Recent advances in c-Met-based dual inhibitors in the treatment of cancers.

The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Potential coupling of microbial methane, nitrogen, and sulphur cycling in the Okinawa Trough cold seep sediments.

The Okinawa Trough (OT) is a back-arc basin with a wide distribution of active cold seep systems. However, our understanding of the metabolic function of microbial communities in the cold seep sediments of the OT remains limited. In this study, we investigated the vertical profiles of functional genes involved in methane, nitrogen, and sulphur cycling in the cold seep sediments of the OT. Furthermore, we explored the possible coupling mechanisms between these biogeochemical cycles. The study revealed that the majority of genes associated with the nitrogen and sulphur cycles were most abundant in the surface sediment layers. However, only the key genes responsible for sulphur disproportionation (sor), nitrogen fixation (nifDKH), and methane metabolism (mcrABG) were more prevalent within sulfate-methane transition zone (SMTZ). Significant positive correlations (P < 0.05) were observed between functional genes involved in sulphur oxidation, thiosulphate disproportionation with denitrification, and dissimilatory nitrate reduction to ammonium (DNRA), as well as between AOM/methanogenesis and nitrogen fixation, and between sulphur disproportionation and AOM. A genome of Filomicrobium (class Alphaproteobacteria) has demonstrated potential in chemoautotrophic activities, particularly in coupling DNRA and denitrification with sulphur oxidation. Additionally, the characterized sulfate reducers such as Syntrophobacterales have been found to be capable of utilizing nitrate as an electron acceptor. The predominant methanogenic/methanotrophic groups in the OT sediments were identified as H2-dependent methylotrophic methanogens (Methanomassiliicoccales and Methanofastidiosales) and ANME-1a. This study offered a thorough understanding of microbial ecosystems in the OT cold seep sediments, emphasizing their contribution to nutrient cycling.IMPORTANCEThe Okinawa Trough (OT) is a back-arc basin formed by extension within the continental lithosphere behind the Ryukyu Trench arc system. Cold seeps are widespread in the OT. While some studies have explored microbial communities in OT cold seep sediments, their metabolic potential remains largely unknown. In this study, we used metagenomic analysis to enhance comprehension of the microbial community's role in nutrient cycling and proposed hypotheses on the coupling process and mechanisms involved in biogeochemical cycles. It was revealed that multiple metabolic pathways can be performed by a single organism or microbes that interact with each other to carry out various biogeochemical cycling. This data set provided a genomic road map on microbial nutrient cycling in OT sediment microbial communities.

Identification of potential key lipid metabolism-related genes involved in tubular injury in diabetic kidney disease by bioinformatics analysis.

AIMS: Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. METHODS: Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. RESULTS: There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. CONCLUSION: Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

Association between serum vitamin A and body mass index in adolescents from NHANES 1999 to 2006.

Vitamin A plays a pivotal role in health, particularly in regulating fat metabolism. Despite its significance, research into the direct relationship between vitamin A levels and obesity, especially among adolescents, is sparse. This study aims to explore this association within the adolescent population in the United States. This cross-sectional study analyzed the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006, with 8218 participants. The levels of vitamin A in the serum were determined based on utilizing high-performance liquid chromatography with photodiode array detection. The relationship between serum vitamin A concentrations and body mass index (BMI) was evaluated using weighted multiple linear regression models, incorporating subgroup analyses by sex and race/ethnicity to provide nuanced insights. A positive correlation was observed between serum vitamin A levels and BMI, with BMI increasing progressively across vitamin A quartiles (P < 0.001). Using the lowest quartile of serum vitamin A as a reference, the BMI of the highest quartile of serum vitamin A was 1.236 times higher (95% CI 0.888, 1.585). Subgroup analyses revealed that this positive association persisted across different genders and racial/ethnic groups (P < 0.001). Notably, smooth curve fitting and saturation threshold analysis unveiled an inverted U-shaped relationship between serum vitamin A and BMI among female adolescents, non-Hispanic Whites, Mexican Americans, and other races/ethnicities groups. Our study substantiates the association between serum vitamin A levels and the risk of obesity/overweight status in adolescents. The findings suggest the potential serum vitamin A is an early biomarker for identifying obesity risk, although further studies are needed to determine to clarify its role as a contributing factor to obesity. This study contributes to the understanding of nutritional influences on adolescent obesity, highlighting the need for targeted interventions based on serum biomarkers.

Verteporfin inhibits TGF-ß signaling by disrupting the Smad2/3-Smad4 interaction.

Transforming growth factor-ß (TGF-ß) signaling plays a crucial role in pathogenesis, such as accelerating tissue fibrosis and promoting tumor development at the later stages of tumorigenesis by promoting epithelial-mesenchymal transition, cancer cell migration, and invasion. Targeting TGF-ß signaling is a promising therapeutic approach, but non-specific inhibition may result in adverse effects. In this study, we focus on the Smad2/3-Smad4 complex, a key component in TGF-ß signaling transduction, as a potential target for cancer therapy. Through a phase-separated condensate-aided biomolecular interaction system, we identified verteporfin (VP) as a small-molecule inhibitor that specifically targets the Smad2/3-Smad4 interaction. VP effectively disrupted the interaction between Smad2/3 and Smad4 and thereby inhibited canonical TGF-ß signaling, but not the interaction between Smad1 and Smad4 in BMP signaling. Furthermore, VP exhibited inhibitory effects on TGF-ß-induced epithelial-mesenchymal transition and cell migration. Our findings indicate a novel approach to develop protein-protein interaction inhibitors of the canonical TGF-ß signaling pathway for treatments of related diseases.

PD-1/PD-L1 axis is involved in the interaction between microglial polarization and glioma.

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.

Integrated analysis of ATAC-seq and transcriptomic reveals the ScDof3-ScproC molecular module regulating the cold acclimation capacity of potato.

Low temperature severely affects the geographical distribution and production of potato, which may incur cold damage in early spring or winter. Cultivated potatoes, mainly derived from Solanum tuberosum, are sensitive to freezing stress, but wild species of potato such as S. commersonii exhibit both constitutive freezing tolerance and/or cold acclimation tolerance. Hence, such wild species could assist in cold hardiness breeding. Yet the key transcription factors and their downstream functional genes that confer freezing tolerance are far from clear, hindering the breeding process. Here, we used ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) alongside RNA-seq to investigate the variation in chromatin accessibility and patterns of gene expression in freezing-tolerant CMM5 (S. commersonii), before and after its cold treatment. Our results suggest that after exposure to cold, transcription factors including Dof3, ABF2, PIF4, and MYB4 were predicted to further control the genes active in the synthetic/metabolic pathways of plant hormones, namely abscisic acid, polyamine, and reductive glutathione (among others). This suggests these transcription factors could regulate freezing tolerance of CMM5 leaves. In particular, ScDof3 was proven to regulate the expression of ScproC (pyrroline-5-carboxylate reductase, P5CR) according to dual-LUC assays. Overexpressing ScDof3 in Nicotiana benthamiana leaves led to an increase in both the proline content and expression level of NbproC (homolog of ScproC). These results demonstrate the ScDof3-ScproC module regulates the proline content and thus promotes freezing tolerance in potato. Our research provides valuable genetic resources to further study the molecular mechanisms underpinning cold tolerance in potato.

Correction: Lattice engineering of noble metal-based nanomaterials via metal-nonmetal interactions for catalytic applications.

Correction for 'Lattice engineering of noble metal-based nanomaterials via metal-nonmetal interactions for catalytic applications' by Long Zheng et al., Nanoscale, 2024, https://doi.org/10.1039/d4nr00561a.

Temporal Alterations in Cerebrovascular Glycocalyx and Cerebral Blood Flow after Exposure to a High-Intensity Blast in Rats.

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.

Comparison of outcomes and characteristics of patients admitted to the ICU with COVID-19 and other community-acquired pneumonia based on propensity score matching.

OBJECTIVE: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. METHODS: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. RESULTS: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). CONCLUSION: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients.

Predictors of Corporal Punishment during the COVID-19 Pandemic.

Although current policies discourage the use of corporal punishment (CP), its use is still widespread in the US. The objective of this study was to assess the proportion of parents who used CP during the pandemic and identify related risk and protective factors. We analyzed results of a nationwide cross-sectional internet panel survey of 9000 US caregivers who responded in three waves from November 2020 to July 2021. One in six respondents reported having spanked their child in the past week. Spanking was associated with intimate partner violence and the use of multiple discipline strategies and not significantly associated with region or racial self-identification. Parents who spanked sought out more kinds of support, suggesting an opportunity to reduce spanking through more effective parenting resources. Additionally, these results suggest that parents who report using CP may be at risk for concurrent domestic violence.

Unveiling new horizons in heart research: the promise of multi-chamber cardiac organoids.

Human cardiac and other organoids have recently emerged as a groundbreaking tool for advancing our understanding the developmental biology of human organs. A recent paper from Sasha Mendjan's laboratory published in the journal Cell on December 7, 2023, reported the generation of multi-chamber cardioids from human pluripotent stem cells, a transformative technology in the field of cardiology. In this short highlight paper, we summarize their findings. Their cardioids remarkably recapitulate the complexity of the human embryonic heart, including tissue architecture, cellular diversity, and functionality providing an excellent in vitro model for investigation of human heart development, disease modeling, precision medicine, and regenerative medicine. Thus, generating cardioids is an important step forward for understanding human heart development and developing potential therapies for heart diseases.

Spontaneous Compositional-Interfacial Co-Modification Engineering via Ion Exchange Reaction Between Perovskite and Electron-Transporting Layer for Exceptionally Long-Term Stability of Photovoltaics.

The long-term stability of perovskite solar cells (PSCs) is still challenging for commercialization and mainly linked to the life span of perovskite films. Herein, a spontaneous compositional-interfacial co-modification strategy is developed based on the ion exchange reaction by introducing ammonium hexafluorophosphate (NH4PF6) into antisolvent to form gradient structures through a simple one-step solvent engineering. With the assistance of the ion exchange reaction, NH4PF6 forms a multifunctional structure to protect perovskite films from both internal and external factors for the exceptionally long-term stability of photovoltaics. The reason for this is linked to the high hydrophobicity of NH4PF6 for preventing H2O invasion, suppressing ion migration by forming hydrogen bonding, and reducing perovskite defects. The resulting unencapsulated devices show exceptionally long-term stability under standardized the International Summit on Organic Photovoltaic Stability (ISOS) protocols, with over 94%, 81%, and 83% retained power conversion efficiencies after aging tests under N2 (ISOS-D-1I), ambient air (ISOS-D-1), and 85 °C (ISOS-D-2I) for 14016, 2500, and 1248 h, respectively. These performances compare well with the state-of-the-art stability of inverted PSCs. Further investigations are conducted to study the evolution of macroscopic morphology and microscopic crystal structure in aged perovskite films, aiming to provide evidence supporting the aforementioned improvements in stability.

Organoid Culture of Different Intestinal Segments from Human and Mouse.

The intestine comprises distinct segments, each characterized by unique cell populations and functions. Intestinal organoids faithfully replicate the cellular composition and functions of the intestine. Over the past decade, the organoid model has garnered considerable attention for its application in investigation of organ development, renewal and functional performance. While the organoid culture systems for mouse small intestine and human large intestine have widely adopted, a comparison summary for different segments of the human or mouse intestine is lacking. In this study, we present a systematically detailed culture methodology for intestinal organoids, encompassing both the small intestine and the large intestine from humans or mice. This method provides a robust in vitro tool for intestinal research, and expands the possible clinical application of organoids.

Comparison of 1-stage and 2-stage Managements for Common Bile Duct Stones and Gallstones (CBDS): A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.

MiRNA-148a-containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model.

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrated that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cells balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of RA patients. Overall, the unique characteristics, including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues, position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.

The association between school educational atmosphere, learning engagement, and professional commitment of nursing students, and learning engagement as the mediator.

BACKGROUND: The current shortage and loss of nurses has become a significant problem in healthcare systems around the world. Professional commitment is essential to prevent the loss of nursing staff and stabilize the nursing workforce. OBJECTIVES: This study aimed to explore the unique relationship between school educational atmosphere, learning engagement, and professional commitment, and whether learning engagement would mediate the relationship between educational atmosphere and professional commitment. DESIGN: A cross-sectional study design was used. SETTINGS: The participants came from six schools in four cities in Hubei Province, China. PARTICIPANTS: A total of 1009 nursing students above the first year of undergraduate studies were included by convenient sampling method. METHODS: Data were collected using the Educational Climate Inventory, the Utrecht Work Engagement Scale-student, and the Professional Commitment Scale. Pearson correlation was used to examine the relationship between educational atmosphere, learning engagement, and professional commitment. Mediation analysis was used to test whether learning engagement mediated the relationship between educational atmosphere and professional commitment. RESULTS: A positive educational atmosphere was associated with a high level of learning engagement, which was associated with a higher level of professional commitment. Learning engagement mediated the relationship between educational atmosphere and professional commitment. CONCLUSIONS: The findings provide empirical evidence for promoting professional commitment in nursing students. Learning engagement is an important mediating variable connecting educational atmosphere and professional commitment. In order to stabilize the career choices of nursing students, it is necessary to take measures to improve their learning engagement during school.

The spatiotemporal epidemiological study on human brucellosis in shenyang, China from 2013 to 2022.

Background: Epidemiological characteristics of human brucellosis (HB) have changed over the last decade. In this study, we depicted the spatiotemporal features of HB in Shenyang, China, from 2013 to 2022 and the objective was to visualise spatiotemporal patterns and identify high-risk regions with the purpose to provide evidence for HB prevention and control. Methods: We performed an observational epidemiological study using HB data obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression analysis was employed to determine the changing trends in the annual incidence. A vector boundary map of Shenyang was used to visualise spatial distribution. Spatial autocorrelation was identified using both global and local Moran's autocorrelation coefficients, while hotspot areas were determined using the Getis-Ord statistic. Results: A combined sum of 4103 HB cases were analysed, and the average level of annual incidence of HB was 5.52 per 100,000. The incidence of HB showed obvious seasonality, with a notable peak observed from April to July (summer peak). The annual incidence in Shenyang has been on the rise since 2013, with an annual percentage change (APC) of 6.39% (95%CI 1.29%, 12.39%). Xinmin County exhibited the most elevated average annual incidence rate, with Faku County ranking second. The average annual incidence in rural areas exhibited a significantly greater disparity compared to suburban areas (P < 0.001), whereas the incidence rate in suburban areas demonstrated a significantly higher contrast when compared to urban areas (P < 0.001). A clustered distribution of the annual incidence of HB was observed for all years from 2013 to 2022. Abnormally high values were found in suburban areas, and no abnormally high values were found after 2017. The low-low clustering areas were found in urban as well as suburban areas from 2013 to 2022. Hotspots (P < 0.05) were located in rural areas, while cold spots (P < 0.05) were found in both urban and suburban areas. Since 2020, there have been no hotspots in Shenyang. Conclusions: Rural areas are high-risk areas for HB and may be key to controlling HB epidemics. Although the annual incidence of HB in rural areas has increased, owing to the stability of spatial relationships and the disappearance of hotspots, there is little possibility of outbreaks; however, stricter monitoring should be applied in rural areas to prevent the emergence of new transmission routes.