Evaluation of probiotic properties of a Brevibacillus laterosporus strain.

Brevibacillus laterosporus is a strain of probiotic bacteria that has been widely used in pest control, cash crop, and other production areas. However, few studies have been conducted on its use as a feed additive in animals. Therefore, the probiotic potential of B. laterosporus PBC01 was evaluated by characterizing hydrophobicity, auto-aggregation activity, bile salt and simulated gastrointestinal fluid tolerance, bienzymatic, and antibacterial activity. Antibiotic susceptibility, hemolysis assays, and supplemental feeding of mice were also performed to evaluate safety features. Our results showed that B. laterosporus PBC01 had moderate hydrophobicity, high auto-agglutination ability. Meanwhile, B. laterosporus PBC01 had good tolerance to bile salt and simulated gastrointestinal fluid. It had the ability to secrete protease, cellulase, and to inhibit various pathogens. In addition, B. laterosporus PBC01 was sensitive to many antibiotics, and did not produce hemolysin. In the safety assessment of mice, it did not cause any deaths, nor did it affect the cell components of blood, antioxidant capacity, and reproductive health. The study indicated the great probiotic characteristics and safety of B. laterosporus PBC01. This may provide a theoretical basis for the clinical application and development of probiotic-based feed additives.

Genome-based taxonomic identification and safety assessment of an Enterococcus strain isolated from a homemade dairy product.

The aim of this study was to explore the taxonomic identification and evaluate the safety of a bacterium, Enterococcus lactis IDCC 2105, isolated from homemade cheese in Korea, using whole genome sequence (WGS) analysis. It sought to identify the species level of this Enterococcus spp., assess its antibiotic resistance, and evaluate its virulence potential. WGS analysis confirmed the bacterial strain IDCC 2105 as E. lactis and identified genes responsible for resistance to erythromycin and clindamycin, specifically msrC, and eatAv, which are chromosomally located, indicating a minimal risk for horizontal gene transfer. The absence of plasmids in E. lactis IDCC 2105 further diminishes the likelihood of resistance gene dissemination. Additionally, our investigation into seven virulence factors, including hemolysis, platelet aggregation, biofilm formation, hyaluronidase, gelatinase, ammonia production, and ß-glucuronidase activity, revealed no detectable virulence traits. Although bioinformatic analysis suggested the presence of collagen adhesion genes acm and scm, these were not corroborated by phenotypic virulence assays. Based on these findings, E. lactis IDCC 2105 presents as a safe strain for potential applications, contributing valuable information on its taxonomy, antibiotic resistance profile, and lack of virulence factors, supporting its use in food products.

Experiences from the initial 3 years of introducing the British Pharmacological Society and UK Medical Schools Council Prescribing Safety Assessment for Danish junior doctors.

AIMS: The British Pharmacological Society and UK Medical Schools Council Prescription Safety Assessment (BPS/MSC PSA) is an electronic platform developed for assessing the prescription skills of medical students. Our aim was to investigate the feasibility of the BPS/MSC PSA in addressing prescribing competencies among junior doctors in a hospital setting. METHODS: The Department of Clinical Pharmacology at Odense University Hospital established a Danish translated programme using the BPS/MSC PSA platform. We launched a formal 3-year programme in 2021, potentially assessing all first-year doctors at Odense University Hospital and Esbjerg Regional Hospital. Participation was followed by a survey. RESULTS: During the period of 2021 to 2023 n = 364 doctors were invited, from which n = 246 participated. The compliance rate increased from 38% in 2021 to 88% in 2023. The mean assessment score (points normalized to percentage) across n = 246 participants was 71%, and 94% achieved a score of at least 50%. A subset of participants responded to the survey, with the majority of those completing the questionnaire indicating that the purpose of the assessment was clear. The items related to difficulty and number of questions received comparable evaluations, and most respondents found the questions clinically relevant. CONCLUSION: It is feasible to translate and implement the BPS/MSC PSA in a Danish hospital setting. The programme provides insight into the prescribing competencies of junior doctors and the participants are generally positive.

Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study.

BACKGROUND: Standard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production. METHODS: We conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared. RESULTS: The real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects. CONCLUSIONS: Utilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.

Advances in performance degradation mechanism and safety assessment of LiFePO4for energy storage.

In the context of 'energy shortage', developing a novel energy-based power system is essential for advancing the current power system towards low-carbon solutions. As the usage duration of lithium-ion batteries for energy storage increases, the nonlinear changes in their aging process pose challenges to accurately assess their performance. This paper focuses on the study LiFeO4(LFP), used for energy storage, and explores their performance degradation mechanisms. Furthermore, it introduces common battery models and data structures and algorithms, which used for predicting the correlation between electrode materials and physical parameters, applying to state of health assessment and thermal warning. This paper also discusses the establishment of digital management system. Compared to conventional battery networks, dynamically reconfigurable battery networks can realize real-time monitoring of lithium-ion batteries, and reduce the probability of fault occurrence to an acceptably low level.

Caffeine intake and its association with nutrition, sleep, and physical activity among schoolchildren in the United Arab Emirates: a national cross-sectional study.

PURPOSE: Recent surveys indicate a significant increase in total caffeine intake among schoolchildren. Limited research has been published concerning the total intake of caffeine among schoolchildren in the Middle East and Gulf Cooperation Council (GCC) countries, including the UAE. METHODS: This cross-sectional survey estimated the total caffeine intake from foods and beverages among 10,275 schoolchildren in the UAE. Caffeine intakes were related to the European Food Safety Authority's level of no safety concern (3.0 mg/kg BW) and level of effects on sleep (1.4 mg/kg BW). RESULTS: More than half (56.2%) of the students consumed more than 100 mg (the upper limit allowed) of caffeine from dietary sources. High intake of caffeine (> 100 mg/day) was significantly associated (p = 0.001) with reduced sleep duration, difficulty falling asleep, infrequent exercising, using smart devices for more than 2 h a day, getting a lower GPA, skipping breakfast, eating fewer servings of vegetables than recommended, frequent consumption of fast food and more frequent snack consumption. CONCLUSION: Excessive intake of caffeine from different dietary sources coexists with unhealthy dietary and lifestyle behaviors and sleep problems. Tailoring educational programs and intervention strategies is warranted to correct the unhealthy intake of caffeine and the associated unhealthy dietary and lifestyle behaviors among schoolchildren in the UAE.

Whole-genome sequencing of Pseudoalteromonas piscicida 2515 revealed its antibacterial potency against Vibrio anguillarum: a preliminary invitro study.

Pseudoalteromonas piscicida 2515, isolated from Litopenaeus vannamei culture water, is a potential marine probiotic with broad anti-Vibrio properties. However, genomic information on P. piscicida 2515 is scarce. In this study, the general genomic characteristics and probiotic properties of the P. piscicida 2515 strain were analysed. In addition, we determined the antibacterial mechanism of this bacterial strain by scanning electron microscopy (SEM). The results indicated that the whole-genome sequence of P. piscicida 2515 contained one chromosome and one plasmid, including a total length of 5,541,406 bp with a G + C content of 43.24%, and 4679 protein-coding genes were predicted. Various adhesion-related genes, amino acid and vitamin metabolism and biosynthesis genes, and stress-responsive genes were found with genome mining tools. The presence of genes encoding chitin, bromocyclic peptides, lantibiotics, and sactipeptides showed the strong antibacterial activity of the P. piscicida 2515 strain. Moreover, in coculture with Vibrio anguillarum, P. piscicida 2515 displayed vesicle/pilus-like structures located on its surface that possibly participated in its bactericidal activity, representing an antibacterial mechanism. Additionally, 16 haemolytic genes and 3 antibiotic resistance genes, including tetracycline, fluoroquinolone, and carbapenem were annotated, but virulence genes encoding enterotoxin FM (entFM), cereulide (ces), and cytotoxin K were not detected. Further tests should be conducted to confirm the safety characteristics of P. piscicida 2515, including long-term toxicology tests, ecotoxicological assessment, and antibiotic resistance transfer risk assessment. Our results here revealed a new understanding of the probiotic properties and antibacterial mechanism of P. piscicida 2515, in addition to theoretical information for its application in aquaculture.

Animal-free safety assessment of chemicals: an innovation system perspective.

This perspective paper, which is the result of a collaborative effort between toxicologists and scholars in innovation and transition studies, presents a heuristic framework based on innovation system literature for understanding and appraising mission achievement to animal-free chemical safety assessment using New Approach Methodologies (NAMs). While scientific and technical challenges in this area are relatively well known, the recent establishment of missions and roadmaps to accelerate the acceptance and effective use of NAMs for chemical safety assessment raises new questions about how we can grasp the systemic nature of all changes needed in this transition. This includes recognising broader societal, institutional, and regulatory shifts necessary for NAM acceptance and uptake. Our paper discusses how the innovation system approach offers insights into key processes and associated activities that include as well as transcend the technical and scientific realm, and can help to accelerate acceptance and uptake of NAMs. Based on these insights, we present a comprehensive framework that, next to scientific and technological developments, recognises the need for coordinated efforts in areas like education, training, funding, policy-making, and public engagement to promote the acceptance and uptake of NAMs. Our framework can be used to perform structural and functional analyses of the innovation system of NAMs and animal-free safety assessment and as such provides handholds to track progress and organise collective efforts of actors to make sure we are moving in the right direction.

In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters.

As part of the safety assessment of salicylate esters in cosmetics, we developed a metabolism factor based on in vitro to in vivo extrapolation (IVIVE) to provide a better estimation of the aggregate internal exposure to the common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring salicylic acid formation from 31 substances. Four control substances, not defined as salicylic esters but which could be mistaken as such due to their nomenclature, did not form salicylic acid. For the remaining substances, higher in vitro intrinsic clearance (CLint, in vitro) values generally correlated with lower LogP values. A "High-Throughput Pharmacokinetic" (HTPK) model was used to extrapolate CLint, in vitro values to human in vivo clearance and half-lives. The latter were used to calculate the percentage of substance metabolised to salicylic acid in 24 h in vivo following human exposure to the ester, i.e. the "metabolism factor". The IVIVE model correctly reproduced the observed elimination rate of 3 substances using in silico or in vitro input parameters. For other substances, in silico only-based predictions generally resulted in lower metabolism factors than when in vitro values for plasma binding and liver S9 CLint, in vitro were used. Therefore, in vitro data input provides the more conservative metabolism factors compared to those derived using on in silico input. In conclusion, these results indicate that not all substances contribute equally (or at all) to the systemic exposure to salicylic acid. Therefore, we propose a realistic metabolism correction factor by which the potential contribution of salicylate esters to the aggregate consumer exposure to salicylic acid from cosmetic use can be estimated.

A minimum specification dataset for liquid ocular endotamponades: recommendations by a European expert panel.

PURPOSE: To propose a minimum specification dataset to characterize liquid ocular endotamponades (OEs), namely silicone oil (SO), heavy SO (HSO), perfluorodecalin (PFD), and perfluoro-octane (PFO), in terms of physicochemical properties, purity and available evidence of safety, in line with ISO16672:2020. METHODS: An evidence-based consensus using the expert panel technique was conducted. Two facilitators led a committee of 11 European experts. Facilitators prepared a dataset for each compound including the list of specifications relevant for the safety, identified by the group members on the basis of expertise and a comprehensive literature review. Each item was ranked by each member using a 9-point scale from 1 "absolutely to not include" to 9 "absolutely to include" in two rounds followed by discussion. Only items reaching consensus (score ≥ 7 from ≥ 75% of members) were included in the final datasets. RESULTS: For all OEs, consensus was reached to include manufacturer, density, refractive index, chemical composition, dynamic viscosity, interfacial and surface tension, endotoxins, in vitro cytotoxicity assessment, and any evidence from ex vivo and/or in vivo tests for safety assessment. Additional specifications were added for SO (molecular weight distribution, content of oligosiloxanes with MW ≤ 1000 g/mol, spectral transmittance) and PFD/PFO (% of pure PFD/PFO in the final product, vapor pressure, chemical analyses performed for safety assessment). CONCLUSION: The proposed evidence-based minimum specification datasets for SO, HSO, PFD, and PFO have the potential to provide surgeons and health service purchasers with an easily available overview of the most relevant information for the safety assessment of OEs.

Drug safety assessment by machine learning models.

The evaluation of drug-induced Torsades de pointes (TdP) risks is crucial in drug safety assessment. In this study, we discuss machine learning approaches in the prediction of drug-induced TdP risks using preclinical data. Specifically, a random forest model was trained on the dataset generated by the rabbit ventricular wedge assay. The model prediction performance was measured on 28 drugs from the Comprehensive In Vitro Proarrhythmia Assay initiative. Leave-one-drug-out cross-validation provided an unbiased estimation of model performance. Stratified bootstrap revealed the uncertainty in the asymptotic model prediction. Our study validated the utility of machine learning approaches in predicting drug-induced TdP risks from preclinical data. Our methods can be extended to other preclinical protocols and serve as a supplementary evaluation in drug safety assessment.

Meta-analysis application to hERG safety evaluation in clinical trials.

One objective of meta-analysis, which synthesizes evidence across multiple studies, is to assess the consistency and investigate the heterogeneity across studies. In this project, we performed a meta-analysis on moxifloxacin (positive control in QT assessment studies) data to characterize the exposure-response relationship and determine the safety margin associated with 10-msec QTc effects for moxifloxacin based on 26 thorough QT studies submitted to the FDA. Multiple meta-analysis methods were used (including two novel methods) to evaluate the exposure-response relationship and estimate the critical concentration and the corresponding confidence interval of moxifloxacin associated with a 10-msec QTc effect based on the concentration-QTc models. These meta-analysis methods (aggregate data vs. individual participant data; fixed effect vs. random effect) were compared in terms of their precision and robustness. With the selected meta-analysis method, we demonstrated the homogeneity and heterogeneity of the moxifloxacin concentration-QTc relationship in studies. We also estimated the critical concentration of moxifloxacin that can be used to calculate the hERG safety margin of this drug.

Safety assessment of drug impurities for patient safety: A comprehensive review.

Drug impurities are undesirable but unavoidable chemicals which can occur throughout the drug life cycle. The safety implications of drug impurities can be significant given that they can impact safety, quality, and efficacy of drug products and that certain drug impurities are mutagenic, carcinogenic, or teratogenic. The characteristics of drug impurities could be specific to drug modalities (e.g., small molecules vs. biologics). The commonly encountered drug impurities include elemental impurity, residual solvent, organic impurity, host cell protein and DNA, residual viral vector, extractable and leachable, and particle. They can cause various adverse effects such as immunogenicity, infection, genotoxicity, and carcinogenicity upon significant exposure. Therefore, the effective control of these drug impurities is central for patient safety. Regulations and guidelines are available for drug developers to manage them. Their qualification is obtained based on authoritative qualification thresholds or safety assessment following the classic toxicological risk assessment. The current review focuses on the safety assessment science and methodology used for diverse types of drug impurities. Due to the different nature of diverse drug impurities, their safety assessment represents a significant challenge for drug developers.

Comprehensive safety assessment of serendipity berry sweet protein produced from Komagataella phaffii.

Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day.

Safety assessment for nail cosmetics: Framework for the estimation of systemic exposure through the nail plate.

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.

How the Xenopus eleutheroembryonic thyroid assay compares to the amphibian metamorphosis assay for detecting thyroid active chemicals.

The Xenopus Eleutheroembryonic Thyroid Assay (XETA) was recently published as an OECD Test Guideline for detecting chemicals acting on the thyroid axis. However, the OECD validation did not cover all mechanisms that can potentially be detected by the XETA. This study was therefore initiated to investigate and consolidate the applicability domain of the XETA regarding the following mechanisms: thyroid hormone receptor (THR) agonism, sodium-iodide symporter (NIS) inhibition, thyroperoxidase (TPO) inhibition, deiodinase (DIO) inhibition, glucocorticoid receptor (GR) agonism, and uridine 5'-diphospho-glucuronosyltransferase (UDPGT) induction. In total, 22 chemicals identified as thyroid-active or -inactive in Amphibian Metamorphosis Assays (AMAs) were tested using the XETA OECD Test Guideline. The comparison showed that both assays are highly concordant in identifying chemicals with mechanisms of action related to THR agonism, DIO inhibition, and GR agonism. They also consistently identified the UDPGT inducers as thyroid inactive. NIS inhibition, investigated using sodium perchlorate, was not detected in the XETA. TPO inhibition requires further mechanistic investigations as the reference chemicals tested resulted in opposing response directions in the XETA and AMA. This study contributes refining the applicability domain of the XETA, thereby helping to clarify the conditions where it can be used as an ethical alternative to the AMA.

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern.

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

Use of in vitro ADME methods to identify suitable analogs of homosalate and octisalate for use in a read-across safety assessment.

Case studies are needed to demonstrate the use of human-relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read-across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties. We describe how technical aspects of conducting assays for these highly lipophilic chemicals were addressed and interpreted. There were several properties that were common to all five chemicals: they all had similar stability in gastrointestinal fluids (in which no hydrolysis to salicylic occurred); were not substrates of the P-glycoprotein efflux transporter; were highly protein bound; and were hydrolyzed to salicylic acid (which was also a major metabolite). The main properties differentiating the chemicals were their permeability in Caco-2 cells, plasma stability, clearance in hepatic models, and the extent of hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogs for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, indicating it is unsuitable. Isoamyl salicylate can be a suitable analog with interpretation for octisalate. In conclusion, in vitro ADME properties of five chemicals were measured and used to pair target and potential analogs. This study demonstrates the importance of robust ADME data for the selection of analogs in a read-across safety assessment.

In-silico analysis of probiotic attributes and safety assessment of probiotic strain Bacillus coagulans BCP92 for human application.

The whole genome sequence (WGS) of Bacillus coagulans BCP92 is reported along with its genomic analysis of probiotics and safety features. The identification of bacterial strain was carried out using the 16S rDNA sequencing method. Furthermore, gene-related probiotic features, safety assessment (by in vitro and in silico), and genome stability were also studied using the WGS analysis for the possible use of the bacterial strain as a probiotic. From the BLAST analysis, bacterial strain was identified as Bacillus (Heyndrickxia) coagulans. WGS analysis indicated that the genome consists of a 3 475 658 bp and a GC-content of 46.35%. Genome mining of BCP92 revealed that the strain is consist of coding sequences for d-lactate dehydrogenase and l-lactate dehydrogenases, 36 genes involved in fermentation activities, 29 stress-responsive as well as many adhesions related genes. The genome, also possessing genes, is encoded for the synthesis of novel circular bacteriocin. Using an in-silico approach for the bacterial genome study, it was possible to determine that the Bacillus (Heyndrickxia) coagulans strain BCP92 contains genes that are encoded for the probiotic abilities and did not harbour genes that are risk associated, thus confirming the strain's safety and suitability as a probiotic to be used for human application.

Safety assessment of coronary arteries during left bundle branch area pacing.

BACKGROUND: This study aimed to assess the safety of left bundle branch area pacing (LBBAP) by measuring the distance from the tip of the electrode to the nearby coronary artery with a nine-partition grid method. METHODS: From January 2019 to October 2020, patients who underwent LBBAP and postoperative coronary angiography in the Second Affiliated Hospital of Nanchang University were included in the study. The patients' fluoroscopic images of LBBAP and coronary angiography were collected and analyzed. Changes in the ST­T segment in the electrocardiogram (ECG), serum troponin, and myocardial enzyme profiles were observed before and after the LBBAP procedure. RESULTS: A total of 50 patients were included in this study, of whom 46 patients underwent implantation with a pacemaker and 4 patients received an implantable cardioverter defibrillator (ICD). The pacing electrodes were confined to the posterior-middle (PM), median (M), Posterior inferior (PI), and middle inferior (MI) positions of the two-dimensional nine-square grid or in the junction area of the above positions, and were concentrated in the rectangle formed by the line of the center points of the four positions. The average vertical distances from the electrode tip to the left anterior descending branch artery (LAD), posterior descending branches (PD) and the left posterior ventricular branches (PL) were 19.69 ± 8.72 mm, 26.09 ± 8.02 mm, and 21.11 ± 7.86 mm, respectively; the minimum was 5.28 mm, 9.51 mm, and 8.69 mm, respectively. Coronary angiography in all patients showed no significant injury to the ventricular septal branch; however, we observed elevated serum troponin and changes in ST­T segment in ECG. CONCLUSION: The study demonstrates that pacing electrodes in LBBAP can be safely implanted over a wide range. Coronary arteries are likely to be safe when the pacing electrodes are located within the rectangle formed by the line connecting the PM, M, PI, and MI zone centroids. The left bundle branch can be quickly captured and the safety of the coronary artery can be improved by locating the electrode in the posterior-mid zone. The potential risk of injury to the LAD from the electrode is greater compared with the PD.