect the clinical implementation of personalized drug prescription recommendation systems.

Targeting mTOR Kinase with Natural Compounds: Potent ATP-Competitive Inhibition Through Enhanced Binding Mechanisms.

Background/Objectives: The mammalian target of the rapamycin (mTOR) signaling pathway is a central regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling contributes to many human diseases, including cancer, diabetes, and obesity. Therefore, inhibitors against mTOR's catalytic kinase domain (KD) have been developed and have shown significant antitumor activities, making it a promising therapeutic target. The ATP-KD interaction is particularly important for mTOR to exert its cellular functions, and such inhibitors have demonstrated efficient attenuation of overall mTOR activity. Methods: In this study, we screened the Traditional Chinese Medicine (TCM) database, which enlists natural products that capture the relationships between drugs targets and diseases. Our aim was to identify potential ATP-competitive agonists that target the mTOR-KD and compete with ATP to bind the mTOR-KD serving as potential potent mTOR inhibitors. Results: We identified two compounds that demonstrated interatomic interactions similar to those of ATP-mTOR. The conformational stability and dynamic features of the mTOR-KD bound to the selected compounds were tested by subjecting each complex to 200 ns molecular dynamic (MD) simulations and molecular mechanics/generalized Born surface area (MM/GBSA) to extract free binding energies. We show the effectiveness of both compounds in forming stable complexes with the mTOR-KD, which is more effective than the mTOR-KD-ATP complex with more robust binding affinities. Conclusions: This study implies that both compounds could serve as potential therapeutic inhibitors of mTOR, regulating its function and, therefore, mitigating human disease progression.

Electroacupuncture for abdominal obesity: protocol for a systematic review and meta-analysis of randomised controlled trials

IntroductionThe prevalence of obesity is rising, significantly impacting health and quality of life. Effective treatment is crucial, particularly for abdominal obesity (AO). Electroacupuncture (EA), which combines acupuncture and moxibustion with...

Network Pharmacology Prediction and Molecular Docking-based Strategy to Explore the Potential Mechanism of Guiyi Tonglong Prescription in the Treatment of Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia (BPH) is a common condition affecting the urinary tract. This study aimed at exploring the potential of Guiyi Tonglong (GYTL) prescription for the treatment of benign prostatic hyperplasia using network pharmacology and molecular docking technology. Methods: The main active ingredients in GYTL prescription were identified from the Traditional Chinese Medicine Systems Pharmacology and the Integrative Pharmacology-based Traditional Chinese Medicine (TCMIP) databases based on drug similarity of ≥ 30% and oral bioavailability of ≥ 0.18. Protein–protein interaction (PPI) networks, gene ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to study the interactions and pathway enrichment and establish ingredient-target-pathway networks. The structure of the active ingredient was docked to that of the potential protein target using the AutoDock molecular docking software. Results: A total of 86 active ingredients and 130 potential targets were screened from GYTL prescription, and a PPI network was constructed to identify the five most important core targets, namely SRC, TP53, STAT3, AKT1, and PIK3CA. Enrichment analysis revealed that GYTL prescription may play a role in the treatment of BPH through multiple signaling pathways, such as PI3K-Akt, EGFR, AGE-RAGE, and HIF-1. Molecular docking indicated a potential interaction between the active ingredients and targets. Conclusion: These results provide further information regarding the active ingredients and molecular mechanisms of GYTL prescription in treating BPH.

Colorectal cancer: local results and significance in Hungary.

Colorectal cancer (CRC) causes substantial morbidity and mortality internationally. In Hungary, the incidence and mortality of CRC are among the world's highest. Fortunately, CRC is a highly preventable disease, since there is a long asymptomatic phase before neoplastic transformation. Numerous countries have instituted programs for CRC screening. However, Hungary did not implement population-based screening programs until December 2018, consisting of a voluntary 2-step screening program based on the fecal immunochemical test (FIT) and if positive, referral to colonoscopy. Asymptomatic individuals aged over 50 years were invited to participate in the 2-step program. This study aims to analyze the results of these colonoscopies and raise public awareness of the CRC disease process and prevention, especially in Hungary. Various literature sources were reviewed, and external information was gathered and consolidated based on CRC etiopathogenesis, management options, screening options, cost, benefits, modalities, and quality control. Semmelweis University Department of Internal Medicine and Hematology's database was accessed for the cross-sectional study results of 168 screening colonoscopies within the 2-step program from 2019 to 2020. I quantified and compared the results obtained during the colonoscopies with that of said literature within Hungary and worldwide. Colonoscopy was performed in 168 patients of average age 63.4 years. The incidence of CRCs in the population was 4.76%. Among the CRC cases, 75% were in the rectosigmoid area and 25% were in the remaining colon. The total adenoma detection rate (ADR) in the study was 57.1%, higher than the recommended 25% for adequate screening colonoscopy. The total number of resected polyps was 270; 8.1% were adenomas with high-grade dysplasia and 0.76% contained CRC. Out of the 185 resected adenomas, 141 were tubular, 34 were tubulovillous, and 10 were villous. Adenoma localizations included 14.6% rectum, 38.4% sigmoid, 11.9% descending colon, 8.6% transverse colon, 17.8% ascending colon, and 8.6% cecum. The average age of CRC patients was 63.9 years (range, 56-68 years) with a slight female predominance (5 females, 3 males). The ADR of the different endoscopists did not seem to correlate with experience. Optimal participation rate of the screening program would be >60%. Population outreach through mailed FIT is evidence-based and shown to increase CRC screening rates in underserved populations. Hungary would benefit immensely in most aspects from mandatory, population-based CRC screening with this 2-step program. This alternative is proposed in lieu of 1-step screening, because of the limited capacity for colonoscopy in the country and the limited participation rates in the screened population. To reach maximum cost-benefit, the participation rate of the screened population must be >60%, with >80% of FIT positive test results being referred to colonoscopy. Consolidation and distribution of the screening program through population outreach will bring about substantial reductions in mortality from CRC. Further studies are warranted on the feasibility and sustainability of this 2-step program.

The characteristics of event-related potentials in generalized anxiety disorder: A systematic review and meta-analysis.

Previous studies have reported inconsistent findings regarding event-related potentials (ERPs) abnormalities in individuals with generalized anxiety disorder (GAD). This meta-analysis aimed to systematically review and synthesize the existing evidence on ERP alterations in individuals with GAD. A comprehensive literature search was conducted in PubMed, the Cochrane Library, Excerpta Medica Database, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang database, and China Biology Medicine (CBM) databases from inception to November 11, 2024. Gray literature and reference lists were also manually searched. Studies investigating ERP component differences between individuals with GAD and healthy controls were included. Two independent reviewers conducted study selection, data extraction, and risk of bias assessment. Influence and sensitivity analyses were performed to assess the robustness of the pooled results. Effect sizes (SMD, Hedge's g) were calculated for latency and amplitude differences. Heterogeneity was assessed using the I2 statistic. Meta-regression and subgroup analyses were conducted to explore the source of heterogeneity. Trim-and-fill analyses were applied to assess potential publication bias. Data synthesis was performed using R (version 4.2.3) software. A total of 37 studies involving 1086 individuals with GAD and 1315 healthy controls were included. The overall risk of bias was rated as low for 25 studies and moderate for 12 studies. Ten ERP components were included in the quantitative meta-analysis: P3, N2, N1, P2, Error Related Negativity (ERN), Correction Related Negativity (CRN), Mismatch Negativity (MMN), P1 (amplitude), Pe, and LPP. Pooled results indicated that individuals with GAD exhibited decreased P3 amplitude (g=-0.54, 95% CI: -0.70 to -0.38, I2=20%, P=0.22) and increased ERN amplitude (g=-0.42, 95% CI: -0.72 to -0.12, I2=40%, P=0.11) compared to healthy controls. In addition, delayed latency of P3 (g=0.43, 95% CI: 0.09 to 0.78, I2=75%, P<0.01), N2 (g=0.36, 95% CI: 0.11 to 0.62, I2=30%, P=0.20), and MMN (g=0.63, 95% CI: 0.52 to 0.75, I2=0%, P<0.0001) was observed in individuals with GAD. Due to the limited number of included studies, the results of N170, N1/P2, N270, N400, VPP, BAEP, P1 (latency), P50, EPN and Nf were summarized narratively. Individuals with GAD were reported to have increased N170, N400, and VPP amplitude and delayed P1 latency compared to healthy controls. Age, sex ratio, sample size, diagnostic criteria, task-related modality, and paradigm were identified as potential influencing factors of ERP characteristics. Individuals with GAD exhibit increased ERN amplitude and decreased P3 amplitude in contrast with healthy controls. In addition, delayed latency of P3, N2, and MMN is detected in individuals with GAD. The identified ERP components in individuals with GAD are associated with attention, cognition, visual perception, error or conflict monitoring, semantic information integration, and auditory sensory memory processes. Due to the limited number of included studies and high heterogeneity, further studies with high quality are needed to confirm these findings.

Comparing and assessing physical activity and sedentary behaviour guidelines for different populations with and without chronic conditions and/or disabilities: a systematic review protocol

Physical activity guidelines targeting different populations with and without chronic diseases or disabilities are required to meet the diverse functional and physiological needs experienced by different subgroups of people to...

Molecular insights into vasicine and butyrylcholinesterase interactions: A complimentary biophysical, multi-spectroscopic, and computational study.

Butyrylcholinesterase (BChE) plays a pivotal role in regulating acetylcholine (ACh) levels during the progression of Alzheimer's disease (AD), so emerged as an attractive target in AD treatment. Vasicine, a naturally occurring pyrroloquinazoline alkaloid, was identified as a natural BChE inhibitor (IC50 = 1.47 ± 0.37 μM) from Traditional Chinese Medicine database. No any detailed research concerning the binding behavior of BChE with small molecule. As the first case, the inhibitory mechanism of vasicine on BChE was investigated using multi-spectroscopic methods (including fluorescence quenching, ANS fluorescence probe, three-dimensional fluorescence, time-resolved fluorescence, circular dichroism), isothermal titration calorimetry, surface plasmon resonance, and computational approaches. As a reversible and mixed inhibitor, vasicine displayed moderate affinity for BChE with an affinity constant KD of 2.111 μM, its binding process was characterized as a spontaneous exothermic reaction with reduced entropy, primarily driven by hydrogen bonding interactions. Vasicine quenched the fluorescence of BChE through both static and dynamic quenching mechanisms, leading to an increase in the α-helix content and surface hydrophobicity of BChE. Furthermore, the fluctuation of the skeleton atoms in the vasicine-BChE complex system remained stable, indicating good stability within the simulated physiological environment. In addition, vasicine exerted good safety for PC12 cells. Above findings provide molecular insights into the inhibitory mechanism of vasicine against BChE for the first time, and offer valuable information for future structure modification and therapeutic applications of vasicine as a BChE inhibitor.

Pulmonary nodule malignancy probability: a meta-analysis of the Brock model.

This study aims to quantify the performance of the Brock model through a systematic review and meta-analysisand to clarify its overall accuracy in predicting malignant pulmonary nodules. A systematic search was conducted in databases including the Cochrane Library, Excerpta Medica database (EMBASE), MEDLINE, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Wanfang from their inception until May 1, 2024, to collect observational cohort studies involving the Brock model. The primary outcome was the pooled area under the receiver operating characteristic curve (ROC) the area under curve (AUC) for the Brock model. Secondary outcomes included sensitivity and specificity. The metaprotocol was registered in the International Prospective Register of Systematic Reviews (CRD42024538163). A total of 52 studies involving 85,558 patients were included. The pooled AUC was 0.796 (95% confidence interval [CI]: 0.771-0.820), with a pooled sensitivity of 0.82 (95% CI: 0.76-0.87) and specificity of 0.80 (95% CI: 0.72-0.86). Subgroup analysis showed that the performance of the full model was significantly better than that of the simplified model (0.822, 95% CI: 0.794-0.849 versus 0.687, 95% CI: 0.611-0.763). The model performed excellently for pulmonary nodules with diameters of 1- to 8 mm (AUC: 0.927, 95% CI: 0.900-0.954). However, its performance was lower in Asian populations (AUC=0.741, 95% CI: 0.703-0.780), solitary pulmonary nodules (AUC=0.767, 95% CI: 0.693-0.842), and subsolid pulmonary nodules (AUC=0.747, 95% CI: 0.661-0.832). This meta-analysis confirms the Brock model's overall strong performance. However, the results indicate certain application limitations of the Brock model, with reduced accuracy for larger nodules (>15 mm), solitary pulmonary nodules, subsolid nodules, and in Asian populations.

Diagnostic Efficacy of 11 SARS-CoV-2 Serological Assays for COVID-19: A Meta-Analysis and Adjusted Indirect Comparison of Diagnostic Test Accuracy.

In the past 5 years, a large number of serological assays for large-scale detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen emerged. Serological assays for SARS-CoV-2 were needed to support clinical diagnosis and epidemiological investigations. However, there were limited data on the diagnostic accuracy of these serological assays. We aimed to compare the diagnostic accuracy of 11 commercial serological assays for coronavirus disease-2019 (COVID-19) by taking the reverse transcriptase polymerase chain reaction (RT-PCR) assays as the reference standard, which served as the control arm to conduct an indirect comparison of diagnostic accuracy for 11 different SARS-CoV-2 serological assays. This meta-analysis was conducted following the PRISMA 2020 reporting guideline. Electronic searches were performed using the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG, and Chinese Weipu (VIP) databases. Fifty-seven articles, including 11 serologic-based IgG, IgM, and total antibodies assays for SARS-CoV-2, published before June 2024, were included in this meta-analysis. The main outcome of this meta-analysis used to evaluate the performance of 11 assays included pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC), and summary receiver operating characteristic curve (SROC). The R software was used for adjusted indirect comparison to calculate the relative diagnostic odds ratio (RDOR) with corresponding 95% confidence intervals (CIs), and indirect comparison forest plots showed the results. A total of 57 articles met the eligibility criteria for inclusion in our meta-analysis. The pooled DOR and the AUC for access SARS-CoV-2 IgG were 564.28 (95% CI 229.58-1386.91) and 1.00, and as for EDI novel coronavirus COVID-19 IgG those were 85.27 (95% CI 53.99-134.68) and 0.95, for EDI novel coronavirus COVID-19 IgM were 49.42 (95% CI 16.47-148.30) and 0.86, for iFlash-SARS-CoV-2 IgG were 652.31 (95% CI 362.32-1174.41) and 0.97, for iFlash-SARS-CoV-2 IgM were 36.72 (95% CI 12.42-108.54) and 0.76, for MAGLUMI 2019-nCoV IgG were 145.44 (95% CI 59.37-356.30) and 0.90, for MAGLUMI 2019-nCoV IgM were 21.59 (95% CI 14.27-32.67) and 0.59, for ortho-clinical anti-SARS-CoV-2 IgG were 719.46 (95% CI 262.34-1973.13) and 1.00, for ortho-clinical anti-SARS-CoV-2 total were 1104.60 (95% CI 395.64-3083.99) and 1.00, for Siemens SARS-CoV-2 total (COV2T) were 1143.37 (95% CI 316.49-4130.62) and 0.99, for Wantai SARS-CoV-2 total Ab were 1014.98 (95% CI 618.48-1665.66) and 1.00. The pooled DOR for assays-based IgG (n = 43), assays-based total antibody (n = 35), and assays-based IgM (n = 20) was 242.88 (95% CI 157.66-374.16), 1215.90 (95% CI 547.14-2702.07), and 40.99 (95% CI 22.63-74.25). The diagnostic accuracy of assays-based total antibody performed better than those of assays-based IgG and assays-based IgM; assays-based IgG performed better than assays-based IgM. This study suggested that the Siemens SARS-CoV-2 total (COV2T), ortho-clinical anti-SARS-CoV-2 total, and Wantai SARS-CoV-2 total had the best overall diagnostic accuracy. The diagnostic efficacy of the assays-based total antibody had statistically significantly higher accuracy than those of assays-based IgG and assays-based IgM for COVID-19.