Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue. Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence, influencing diverse physiological activities, including immune response, inflammation, and bone metabolism. Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition. However, the impact of these factors on peri-implantitis remains inconclusive. To address this gap, we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis, specifically focusing on DNA methylation and microRNAs (miRNAs or miRs). We searched for relevant literature on PubMed, Web of Science, Scopus, and Google Scholar with keywords including "epigenetics," "peri-implantitis," "DNA methylation," and "microRNA." DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants. Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis. In addition, we assessed the potential application of DNA methylation and miRNAs in the prevention, diagnosis, and treatment of peri-implantitis, aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition. These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.
Peri-Implantitis/genetics* ; Humans ; Epigenesis, Genetic ; DNA Methylation ; MicroRNAs/genetics*

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as POU3F2 (BRN2), ASCL1/2, NeuroD1, SOX2/9, RUNX1/2 and DLL3. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both de novo neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.

AIM:To explore the role of stromal interaction molecule 1(STIM1)in the migration,invasion and angiogenesis of salivary adenoid cystic carcinoma(SACC),as well as its molecular mechanism.METHODS:Immu-nohistochemistry and Western blot were used to detect the expression level of STIM1 in human SACC tumor tissues and ad-jacent normal tissues.The TCGA database was analyzed to investigate the relationship between STIM1 expression and sur-vival in patients.A SACC-83 cell line with stable STIM1 overexpression(STIM1-OE)was established and divided into two groups:blank control(STIM1-Vec)group and STIM1-OE group.A nude mouse subcutaneous xenograft tumor model(n=6)was used to detect SACC growth.Transwell chamber assay,scratch test and dorsal root ganglion model were ap-plied to assess SACC migration and invasion.Immunohistochemistry was performed to detect the expression of CD34 and STIM1 in tumor tissues of nude mice.A nude mouse Matrigel plug model and human umbilical vein endothelial cell(HUVEC)tube formation assay were used to evaluate angiogenesis.Enzyme linked immunosorbent assay was employed to detect the levels of vascular endothelial growth factor(VEGF)and epidermal growth factor(EGF)in cell culture supernatants.RT-qPCR and Western blot were performed to detect the mRNA and protein expression levels of c-Myc,ribosomal protein L35(RPL35),ribosomal protein SA(RPSA),mitochondrial ribosomal protein L11(RPL11)and FAU ubiquitin like and ribo-somal protein S30 fusion(FAU).The STIM1-siRNA and RPL35-siRNA were transfected into SACC-83 cells,and the mi-gration,invasion and angiogenesis abilities of the cells were detected using the same methods as above.RESULTS:STIM1 was highly expressed in SACC,and the patients with high STIM1 expression had shorter survival time.In vivo,compared with STIM1-Vec group,STIM1-OE promoted tumor growth.In vitro,the number of migrating and invading SACC cells in STIM1-OE group was significantly increased,and the nerve invasion ability was also significantly en-hanced.Conversely,STIM1-siRNA significantly reduced the migration and invasion abilities of SACC cells.Additional-ly,STIM1-OE significantly promoted the expression of the vascular marker CD34,the secretion of VEGF and EGF,and the results of Matrigel plug and HUVEC tube formation assays indicated that STIM1-OE significantly promoted angiogene-sis.Silencing of RPL35 significantly inhibited SACC migration,invasion,and angiogenesis.RT-qPCR and Western blot results showed that the mRNA levels of RPL35,RPSA,MRPL11 and FAU were significantly increased(P<0.05),and the protein expression levels of STIM1,c-Myc and RPL35 were significantly increased(P<0.01).CONCLUSION:STIM1 drive the migration,invasion and angiogenesis of SACC by activating c-Myc/RPL35-mediated ribosome pathway.

AIM:To investigate the effect of cryptotanshinone(CPT)on myocardial hypertrophy induced by isoprenaline(ISO)in rats and explore its potential mechanism.METHODS:The experimental design consisted of two parts.The first aimed to investigate the effects of CPT on cardiac function,pathological manifestations,and the Janus ki-nase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in rats with myocardial hyper-trophy.The rats were divided into six groups,namely the control,CPT control,and model groups and low-(15 mg·kg-1·d-1),medium-(30 mg·kg-1·d-1),and high-dose(60 mg·kg-1·d-1)CPT treatment groups,with six rats per group.The sec-ond part aimed to validate the role of the JAK2/STAT3 signaling pathway in the CPT-mediated myocardial hypertrophy treatment.Rats were divided into four groups,namely the control,model,high-dose CPT treatment,and coumermycin A1(CA1,a JAK2/STAT3 agonist)intervention(rats received ISO injection followed by 60 mg·kg-1·d-1 of high-dose CPT and 1 mg·kg-1·d-1 of CA1 for 15 d)groups,with five rats per group.Myocardial hypertrophy was induced in rats via intra-peritoneal injection of ISO(5 mg/kg),and CPT intervention lasted for 15 days.Cardiac function-related parameters were assessed using echocardiography,and pathological changes were evaluated through hematoxylin-eosin,Masson,and wheat germ agglutinin staining.Protein expression levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),and JAK2/STAT3 signaling pathway-related proteins were detected by Western blot analysis.RESULTS:Compared with the model group,CPT administration improved cardiac dysfunction-related ul-trasound markers and significantly reduced ISO-induced cardiomyocyte hypertrophy and myocardial fibrosis in rats with hy-pertrophy in a dose-dependent manner(P<0.05).Additionally,CPT decreased the levels of ANP,BNP,and β-MHC in-duced by ISO modeling(P<0.05),and inhibiting the phosphorylation of JAK2 and STAT3(P<0.05).Furthermore,a partial reversal of the therapeutic effect on myocardial hypertrophy induced by ISO modeling was observed when CA1 was administered(P<0.05).CONCLUSION:The CPT exhibits potential as a therapeutic agent for cardiac hypertrophy by effectively attenuating ISO-induced cardiac hypertrophy in rats through JAK2/STAT3 signaling inhibition.

Objective:To explore the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) placed in the uterine cavity after transcervical preparation for the treatment of adenomyosis (AM).Methods:A retrospective study analyzed 219 cases of AM patients treated at Department of Obstetrics and Gynaecology, the Second Hospital of Hebei Medical University from March 2022 to February 2023. Among them, 112 cases were treated with LNG-IUS after hysteroscopy due to abnormal uterine bleeding or abnormal uterine echo suggested by gynecological ultrasound, and were recorded as the hysteroscopy+LNG-IUS group; 107 cases without the above manifestations were treated with LNG-IUS alone, and were recorded as the LNG-IUS group. The two groups were observed for dysmenorrhea severity, menstrual volume, endometrial thickness, anemia, serum CA125 levels, uterine volume, and adverse reactions such as abnormal vaginal bleeding and intrauterine contraceptive device displacement or shedding before and 1, 3, 6, and 12 months after treatment.Results:1) Postoperative pathology of hysteroscopy+LNG-IUS group after hysteroscopy included endometrial polyps [39.3% (44/112)], proliferative endometrium [16.1% (18/112)], uterine leiomyoma [11.6% (13/112)], secretory endometrium [8.9% (10/112)], irregular endometrial hyperplasia [6.2% (7/112)], simple hyperplasia [5.4% (6/112)], AM lesions [4.5% (5/112)], and others [8.0% (9/112)]. 2) The degree of dysmenorrhea and menstrual volume, as well as other indicators, improved after treatment in both groups (all P<0.001). 3) When comparing the two groups, the degree of dysmenorrhea, menstrual volume, endometrial thickness, anemia, and serum CA125 at 1, 3, 6, and 12 months of treatment, the hysteroscopy+LNG-IUS group was significantly better than those in the LNG-IUS group (all P<0.05), the difference of uterine volume at 12 months of treatment between the hysteroscopy+LNG-IUS group [(109.76±32.90) cm 3] and the LNG-IUS group [(120.84±31.30) cm 3] was statistically significant ( P=0.011). 4) The cumulative incidence of adverse reactions of the two groups was statistically significant ( P=0.001) between the hysteroscopy+LNG-IUS group [24.1% (27/112)] and the LNG-IUS group [52.3% (56/107), P=0.001]. The hysteroscopy+LNG-IUS group had lower rates of vaginal irregular bleeding [8.0% (9/112)] and ring displacement or shedding [3.6% (4/112)] than those in the LNG-IUS group [23.4% (25/107), P=0.002; 11.2% (12/107), P=0.030]. Conclusion:After treatment with hysteroscopy, the placement of LNG-IUS and the simple intrauterine placement of LNG-IUS both significantly improve the severity of dysmenorrhea, endometrial thickness, anemia, menstrual volume, CA125, and uterine volume. The treatment effect of the LNG-IUS group after hysteroscopy is better and adverse reactions are milder, and it is expected to become the preferred option for the long-term management of conservative treatment of AM.

Objective:To explore the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) placed in the uterine cavity after transcervical preparation for the treatment of adenomyosis (AM).Methods:A retrospective study analyzed 219 cases of AM patients treated at Department of Obstetrics and Gynaecology, the Second Hospital of Hebei Medical University from March 2022 to February 2023. Among them, 112 cases were treated with LNG-IUS after hysteroscopy due to abnormal uterine bleeding or abnormal uterine echo suggested by gynecological ultrasound, and were recorded as the hysteroscopy+LNG-IUS group; 107 cases without the above manifestations were treated with LNG-IUS alone, and were recorded as the LNG-IUS group. The two groups were observed for dysmenorrhea severity, menstrual volume, endometrial thickness, anemia, serum CA125 levels, uterine volume, and adverse reactions such as abnormal vaginal bleeding and intrauterine contraceptive device displacement or shedding before and 1, 3, 6, and 12 months after treatment.Results:1) Postoperative pathology of hysteroscopy+LNG-IUS group after hysteroscopy included endometrial polyps [39.3% (44/112)], proliferative endometrium [16.1% (18/112)], uterine leiomyoma [11.6% (13/112)], secretory endometrium [8.9% (10/112)], irregular endometrial hyperplasia [6.2% (7/112)], simple hyperplasia [5.4% (6/112)], AM lesions [4.5% (5/112)], and others [8.0% (9/112)]. 2) The degree of dysmenorrhea and menstrual volume, as well as other indicators, improved after treatment in both groups (all P<0.001). 3) When comparing the two groups, the degree of dysmenorrhea, menstrual volume, endometrial thickness, anemia, and serum CA125 at 1, 3, 6, and 12 months of treatment, the hysteroscopy+LNG-IUS group was significantly better than those in the LNG-IUS group (all P<0.05), the difference of uterine volume at 12 months of treatment between the hysteroscopy+LNG-IUS group [(109.76±32.90) cm 3] and the LNG-IUS group [(120.84±31.30) cm 3] was statistically significant ( P=0.011). 4) The cumulative incidence of adverse reactions of the two groups was statistically significant ( P=0.001) between the hysteroscopy+LNG-IUS group [24.1% (27/112)] and the LNG-IUS group [52.3% (56/107), P=0.001]. The hysteroscopy+LNG-IUS group had lower rates of vaginal irregular bleeding [8.0% (9/112)] and ring displacement or shedding [3.6% (4/112)] than those in the LNG-IUS group [23.4% (25/107), P=0.002; 11.2% (12/107), P=0.030]. Conclusion:After treatment with hysteroscopy, the placement of LNG-IUS and the simple intrauterine placement of LNG-IUS both significantly improve the severity of dysmenorrhea, endometrial thickness, anemia, menstrual volume, CA125, and uterine volume. The treatment effect of the LNG-IUS group after hysteroscopy is better and adverse reactions are milder, and it is expected to become the preferred option for the long-term management of conservative treatment of AM.

AIM:To explore the role of stromal interaction molecule 1(STIM1)in the migration,invasion and angiogenesis of salivary adenoid cystic carcinoma(SACC),as well as its molecular mechanism.METHODS:Immu-nohistochemistry and Western blot were used to detect the expression level of STIM1 in human SACC tumor tissues and ad-jacent normal tissues.The TCGA database was analyzed to investigate the relationship between STIM1 expression and sur-vival in patients.A SACC-83 cell line with stable STIM1 overexpression(STIM1-OE)was established and divided into two groups:blank control(STIM1-Vec)group and STIM1-OE group.A nude mouse subcutaneous xenograft tumor model(n=6)was used to detect SACC growth.Transwell chamber assay,scratch test and dorsal root ganglion model were ap-plied to assess SACC migration and invasion.Immunohistochemistry was performed to detect the expression of CD34 and STIM1 in tumor tissues of nude mice.A nude mouse Matrigel plug model and human umbilical vein endothelial cell(HUVEC)tube formation assay were used to evaluate angiogenesis.Enzyme linked immunosorbent assay was employed to detect the levels of vascular endothelial growth factor(VEGF)and epidermal growth factor(EGF)in cell culture supernatants.RT-qPCR and Western blot were performed to detect the mRNA and protein expression levels of c-Myc,ribosomal protein L35(RPL35),ribosomal protein SA(RPSA),mitochondrial ribosomal protein L11(RPL11)and FAU ubiquitin like and ribo-somal protein S30 fusion(FAU).The STIM1-siRNA and RPL35-siRNA were transfected into SACC-83 cells,and the mi-gration,invasion and angiogenesis abilities of the cells were detected using the same methods as above.RESULTS:STIM1 was highly expressed in SACC,and the patients with high STIM1 expression had shorter survival time.In vivo,compared with STIM1-Vec group,STIM1-OE promoted tumor growth.In vitro,the number of migrating and invading SACC cells in STIM1-OE group was significantly increased,and the nerve invasion ability was also significantly en-hanced.Conversely,STIM1-siRNA significantly reduced the migration and invasion abilities of SACC cells.Additional-ly,STIM1-OE significantly promoted the expression of the vascular marker CD34,the secretion of VEGF and EGF,and the results of Matrigel plug and HUVEC tube formation assays indicated that STIM1-OE significantly promoted angiogene-sis.Silencing of RPL35 significantly inhibited SACC migration,invasion,and angiogenesis.RT-qPCR and Western blot results showed that the mRNA levels of RPL35,RPSA,MRPL11 and FAU were significantly increased(P<0.05),and the protein expression levels of STIM1,c-Myc and RPL35 were significantly increased(P<0.01).CONCLUSION:STIM1 drive the migration,invasion and angiogenesis of SACC by activating c-Myc/RPL35-mediated ribosome pathway.

AIM:To investigate the effect of cryptotanshinone(CPT)on myocardial hypertrophy induced by isoprenaline(ISO)in rats and explore its potential mechanism.METHODS:The experimental design consisted of two parts.The first aimed to investigate the effects of CPT on cardiac function,pathological manifestations,and the Janus ki-nase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in rats with myocardial hyper-trophy.The rats were divided into six groups,namely the control,CPT control,and model groups and low-(15 mg·kg-1·d-1),medium-(30 mg·kg-1·d-1),and high-dose(60 mg·kg-1·d-1)CPT treatment groups,with six rats per group.The sec-ond part aimed to validate the role of the JAK2/STAT3 signaling pathway in the CPT-mediated myocardial hypertrophy treatment.Rats were divided into four groups,namely the control,model,high-dose CPT treatment,and coumermycin A1(CA1,a JAK2/STAT3 agonist)intervention(rats received ISO injection followed by 60 mg·kg-1·d-1 of high-dose CPT and 1 mg·kg-1·d-1 of CA1 for 15 d)groups,with five rats per group.Myocardial hypertrophy was induced in rats via intra-peritoneal injection of ISO(5 mg/kg),and CPT intervention lasted for 15 days.Cardiac function-related parameters were assessed using echocardiography,and pathological changes were evaluated through hematoxylin-eosin,Masson,and wheat germ agglutinin staining.Protein expression levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),and JAK2/STAT3 signaling pathway-related proteins were detected by Western blot analysis.RESULTS:Compared with the model group,CPT administration improved cardiac dysfunction-related ul-trasound markers and significantly reduced ISO-induced cardiomyocyte hypertrophy and myocardial fibrosis in rats with hy-pertrophy in a dose-dependent manner(P<0.05).Additionally,CPT decreased the levels of ANP,BNP,and β-MHC in-duced by ISO modeling(P<0.05),and inhibiting the phosphorylation of JAK2 and STAT3(P<0.05).Furthermore,a partial reversal of the therapeutic effect on myocardial hypertrophy induced by ISO modeling was observed when CA1 was administered(P<0.05).CONCLUSION:The CPT exhibits potential as a therapeutic agent for cardiac hypertrophy by effectively attenuating ISO-induced cardiac hypertrophy in rats through JAK2/STAT3 signaling inhibition.

Objective:To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model.Methods:Based on the information of septic patients in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7∶3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model.Results:A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio ( HR) = 1.266, 95% confidence interval (95% CI) was 1.150-1.393], heart failure ( HR = 1.348, 95% CI was 1.217-1.493), respiratory failure ( HR = 1.565, 95% CI was 1.428-1.715), heart rate ( HR = 1.004, 95% CI was 1.002-1.007), mean arterial pressure ( HR = 1.245, 95% CI was 1.126-1.377), lactic acid ( HR = 1.051, 95% CI was 1.025-1.077), simplified acute physiology score Ⅱ (SAPSⅡ, HR = 1.019, 95% CI was 1.016-1.023), serum creatinine ( HR = 1.171, 95% CI was 1.127-1.216), anion gap ( HR = 1.024, 95% CI was 1.010-1.038), serum potassium ( HR = 1.155, 95% CI was 1.079-1.236), white blood cell count ( HR = 1.006, 95% CI was 1.003-1.009) and furosemide use ( HR = 0.414, 95% CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95% CI was 0.782-0.808), 0.792 (95% CI was 0.780-0.805), and 0.775 (95% CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95% CI was 0.784-0.823), 0.791 (95% CI was 0.772-0.810), and 0.773 (95% CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. Conclusion:The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.