Joint Exposure to Multiple Air Pollutants, Genetic Susceptibility, and Incident Dementia: A Prospective Analysis in the UK Biobank Cohort.

Objectives: This study aimed to evaluate the joint effects of multiple air pollutants including PM2.5, PM10, NO2, and NOx with dementia and examined the modifying effects of genetic susceptibility. Methods: This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance weighted meta-analyses were performed to create a pooled effect. The modifying effect of genetic susceptibility on air pollution score was assessed by genetic risk score and APOE ε4 genotype. Results: The HR (95% CI) of dementia for per interquartile range increase of air pollution score was 1.13 (1.07∼1.18). Compared with the lowest quartile (Q1) of air pollution score, the HR (95% CI) of Q4 was 1.26 (1.13∼1.40) (P trend = 2.17 × 10-5). Participants with high air pollution score and high genetic susceptibility had higher risk of dementia compared to those with low air pollution score and low genetic susceptibility. Conclusion: Our study provides evidence that joint exposure to multiple air pollutants substantially increases the risk of dementia, especially among individuals with high genetic susceptibility.

Assessing the stress-relief impact of an art-based intervention inspired by the broaden-and-build theory in college students.

Background and objectives: This study's primary objective is to investigate the impact of art-making on the mental well-being of college students, who often experience heightened stress during their initial university years. Methods: Employing a comprehensive methodology, combining interviews and the Perceived Stress Scale (PSS), the research aimed to assess whether a four-week art-making intervention can effectively alleviate stress levels among college students. In the experimental group, participants engaged in a variety of art-making activities, including freehand drawing, clay modeling, and crafting. Results: The results revealed that, in the pre-test, there were no significant differences between the experimental and control groups for each assessed indicator. However, in the post-test, significant differences emerged across all indicators. Further analysis demonstrated a significant reduction in stress perception among the experimental group participants between the pre-test and post-test phases. Conclusion: In conclusion, this study provides compelling evidence that art-making has the potential to foster positive personal development and significantly reduce stress levels among college students.

Long-term adverse influence of smoking during pregnancy on height and body size of offspring at ten years old in the UK Biobank cohort.

Background: To explore the long-term relationship between maternal smoking during pregnancy and early childhood growth in the UK Biobank cohort. Methods: To estimate the effect of maternal smoking during pregnancy on offspring height and body size at ten years old, we performed binary logistic analyses and reported odds ratios (OR) as well as 95% confidence intervals (95%CIs). We also implemented the cross-contextual comparison study to examine whether such influence could be repeatedly observed among three different ethnicities in the UK Biobank cohort (n = 22,140 for White, n = 7094 for South Asian, and n = 5000 for Black). In particular, we conducted the sibling cohort study in White sibling cohort (n = 9953 for height and n = 7239 for body size) to control for unmeasured familial confounders. Results: We discovered that children whose mothers smoked during pregnancy had greater risk of being shorter or plumper at age ten in the full UK Biobank White cohort, with 15.3% (95% CIs: 13.0%∼17.7%) higher risk for height and 32.4% (95%CIs: 29.5%∼35.4%) larger risk for body size. Similar associations were identified in the South Asian and Black ethnicities. These associations were robust and remained significant in the White sibling cohort (12.6% [95%CIs: 5.0%∼20.3%] for height and 36.1% [95%CIs: 26.3%∼45.9%] for body size) after controlling for family factors. Conclusion: This study robustly confirms that maternal smoking during pregnancy can promote height deficit and obesity for offspring at ten years old. Our findings strongly encourage mothers to quit smoking during pregnancy for improving growth and development of offspring.

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature.

BACKGROUND: Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY: A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION: This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

Enhanced active-site electric field accelerates enzyme catalysis.

The design and improvement of enzymes based on physical principles remain challenging. Here we demonstrate that the principle of electrostatic catalysis can be leveraged to substantially improve a natural enzyme's activity. We enhanced the active-site electric field in horse liver alcohol dehydrogenase by replacing the serine hydrogen-bond donor with threonine and replacing the catalytic Zn2+ with Co2+. Based on the electric field enhancement, we make a quantitative prediction of rate acceleration-50-fold faster than the wild-type enzyme-which was in close agreement with experimental measurements. The effects of the hydrogen bonding and metal coordination, two distinct chemical forces, are described by a unified physical quantity-electric field, which is quantitative, and shown here to be additive and predictive. These results suggest a new design paradigm for both biological and non-biological catalysts.

Ecological shifts of salivary microbiota associated with metabolic-associated fatty liver disease.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota. Methods: Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests. Results: The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct ß-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups. Conclusions: Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG3Glu-co-Cys) and maleimide-functionalized polysarcosine under biologically benign conditions. The PAA-RGD hydrogel shows suitable biodegradability, excellent biocompatibility, and low immunogenicity, which together lead to optimal performance for osteochondral repair in New Zealand white rabbits even at the early stage of implantation. Further in vitro and in vivo mechanistic studies corroborate the immunomodulatory role of the PAA-RGD hydrogel, which induces minimum FBR responses and a high level of polarization of macrophages into the immunosuppressive M2 subtypes. These findings demonstrate the promising potential of the PAA-RGD hydrogel for osteochondral regeneration and highlight the importance of immunomodulation. The results may inspire the development of PAA-based materials for not only osteochondral defect repair but also various other tissue engineering and bio-implantation applications.

Design and application of auxiliary system for drug distribution in outpatient pharmacy / 药学实践杂志

Objective To construct the auxiliary system of outpatient drug distribution, reduce errors and improve the quality of outpatient pharmaceutical service. Methods The bar code technology was used to independently develop outpatient pharmacy dispensing assistant system. The system design and function are introduced. The practical application effect of the system was evaluated on dispensing errors, efficiency and pharmacist evaluation. Results Based on the special network environment of the hospital, the system integrated the functions of drug check, prescription right management, expiration date management and medication instruction. After using the system, the number of dispensing errors decreased from 84 to 25. The waiting time for patients to receive medicine decreased by 151 seconds. All pharmacists surveyed agreed that auxiliary system was helpful to pharmacists’ work. Conclusion The system reduced the medication dispensing error in outpatient pharmacy, improved work efficiency and the quality of pharmaceutical care.

Variety ACEs and risk of developing anxiety, depression, or anxiety-depression co-morbidity: the 2006-2022 UK Biobank data.

Objectives: Adverse childhood experiences (ACEs) and anxiety-depression co-morbidity are attracting widespread attention. Previous studies have shown the relationship between individual psychiatric disorders and ACEs. This study will analyze the correlation between anxiety-depression co-morbidity and different levels of ACEs. Methods: Seven categories of ACE and four classifications of psychiatric disorders were defined in a sample of 126,064 participants identified by the UK Biobank from 2006-2022, and correlations were investigated using logistic regression models. Then, to explore nonlinear relationships, restricted spline models were developed to examine differences in sex and age across cohorts (n = 126,064 for the full cohort and n = 121,934 for the European cohort). Finally, the impact of the category of ACEs on psychiatric disorders was examined. Results: After controlling for confounders, ACEs scores showed dose-dependent relationships with depression, anxiety, anxiety-depression co-morbidity, and at least one (any of the first three outcomes) in all models. ACEs with different scores were significantly positively correlated with the four psychiatric disorders classifications, with the highest odds of anxiety-depression co-morbidity (odds ratio [OR] = 4.87, 95% confidence intervals [CI]: 4.37 ~ 5.43), p = 6.08 × 10-178. In the restricted cubic spline models, the risk was relatively flat for females at ACEs = 0-1 and males at ACEs = 0-2/3 (except in males, where ACEs were associated with a lower risk of anxiety, all other psychiatric disorders had an increased risk of morbidity after risk smoothing). In addition, the risk of having anxiety, depression, anxiety-depression co-morbidity, and at least one of these disorders varies with each category of ACEs. Conclusion: The prevalence of anxiety-depression comorbidity was highest across ACE scores after controlling for confounding factors and had a significant effect on each category of ACEs.

LncRNA LINC01537 Promotes Gastric Cancer Metastasis and Tumorigenesis by Stabilizing RIPK4 to Activate NF-κB Signaling.

Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.

Screening high-risk population of persistent postpartum hypertension in women with preeclampsia using latent class cluster analysis.

BACKGROUND: A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN. METHODS: This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN. RESULTS: The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92-8.27) and three times (OR, 2.931; 95% CI, 1.91-4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups. CONCLUSION: Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study's findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Joint elasticity produces energy efficiency in underwater locomotion: Verification with deep reinforcement learning.

Underwater snake robots have received attention because of their unique mechanics and locomotion patterns. Given their highly redundant degrees of freedom, designing an energy-efficient gait has been a main challenge for the long-term autonomy of underwater snake robots. We propose a gait design method for an underwater snake robot based on deep reinforcement learning and curriculum learning. For comparison, we consider the gait generated by a conventional parametric gait equation controller as the baseline. Furthermore, inspired by the joints of living organisms, we consider elasticity (stiffness) in the joints of the snake robot to verify whether it contributes to the generation of energy efficiency in the underwater gait. We first demonstrate that the deep reinforcement learning controller can produce a more energy-efficient gait than the gait equation controller in underwater locomotion, by finding the control patterns which maximize the effect of energy efficiency through the exploitation of joint elasticity. In addition, appropriate joint elasticity can increase the maximum velocity achievable by a snake robot. Finally, simulation results in different liquid environments confirm that the deep reinforcement learning controller is superior to the gait equation controller, and it can find adaptive energy-efficient motion even when the liquid environment is changed. The video can be viewed at https://youtu.be/wpwQihhntEY.

Chordoma of petrosal mastoid region: A case report.

BACKGROUND: Chordoma is a rare low-grade malignant tumor originating from embryonic notochordal tissue mainly occurring in the axial bone, mostly in the spheno-occipital junction and sacrococcyx, which accounts for approximately 1% of all malignant bone tumors and 0.1%-0.2% of intracranial tumors. Chordoma in the petrous mastoid region is rare. CASE SUMMARY: We describe a 36-year-old male patient with chordoma in the left petrous mastoid region. The main clinical manifestations were pain and discomfort, which lasted for 2 years. Magnetic resonance imaging showed a lobulated mass in the left petrous mastoid with an unclear boundary and obvious enhancement. The tumor was completely removed after surgical treatment, and a histological examination confirmed that the tumor was a chordoma. During 5 years of follow-up, no clinical or radiological evidence of recurrence or metastasis was found. CONCLUSION: Chordoma in the petrosal mastoid region is rare but should be included in differential diagnosis of petrosal mastoid tumors.

Solvent Organization and Electrostatics Tuned by Solute Electronic Structure: Amide versus Non-Amide Carbonyls.

The ability to exploit carbonyl groups to measure electric fields in enzymes and other complex reactive environments by using the vibrational Stark effect has inspired growing interest in how these fields can be measured, tuned, and ultimately designed. Previous studies have concentrated on the role of the solvent in tuning the fields exerted on the solute. Here, we explore instead the role of the solute electronic structure in modifying the local solvent organization and electric field exerted on the solute. By measuring the infrared absorption spectra of amide-containing molecules, as prototypical peptides, and contrasting them with non-amide carbonyls in a wide range of solvents, we show that these solutes experience notable differences in their frequency shifts in polar solvents. Using vibrational Stark spectroscopy and molecular dynamics simulations, we demonstrate that while some of these differences can be rationalized by using the distinct intrinsic Stark tuning rates of the solutes, the larger frequency shifts for amides and dimethylurea primarily result from the larger solvent electric fields experienced by their carbonyl groups. These larger fields arise due to their stronger p-π conjugation, which results in larger C═O bond dipole moments that further induce substantial solvent organization. Using electronic structure calculations, we decompose the electric fields into contributions from solvent molecules that are in the first solvation shell and those from the bulk and show that both of these contributions are significant and become larger with enhanced conjugation in solutes. These results show that structural modifications of a solute can be used to tune both the solvent organization and electrostatic environment, indicating the importance of a solute-centric paradigm in modulating and designing the electrostatic environment in condensed-phase chemical processes.

NCP-BiRW: A Hybrid Approach for Predicting Long Noncoding RNA-Disease Associations by Network Consistency Projection and Bi-Random Walk.

Long non-coding RNAs (lncRNAs) play significant roles in the disease process. Understanding the pathological mechanisms of lncRNAs during the course of various diseases will help clinicians prevent and treat diseases. With the emergence of high-throughput techniques, many biological experiments have been developed to study lncRNA-disease associations. Because experimental methods are costly, slow, and laborious, a growing number of computational models have emerged. Here, we present a new approach using network consistency projection and bi-random walk (NCP-BiRW) to infer hidden lncRNA-disease associations. First, integrated similarity networks for lncRNAs and diseases were constructed by merging similarity information. Subsequently, network consistency projection was applied to calculate space projection scores for lncRNAs and diseases, which were then introduced into a bi-random walk method for association prediction. To test model performance, we employed 5- and 10-fold cross-validation, with the area under the receiver operating characteristic curve as the evaluation indicator. The computational results showed that our method outperformed the other five advanced algorithms. In addition, the novel method was applied to another dataset in the Mammalian ncRNA-Disease Repository (MNDR) database and showed excellent performance. Finally, case studies were carried out on atherosclerosis and leukemia to confirm the effectiveness of our method in practice. In conclusion, we could infer lncRNA-disease associations using the NCP-BiRW model, which may benefit biomedical studies in the future.

A two-directional vibrational probe reveals different electric field orientations in solution and an enzyme active site.

The catalytic power of an electric field depends on its magnitude and orientation with respect to the reactive chemical species. Understanding and designing new catalysts for electrostatic catalysis thus requires methods to measure the electric field orientation and magnitude at the molecular scale. We demonstrate that electric field orientations can be extracted using a two-directional vibrational probe by exploiting the vibrational Stark effect of both the C=O and C-D stretches of a deuterated aldehyde. Combining spectroscopy with molecular dynamics and electronic structure partitioning methods, we demonstrate that, despite distinct polarities, solvents act similarly in their preference for electrostatically stabilizing large bond dipoles at the expense of destabilizing small ones. In contrast, we find that for an active-site aldehyde inhibitor of liver alcohol dehydrogenase, the electric field orientation deviates markedly from that found in solvents, which provides direct evidence for the fundamental difference between the electrostatic environment of solvents and that of a preorganized enzyme active site.

Octreotide ameliorates hepatic ischemia-reperfusion injury through SNHG12/TAF15-mediated Sirt1 stabilization and YAP1 transcription.

BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a pathological condition initiated by interrupted hepatic blood supply and exaggerated after reperfusion, which is one of the most lethal risks in liver transplantation and other liver surgeries. We aimed to investigate the protective mechanism of octreotide (Oct) against HIR injury. METHODS: The function of Oct was evaluated in the in vivo mouse model of HIR injury. Histological examinations were performed to assess the pathological changes. Serum parameters including ALT and AST were measured to evaluate the liver damage. qRT-PCR and western blot analysis were employed to determine the levels of long non-coding RNA SNHG12 (SNHG12) and autophagy or apoptosis-related proteins. RNA pull-down and RIP assays were used to verify the interaction between SNHG12 and TAF15. The transcriptional regulation of TAF15 in YAP1 was validated by ChIP and luciferase reporter assays. RESULTS: In the in vivo HIR injury model, Oct efficiently alleviated HIR-caused hepatic damage by suppressing apoptosis and activating autophagy. However, silencing of SNHG12 abrogated the protective effects of Oct via inactivating autophagy. Further mechanism investigation revealed that SNHG12 promoted the stabilization of Sirt1 and increased YAP1 transcriptional activity via interacting with TAF15. Up-regulation of Sirt1 and YAP1 was essential for maintaining the protective effect of Oct against HIR injury through increasing autophagic flux and suppressing apoptosis. CONCLUSIONS: Oct-induced up-regulation of SNHG12 attenuated HIR injury via promoting Sirt1 stabilization and YAP1 transcription to activate autophagy and repress apoptosis.

Hierarchical management of chronic heart failure: a perspective based on the latent structure of comorbidities.

AIMS: Chronic heart failure (CHF) has an increasing burden of comorbidities, which affect clinical outcomes. Few studies have focused on the clustering and hierarchical management of patients with CHF based on comorbidity. This study aimed to explore the cluster model of CHF patients based on comorbidities and to verify their relationship with clinical outcomes. METHODS AND RESULTS: Electronic health records of patients hospitalized with CHF from January 2014 to April 2019 were collected, and 12 common comorbidities were included in the latent class analysis. The Fruchterman-Reingold layout was used to draw the comorbidity network, and analysis of variance was used to compare the weighted degrees among them. The incidence of clinical outcomes among different clusters was presented on Kaplan-Meier curves and compared using the log-rank test, and the hazard ratio was calculated using the Cox proportional risk model. Sensitivity analysis was performed according to the left ventricular ejection fraction. Four different clinical clusters from 4063 total patients were identified: metabolic, ischaemic, high comorbidity burden, and elderly-atrial fibrillation. Compared with the metabolic cluster, patients in the high comorbidity burden cluster had the highest adjusted risk of combined outcome and all-cause mortality {1.67 [95% confidence interval (CI), 1.40-1.99] and 2.87 [95% CI, 2.17-3.81], respectively}, followed by the elderly-atrial fibrillation and ischaemic clusters. The adjusted readmission risk of patients with ischaemic, high comorbidity burden, and elderly-atrial fibrillation clusters were 1.35 (95% CI, 1.08-1.68), 1.39 (95% CI, 1.13-1.72), and 1.42 (95% CI, 1.14-1.77), respectively. The comorbidity network analysis found that patients in the high comorbidity burden cluster had more and higher comorbidity correlations than those in other clusters. Sensitivity analysis revealed that patients in the high comorbidity burden cluster had the highest risk of combined outcome and all-cause mortality (P < 0.05). CONCLUSIONS: The difference in adverse outcomes among clusters confirmed the heterogeneity of CHF and the importance of hierarchical management. This study can provide a basis for personalized treatment and management of patients with CHF, and provide a new perspective for clinical decision making.