Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis.

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

[Identification of Protein-Coding Gene Markers in Breast Invasive Carcinoma Based on Machine Learning].

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Proteome, Lysine Acetylome, and Succinylome Identify Posttranslational Modification of STAT1 as a Novel Drug Target in Silicosis.

Inhalation of crystalline silica dust induces incurable lung damage, silicosis, and pulmonary fibrosis. However, the mechanisms of the lung injury remain poorly understood, with limited therapeutic options aside from lung transplantation. Posttranslational modifications can regulate the function of proteins and play an important role in studying disease mechanisms. To investigate changes in posttranslational modifications of proteins in silicosis, combined quantitative proteome, acetylome, and succinylome analyses were performed with lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Combined analysis was applied to the three omics datasets to construct a protein landscape. The acetylation and succinylation of the key transcription factor STAT1 were found to play important roles in the silica-induced pathophysiological changes. Modulating the acetylation level of STAT1 with geranylgeranylacetone effectively inhibited the progression of silicosis. This report revealed a comprehensive landscape of posttranslational modifications in silica-injured mouse and presented a novel therapeutic strategy targeting the posttranslational level for silica-induced lung diseases.

Baicalin Attenuates Diabetic Cardiomyopathy In Vivo and In Vitro by Inhibiting Autophagy and Cell Death through SENP1/SIRT3 Signaling Pathway Activation.

AIMS: Diabetic heart damage can lead to cardiomyocyte death, which endangers human health. Baicalin (BAI) is a bioactive compound that plays an important role in cardiovascular diseases. Sentrin/SUMO-specific protease 1 (SENP1) regulates the de-small ubiquitin-like modifier (deSUMOylation) process of Sirtuin 3 (SIRT3) and plays a crucial role in regulating mitochondrial mass and preventing cell injury. Our hypothesis is that BAI regulates the deSUMOylation level of SIRT3 through SENP1 to enhance mitochondrial quality control and prevent cell death, ultimately improving diabetic cardiomyopathy (DCM). RESULTS: The protein expression of SENP1 decreased in cardiomyocytes induced by high glucose and in db/db mice. The cardioprotective effects of BAI were eliminated by silencing endogenous SENP1, while overexpression of SENP1 showed similar cardioprotective effects to those of BAI. Furthermore, Co-Immunoprecipitation (CO-IP) experiments showed that BAI's cardioprotective effect was due to the inhibition of the SUMOylation modification level of SIRT3 by SENP1. Inhibition of SENP1 expression resulted in an increase in SUMOylation of SIRT3. This led to increased acetylation of mitochondrial protein, accumulation of reactive oxygen species, impaired autophagy, impaired mitochondrial oxidative phosphorylation and increased cell death. None of these changes could be reversed by BAI. CONCLUSION: BAI improves DCM by promoting SIRT3 deSUMOylation through SENP1, restoring mitochondrial stability, and preventing the cell death of cardiomyocytes. INNOVATION: This study proposes for the first time that SIRT3 SUMOylation modification is involved in the development of DCM, provides in vivo and in vitro data support that BAI inhibits cardiomyocyte ferroptosis and apoptosis in DCM through SENP1.

Toward High-Energy-Density Fuels for Direct Liquid Organic Hydrogen Carrier Fuel Cells: Electrooxidation of 1-Cyclohexylethanol.

Electrochemically active liquid organic hydrogen carriers (EC-LOHCs) can be used directly in fuel cells; so far, however, they have rather low hydrogen storage capacities. In this work, we study the electrooxidation of a potential EC-LOHC with increased energy density, 1-cyclohexylethanol, which consists of two storage functionalities (a secondary alcohol and a cyclohexyl group). We investigated the product spectrum on low-index Pt single-crystal surfaces in an acidic environment by combining cyclic voltammetry, chronoamperometry, and in situ infrared spectroscopy, supported by density functional theory. We show that the electrooxidation of 1-cyclohexylethanol is a highly structure-sensitive reaction with activities Pt(111) ≫ Pt(100) > Pt(110). Most importantly, we demonstrate that 1-cyclohexylethanol can be directly converted to acetophenone, which desorbs from the electrode surface. However, decomposition products are formed, which lead to poisoning. If the latter side reactions could be suppressed, the electrooxidation of 1-cyclohexylethanol would enable the development of EC-LOHCs with greatly increased hydrogen storage capacities.

Lactylation prediction models based on protein sequence and structural feature fusion.

Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.

Polyurethane foam dressing with non-adherent membrane improves negative pressure wound therapy in pigs.

OBJECTIVE: Negative pressure wound therapy (NPWT) is considered to be an effective technique to promote the healing of various wounds. The aim of this study was to evaluate different wound dressings combined with NPWT in treating wounds in Wuzhishan pigs. METHOD: Excisions were made in the backs of the pigs and were covered with polyvinyl alcohol (PVA) dressing, polyurethane (PU) dressing or PU dressing with non-adherent membrane (PU-non-ad). NPWT was applied to the wound site. In the control group, basic occlusive dressing (gauze) without NPWT was applied. On days 0, 3, 7, 14, 21 and 28 post-surgery, the wound size was measured during dressing change, and wound healing rate (WHR) was calculated. In addition, blood perfusion within 2cm of the surrounding wound was measured by laser doppler flowmetry. Dressing specimen was collected and microbiology was analysed. Granulation tissues from the central part of the wounds were analysed for histology, vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) mRNA expression. RESULTS: The PU-non-ad-NPWT significantly (p<0.01) accelerated wound healing in the pigs. Further pathological analysis revealed that the non-adherent membrane effectively protected granulation tissue formation in PU-NPWT treated wounds. The blood perfusion analysis suggested that the non-adherent membrane improved the blood supply to the wound area. Microbiological analysis showed that non-adherent membrane decreased the bacterial load in the PU-NPWT dressing. VEGF and CD31 mRNA expression was upregulated in the wound tissue from the PU-non-ad-NPWT treated groups. CONCLUSION: In this study, the PU dressing with non-adherent membrane was an ideal dressing in NPWT-assisted wound healing.

Cellulose-based carbon nanotubes array with lawn-like 3D architecture for oxygen reduction reaction.

The conversion of biomass into high-performance carbon-based materials provides an opportunity to valorize biomass for advanced applications. Achieving this necessitates requires dedicated efforts and innovations in biocarbon synthesis, design, and applications. This study proposes the controllable conversion of biomass-derived cellulose into well-distributed carbon nanotubes (CNTs) by tuning the precipitation of cellulose pyrolysis generated vapors with in-situ formed ferric metal nanoparticles. The obtained CNTs exhibited lawn-like 3D architecture with similar length, uniform alignment, and dense distribution. The combined use of ferric chloride and dicyandiamide as the reagents with a mass ration of 0.162:1.05, demonstrated optimal performance in controlling the morphology of CNTs, enhancing the graphitization, and increasing the content of graphitic-N and pyridine-N. This multi-dimensional modification enhanced the electrocatalytic performance of the obtained CNTs, achieving an onset potential of 0.875 V vs. relative hydrogen electrode (RHE), a half-wave potential of 0.703 V vs. RHE, and a current density of -4.95 mA cm-2 during the oxygen reduction reaction. Following microbial fuel cells (MFCs) tests achieved an output voltage of 0.537 V and an output power density of 412.85 mW m-2, comparable to MFC with Pt/C as the cathode catalyst. This biomass-derived catalyst is recommended as a high-quality, non-noble metal alternative to traditional noble-metal catalysts.

Dark chocolate intake and cardiovascular diseases: a Mendelian randomization study.

Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60-0.88; p = 1.06 × 10-3), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50-0.96; p = 2.81 × 10-2). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.

Paeoniflorin confers ferroptosis resistance by regulating the gut microbiota and its metabolites in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is closely related to ferroptosis, a new type of cell death that mainly manifests as intracellular iron accumulation and lipid peroxidation. Paeoniflorin (PA) helps to improve impaired glucose tolerance, influences the distribution of the intestinal flora, and induces significant resistance to ferroptosis in several models. In this study, we found that PA improved cardiac dysfunction in mice with DCM by alleviating myocardial damage, resisting oxidative stress and ferroptosis, and changing the community composition and structure of the intestinal microbiota. Metabolomics analysis revealed that PA-treated fecal microbiota transplantation affected metabolites in DCM mice. Based on in vivo and in vitro experiments, 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor that mediates the cardioprotective and antiferroptotic effects of PA-treated fecal microbiota transplantation (FMT) in DCM mice.NEW & NOTEWORTHY This study demonstrated for the first time that paeoniflorin (PA) exerts protective effects in diabetic cardiomyopathy mice by alleviating myocardial damage, resisting ferroptosis, and changing the community composition and structure of the intestinal microbiota, and 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor in its therapeutic efficacy.

Global profiling of protein lactylation in Caenorhabditis elegans.

Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.

RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation.

Diabetic cardiomyopathy (dCM) is a major complication of diabetes; however, specific treatments for dCM are currently lacking. RTA 408, a semisynthetic triterpenoid, has shown therapeutic potential against various diseases by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. We established in vitro and in vivo models using high glucose toxicity and db/db mice, respectively, to simulate dCM. Our results demonstrated that RTA 408 activated Nrf2 and alleviated various dCM-related cardiac dysfunctions, both in vivo and in vitro. Additionally, it was found that silencing the Nrf2 gene eliminated the cardioprotective effect of RTA 408. RTA 408 ameliorated oxidative stress in dCM mice and high glucose-exposed H9C2 cells by activating Nrf2, inhibiting mitochondrial fission, exerting anti-inflammatory effects through the Nrf2/NF-κB axis, and ultimately suppressing apoptosis, thereby providing cardiac protection against dCM. These findings provide valuable insights for potential dCM treatments.NEW & NOTEWORTHY We demonstrated first that the nuclear factor erythroid 2-related factor 2 (Nrf2) activator RTA 408 has a protective effect against diabetic cardiomyopathy. We found that RTA 408 could stimulate the nuclear entry of Nrf2 protein, regulate the mitochondrial fission-fusion balance, and redistribute p65, which significantly alleviated the oxidative stress level in cardiomyocytes, thereby reducing apoptosis and inflammation, and protecting the systolic and diastolic functions of the heart.

Emodin ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through the remodeling of gut microbiota composition.

The relationship between gut microbiota and doxorubicin-induced cardiotoxicity (DIC) is becoming increasingly clear. Emodin (EMO), a naturally occurring anthraquinone, exerts cardioprotective effects and plays a protective role by regulating gut microbiota composition. Therefore, the protective effect of EMO against DIC injury and its underlying mechanisms are worth investigating. In this study, we analyzed the differences in the gut microbiota in recipient mice transplanted with different flora using 16S-rDNA sequencing, analyzed the differences in serum metabolites among groups of mice using a nontargeted gas chromatography-mass spectrometry coupling system, and assessed cardiac function based on cardiac morphological staining, cardiac injury markers, and ferroptosis indicator assays. We found EMO ameliorated DIC and ferroptosis, as evidenced by decreased myocardial fibrosis, cardiomyocyte hypertrophy, and myocardial disorganization; improved ferroptosis indicators; and the maintenance of normal mitochondrial morphology. The protective effect of EMO was eliminated by the scavenging effect of antibiotics on the gut microbiota. Through fecal microbiota transplantation (FMT), we found that EMO restored the gut microbiota disrupted by doxorubicin (DOX) to near-normal levels. This was evidenced by an increased proportion of Bacteroidota and a decreased proportion of Verrucomicrobiota. FMT resulted in changes in the composition of serum metabolites. Mice transplanted with EMO-improved gut microbiota showed better cardiac function and ferroptosis indices; however, these beneficial effects were not observed in Nrf2 (Nfe2l2)-/- mice. Overall, EMO exerted a protective effect against DIC by attenuating ferroptosis, and the above effects occurred by remodeling the composition of gut microbiota perturbed by DOX and required Nrf2 mediation.NEW & NOTEWORTHY This study demonstrated for the first time the protective effect of emodin against DIC and verified by FMT that its cardioprotective effect was achieved by remodeling gut microbiota composition, resulting in attenuation of ferroptosis. Furthermore, we demonstrated that these effects were mediated by the redox-related gene Nrf2.

The effect of ivabradine therapy on dilated cardiomyopathy patients with congestive heart failure: a systematic review and meta-analysis.

Background: Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and meta-analysis to study the efficacy and potential mechanisms of ivabradine's effect on cardiac function and prognosis in patients with DCM. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and four registers through September 28, 2022. All controlled trials of ivabradine for the treatment of DCM with congestive heart failure were included. Articles were limited to English, with the full text and necessary data available. We performed random- or fixed effects meta-analyses for all included outcome measures and compared the effect sizes for outcomes in patients treated with and without ivabradine. The quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2.0). Findings: Five trials with 357 participants were included. The pooled risk ratio was 0.48 [95% confidence interval (CI) (0.18, 1.25)] for all-cause mortality and 0.38 [95% CI (0.12, 1.23)] for cardiac mortality. The pooled mean difference was -15.95 [95% CI (-19.97, -11.92)] for resting heart rate, 3.96 [95% CI (0.99, 6.93)] for systolic blood pressure, 2.93 [95% CI (2.09, 3.77)] for left ventricular ejection fraction, -5.90 [95% CI (-9.36, -2.44)] for left ventricular end-systolic diameter, -3.41 [95% CI (-5.24, -1.58)] for left ventricular end-diastolic diameter, -0.81 [95% CI (-1.00, -0.62)] for left ventricular end-systolic volume, -0.67 [95% CI (-0.86, -0.48)] for left ventricular end-diastolic volume, -11.01 [95% CI (-19.66, -2.35)] for Minnesota Living with Heart Failure score, and -0.52 [95% CI (-0.73, -0.31)] for New York Heart Association class. Interpretation: Ivabradine reduces heart rate and ventricular volume, and improves cardiac function in patients with DCM, but showed no significant effect on the prognosis of patients.

Fecal Microbiota Transplantation in Mice Exerts a Protective Effect Against Doxorubicin-Induced Cardiac Toxicity by Regulating Nrf2-Mediated Cardiac Mitochondrial Fission and Fusion.

Aims: The relationship between the gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combating doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood. Results: During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieve this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing reactive oxygen species production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress. Innovation: FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart. Conclusion: FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.

Profiling of SARS-CoV-2 neutralizing antibody-associated antigenic peptides signature using proteome microarray.

The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS-CoV-2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID-19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S-82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10-3), were closely associated with the presence of SARS-CoV-2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID-19 cases in 2020, S82-IgG titers were higher in NAbs-positive samples (p = 0.002) than in NAbs-negative samples using enzyme-linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82-IgG titers, NAb titers were significantly higher in the samples with higher S82-IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay-associated signatures of SARS-CoV-2 NAbs.

Multidimensional risk factor analysis of acute low back pain progressing to chronicity: a longitudinal cohort study protocol.

Introduction: Approximately 40% of patients with acute low back pain (LBP) develop chronic low back pain, which significantly increases the risk of poor prognosis. To reduce the risk of acute LBP becoming chronic, effective preventive strategies are needed. Early identification of risk factors for the development of chronic LBP can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim of this study is to identify factors that can predict the risk of acute LBP becoming chronic based on clinical information, pain and disability assessment, and MRI imaging findings. This protocol describes the methodology and plan for investigating multidimensional risk factors for acute LBP becoming chronic, in order to better understand the development of acute LBP and prevent chronic LBP. Methods: This is a prospective multicenter study. We plan to recruit 1,000 adult patients with acute low back pain from four centers. In order to select four representative centers, we find the larger hospitals from different regions in Yunnan Province. The study will use a longitudinal cohort design. Patients will undergo baseline assessments upon admission and will be followed up for 5 years to collect the time of chronicity and associated risk factors. Upon admission, patients will be collected detailed demographic information, subjective and objective pain scores, disability scale, and lumbar spine MRI scanning. In addition, patient's medical history, lifestyle, psychological factors will be collected. Patients will be followed up at 3 months, 6 months, 1 year, 2 years and up for 5 years after admission to collect the time of chronicity and associated factors. Multivariate analysis will be used to explore the multidimensional risk factors affecting the chronicity of acute LBP patients (such as age, gender, BMI, degree of intervertebral disc degeneration, etc.), and survival analysis will be performed to explore the impact of each factor on the time of chronicity. Ethics and dissemination: The study has been approved by the institutional research ethics committee of each study center (main center number: 2022-L-305). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.