Small noncoding RNAs (sncRNAs) constitute a diverse class of endogenous transcripts, including miRNAs, piRNAs, tRNA-derived fragments (tDRs), rRNA-derived fragments (rRFs), and other small RNAs. They have been identified as pivotal regulatory elements in a wide array of biological processes and diseases. Among these, miRNA is the most extensively studied and confirmed as a key regulatory and diagnostic biomarker in tumorigenesis and development. However, the current understanding of sncRNAs other than miRNA remains limited, particularly in the field of oncology. To this end, we collected 190 datasets from GEO/SRA database, encompassing 11 114 samples across 19 cancer types, and built a user-friendly database, the Pan-Cancer Small Non-Coding RNA Database (PCsRNAdb, http://pcsrnadb.cloudna.cn/#/Home), which is developed to provide abundant resources of sncRNAs specifically designed to investigate the association between sncRNAs and cancers. PCsRNAdb comprehensively provides basic information such as the sequence, length, abundance, and target genes of sncRNAs, and further offers four advanced functionalities, including differential expression analysis, survival analysis, expression profiling analysis, and network regulatory analysis. We anticipate that such platform offers invaluable resources and effective analytical tools for researchers in related fields and is expected to facilitate cancer-related research in this domain.

Bladder cancer is a common and aggressive disease with limited treatment options, highlighting the urgent need for new therapeutic strategies. Although mitochondrial proteins have been implicated in cancer progression, their role in bladder cancer remains unclear. This study aimed to investigate the function of the mitochondrial protease YME1L1 and its regulation by the E3 ubiquitin ligase TRIM21. By analyzing patient tissue samples, single-cell RNA data and performing experiments manipulating YME1L1 and TRIM21 levels in bladder cancer cells, we found that YME1L1 promotes cancer cell proliferation, invasion and mitochondrial energy production. Mechanistically, TRIM21 interacts with YME1L1 through its SPRY domain, facilitating K63-linked polyubiquitination of YME1L1 and accelerating its degradation. Furthermore, the K237 residue of YME1L1 is critical for TRIM21-mediated ubiquitination. These findings suggest that targeting the TRIM21-YME1L1 pathway could offer a novel strategy to inhibit bladder cancer progression.

Efficient clearance of apoptotic cells by macrophages (efferocytosis) is essential for maintaining immune homeostasis, and its disruption contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here, we identify FAM76B as a key regulator of macrophage-mediated apoptotic cell clearance through modulation of autophagy. Loss of FAM76B impaired degradation of engulfed apoptotic cells without affecting phagocytic uptake, indicating a selective defect in post-phagocytic processing. Mechanistically, FAM76B restricts cytoplasmic translocation of the m6A reader HNRNPA2B1, thereby limiting m6A-dependent stabilization of ISG15 mRNA. Fam76b deficiency leads to increased ISG15 expression, which suppresses autophagy via a noncanonical, ISGylation-independent mechanism. Specifically, ISG15 interacts with HSPA8 and disrupts its association with BECN1, resulting in impaired autophagic activity. In vivo, Fam76b deficiency exacerbates pristane-induced lupus-like disease, characterized by defective apoptotic cell clearance, elevated ISG15 expression, and reduced autophagy. Targeted inhibition of ISG15 partially restores autophagy, improves efferocytosis, and alleviates disease manifestations. Collectively, these findings define a FAM76B–HNRNPA2B1–ISG15–HSPA8 regulatory axis linking RNA modification to autophagy and efferocytosis, thereby providing mechanistic insight into immune homeostasis and lupus pathogenesis.

Purpose To develop a deep learning segmentation model that can segment abdominal organs on CT and MRI scans with high accuracy and generalization ability. Materials and Methods In this study, an extended nnU-Net model was trained for abdominal organ segmentation. A domain randomization method in both the image and feature space was developed to improve the generalization ability under cross-site and cross-modality settings on public prostate MRI and abdominal CT and MRI datasets. The prostate MRI dataset contains data from multiple health care institutions, with domain shifts. The abdominal CT and MRI dataset is structured for cross-modality evaluation: training on one modality (eg, MRI) and testing on the other (eg, CT). This domain randomization method was then used to train a segmentation model with enhanced generalization ability on the abdominal multiorgan segmentation challenge dataset to improve abdominal CT and MR multiorgan segmentation, and the model was compared with two commonly used segmentation algorithms (TotalSegmentator and MRSegmentator). Model performance was evaluated using the Dice similarity coefficient (DSC). Results The proposed domain randomization method showed improved generalization ability on the cross-site and cross-modality datasets compared with the state-of-the-art methods. The segmentation model using this method outperformed two other publicly available segmentation models on data from unseen test domains (mean DSC, 0.88 vs 0.79 [P < .001] and 0.88 vs 0.76 [P < .001]). Conclusion The combination of image and feature domain randomizations improved the accuracy and generalization ability of deep learning-based abdominal segmentation on CT and MR images. Keywords: Segmentation, CT, MR Imaging, Neural Networks, MRI, Domain Randomization Supplemental material is available for this article. © RSNA, 2025 See also commentary by Mayfield in this issue.

Fbxo2 is part of the SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. While increasing evidence indicates that Fbxo2 influences tumorigenesis and progression in various human malignancies, its biological importance and molecular mechanisms in renal cell carcinoma (RCC) are poorly understood. Bioinformatic analysis of publicly available datasets was utilized to determine the association between Fbxo2 expression and survival in RCC patients. CCK8, colony-formation, and EdU assays were carried out to measure cell proliferation after Fbxo2 modulation in RCC cells. Coimmunoprecipitation, mass spectrometry, Western blotting, and ubiquitin assays were performed to explore the molecular mechanism of Fbxo2-involved tumorigenesis in RCC. Fbxo2 suppresses RCC cell growth. Moreover, higher Fbxo2 expression was positively associated with improved overall survival in RCC patients. In RCC, Fbxo2 inhibition increased cell motility and proliferation and inhibited cell apoptosis. WEE1 was identified as a novel substrate of Fbxo2 in RCC. Fbxo2 binds to the kinase domain of WEE1 through its FBA domain. Consistently, in xenograft mouse models, Fbxo2 knockdown increased tumor growth, whereas WEE1 depletion partially abolishes the tumorigenic effects caused by Fbxo2 silencing in vivo. Our research revealed that Fbxo2 impedes the progression of RCC by interacting with WEE1, promoting its ubiquitination and degradation. Therefore, targeting the Fbxo2/WEE1 axis may represent a promising therapeutic strategy for treating RCC.

Purpose To improve the generalizability of pathologic complete response prediction following neoadjuvant chemotherapy using deep learning-based retrospective pharmacokinetic quantification of early treatment dynamic contrast-enhanced MRI. Materials and Methods This multicenter retrospective study included breast MRI data from four publicly available datasets of patients with breast cancer acquired from May 2002 to November 2016. Pharmacokinetic quantification was performed using a previously developed deep learning model for clinical multiphasic dynamic contrast-enhanced MRI datasets. Radiomic analysis was performed on pharmacokinetic quantification maps and conventional enhancement maps. These data, together with clinicopathologic variables and shape-based radiomic analysis, were subsequently applied for pathologic complete response prediction using logistic regression. Prediction performance was evaluated by area under the receiver operating characteristic curve (AUC). Results A total of 1073 female patients with breast cancer were included. The proposed method showed improved consistency and generalizability compared with the reference method, achieving higher AUC values across external datasets (0.82 [95% CI: 0.72, 0.91], 0.75 [95% CI: 0.71, 0.79], and 0.77 [95% CI: 0.66, 0.86] for datasets A2, B, and C, respectively). For dataset A2 (from the same study as the training dataset), there was no significant difference in performance between the proposed method and reference method (P = .80). Notably, on the combined external datasets, the proposed method significantly outperformed the reference method (AUC, 0.75 [95% CI: 0.72, 0.79] vs AUC, 0.71 [95% CI: 0.68, 0.76]; P = .003). Conclusion This work offers an approach to improve the generalizability and predictive accuracy of pathologic complete response for breast cancer across diverse datasets, achieving higher and more consistent AUC scores than existing methods. Keywords: Tumor Response, Breast, Prognosis, Dynamic Contrast-enhanced MRI Supplemental material is available for this article. © RSNA, 2025 See also commentary by Schnitzler in this issue.

Deregulation of E3 ubiquitin ligases is associated with increased proliferation and metastasis in prostate cancer (PCa); however, the underlying mechanisms remain largely unclear. This study aimed to explore the role of Fbxo2, a SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase, in PCa progression. Analysis of prostate tissue samples revealed that Fbxo2 is downregulated in PCa, and higher Fbxo2 expression correlates with better patient prognosis. Functional assays conducted both in vitro and in vivo demonstrated that Fbxo2 reduces cell proliferation and metastasis in PCa. Using co-immunoprecipitation mass spectrometry (co-IP-MS), co-IP, western blotting, and ubiquitin assays, we identified that m6A reader YTHDF2, an oncoprotein that is upregulated in PCa, was a substrate of Fbxo2-mediated degradation. Notably, Fbxo2 mutants lacking the C-terminal region were less effective in promoting YTHDF2 ubiquitination and destruction. Furthermore, lysine 286 (K286) of YTHDF2 was identified as the key ubiquitination site. A series of rescue experiments revealed that silencing or overexpressing YTHDF2 modulated the effects of Fbxo2 knockdown or overexpression, confirming their functional interplay. Mechanistically, YTHDF2 enhanced the PCa progression and metastasis by modulating the m6A methylation of CDKN1C mRNA. Together, these findings suggest that Fbxo2 axis may serve as a potential prognostic marker and therapeutic target in PCa.

Background and study aims Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates. In vitro model is an indispensable tool to study the pathogenesis of NEC. This study explored the effects of different stress factors on intestinal injury in vitro. Material and methods Rat intestinal epithelial cell line-6 (IEC-6) cells were exposed to different stressors, including lipopolysaccharide (LPS), cobalt chloride (CoCl2), and a combination of both. We estimated the cell viability, the expression of inflammatory cytokines and tight junction proteins. Results The decrease in IEC-6 cell viability was observed after stimulation by CoCl2 alone or in combination with LPS, but not after stimulation with LPS alone. The expression of interleukin6 (IL-6) and tumornecrosisfactoralpha (TNFα) increased in each group. After stimulation with CoCl2 alone or in combination with LPS, a decrease in Claudin-1 was observed, but an increase was detected after stimulation with LPS alone. Zona occludens 1 (ZO-1) decreased in both mRNA and protein levels after combined stimulation. Conclusion The combined stimulation of LPS and CoCl2 on IEC-6 cells could simultaneously induce severe inflammation and barrier damage, which may better simulate the pathological process of NEC.

Background: Multiparametric MRI (mpMRI) as a non-invasive imaging tool is important in prostate cancer (PCa) detection and localization. Combined with radiomics analysis, features extracted from mpMRI have been utilized to predict PCa aggressiveness. T2 mapping provides quantitative information in PCa diagnoses but is not routinely available in clinical practice. Previous work from our group developed a deep learning-based method to estimate T2 maps from clinically acquired T1- and T2-weighted images. This study aims to evaluate the added value of the estimated T2 map by combining it with conventional T2-weighted images for detecting clinically significant PCa (csPCa). Methods: An amount of 76 peripheral zone prostate lesions, including clinically significant and insignificant cases, were retrospectively analyzed. Radiomic features were extracted from conventional T2-weighted images and deep learning-estimated T2 maps, followed by feature selection and model development using five-fold cross-validation. Logistic regression and Gaussian Process classifiers were employed to develop the prediction models, with performance evaluated by area under the curve (AUC) and accuracy metrics. Results: The model incorporating features from both T2-weighted images and estimated T2 maps achieved an AUC of 0.803, significantly outperforming the model based solely on T2-weighted image features (AUC of 0.700, p = 0.048). Conclusions: Radiomics features extracted from deep learning-estimated T2 maps provide additional quantitative information that improves the prediction of peripheral zone csPCa aggressiveness, potentially enhancing risk stratification in non-invasive PCa diagnostics.

Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.

Currently, radiotherapy is one of the most attractive treatments for prostate cancer (PCa) patients. However, radioresistance remains a challenging issue and the underlying mechanism is unknown. Growing evidence has demonstrated that CDC20 (Cell division cycle protein 20) plays a pivotal role in a variety of tumors, including PCa. Here, GEPIA database mining and western blot analysis showed that higher expression of CDC20 was observed in PCa tissues and cells. We demonstrated that the expression of CDC20 was increased in PCa cells by irradiation, and knockdown of CDC20 resulted in inhibition of cell proliferation, migration, tumor formation, induced cell apoptosis and increased radiosensitivity in PCa in vitro and in vivo. Furthermore, we observed that CDC20 regulated Twist1 pathway, influencing cell proliferation and migration. These results suggest that targeting CDC20 and Twist1 may be an effective way to improve the radiosensitivity of PCa.

Abstract Purpose Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, with high death rate. The pathogenesis of NEC is particularly complex, mainly involving inflammation and hypoxic damage. In vitro cell model is an indispensable tool to study the pathogenesis of NEC. This study explored the effects of different stress factors on intestinal injury in vitro. Methods IEC-6 cells were stimulated by exposure to different stressors, including lipopolysaccharide (LPS), cobalt chloride (CoCl2), and a combination of both. Cell viability was detected by CCK-8 assay. The expression of inflammatory cytokines (IL-6 and TNFα) at the gene and protein levels were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immune-sorbent assay (ELISA). While the expression of tight junction proteins (Claudin-1 and zonula occludens [ZO]-1) were evaluated by qRT-PCR and western blotting, respectively. Results The decrease in IEC-6 cell viability was observed after stimulation by CoCl2 alone or in combination with LPS, but not after stimulation with LPS alone. The expression of IL-6 and TNFα increased in each group, especially in the combined stimulation group. After stimulation with CoCl2 alone or in combination with LPS, a decrease in Claudin-1 was observed, but an increase was detected after stimulation with LPS alone. ZO-1 decreased in both mRNA and protein levels after combined stimulation. Conclusion The combined stimulation of CoCl2 and LPS on IEC-6 cells could simultaneously induce severe inflammation and barrier damage, which may better simulate the pathological process of NEC. Further research is needed to determine whether this in vitro model can be used to study the pathogenesis of NEC.

Identifying an epidermal growth factor receptor (EGFR) mutation is important because EGFR tyrosine kinase inhibitors are the first-line treatment of choice for patients with EGFR mutation-positive lung adenocarcinomas (LUAC). This study is aimed at developing and validating a radiomics-based machine learning (ML) approach to identify EGFR mutations in patients with LUAC. We retrospectively collected data from 201 patients with positive EGFR mutation LUAC (140 in the training cohort and 61 in the validation cohort). We extracted 1316 radiomics features from preprocessed CT images and selected 14 radiomics features and 1 clinical feature which were most relevant to mutations through filter method. Subsequently, we built models using 7 ML approaches and established the receiver operating characteristic (ROC) curve to assess the discriminating performance of these models. In terms of predicting EGFR mutation, the model derived from radiomics features and combined models (radiomics features and relevant clinical factors) had an AUC of 0.79 (95% confidence interval (CI): 0.77-0.82), 0.86 (0.87-0.88), respectively. Our study offers a radiomics-based ML model using filter methods to detect the EGFR mutation in patients with LUAC. This convenient and low-cost method may be of help to noninvasively identify patients before obtaining tumor sample for molecule testing.

Recent studies have shown that lycorine, a natural alkaloid compound, plays its anti-cancer role in several human malignancies including bladder cancer. However, the molecular mechanism of lycorine-induced antitumor activity has not been sufficiently investigated. The E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated protein 4 (NEDD4, also known as NEDD4-1) plays a crucial role in tumorigenesis and progression of human cancer. Therefore, depletion of NEDD4 could be a prospective therapeutic strategy for the treatment of cancer. In this study, we investigated whether lycorine restrains tumor by inhibiting the expression of NEDD4 in bladder cancer. We observed that lycorine blocked bladder cancer cell proliferation, colony formation, metastasis and invasion. Moreover, we found that overexpression of NEDD4 in bladder cancer cells significantly promoted cell proliferation and motility, whereas downregulating of the NEDD4 gene expression by lycorine or siRNA suppressed cell growth and movement. Notably, lycorine increased gemcitabine sensitivity in bladder cancer cells. Importantly, lycorine significantly reduced tumor growth, whereas overexpression of NEDD4 accelerated tumor growth and rescued lycorine-triggered tumor inhibition in xenograft mouse model. In conclusion, our study demonstrated that lycorine could exert its antineoplastic activity via suppressing NEDD4 pathway in vitro and in vivo. Therefore, inhibition of NEDD4 expression by lycorine might be a potential efficient strategy for bladder cancer.

Fbxo45, a conserved F-box protein, comprises of an atypical SKP1, CUL1, F-box protein (SCF) ubiquitin ligase complex that promotes tumorigenesis and development. However, the biological function and molecular mechanisms of Fbxo45 involved in pancreatic carcinogenesis are ambiguous. We conducted several approaches, including transfection, coIP, real-time polymerase chain reaction (RT-PCR), Western blotting, ubiquitin assays, and animal studies, to explore the role of Fbxo45 in pancreatic cancer. Here, we report that USP49 stability is governed by Fbxo45-mediated ubiquitination and is enhanced by the absence of Fbxo45. Moreover, Fbxo45 binds to a short consensus sequence of USP49 through its SPRY domain. Furthermore, Fbxo45-mediated USP49 ubiquitination and degradation are enhanced by NEK6 kinase. Functionally, Fbxo45 increases cell viability and motility capacity by targeting USP49 in pancreatic cancer cells. Xenograft mouse experiments demonstrated that ectopic expression of Fbxo45 enhanced tumor growth in mice and that USP49 overexpression inhibited tumor growth in vivo. Notably, Fbxo45 expression was negatively associated with USP49 expression in pancreatic cancer tissues. Fbxo45 serves as an oncoprotein to facilitate pancreatic oncogenesis by regulating the stability of the tumor suppressor USP49 in pancreatic cancer.

Non-small cell lung cancer (NSCLC) is one of the most general malignant tumors. The overexpression of epidermal growth factor receptor (EGFR) is a common marker in NSCLC, and it plays an important role in the proliferation, invasion, and metastasis of cancer cells. At present, drugs developed with EGFR as a target suffer from drug resistance, so it is necessary to study new compounds for the treatment of NSCLC. The active substance in green tea is EGCG, which has anti-cancer effects. In this study, we synthesized dimeric-(-)-epigallocatechin-3-gallate (prodelphinidin B-4-3,3'''-di-O-gallate, PBOG), and explored the effect of PBOG on lung cancer cells. PBOG can inhibit the proliferation and migration of NCI-H1975 cells, promote cell apoptosis, and inhibit cell cycle progression. In addition, PBOG can bind to the EGFR ectodomain protein and change the secondary structure of the protein. At the same time, PBOG decreases the expression of EGFR and downstream protein phosphorylation. Animal experiments confirmed that PBOG can inhibit tumor growth by inhibiting EGFR phosphorylation. Collectively, our study results show that PBOG may induce a decrease in intracellular phosphorylated EGFR expression by binding to the EGFR ectodomain protein, thereby inducing apoptosis and inhibiting cell cycle progression, thus providing a new strategy to treat lung cancer.

Background Preoperative prediction of microsatellite instability (MSI) status in colorectal cancer (CRC) patients is of great significance for clinicians to perform further treatment strategies and prognostic evaluation. Our aims were to develop and validate a non-invasive, cost-effective reproducible and individualized clinic-radiomics nomogram method for preoperative MSI status prediction based on contrast-enhanced CT (CECT)images. Methods A total of 76 MSI CRC patients and 200 microsatellite stability (MSS) CRC patients with pathologically confirmed (194 in the training set and 82 in the validation set) were identified and enrolled in our retrospective study. We included six significant clinical risk factors and four qualitative imaging data extracted from CECT images to build the clinics model. We applied the intra-and inter-class correlation coefficient (ICC), minimal-redundancy-maximal-relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) for feature reduction and selection. The selected independent prediction clinical risk factors, qualitative imaging data and radiomics features were performed to develop a predictive nomogram model for MSI status on the basis of multivariable logistic regression by tenfold cross-validation. The area under the receiver operating characteristic (ROC) curve (AUC), calibration plots and Hosmer-Lemeshow test were performed to assess the nomogram model. Finally, decision curve analysis (DCA) was performed to determine the clinical utility of the nomogram model by quantifying the net benefits of threshold probabilities. Results Twelve top-ranked radiomics features, three clinical risk factors (location, WBC and histological grade) and CT-reported IFS were finally selected to construct the radiomics, clinics and combined clinic-radiomics nomogram model. The clinic-radiomics nomogram model with the highest AUC value of 0.87 (95% CI, 0.81-0.93) and 0.90 (95% CI, 0.83-0.96), as well as good calibration and clinical utility observed using the calibration plots and DCA in the training and validation sets respectively, was regarded as the candidate model for identification of MSI status in CRC patients. Conclusion The proposed clinic-radiomics nomogram model with a combination of clinical risk factors, qualitative imaging data and radiomics features can potentially be effective in the individualized preoperative prediction of MSI status in CRC patients and may help performing further treatment strategies.

Ionizing radiation is a conventional therapy for cancer patients, but patients often experience distant metastasis and recurrence, which lead to a poor prognosis after the implementation of this treatment. Moreover, the underlying mechanisms by which radioresistance contributes to metastatic potential is still elusive. Here, we explored the molecular mechanisms that contribute to radioresistance in bladder cancer. To achieve this, we established two irradiation-resistant (IR) cell lines, T24R and 5637R, which were derived from parental bladder cancer cell lines. Cell viability was detected by CCK-8 assay, while migration and invasion abilities were examined by wound healing and Transwell chamber assays, respectively. Furthermore, the role of Cdc20 in the regulation of epithelial to mesenchymal transition (EMT) in IR cells was explored by Western blotting, immunoprecipitation and immunofluorescence staining. The IR cells exhibited EMT properties, and our data showed that Cdc20 expression was significantly elevated in IR cells. Remarkably, Cdc20 silencing reversed the EMT phenotype in IR cells. Mechanistically, Cdc20 governed IR-mediated EMT in part by governing forkhead box O1 (FoxO1) degradation. Taken together, our findings showed that the inactivation of Cdc20 or the activation of FoxO1 might be a potential strategy to overcome radioresistance in bladder cancer.

Background: Neonatal sepsis is a systemic inflammatory response syndrome in neonates. The molecular mechanism of neonatal sepsis remains incompletely clarified. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in neonatal sepsis. Methods: 93 neonates with sepsis and 93 neonates without infectious diseases were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with whole blood hypersensitive C-reactive protein (hs-CRP) and platelet count (PLT). Differences of RIP3, hs-CRP and PLT between the two groups were compared. Changes of the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for neonatal sepsis was evaluated by receiver operating characteristic (ROC) curve. Results: In sepsis group, RIP3 and hs-CRP levels were significantly higher than those in control group (RIP3, p ＜ 0.0001; hs-CRP, p ＜ 0.0001), and PLT level was significantly lower than that in control group (p＜0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors had a significant decrease (p＜0.0001) and PLT level had a significant improvement (p=0.0028). With RIP3＞15464.72 pg/mL, CRP>3.24 mg/L, PLT<205.00×10 9 /L as the positive criteria, the sensitivity of the three indicators in the diagnosis of neonatal sepsis was 68.8%, 64.5%, 59.1%, and the specificity was 91.4%, 82.8%, 79.6%, respectively. The combination of RIP3, CRP and PLT showed 76.3% sensitivity and 94.6% sensitivity. Conclusions: RIP3 may attribute to the early diagnosis and understanding therapeutic effect of neonatal sepsis. The combined detection of RIP3, CRP and PLT may be more effective than individual ones in the diagnosis of neonatal sepsis.