Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Implementation of Hepatic Artery Infusion Pump Therapy: Real-World Single-Center Experience.

BACKGROUND AND OBJECTIVES: Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center. METHODS: Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months. CONCLUSIONS: HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.

Significance of serological atrophic gastritis on proton pump inhibitor prescriptions and referrals to gastroscopy in the general population.

Background and Aim: We aimed to investigate whether individuals with low pepsinogen I levels differed from those with normal pepsinogen I levels in terms of proton pump inhibitors (PPIs) use, referral to gastroscopy, and findings on gastroscopy. Methods: Serum pepsinogen I was measured in 518 persons (mean age 51.6, SD 8.8; 49% women). A medical chart review focused on PPI prescriptions and gastroscopic findings in the follow-up period. Results: Patients with serological atrophic gastritis (pepsinogen I < 28 µg/L) had higher body mass index (27.5 vs 26.2 kg/m2; P = 0.007), were less likely to be current smokers (8% vs 17%; P = 0.025), and had higher prevalence of Helicobacter pylori seropositivity (57% vs 36%; P < 0.001) compared with those without. During follow-up (mean 21.4 years, SD 6.5 years), the patients with serological atrophic gastritis had more often findings of atrophic gastritis or gastric polyps on gastroscopy (20% vs 8%; P < 0.001), despite no differences in the mean number of gastroscopies per 1000 person-years (33 vs 23; P = 0.19) and the mean prescribed PPI dose (omeprazole equivalents) per year (1064 mg vs 1046 mg; P = 0.95). Persons with serological atrophic gastritis had lower odds of being prescribed PPIs at least once (odds ratio [95% confidence interval]: 0.58 [0.35-0.96]), but there was no significant difference in the chance of being referred to gastroscopy at least once (1.15 [0.70-1.96]). Conclusion: Persons with serological atrophic gastritis were less likely to be prescribed PPIs. Persons with serological atrophic gastritis had more often gastric polyps and atrophic gastritis when referred to gastroscopy.

Dynamic VAD simulations: Performing accurate simulations of ventricular assist devices in interaction with the cardiovascular system.

Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic H-Q curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic H-Q curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic H-Q curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic H-Q curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes.

Classification of Gastric Neuroendocrine Tumors and Associations With Survival.

BACKGROUND AND OBJECTIVES: Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes. METHODS: Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated. RESULTS: Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS. CONCLUSIONS: PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. METHODS: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. RESULTS: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. CONCLUSION: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Single-ion-conducted covalent organic framework serving as Li-ion pump in polyethylene oxide-based electrolyte for robust solid-state Li-S batteries.

Poly(ethylene oxide) (PEO)-based electrolytes are widely used for building solid-state lithium-sulfur (Li-S) batteries but suffer from poor lithium-ion (Li+) transportation kinetics. Here, a lithium-sulfonated covalent organic framework (TpPa-SO3Li) was synthesized and functionalized as a Li+ pump in a PEO-based solid-state electrolyte to fabricate robust Li-S batteries. The designed TpPa-SO3, Li with its porous skeleton and abundant lithium sulfonate groups not only provided iontransport channels but also enhanced the fast migration of Li+. The PEO composite electrolyte containing 5 %-TpPa-SO3Li exhibited a notable ionic conductivity of 6.28 × 10-4 S cm-1 and an impressive Li+ transference number of 0.78 at 60 °C. As a result, Li-Li symmetric batteries with the optimized PEO/TpPa-SO3Li composite electrolyte stably cycled for 300 h, with a minimal overpotential of only 100 mV at 0.5 mA cm-2. Moreover, the customized solid-state Li-S batteries based on PEO/TpPa-SO3Li were stable for 600 cycles at 60 oC with a high Coulombic efficiency of approximately 98 %. This study provides a promising strategy for introducing covalent-organic-framework (COF)-based Li+ pumps to build robust solid-state Li-S batteries.

Medications Affecting Outcomes and Prognosis of Dental Treatment: Part 1.

This article gives valuable insight into the effect of selected groups of medications on dental treatment outcome and prognosis. The review emphasizes the importance of thorough medical history, which may have an impact on the prognosis of dental treatment. We discuss drugs acting on the central nervous system, gastrointestinal tract, respiratory tract, endocrine system, and bone metabolism among others. Other pertinent drugs are discussed elsewhere in this special issue.

Mealtime prediction using wearable insulin pump data to support diabetes management.

Many patients with diabetes struggle with post-meal high blood glucose due to missed or untimely meal-related insulin doses. To address this challenge, our research aims to: (1) study mealtime patterns in patients with type 1 diabetes using wearable insulin pump data, and (2) develop personalized models for predicting future mealtimes to support timely insulin dose administration. Using two independent datasets with over 45,000 meal logs from 82 patients with diabetes, we find that the majority of people ( ∼ 60%) have irregular and inconsistent mealtime patterns that change notably through the course of each day and across months in their own historical data. We also show the feasibility of predicting future mealtimes with personalized LSTM-based models that achieve an average F1 score of > 95% with less than 0.25 false positives per day. Our research lays the groundwork for developing a meal prediction system that can nudge patients with diabetes to administer bolus insulin doses before meal consumption to reduce the occurrence of post-meal high blood glucose.

The left axillary artery is a reasonable option as the inflow site for saphenous vein graft in minimally invasive coronary artery bypass grafting.

Introduction: This study aims to clarify the good inflow site for saphenous vein grafts (SVG) in minimally invasive off-pump coronary artery bypass grafting (mini-CABG), between the ascending aorta, the internal thoracic arteries (ITAs) and the left axillary artery (LAA). Methods: This retrospective study included 126 patients who underwent Mini-CABG at our center between January 2014 and July 2023. Patients were divided into three groups according to the SVG inflow site for patency comparison: Aorta group (n = 56), LAA group (n = 23), and ITA group (n = 47). Results: There were 84 males, with mean age of 65.9 ± 7.0 years. There were no significant differences in preoperative characteristics between groups. Mean operation times were 254.6 ± 72.2, 213.7 ± 57.6, and 253.0 ± 81.2 min, and the average numbers of distal anastomoses were 2.9 ± 0.9, 2.4 ± 0.7 and 2.9 ± 1.1 in the Aorta, ITA and LAA groups respectively. Days in intensive care, hospital stay, and major complications did not differ between the groups. Early patency of SVG did not significantly differ among groups: 93.0% in the Aorta group, 98.0% in the ITA group, and 100% in the LAA group. Mean follow-up period was 136.7 ± 295.7 days, and follow-up coronary CTA revealed 18 SVG occlusions (Aorta group n = 8, ITA group n = 5, LAA group n = 5). The Kaplan-Meier curve for SVG patency rates did not show any significant differences among the three groups. Conclusion: The ascending aorta, the ITAs, and the LAA serve as reliable inflow sites with similar results in mini-CABG.

Proton pump inhibitor alters Th17/Treg balance and induces gut dysbiosis suppressing contact hypersensitivity reaction in mice.

Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1ß, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαß+ CD4+ IL-17A+ and TCRαß+ CD8+ IL-17A+ T cells and increased frequency of TCRαß+ CD4+ CD25+ FoxP3+ Treg, and TCRαß+ CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.

Organic carbon cycling in the sediments of Prydz Bay, Eastern Antarctica: Implications for a high carbon sequestration potential.

Understanding the dynamics of sedimentary organic carbon (SOC) in the productive continental marginal sea surrounding Antarctica is crucial for elucidating the effect of this sea on the global carbon cycle. We analyzed 31 surface sediment samples and eight sediment cores collected from Prydz Bay (PB) and the adjacent basin area. The element and stable isotope compositions, grain size compositions, and biogenic silica and lithogenic minerals of these samples were used to evaluate the spatial variations in the sources, transport mechanisms, and preservation patterns of SOC, with a particular focus on the efficiency of the biological carbon pump (BCP). Our findings reveal that the SOC originated from mixed marine/terrestrial sources. The δ13C values were higher in the Prydz Bay Gyre (PBG) region than in the open sea area. Biogenic matter-rich debris, associated with fine-grained particles (silt and clay), was concentrated in the PBG, while abiotic ice-rafted debris and coarse-grained particles were preferentially deposited in the bank and ice shelf front regions. Lithogenic matter predominated in the basin sediments. The annual accumulation rate of SOC in PB ranged from 1.6 to 6.2 g·m-2·yr-1 (mean 4.2 ± 1.9 g·m-2·yr-1), and the rates were higher in the PBG than in the ice shelf front region. Estimates based on our tentative box model suggest that the efficiency of the BCP, which refers to the proportion of surface-produced organic carbon successfully transferred to deep waters, is approximately 5.7 % in PB, surpassing the global average (∼0.8 %) and the efficiencies reported for other polar environments. Furthermore, our calculations indicate that the SOC preservation efficiency (the ratio of preserved to initially deposited organic carbon in sediments) in PB is approximately 79 % ± 20 %, underscoring the significant carbon sequestration potential within PB. The results of this study have important implications for the effects of sediment dynamics on the carbon cycle in the sea surrounding Antarctica.

acetylcysteine promotes doxycycline resistance in the bacterial pathogen edwardsiella tarda.

Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.

Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion.

INTRODUCTION: Insulin pump therapy can be adversely affected by interruption of insulin flow, leading to a rise in blood glucose (BG) and subsequently of blood beta-hydroxybutyrate (BHB) ketone levels. METHODS: We performed a PubMed search for English language reports (January 1982 to July 2024) estimating the rate of rise in BG and/or BHB after ≥ 60 minutes of interruption of continuous subcutaneous insulin infusion (CSII) in persons with type 1 diabetes (PwT1D). We also simulated the rise in BG in a virtual population of 100 adults with T1D following suspension of continuous subcutaneous insulin infusion. RESULTS: We identified eight relevant studies where BG and BHB (seven of these eight studies) were measured following suspension of CSII as a model for occlusion. After 60 minutes post-suspension, the mean extracted rates of rise averaged 0.62 mg/dL/min (37 mg/dL/h) for BG and 0.0038 mmol/L/min (0.20 mmol/L/h) for BHB. Mean estimated time to moderately/severely elevated BG (300/400 mg/dL) or BHB (1.6/3.0 mmol/L) was, respectively, 5.8/8.5 and 8.0/14.2 hours. The simulation model predicted moderately/severely elevated BG (300/400 mg/dL) after 9.25/12, 6.75/8.75, and 4.75/5.75 hours in the virtual subjects post-interruption with small (5th percentile), medium (50th percentile), and large (95th percentile) hyperglycemic changes. DISCUSSION: Clinical studies and a simulation model similarly predicted that, following CSII interruption, moderate/severe hyperglycemia can occur within 5-9/6-14 hours, and clinical studies predicted that moderate/severe ketonemia can occur within 7-12/13-21 hours. Patients and clinicians should be aware of this timing when considering the risks of developing metabolic complications after insulin pump occlusion.

Spinal Cord Infarction During Extracorporeal Membrane Oxygenation：A Case Series and Review of the Literature.

Background: Little is known about extracorporeal membrane oxygenation (ECMO)-related spinal cord infarction (SCI), and reports regarding this rare and catastrophic complication are rare. Here, we report two cases of ECMO-related SCI that occurred between April and December 2023. Data were collected from patients' medical records, with SCI as the endpoint. We reviewed previously published reports by searching PubMed and summarizing the findings. Case summary: One female patient presenting with multiple traumas required oxygenation support through veno-venous ECMO (VV ECMO) due to pulmonary hemorrhage, while one male patient required circulatory support via veno-arterial ECMO (VA ECMO) concurrently with an intra-aortic balloon pump due to cardiac arrest. Neither patient had preexisting neurological deficits; however, upon weaning from ECMO, they presented with severe neurological deficits of uncertain etiology, subsequently confirmed as SCI using magnetic resonance imaging. Conclusion: ECMO-related SCI remains elusive and intricate, and this is the first report of adult VV ECMO-related SCI.

Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential.

Efflux pumps are well known to be an important mechanism for removing noxious substances such as antibiotics from bacteria. Given that many antibiotics function by accumulating inside bacteria, efflux pumps contribute to resistance. Efflux pump inactivation is a potential strategy to combat antimicrobial resistance, as bacteria would not be able to pump out antibiotics. We recently discovered that the impact of loss of efflux function is only apparent in actively growing cells. We demonstrated that the global transcriptome of Salmonella Typhimurium is drastically altered during slower growth leading to stationary-phase cells having a remodeled, less permeable envelope that prevents antibiotics entering the cell. Here, we investigated the effects of deleting the major efflux pump of Salmonella Typhimurium, AcrB, on global gene transcription across growth. We revealed that an acrB knockout entered stationary phase later than the wild-type strain SL1344 and displayed increased and prolonged expression of genes responsible for anaerobic energy metabolism. We devised a model linking efflux and membrane potential, whereby deactivation of AcrB prevents influx of protons across the inner membrane and thereby hyperpolarization. Knockout or deactivation of AcrB was demonstrated to increase membrane potential. We propose that the global transcription regulator ArcBA senses changes to the redox state of the quinol pool (linked to the membrane potential of the bacterium) and coordinates the shift from exponential to stationary phase via the key master regulators RpoS, Rsd, and Rmf. Inactivation of efflux pumps therefore influences the fundamental physiology of Salmonella, with likely impacts on multiple phenotypes.IMPORTANCEWe demonstrate for the first time that deactivation of efflux pumps brings about changes to gross bacterial physiology and metabolism. Rather than simply being a response to noxious substances, efflux pumps appear to play a key role in maintenance of membrane potential and thereby energy metabolism. This discovery suggests that efflux pump inhibition or inactivation might have unforeseen positive consequences on antibiotic activity. Given that stationary-phase bacteria are more resistant to antibiotic uptake, late entry into stationary phase would prolong antibiotic accumulation by bacteria. Furthermore, membrane hyperpolarization could result in increased generation of reactive species proposed to be important for the activity of some antibiotics. Finally, changes in gross physiology could also explain the decreased virulence of efflux mutants.

Off-pump vs. on-pump coronary artery bypass grafting in patients with chronic kidney disease: an updated systematic review and meta-analysis.

BACKGROUND: In patients with chronic kidney disease (CKD), cardiovascular disease is found to be the primary cause of mortality, and after coronary artery bypass grafting (CABG), their prognosis deteriorates. METHODS: We conducted a meta-analysis comparing off-pump CABG versus on-pump CABG in CKD patients. We searched electronic databases, including PubMed, Cochrane, and Google Scholar, using relevant keywords. We included studies comparing off-pump CABG with on-pump CABG in patients with chronic kidney disease, which was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2. Effect estimates were synthesized using a random-effects model and expressed as risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with corresponding 95% confidence intervals (CIs). Our primary outcome was short-term mortality. RESULTS: A total of 25 studies, of which 23 were observational and 2 were RCTs, were included in this meta-analysis, comprising 234,585 patients (66,591 in the off-pump group and 167,994 in the on-pump group). Our meta-analysis showed that there was a significantly higher mortality rate in the on-pump CABG group as compared to the off-pump CABG group (RR: 0.73, 95% CI [0.61, 0.88]; P = 0.0006, I2 = 60%). CONCLUSION: Compared with OPCAB, short-term mortality was significantly higher in ONCAB.

Global genomic epidemiology and transmission dynamics of plasmid-borne tmexCD-toprJ-carrying Klebsiella pneumoniae in a one health context.

The emergence of tmexCD-toprJ, a novel plasmid-mediated resistance-nodulation-division (RND) type efflux pump gene cluster, poses a significant threat to public health by diminishing bacterial susceptibility to the last-resort antibiotics, including tigecycline. Between 2020 and 2022, 18 Klebsiella pneumoniae strains carrying the tmexCD-toprJ gene were recovered from over 30,000 human stool samples collected from patients across five hospitals in China. Phylogenetic analysis of these 18 strains revealed clonal transmission of tmexCD-toprJ-carrying K. pneumoniae among patients and hospital settings. Comparative analysis of the 18 tmexCD-toprJ-carrying plasmids showed conservation in the genetic backgrounds of tmexCD-toprJ, despite the diverse backbone structures among the plasmids. The inactive suppressor, TNfxB1, is located in front of all tmexCD1-toprJ1, while TNfxB3 is located upstream of tmexCD3-toprJ3. Conjugation experiments demonstrated the transferability of plasmids from three strains to the recipient Escherichia coli J53. Among all 237 globally distributed tmexCD-toprJ-carrying strains, the majority (92.83 %) were from China. These strains encompassed 50 sequence types, with the most prevalent being ST11 (12.66 %), ST37 (11.81 %), and ST15 (11.39 %). Samples originated from various sources: 47.26 % from human, 38.82 % from livestock, and 13.08 % from the environment. The most common tmexCD-toprJ genotype was tmexCD1-toprJ1 (86.92 %, n = 206), followed by tmexCD2-toprJ2 (8.86 %, n = 21) and tmexCD3-toprJ3 (4.22 %, n = 10). The tmexCD1-toprJ1 gene was found in livestock (44.66 %, n = 92), humans (39.81 %, n = 82), and environmental samples (15.05 %, n = 31). In contrast, tmexCD2-toprJ2 and tmexCD3-toprJ3 were only found in human samples. Additionally, tmexCD-toprJ has been detected in 79 strains of K. pneumoniae harboring carbapenem-resistance genes. Given the presence of tmexCD-toprJ across various hosts and environments, establishing a comprehensive surveillance system from a One Health perspective is particularly vital.